A Brief History of Attempts to Create and Implement Minimum Standards in Cryonics

INTRODUCTION

First Era 1964-1972

The first attempt to create formal minimum standards for cryonics organizations in the form of the Cryonics Societies of America (CSA) was initiated by in 1968 and was implemented largely through the efforts of the Cryonics Society of New York. The CSA was to be a national standards and enforcement organization, comprised of representatives elected by the individual, member cryonics societies.

Figure 1: Requirements for membership in the Cryonics Societies of America.

Creation of the CSA, and the terms of its incorporation were agreed to by the Officers/Directors of the then extant cryonics organizations: Cryonics Society of New York (CSNY), Cryonics Society of Michigan (CSM) and Cryonics Society of California (CSC). CSA was incorporated late in 1969.

The CSA called for basic accountability in matters such as public communications, information inquiries, membership rolls, financial and member/patient record keeping (submission of quarterly financial records), documentation of cryopreservations (including at least one “confidential” photo), uniformity of letterhead and logos, submission of regular progress reports and investigation of all persons or corporations offering cryonics services or promoting cryonics. Basic requirements were maintenance  of a phone and book listing under the heading “cryonics”, updated list of Officers & Directors, valid addresses for organization and Officers,  and subscription to “Cryonics Reports” for all local group members and a complete log of all written and telephonic information inquiries.

Ironically, one of the driving forces behind CSA was Robert Nelson who, in particular, wanted a standardized procedure generated to administer cryopreservation, particularly with respect to perfusion. A committee consisting of Ettinger, Nelson and Saul Kent was created in April of 1968 to do this, however, according to Kent and Henderson, there was no progress on this, the committee never met, and Nelson did not answer correspondence nor generate the promised liaison with Dante Brunol, M.D., and the CSC mortician Jeff Hicks. Despite misgivings, CSNY committed to be the central body and administration for CSA, and the artist Vaugn Bode generated a logo. Letterhead for national organization was created and standards for regional letterheads were created and implemented.

Figure 2: Vaughn Bode’s CSA logo of a side-view of a Phoenix in flight.

Another critical function of the CSA, and the one which may have motivated its initiation, was the creation of a Scientific Advisory Council (SAC) to the CSA. This Board was to have provided scientific and technical advice related to patient care, evaluated research proposals and recommended funding, and lastly and most importantly, serve to improve the public and professional credibility of cryonics. By 1968, resistance in the scientific community at large was hardening and the cryobiological community was well on its way to becoming highly polarized against cryonics. By this time the mother of cryobiology, Audrey Smith, had already made her public statement calling Ettinger “that horrible man” and Robert W. Prehoda was writing his virulently anti-cryonics book chapters in Suspended Animation: “The Night of January 12, 1967 and “The Lunatic Fringe.” There is some indication that Saul Kent, and perhaps others, may have either seen a precis of these chapters, or otherwise been appraised of their tone, if not their content (CSNY Correspondence Log, 1968).

Figure 2: The 28 April, 1969 letter from Saul Kent laying out the basic parameters required for a national cryonics standards organization to operate.

The SAC was formed on 05 August, 1968 and the relevant documents as well as its composition were published in Cryonics Reports in September, 1968:

Figure 3: The charter of the Scientific Advisory Council (SAC) to the Cryonics Societies of America (CSA). The SAC was to provide the scientific oversight and vetting that would be needed to determine which cryopreservation procedures were applied clinically, and to help direct research to improve them.

There is little known surviving historical documentation of the activities of SAC. According to both Saul Kent and Curtis Henderson, the SAC was not very active and not very responsive to requests for help, although, as they both noted, the areas in which help were most urgently needed either required speculation and expertise (expert speculation from a cryonics perspective, as it were) that the SAC scientists did not have (e.g., formulating perfusion, cooling and storage protocols) or required resources neither the CSA nor its member organizations had available (financing for research). It is clear from correspondence and conversations with some of the principals (Henderson, Kent, Barner and Gouras) that the major obstacle to the SAC’s long term viability was the inability of the CSA to provide anticipated funds for research to be generated by the CSA. There is no evidence that the CSA, acting as unit, provided any input or material support, scientific or technical. The list of the SAC members was used extensively to lend credibility to cryonics for promotional purposes and the list was reprinted as a full page of Cryonics Reports magazine until the SAC gradually disintegrated due to members resigning.

The CSA did remain modestly active for perhaps a year after its inception. There is documentation of essentially complete compliance with the CSA’s requirements in the archival files of CSNY, and much of this material survives and is being digitized. There is evidence that CSM provided substantial compliance, including providing membership rolls, records of information requests, and at least semi-annual bookkeeping summaries. CSC did not provide membership lists, patient records, or financial data. They did provide photographic evidence of the cryopreservation of Marie Phelps Sweet, under substantial pressure and amid allegations (untrue as it turned out) that Ms. Sweet‘s cryopreservation may have been a hoax used to raise money for CSC or Robert Nelson, and those photographs have survived and been digitized.

Figure 4: Robert F. Nelson, President of the Cryonics Society of California

While the CSA was neither very active nor effective, it did continue to exist, at least in name, until serious concerns about the operations of CSC, Cryonic Interment and the integrity of Robert F. Nelson were raised, and finally aired publicly by Saul Kent in an editorial in Cryonics Reports entitled “Trouble in Southern California?” which questioned the integrity of CSC’s patient storage operations (Cryonics Reports: 4(12) 1969; p 2) as noted in this quote from that article:

“At last years’ national cryonics conference in Ann Arbor, Mich. [actually held in April 1969, 8 months before--MP], and Marshall Neel’s presentation concerned a new cryonic storage facility which, according to Mr. Neel, was close to completion. Slides showing the process of construction were offered, and it was stated that within a short time there would be a grand opening before the media, at which several bodies then in individual cryonic storage would be placed into a large multiple-body unit. Cryonic Interment Inc. was the name of the company that was said to own the facility; Mr. Neel was announced as President.

 Since the conference there have been continual statements emanating from the leadership of the Los Angeles based company about the imminence of the opening of the facility.

 As of December, 1969, the facility has not been opened and there is no evidence to indicate that it will.

 We don’t know what has been going on in Southern California because the entire operation has been veiled in secrecy. It is just this air of secrecy that troubles us.”

 The CSA probably became legally defunct within a year or so thereafter since there are unpaid bills for corporation taxes and no evidence of disbursements for these from, either the CSNY or CSC financial archives which are complete for this period. Unless the fees were paid by CSM or by an individual(s) the CSA would have legally ceased to exist sometime in 1970.

 Second Era 1972-1976

Figure 5: Fred and Linda Chamberlain began a second round of unsuccessful efforts in the early 1970s to create a minimum standards  and compliance self- regulatory framework for cryonics. This effort, as had the previous one in the form of the CSA, proved unsuccessful.

The next attempt to establish industry-wide binding standards was initiated by Fred and Linda Chamberlain of the Alcor Foundation in 1972. The effort had, if I recall correctly, the acronym DOMSAC which stood for ” Document of Minimum Standards and Compliance” (DOMSAC). The core requirement of the DOMSAC were to:

“Set minimum standards for all technical aspects of perfusion and cool-down, including data collection formats, parameters to be logged, frequency of data acquisition, minimum equipment and chemical to kept on hand at all times, and so on.” The objectives of the DOMSAC were to:

• Established a basic standard for organization, reporting and public disclosure of patient case data.
• Required continuous public accountability (address, identification, a.k.a. and d.b.a. history on all Officers and Directors).
• Established minimum requirements for emergency notification and communication systems.
• Limited the scope and nature of claims that could be made to the public or prospective members/clients about cryonics.
• Impose substantial administrative requirements, as well as mechanics for handling non-compliance and provisions for punitive measures if necessary.

Figure 6: Former President of the Cryonics Society of California, Robert F. Nelson (aka Frank Bucelli) being warmly received by Robert C. W. Ettinger, one of the two originators of the cryonics movement in 20

This document provoked extended haggling and arguments from Trans Time (TT) and the Bay Area Cryonics Society (BACS). (BACS and TT were essentially run by the same management at that time), and to a lesser extent from the Cryonics Society of Michigan (CSM).  The was concern expressed on the part of TT/BACS that the DOMSAC constituted an unacceptable step towards the surrender of autonomy, even if it was in the form of mutual oversight.” To what extent these sentiments were justified it is impossible to know. It certainly has been the case that getting cryonicists, even within their own organizations, to submit to oversight and regulation has so far proven impossible. For instance, Robert F. Nelson was in no way punished for his misdeeds at Chatsworth within the cryonics community, and he is welcomed at both CI and other cryonics functions, where he is treated cordially and has indicated he might reenter the cryonics business in the future.

What was clearly not understood then, or now, is that this “issue” inside cryonics is not a drawing room matter, or even a dirty political backroom matter. It stopped being either of those things when the first patient decomposed at Chatsworth or, more accurately, when Bedford was mishandled by Cryonics Society of California personnel on 12 January, 1967, with the knowledge and complicity of other key people in the cryonics movement.

Specimen Standards for Human

Cryopreservation Organizations Draft 2.4

Core Objectives and Related Considerations

The objective of these specimen standards is to return cryonics to the paradigm that was developed initially by the Cryonics Society of New York (i.e., fairness, openness, use of the scientific method, Evidence Based Cryonics (EBC) and diligent communication of comprehensive and accurate information to cryonics organization members or clients), and greatly elaborated by Alcor under the influence of Jerry Leaf and Mike Darwin in the 1980s. This paradigm can be articulated by the following points:

Organizational (Corporate) Structure & Governance

The organizational structure considered here will be that of the non-profit corporation United States corporation,  either charitable (501(c)3) or non-charitable.

The cryonics organization shall be a legally incorporated entity which complies with all applicable federal laws and regulations, as well as applicable laws and regulations of the states and the local jurisdictions in which it is based or operates. If the organization conducts programs outside the United States, it must also abide by applicable international laws, regulations and conventions that are legally binding on the United States.

The organization shall have a formally adopted, written code of ethics with which all of its directors or trustees, staff and volunteers are familiar and to which they adhere and they will adopt and implement policies and procedures to ensure that all conflicts of interest, or the appearance thereof, within the organization and the board are appropriately managed through disclosure, recusal, or other means. This Code of Ethics shall cover accountability, finances, openness, client/member rights, patient rights, confidentiality of medical and cryopreservation records, conduct of staff, and basic procedures for filing and adjudicating grievances within the organization by clients/patients and professional employees.

The cryonics organization shall establish and implement policies and procedures that enable individuals to come forward with information on illegal practices or violations of organizational policies. This “whistle blower” policy should specify that the organization will not retaliate against, and will protect the confidentiality of, individuals who make good-faith reports.

The organization shall have in place policies and procedures to protect and preserve the organization’s important documents and business records.

The organization’s board must ensure that the organization has adequate plans to protect its assets—its property, financial and human resources, programmatic content and material, and its integrity and reputation—against damage or loss. The board should review regularly the organization’s need for general liability and directors’ and officers’ liability insurance, as well as take other actions necessary to mitigate risks.

The organization must have a detailed, written plan of action to protects its patients in cryopreservation against legal or legislative attack, economic instability, insurgent attack by anti-cryonics individuals or entities, as well as plans to cope with and prevail over known existential risks to which its patients may be subject (i.e., hurricanes, tornadoes, earthquakes, blizzards, etc.).

Figure 1: Cryonics organizations must maintain transparency with respect to administrative, financial, scientific, technical and patient care procedures.

The organization must  make information about its operations, including its governance, finances, programs and activities, widely available to the public. Charitable (501(c)3) organizations shall make information available on the methods they use to evaluate the outcomes of their work and must share the results of those evaluations with members.

The cryonics organization must have a governing body that is responsible for reviewing and approving the organization’s mission and strategic direction, annual budget and key financial transactions, compensation practices and policies, and fiscal and governance policies.

Figure 2: The board of directors of the cryonics organization are elected by the cryopreservation members or clients of the organization who have been cryopreservation members or clients of the cryonics organization for at least 3 consecutive years. Directors’ terms may not exceed 4 years.

The board of directors shall be elected by the cryopreservation members or clients of the organization who have been cryopreservation members or clients of the cryonics organization for at least 3 consecutive years. Cryopreservation members with 10 or more years of consecutive cryopreservation arrangements may, at the organization’s discretion, be granted 2 votes in electing directors.

Candidates for the board shall be examined for psychosocial and fiscal suitability by a thorough, objective and written set of standards and examinations.

Directors term limits, order of service (staggered or otherwise) are that the discretion of the cryonics organization. However the length of any director’s term in office cannot exceed 4 years.

The organization must meet regularly enough to conduct its business and fulfill its duties. Directors’ meetings shall be held monthly and combined directors and membership meeting shall be held no less than annually.

The board of organization should establish its own size and structure and review these periodically. The board should have enough members to allow for full deliberation and diversity of thinking on governance and other organizational matters. Except for very small organizations, this generally means that the board should have at least five members.

The board of the  organization must include members with the diverse background (including, but not limited to, ethnic, racial and gender perspectives), experience, and organizational and financial skills necessary to advance the organization’s mission. All directors and officers must be have been cryopreservation members or clients of the organization for a minimum of 3 consecutive years before becoming eligible to serve as a director or officer. In the case of newly forming cryonics organizations, officers and directors must have been members or clients of another cryonics organization for a minimum of 3 consecutive years.

At least two-thirds of the board members, should be independent. Independent members should not: (1) be compensated by the organization as employees or independent contractors; (2) have their compensation determined by individuals who are compensated by the organization; (3) receive, directly or indirectly, material financial benefits from the organization except as a member of the charitable class served by the organization; or (4) be related to anyone described above (as a spouse, sibling, parent or child), or reside with any person so described.

The board shall hire, oversee, and biannually evaluate the performance of the chief executive officer of the organization, and should conduct such an evaluation prior to any change in that officer’s compensation, unless there is a multi-year contract in force or the change consists solely of routine adjustments for inflation or cost of living.

The board of any cryonics organization that has paid staff should ensure that the positions of chief staff officer, board chair, and board treasurer are held by separate individuals. Organizations without paid staff should ensure that the positions of board chair and treasurer are held by separate individuals.

The board shall establish an effective, systematic process for educating and communicating with board members to ensure that they are aware of their legal and ethical responsibilities, are knowledgeable about the programs and activities of the organization, and can carry out their oversight functions effectively.

Board members should evaluate their performance as a group and as individuals no less frequently than every 2 years, and should have clear, written  procedures for removing board members who are unable to fulfill their responsibilities.

Beyond the requirement of 3 consecutive years as a cryopreservation member or client, the board shall establish clear policies and procedures setting the length of terms and the number of consecutive terms a board member may serve.

The board should review organizational and governing instruments no less frequently than every 3 years.

The board shall establish and review regularly the organization’s mission and goals and should evaluate, no less frequently than every five years, the organization’s programs, goals and activities to be sure they advance its mission and make prudent use of its resources.

Board members are generally expected to serve without compensation, other than reimbursement for expenses incurred to fulfill their board duties. A charitable organization that provides compensation to its board members should use appropriate comparability data to determine the amount to be paid, document the decision and provide full disclosure to anyone, upon request, of the amount and rationale for the compensation.

The cryonics organization must keep complete, current, and accurate financial records. Its board should receive and review timely reports of the organization’s financial activities and should have a qualified, independent financial expert audit or review these statements annually in a manner appropriate to the organization’s size and scale of operations. For cryonics organizations with more than $500,000 U.S. in assets the independent financial expert must be certified public accountant (CPA).

Cryonics organizations with assets of $1 million U.S., shall have an audit committee composed of independent board members with appropriate financial expertise. By reducing possible conflicts of interest between outside auditors and the organization’s paid staff, an audit committee can provide the board greater assurance that the audit has been conducted appropriately. If state law permits, the board may appoint non-voting, non-staff advisers, rather than board members, to the audit committee.

The board of the organization must institute policies and procedures to ensure that the organization (and, if applicable, its subsidiaries) manages and invests its funds responsibly, in accordance with all legal requirements. The full board should review and approve the organization’s annual budget and should monitor actual performance against the budget.

The cryonics organization should not provide loans (or the equivalent, such as loan guarantees, purchasing or transferring ownership of a residence or office, or relieving a debt or lease obligation) to directors, officers, or trustees.

The organization shall spend at least 30% of its annual budget on programs that pursue its mission. The budget should also provide sufficient resources for effective administration of the organization, and, if it solicits contributions, for appropriate fundraising activities.

Figure 3:  Reimbursement for expenses, as well as compensation for services for directors must be unambiguous and in written form.

The  cryonics organization shall establish clear, written policies for paying or reimbursing expenses incurred by anyone conducting business or traveling on behalf of the organization, including the types of expenses that can be paid for or reimbursed and the documentation required. Such policies should require that travel on behalf of the organization is to be undertaken in a cost-effective manner.

The organization shall neither pay for nor reimburse travel expenditures for spouses, dependents or others who are accompanying someone conducting business for the organization unless they, too, are conducting such business.

Solicitation materials and other communications addressed to donors and the public must clearly identify the organization and be accurate and truthful.

Without exception, contributions must be used for purposes consistent with the donor’s intent, whether as described in the relevant solicitation materials or as specifically directed by the donor.

The organization, if a 501(c)3, must provide donors with specific acknowledgments of charitable contributions, in accordance with IRS requirements, as well as information to facilitate the donors’ compliance with tax law requirements.

The organization must have clear, written policies, based on its purpose as a cryonics organization to determine whether accepting a gift would compromise its ethics, financial circumstances, program focus or the well-being of the patients in its care.

The cryonics organization should provide appropriate training and supervision of the people soliciting funds on its behalf to ensure that they understand their responsibilities and applicable federal, state and local laws, and do not employ techniques that are coercive, intimidating, or intended to harass potential donors.

The organization shall not compensate internal or external fundraisers based on a commission or a percentage of the amount raised.

The cryonics organization shall respect the privacy of individual donors and, except where disclosure is required by law, shall not sell or otherwise make available the names and contact information of its donors without providing them an opportunity at least once a year to opt out of the use of their names.

The board shall prepare a written job description for individual board members as well as prepare an annual schedule of meetings, determined a year in advance.

The board she see to it its members receive clear and thorough information materials, including an agenda, to all members two to three weeks before each meeting.

Figure 4: The comprehensive and complete minutes of every directors’ meeting must be recorded on paper, as well as electronically and must be c9ompiled into readily accessible books or volumes for inspection by cryopreservation members or clients at any reasonable time. Similarly, electronic copies of minutes shall also be available so that members distant from the organization’s headquarters may have access to the minutes.

The cryonics organization shall maintain complete and accurate minutes of all meetings which shall be gathered into volumes organized by month and year. These minutes shall be kept at the cryonics organization’s principal place of business and be available for inspection upon the request of any  cryopreservation member or client. Additionally, multiple electronic copies  shall be kept in discrete separate locations to prevent loss due to existential or other disasters and so that they can be made available to members or clients who are far distant from the organization’s principal place of business.

Each board member shall serve on at least one board committee or task force. (For new members, one committee assignment is sufficient.)

The board shall prepare written statements of committee and task force responsibilities, guidelines and goals. These organizational documents, which should be approved by the board chair, are to be reviewed annually, and revised if necessary. The CEO shall assign an appropriate staff member to work with each committee

The board shall create a written system of checks and balances to monitor committee members’ work and assure that tasks are completed on schedule.

Nondiscrimination

The medical model of cryonics as an emergency room (Accident & Emergency) where all comers able to meet the publicly specified requirements of the organization are competently and equally treated, regardless of age, religion, politics, criminal history, gender, sexual orientation, community influence, or celebrity. “Equally” is understood to mean here that all clients will receive the same minimum standards of care set out as being available upon meeting the specified minimum requirements of the organization. It does not imply that higher standards of care may not be paid for by clients able to afford them.  However, it does mean that if such higher standards are offered, or are available for an added fee or other considerations, that all clients shall be apprised of the availability of such non-standard services, as soon as such options are made available.

Figure 5: Cryonics organizations must not discriminate on the basis of age, religion, politics, criminal history, gender, sexual orientation, community influence, or celebrity.

Additionally, the cryonics organization shall adopt the following non-discrimination policy:

The cryonics organization believes that every person has a right to choose and arrange for his or her own cryopreservation and to enjoy its possible benefits of greatly extended lifespan. To this end, the cryonics organization does not discriminate against any person on the basis of race, religion, color, creed, age, marital status, national origin, ancestry, sex, sexual orientation or preference, medical condition, or handicap.

However, nothing in this statement prevents the cryonics organization from avoiding any situation that genuinely threatens the health or safety of cryonics organization employees, volunteers, patients in cryopreservation, or the public, or from requiring reasonable medical evaluations in some instances where a genuine threat to health or safety may be suspected to exist, or where the legal status of an individual with regard to mental competency may be in question.

Feedback, Quality Assurance & Quality Control

Quality control measures which provide feedback about the nature and effectiveness of all of the organization’s procedures will be publicly disclosed in an open and timely fashion. This is understood to include not only medical, cryobiological, patient care, or other technical and scientific procedures, but also financial, administrative and business procedures as well. Both classes of disclosure, technical and administrative, will be discussed with varying level of detail in this document. In administrative areas where there are long established and demonstrably workable resources, the discussion will be more superficial. In technical, ethical and other areas where there is little or no precedent, the discussion will be exhaustive and often accompanied by detailed examples of the required work product.

The clear message of this point is that a culture of openness and accountability is perhaps the most important ingredient to the long term success of any cryonics organization or, for that matter, any quality scientific, technical, or medical institution.

It is important to digress briefly here and discuss the problematic nature of such a high degree of accountability with respect to cryonics organizations, in particular. All human institutions, whether cryonics organizations or otherwise, find this level of accountability difficult to achieve. There are many reasons for this; however these two are by far the most significant: the basic human desire to avoid owning failure, error or misdeeds, and the ammunition public knowledge of failure, error, or misdeeds provides an enemy[1] — which segues into the next point.

Need for a Defensive Organization (a.k.a. Cryonics Defense League)

Cryonics as a whole has become fear-driven and in nearly constant crisis mode. Crises driven operation is necessarily mostly reactive rather than proactive. This is not how any successful organization advances scientifically or financially. Indeed, it is not how success is achieved in any area of organizational operations, even in successfully defending the organization in the long run. Because of this situation it is especially difficult for cryonics organizations to have a high level of accountability, even about seemingly harmless facts pertaining to their procedures and policies, because cryonics is not an established business institution, has an (arguably) increasing number of serious enemies, is widely misunderstood, has been subject to unjustified distortion and sensationalism, has been subjected to repeated rounds of invasive and destructive media siege, and is increasingly coming under governmental scrutiny. Under such circumstances it is completely understandable for a “bunker mentality” to develop.

Further, in order to protect its human cryopatients, a cryonics organization may have to develop not only a bunker mentality, but very aggressive and covert means to defend the well being of its patients. The author has spent the past several years reading extensively the history of emerging medical, social, political and religious movements. In no case was social acceptance or tolerance of any major paradigm changing movement achieved without the use of force and fraud. I even include Darwin’s theory of evolution in this analysis since, as Stephen Jay Gould noted just a few years ago in his book The Structure of Evolutionary Theory, Evolution is neither widely understood nor accepted – this, more than a hundred years after it was publicly espoused.

Cryonics organizations need a separate, defensive organization which can act semi-covertly or covertly as needed to deal with lethal threats, which all conventional approaches have failed to stop. Separating defensive capability from other operations would allow accountability to continue in every area of operations except the last and most desperate measures needed for defense of patients and members. This would allow some measure of psychological tranquility to exist in the organization as a whole, even in the midst of extreme threats, and thus for business as usual to continue and a high degree of experimentation and openness to be maintained even under difficult circumstances.  The most immediate analogy is one of the intelligence and military apparatus of a nation-state. Because these assets exist in a hostile world it is not necessary for citizens, businesses, churches, or charities to anguish over every threat to their existence. Yes, in times of severe crises, or all out attack, all of these entities may divert some or all of their efforts, attention, and support to the crisis, but on a daily basis, it is not necessary that they be consumed with the problems of their own defense. However, more relevant analogies would the Jewish Defense League (JDL) or the Worldwide Guardian Office employed by Scientology.

Until cryonics organizations can rely on a defense force which is competent and properly equipped to deal with even the worst crises, the organization as a whole will be drained of energy and other resources, and most importantly, will be paralyzed by anxiety, and become increasingly afraid to take any actions which expose more of its flank to attack. This is a response characteristic of most life forms more complex than viruses, and is one which must be dealt with. Every organization charged with protecting the survival of its members has such defensive mechanisms, from the amoebae to the U.S. Federal Government.  This is a critical need, which has heretofore been unappreciated in cryonics. The absence of such a defensive mechanism in cryonics is the principal cause of the increasing risk-averseness, and willingness to surrender authority over patients to the regulatory bodies of nation-states.

End of Part 1

By Mike Darwin

 Show: “Castle”

Season: 4

Episode: 3, “Head Case”

Air Date: 10/03/11

Series Creator: Andrew W. Marlowe

Writer: David Grae

Characters: Rick Castle, Kate Beckett

Location: Los Angeles, CA

Photos Credit: ABC/Adam Taylor

“Castle” Stars: Nathan Fillion as Richard Castle, Stana Katic as NYPD Detective Kate Beckett, Susan Sullivan as Martha Rodgers, Molly Quinn as Alexis Castle, Penny Johnson Jerald as NYPD Captain Victoria Gates, Tamala Jones as Medical Examiner Lanie Parish, Jon Huertas as NYPD Detective Javier Esposito, and Seamus Dever as NYPD Detective Kevin Ryan.

Guest Cast: William Atherton as Dr. Ari Weiss, Andy Umberger as Johnny Rosen, Judith Hoag as Cynthia Hamilton, Shaun Toub as Dr. Philip Boyd, Jordan Belfi as Beau Randolph, Jared Hillman as Eddie Peck.

NOTE: You can watch the full episode of “Castle” reviewed here on line at no charge: http://www.hulu.com/watch/282426/castle-head-case

ESSENTIAL BACKGROUND

 Figure 1: Stana Katic as NYPD Homicide Detective Kate Beckett enters the Passage cryonics facility with her gun drawn in search of the missing body of a homicide victim.

 I’m a regular viewer of “Castle,” so my take may be prejudiced. “Castle” is very light TV fare – it is a fanciful police procedural comedy/drama that centers on the adventures of a crime novelist, Rick Castle, who is on a perpetual “ride along” with an attractive female homicide detective named Kate Beckett. Beckett has served as the inspiration for one of Castle’s most successful characters, Detective Nikki Heat. Superficially, “Castle” is escapist fare that offers some respite from sadistic pornography of “Criminal Minds” or the now predictable, hard-boiled and increasingly preachy cynicism of the “Law and Order” franchises.“

Castle” is a throwback to the humorous, but morality and issue driven “detective” writing of Anthony Boucher, Herbert Brean, and perhaps the most talented master of this genre, John Dickson Carr. As critic S. T. Karnick has aptly said of “Castle”and its predecessors:

“What these and their contemporaries excelled at was creating a sense of wonder, building a fantastic situation that has an inexorable logic of its own. In their way, they conveyed a sense of American life as a realm of astonishing possibilities ultimately grounded in common sense, logic and morality. It’s a form of fiction I enjoy greatly and which I think has much to recommend it.”

As TV fare it has more in common with “Ellergy Queen” or “Murder She Wrote” than CSI or “Blue Bloods.” Often I hear more of “Castle” episodes than I see of them, but it is good, non-traumatic, “wind down” entertainment before bed; nice to watch while reading book and preparing to doze off. However, a “good” episode will cause the book to be put down and will fully command my attention. This was a good episode of “Castle”, in fact I would argue that it was an extraordinary episode. I say this because “Castle” doesn’t usually explore ideas in any nuanced way, other than those surrounding romantic and family life, which are the core values the show seeks to explore, albeit 21^st century style.

Castle is a highly successful author, divorced, more than a bit juvenile and a something of rake who finds his way into the beds of the occasional vixen who strays into the plotline. Detective Beckett is the serious, sober and grounded half of the duo, whose job it is to burst the bubble of most of Castle’s outrageous, and usually erroneously wild conspiracy theories of the crimes they encounter together.  The emotional subtext is that Castle is madly in love with Beckett, Beckett is arguably is in love with Castle and neither has the confidence in themselves, or their life choices to admit these feelings to each other, or to anyone else, for that matter.

Because “Castle” is, at least superficially not a serious TV drama, the idea of a cryonics-themed episode made me squirm more than a bit. The whole idea screamed “clichéd mockery.” As it turned out, this episode was some of the best cryonics-themed TV programming I’ve ever seen – at least in terms of thoughtfully exploring the multiple significant issues cryonics poses to the culture. Without as doubt this episode’s presentation of the emotional and value-driven reasons for why we cryonicists are doing what we are was the most accurate and moving of any I’ve seen  to date.

Figure 2: Nathan Fillion as the crime fiction writer Richard Castle exploring the cryonics facility. Passage Cryonics either has really bad Superinsulation, or they just finished filling every dewar in the facility.

CRYONICS AND HOMICIDE INTERSECT ON TV (AGAIN)

The plot line (warning, spoiler alert) is that a murder has occurred in a New York City street, but there is no body; just so much blood on the scene that the victim would have almost completely exsanguinated. Through various twists and turns, the victim is determined to be an academic who was pursuing promising research on a life extension technology that would add ~ 10 healthy years to a person’s life by causing the body’s dividing cells to produce young, rather old replacements for themselves. The identification of the likely victim leads Beckett, Castle and crew to a “self storage warehouse” where they discover an “under the radar” cryonics facility called “Passage.”

       Dr. Weiss: “He conducted cutting-edge research developing        life-extension techniques.”

       Castle: “Not that it did him any good.”

It was at this point that I started to grin.  This set-up precisely describes Alcor and its location from mid-1970s to the mid-1980s in Fullerton, CA. What’s more, the first man ever cryopreserved, James H. Bedford, was stored for a number of years by his family in a San Fernando Valley mini-warehouse that was part of franchise called “Self Storage;” something I found more than a bit of an irony at the time. Could the “Castle” writers have done their homework that well? Surely not; but, it was good for a grin, anyway.

Figure 3: Seamus Dever as NYPD Detective Kevin Ryan (left) Kate Beckett (center) and  Jon Huertas as NYPD Detective Javier Esposito draw a bead on the two cryonics technicians who are in the process of placing the missing homicide victim into long-term cryogenic storage.

Almost immediately after entering the cryonics facility, the homicide investigative crew encounters the Passage personnel sliding the missing murder victim into a dewar. Beckett informs them that the police are going to take custody and that the Medical Examiner (ME) will need to autopsy the body. Enter the smarmy, self-righteous and utterly self-assured President of Passage Cryonics, accompanied by his even more self assured, viperous and lawsuit threatening caricature of a lawyer. Remove the patient from cryopreservation (yeah, they actually use that word; we’re making progress) and Passage will sue the NYPD and the ME’s Office into financial oblivion! the attorney informs them.

       Castle: “You got any celebrities in here? Ted Williams? Jack Frost”

Beckett and crew phone the District Attorney for a warrant to seize the body, only to be told that, “the case law is murky on the issue of whether or not a coroner can autopsy a cryonics patient.” Incredible!  now the writers really have my attention, because the Dora Kent case was not a “recorded” case that definitively established precedent; the California Appellate Court let the lower (Superior) court’s ruling stand, but declined to grant the case “precedent setting status.”[1] Maybe these guys really did do their homework after all!

ART IMITATES LIFE

The researcher/patient’s wife is questioned by Detective Beckett (and Castle) and she comes across as a sympathetic person who wants, above all else, to defend her husband’s cryopreservation and ensure that he has another chance at an indefinitely extended life. In fact, she reminisces during her interview that, when she and her husband first met, he told her that he was so in love wit her that “one lifetime would never be enough” – he wanted to spend eternity with her – and life extension and cryonics were the tools to achieve that end.

Figure 4: At left, fictional pornographer Beau Randolph as portrayed by actor Jordan Belfi and at right, real pornographer Larry Flynt who did indeed at one time have a serious interest in cryonics. [2)

However, as it turns out, the ME may not need to do an autopsy after all. One of the victim’s associates, a famous pornographer who created the “College Girls Gone Wild” franchise has been bankrolling the life extension researchers academic’s work. And tellingly, they’ve just argued repeatedly over the “dead” man’s desire to make his life extending discovery “open source” for the entire world to further advance and benefit from. By now, I’m chuckling. Is this a reference to Hustler’s Larry Flynt? I’m beginning to think that I’m starting to see my life played out on a very B-list (but nevertheless amusing) TV show. [2]

 Figure 5: At left actor William Atherton as Dr. Ari Weiss, CEO of Passage Cryonics (shades of Avi Ben Abraham, center?) and at right, Dr. Max More, CEO of the Alcor Life Extension Foundation. [3]

Alas, the pornographer owns a gun, fired the very morning of the murder, that could possibly be the murder weapon. The cops need the slug, and the slug is in the cryopreserved body of the victim.  Cut to a testy conference between the ME, the cops, the CEO of Passage Cryonics and their oily lawyer. The ME insists on an autopsy of the body and it’s clear that she now has probable cause and will likely get the necessary court order. Suddenly, the Passage CEO stands up and announces that he has the answer; all cryonics requires is the brain, so why not give the ME the body for autopsy and allow the cryonics organization to keep the head? Now, I know the writers have done their homework. [3,4] One, two, or three coincidences? Maybe. But this many? Not a chance!

Figure 6: At right, Tamala Jones as Medical Examiner Lanie Parish discloses the results of her autopsy on the headless body of the murder victim. A plot lifted right from the Dora Kent case. [4,5]

A TANGLED STORYLINE

The head is removed, the body is autopsied, the slug is recovered, and, just like in real life (Larry Flynt), the wily pornographer is off the hook; they can’t pin the crime on him because he didn’t do it. He was, as he told the police, otherwise occupied murdering a noisy pigeon on his roof that morning. A compliant of animal cruelty is sworn out against him and he vanishes from the proceedings.

The once cooperative ME now demands the patient’s head, because, as it turns out,  he appears to have been serving as his own guinea pig by having the implants that cause tissue rejuvenation placed in his brain. The 0nly problem is that when the investigators go to retrieve the head (patient), surprise, he’s missing from the cryonics organization’s facilities!

       Beckett: Are you saying you lost his head?

So, who took him and why? It is soon discovered that the patient’s researcher friend has removed him from Passage in order to prevent his destruction by cranial autopsy. What was really going on was that the patient was dying of an inoperable malignant brain tumor (glioblastma multiforme) and this colleague was undertaking to try and save him with a highly experimental, and unfortunately, ineffective nanoparticle cancer treatment. Our cryonics patient was thus doomed to die of a brain tumor – a brain tumor that would, before it killed him, utterly destroy his brain, thus making any hope of recovery from cryopreservation impossible. So now, in addition to the Dora Kent case, the writers have folded in the Donaldson v. the Attorney General of the State of California case. [6]

The nano-cancer researcher colleague explains to the homicide investigators that even though the tumor was growing rapidly, the patient had decided to continue pursuing his life extension research and forgo being cryopreserved. He turns over the MRIs and other documentary evidence explaining why trace evidence of brain matter from the patient had been found in a secret lab, ending the need for further postmortem dissection.

Revelation of these facts also explained the seemingly anomalous download of a “cryopreservation cancellation document” for Passage Cryonics, recovered from the patient’s laptop. Finally, it dawns on Castle and Beckett that the shooting that ended this life cycle for the patient was the very thing that might be responsible for saving his life. They correctly reason that if he wasn’t cryopreserved while his brain was reasonably intact, then he would be lost forever.

THE 21^ST CENTURY ROMEO & JULIET

Figure 7: 21st Century Romeos and Juliets use cryonics as a way to overcome the tragic circumstances of disease and death which threaten to separate them forever.

Bingo (!); the missing motive in the case in now apparent. If his wife was aware he was not only dying of brain cancer, but also that he planned to terminate his cryopreservation arrangements, then the only way she could hope to ensure their future together was to “kill” her husband now, while both his brain and his cryopreservation arrangements were still reasonably intact.

This was, in fact, exactly what she had done. As the show winds up there is a touching and very emotional monologue from the wife explaining that the tumor had warped her husband’s judgment and that he was no longer making decisions as he had when was well; she had no choice but to stop his heart with a gunshot, triggering his GPS-enabled bio-monitoring watch and summing the cryonics team.  The wife is placed in a holding cell and Castle, Beckett and the Passage President confer about the situation. Suddenly, the Passage CEO’s smartphone registers an alarm: a Passage client has experienced cardiac arrest, butit makesno sense since the GPS feature shows the location as right there in the jail.  It is quickly discovered that the wife has taken a cyanide tablet concealed in a ring she was wearing.[1] The wife lies lifeless on the floor of the cell and there is a moment of stunned silence, broken by the Passage CEO, who pleadingly asks if he can summon the cryonics team so that the wife can join her husband on the long journey into the future. Beckett says, “Yes,” having already expressed her sympathy with the wife for her act of “involuntary euthanasia” that put in him Passage cryonics with two bullets in his chest at the start of the story.

Whew! Every significant medico-legal issue in the public history of cryonics to date, all rolled into one ~ 45-minute long TV episode! That’s quite a feat! But a much more impressive one was that writer and the creator of “Castle” got all the important things right. No, they didn’t get much the technical side of cryonics right, and for that, we may arguably be thankful. The Passage cryonics patients, unlike the real ones, look like very startled solid-state versions of their living selves. This is the first time I’ve ever seen cryonics patients depicted with their eyes open – wide open, in fact.

But the shortcomings in the technical depictions of cryonics were more than compensated for by the fact that the show’s creative talents got the core messages of cryonics right. Medico-legal death is a process not a condition, and “irreversibility” is a function of brain structure and the sophistication (or lack thereof) of available medical science and technology. Life is a good thing, and the desire for indefinitely long and healthy lives, free from the burdens of aging, disease and death are reasonable goals being pursued by reasonable people. Indeed, they are romantic goals and they are technologies that offer everyday people the opportunity to continue expressing the best and brightest of their humanity; their love of each other, their pursuit of knowledge and growth, and their desire to transcend time.

Wow! That’s a lot, coming as it is from the principal engine of the popular culture: television. We cryonicists owe a sincere debt of gratitude and some heartfelt thanks to the writer, director and the  producers of this “Castle” episode.

Please, write them and communicate your appreciation:

http://beta.abc.go.com/shows/castle/discuss#linkIdAll

REFERENCES

By Mike Darwin

It’s astounding;
Time is fleeting;
Madness takes its toll.
But listen closely…

Not for very much longer.

I’ve got to keep control.

I remember doing the time-warp
Drinking those moments when
The Blackness would hit me

And the void would be calling…

Let’s do the time-warp again.

             — “The Time Warp,” Rocky Horror Picture Show by Richard O’Brien.

Yesterday, on Cryonet2, a post caught my eye and ended up having a special resonance for me. The subject under discussion was a media story about a man who had been in prison for ~20 years and who, upon his release, found it so difficult to adapt to the technological and social change that occurred during his time in confinement, that he set fire to an abandoned building in order to be returned to prison for a good long time. The person commenting on this article wrote, “I find the story is bit hard to swallow, having some familiarity with the general issue. Prisons have televisions. Cell phones are commonly smuggled into prisons, and computers are common in prisons, including some for prisoner use.”

At first blush, his incredulity seems justified, and even with deeper consideration his skepticism may seem appropriate, because people from Bronze Age cultures can and do adjust just to cultural change and displacement far more massive than that prisoner experienced. For example, some of the Hmong People from Vietnam successfully made the jump to the US at the end of the Vietnam War (by 1978 some 30,000 were living in the US) and many actually out-competed their new compatriots in the US.

Figure 1: The Hmong people of South Vietnam lived a culture suspended in time between the Stone and Bronze and ages in the 1970s. Above is a typical Hmong village from that time period.

Figure 2: A Hmong village in southern Vietnam in 2004.

Nevertheless, the phenomenon of the culturally and temporally displaced prisoner who is unable to adjust to a changed world is, in fact, a commonplace that has been observed for many years in US prisoners who’ve served long sentences – certainly, since the 1940s. It is very real, and television and conversation with other recently interned inmates does little to relieve it, at least in some people. There is a huge and material difference between seeing a novel technology in use, and experiencing the transformative effect it has, not only on your life in general terms, but on your way of thinking and behaving. The science fiction author Larry Niven captured something of this when he posited “flash crowds” as an unforeseen social effect of teleportation technology. As it turn out, Niven’s “flash crowds” didn’t have to wait teleportation: the development and widespread application of smartphone and social networking technologies have not only created flash crowds, but enabled flash mobs that propel revolution forward (the Arab Spring) or coordinate riotous looting (the London Riots of the Summer of 2011).

This phenomenon should arguably be of special interest to cryonicists , because we propose to cross many decades or even centuries or longer, without even the advantage of network television programming, or tales of the outside world told by the newer inmates on our ward, or cell block. Because the average person is inescapably enveloped in and carried along by the time stream of the culture he inhabits, it is unlikely that he will have any experience of what it means to be cut off from technological advance and the enormous cultural change that accompanies it.

It’s so dreamy, oh fantasy free me.
So you can’t see me, no, not at all.
In another dimension, with
voyeuristic intention,
Well secluded, I see all.

With a bit of a mind flip

You’re into the time slip.

And nothing can ever be the same.

You’re spaced out on sensation.

Like you’re under sedation.

Let’s do the time-warp again.

                    – “The Time Warp,” Rocky Horror Picture Show by Richard O’Brien.

You can get a potentially deadly taste of this by traveling back in time by the expedient of “geographical atavism,” which is what I call going to places on earth where the technological level is decades, centuries or millennia earlier than the present, and then living there. This is getting difficult to do, since even the lepers in India now have cell phones.

You can also do it by virtue of living off the street, either in the US, or preferably in a “foreign” country. At first, you try to reach for all sorts of technology that isn’t there, and only gradually do you stop doing this and realize that you are now fundamentally different from them – e.g., all the other people in the world. You can no longer communicate effortlessly any further than you can shout. There is no medical care beyond basic first aid, and every step you take is taken with the knowledge that a misstep could be lethal. You are hot when it is hot, and you are cold if you haven’t prepared well, and you are still cold often even if you have prepared. If you can’t find food to eat you are hungry, or you have to ask (beg) for food.

Figure 3: Marks and Spencer was originally a moderately upscale department store chain in the United Kingdom. In recent years they have branched out into selling high quality foods, including “luxury” sandwiches and prepared meals under the brand name of M&S Simply Food. M&S adheres to a rigid policy of discarding most unsold prepared foods at the end of each business day, as well as to discarding baked goods, chocolates, flowers and most other food items at, or just beyond their peak of freshness. This creates the opportunity for “no cash outlay” gourmet meals for those with a dustbin key, a thick hide and a near total lack of “normal” social inhibition.

Figure 4: In the UK, as opposed to the US, dustbins (aka dumpsters in the US) are typically locked with a mechanism that looks a bit like a 3-sided Allen wrench (inset photo at left).  It seems deceptively simple to open, say with needle nose pliers, but this is not the case. The triangular post that operates the mechanism has rounded edges, is recessed and requires substantial force to turn. It is thus highly desirable, if not necessary, to have a “dustbin key;” an item which can be procured at some £ (dollar) stores for  £ 1 (about $1.60 US). This locking mechanism on UK dumpsters appears to be universal, and is considered in the same light as other keyed utility mechanisms, such as water, gas and electricity.

Figure 5: Kitchen, or food waste, must be segregated from other waste in the UK. Typically, the chain merchants such as the Co-Op, M&S Simply Food, and Pret a Manger (another upscale ready-to-eat sandwich shop) conveniently over-bag their various types of food waste in clean, unused plastic bags – often double-bagging it. Food is also discarded on a fairly predictable schedule, so it is possible to retrieve refrigerated and frozen goods in pristine condition, whilst still safely chilled or frozen. The letters “KP” stand for “kitchen policing” wherein the word “police” is used as a verb to mean “to clean” or “to restore to order.”

 
Figure 6: A not untypical haul from an hour or so of foraging in the dustbin at M&S, the local fruit monger and one of the high-end green grocers. One broken egg in a carton of 6 or 12 eggs means the entire lot is discarded. Since I don’t eat land vertebrates, my flat mate had a steady supply of choice cuts of meats – fresh and frozen.

 Figure 7: Living “off the street” as a latter day hunter-gatherer carries with it wholly unexpected difficulties in readjusting to the more typical existence of the technologically sophisticated work-a-day world. I had not previously understood why people would pay good money for something as trivial and ephemeral as fresh flowers. When I returned to the US this past July, after experiencing months of beautiful, sweet smelling flowers in the flat every day, I was disconcerted to find that I had acquired a costly and wholly unsupportable new taste.

Figure 8: Sadly, my difficulty in readjusting to “normal” life was not confined to missing the presence of the severed reproductive organs of plants. I found I had grown accustomed to what were, to me, gourmet meals: good bread and fresh fruit whenever I felt like having them. Above, cold potato leek vichyssoise, smoked salmon with organic string beans, an organic free range egg and Italian tomatoes with a vinaigrette dressing. I have never before (or since) eaten so well so consistently.

 Figure 9: Dishes, cutlery, pots, pans and household appliances were available in dustbins for the taking and with very little competition. The books, clothing, duvet, TV and 3-shelf stand in the photo at bottom right were all acquired from the street within a matter of ~2 weeks. In the UK a TV license is required to watch television – something that, fortunately, both of my flat mates possessed. Failing this, the advent of Blue Ray technology has caused conventional DVD players (and DVDs) to be treated as barely better than rubbish in many large cities in the US & UK.

If you live this way for quite awhile you become transformed. If you return to a world of truly enormous choices and possibilities, even if it is one you formerly inhabited with ease, it is very fatiguing, and it can be confusing and stressful, as well. Since time immemorial men have set on journeys of transformation and enlightenment. From the travels of Gilgamesh to Jesus Christ to Buddha, to the mythical travels of Swift’s Gulliver, all such journeys have in common the individual removing himself more or less completely from his normal environment and thus from his accustomed, culturally imposed way of experiencing and seeing his own life. And there is one more thing; they involve danger and some degree of hardship. The important lesson in this latter element for cryonicists is that any environment different from that in which you have grown to maturity in is a dangerous one. The nuances of other languages and cultures, and the even more subtle nuances of the myriad unspoken but vital cues for survival are necessarily inaccessible to the stranger in a strange land.

Many men who take such a journey return transformed – and sadly – inarticulate and unable to communicate what they have experienced. It is not uncommon for them to repeatedly return to such sojourns, or to attempt to rework the “mundane” lives they have returned to, in an effort to mirror the transcendence they have experienced during their journey(ies). This transcendence, so elusive and so impossible to put into words, consists mostly of the radical change in perspective that occurs when a person is removed from his “time stream.” If we grow up in a reasonably stable culture and remain there throughout our lives with our cohorts, our perception of reality necessarily becomes circumscribed.

The exigences of daily life act to preclude our living in the world that exists beyond our moment-to-moment experience of it. The time we spend in conscious contemplation of the distant past and the far future becomes negligible – we become both confined and defined by the time stream we inhabit; the unfolding of events that are largely determined by our culture and our cohorts. And so it is all over the world – different peoples in different lands, all existing at the same time, but in different currents, eddies and streams that are largely isolated from each other. This is a crippling state of affairs, because we either lose, or altogether fail grasp the larger perspective of the universe as a vast, complex place which is unfolding not only in myriad ways, but over myriad different timescales, as well. That reality has important implications for our survival, both as individuals, and as a species.

Well I was walking down the street
just a-having a think
When a snake of a guy gave me an
evil wink.
He shook-a me up, he took me by surprise.
He had a pickup truck, and the
devil’s eyes.
He stared at me and I felt a change.
Time meant nothing, never would again.

Let’s do the time-warp again.

       — “The Time Warp,” Rocky Horror Picture Show by Richard O’Brien.
 

Several years ago, I was digging through a dustbin in back of a charity shop in London. They were usually a good source for classical CDs (they toss any CD without a jewel case, and any that don’t sell in a fortnight). I found this device in the dustbin (Figure 10).

Figure 10: My first MP3 player was mistakenly acquired because I thought it was a jump drive. I was stunned when I puzzled out that this tiny device could store up to 100 popular songs and index and “shuffle” them! The carrying lanyard was a promotional giveaway handed out on the street in Soho during London’s Gay Pride celebration.

I pulled the end off of it and saw it had a male USB plug. I figured I’d found myself a jump drive – a brand new one, too, since it still had the adhesive protective plastic covering the little screen on the front of it. I took it home and hooked it up to my computer. It took me a fair bit of time before I could understand what it was; an MP3 player. In fact, I didn’t know what an MP3 player was. I did know about iPODs, but only from TV; because they are small, they are also inconspicuous, and I’d not really seen them up close, nor did I know anyone who had one. I had noticed that people no longer used CD players in public and that they, along with CDs, were now a commonplace in the charity shop dustbins (just as perfectly “good” Sony Trinitron, and other nice color CRT TVs are now a commonplace outside thrift stores in the US and the UK (they can’t throw then in the trash because of the heavy metal content, so they set them out to be carted away by people who can’t afford flat screen technology).

 The MP3 player I had found had something like a 100 songs on it! Imagine that! I had no idea that you could carry around a hundred songs, let alone hundreds, or thousands, on such a tiny thing! What was even more astonishing to me was when I realized that MOST of the volume of the device was consumed by the primitive mid-20th century AAA alkaline batteries that powered it. Gradually, I realized that I could get most of the music I liked for free on-line, or from my UK CD collection, and organize it such that I could have the music “match” my travels around London. I could go to the Design Museum, the V&A, or anywhere else I liked and create a perfect soundtrack of music, period or otherwise, to accompany me! In effect, I could make a personalized soundtrack for my life! I quickly realized that if I had several MP3 players, I could select from a nearly endless variety of “collections” to suit my mood – Edith Piaf, The Beatles, Louis Armstrong, torch singers from Dietrich to Sara Vaughn, or the Goldberg Variations (while dozing on a long train or bus ride).

The dustbins of charity shops (thrift stores in the US) are a seemingly inexhaustible source of all manner goods. Many urban charity shops have no laundry facilities and do not find it profitable to carry bedding, linens, or items of clothing such as underwear, socks, and the like – even if they are new and still in the packaging. These things are thus often discarded outright. Items not sold within a fortnight are also typically discarded, as are items that the shop chooses not to sell; medical supplies and equipment, some kinds of music or art, many types of books (most confine themselves to the trendy, bestselling authors and “coffee table” books; the rest are discarded, often still in the boxes). Often,. Whole households of goods flow into the shop as a result of the death of an elderly person whose relatives live far away, or who are uninterested. In such cases the overflow of goods (beyond the capacity of the shop’s shelves) passes immediately into the waste stream.  Furniture, dishes, every kind of household appliance and gadget imaginable, and “obsolete” technology such as CD players, low megapixel digital cameras, flatbed scanners, cordless and mobile (cellular) telephones are present in abundance, as are all manner of toys and child-related items (car seats, cribs).  Finally, and very importantly, anything that the staff who work or volunteer in the shops do not recognize, understand or value, is also discarded.

The shop where I found the MP3 player was staffed by elderly female volunteers. I quickly learned to seek out shops staffed in this manner, because they were almost a guaranteed source of the most exotic technological goods.  In a few short weeks I had accumulated 3 MP3 players, an ASUS EAH6670/DIS/1GD5 Radeon HD 6670 video card[1], two “tiny” digital recorders on neck lanyards and ~ 5 gigs of add-on memory for my laptop and my desktop computers, as well as half a dozen jump drives.

Interestingly, just as the charity store staff was blind to things of value they did not understand (and thus they discarded them), I soon discovered that the same phenomenon applied to me, and others like me, but in reverse. It was impossible for us to see things of value, sometimes of considerable value, even when they were right in front of our eyes, unless we knew what to look for! The ASUS video card was a prime example. There are countless electronic bits and boards in dustbins, and in this case, it took the savvy of a young man who played computer games to recognize the manufacturer, thus saving the card from being salvaged for its muffin fan and instead allowing it to make its way into my desktop computer.

Figure 11: An ASUS EAH6670/DIS/1GD5 Radeon HD 6670 video card. I picked it out of the dustbin for the muffin fan, only to be told it was likely a working video card.

 The technology embodied in the MP3 players was transformative in ways I had not even begun to understand from watching television – and I watch/listen to a lot of television. I had no idea that there were competing brands of tiny, non-hard drive, digital music machines – let alone that they had gotten so small. The people on the street that I interacted with surely had them, but I paid no mind, because I assumed that the earbuds they often sported were connected to radios. Radios had gotten very small; I knew that, because I found AM/FM radios the size of matchboxes in the dustbins frequently. But that was the limit of my understanding; even though I was immersed in a culture where such devices had become commonplace.

I don’t like social media, like Facebook and Linkedin (please, stop sending me spam for Linkedin!), but I do understand them, and I know how powerful they are. A guy in prison hasn’t a clue, and he can’t get a clue from TV, or from hearing about it from another inmate. In fact, his position is much like me and the MP3 player; no one saw fit to explain to me that such technology had evolved, let alone that it was so inexpensive and commonplace that MP3 players were given away as promotional items and might easily be so little valued as to be tossed into the waste stream.

Figure 11: In the UK, homeless people on the street are a rarity, compared to the US. Both the UK and most of Western Europe maintain social welfare programs that are readily available to almost all residents who want them. Three of the most common reasons that people refuse this safety net are substance abuse, having a dog, or some other unwillingness or inability, such as mental illness, to comply with the rules of Council housing or other government social welfare requirements (including criminal activities).

And, why would they? Such technology is a commonplace for those in the mainstream of the culture, something they take for granted, and it is not likely to be a topic of conversation except amongst peers. When you cease to be a peer, and you step outside of your cohort, you have exited one of the time streams that the rest of the world inhabits. If you have children, they will help keep you oriented and in sync with the culture. However, if you are isolated by prison (or by choice) in a rapidly technologically evolving world, you are in for some major surprises – and for no small amount of cognitive dissonance.

I am a technophile who became involved in cryonics as a child. I’ve lived my whole life in expectation (and largely in welcoming anticipation) of technological advance. Statistically, people who are in prisons, or who gather at watering holes such as urban dustbins, are very different from most of the rest of Western, “civilized” humanity. Many are emotionally or intellectually damaged, and most tend to “live in the moment.” Their event horizon extends only so far as the next cigarette, the next hit of spliff or Tina, and maybe to some consideration of where and how they will spend that coming night. They know almost nothing about the past, and are constitutionally unable to see beyond a few days, or weeks into the future. Many will start to forage for a tarp or a piece of plastic to protect them from the rain only when the sky clouds over, or it actually begins to rain.  This, as it turns out, is a critically important observation, because it points up the powerful leverage to be had by living in longer timescales.

The capitalist philosopher A. J. Galambos divided the timescales we humans inhabit in the following way: [2]

Trivial Timescale: Moment to activities and thoughts which dominate most of our daily awareness time; I need to make a phone call, check my mail, brush my teeth, get something to eat, go to the loo.

Personal Timescale: What kind of training should I take, whom should I marry, how should I plan for my retirement, how should I apportion my estate, how can I provide from my children and grandchildren?

Species Timescale: Concern and involvement with history, the environment, the future of mankind. The Species Timescale lasts as long as man himself.

Cosmic Timescale: How does the universe work, what causes the stars to shine, how long will the universe last, can we live forever?

Galambos correctly pointed out that while almost all of us (of necessity) spend most of our time in the Trivial Timescale, preoccupied with things of the moment, to the extent we transcend the trivial we gain power and control over the world around. Newton and Einstein may have spent only a brief moment of their total conscious time in the Cosmic Timescale, but the benefits in terms of technological advance were enormous and gave us not just the laws of Classical Physics and of Relativity, but the calculus, the tools for spaceflight and the capability for self annihilation with the hydrogen bomb.

So, in the sense that people inhabit prisons, or who are squatters or otherwise homeless, are so often condemned to live only in the moment, and thus exclusively in the Trivial Timescale, they are fundamentally different.They are “transtemporally crippled,” and in many ways have less foresight than a really clever dog or cat. It is not uncommon for such people to be unable to retain even very basic possessions, such as a sleeping bag, a CD player and essential toiletries such as a toothbrush, deodorant and a razor. “Now” pretty much encompasses their sphere of action with respect to the past and the future. To expect such people to stay technologically and culturally integrated with a rapidly changing world – especially when imprisoned away from it for decades – is akin to expecting your dog or cat to discourse learnedly on the nuances of Shakespeare, or to explain to your the excitement experienced whilst listening to Justin Bieber.

Of course, slipping out of the time stream is not confined to the sphere of technology, or to prisoners behind bars. It is the fate of every kind of exile everywhere. I have been long exiled from cryonics, and much longer still isolated from the social wellsprings (scant that they may be) that constitute cryonics organizations. Thus, I have no idea if many of the people with whom I once worked and socialized with are still alive, and if they are, where, what and who they are now. I wonder, often, at the anonymous case reports that appear on-line, and try to fathom if it is one of the many people I once knew so well, but that exile for over 20 years has left me isolated from? And those are just the people from my past…

Figure 12: Frank Cole crossing the Sahara desert and the whole of the African continent, from the Atlantic Ocean to the Red Sea on camel in 1990. Cole was murdered by Tuareg bandits near Timbuktu, Mali, in late October 2000.

 Very recently, someone made a derogatory remark about a man I had not previously heard of. He was a cryonicist and a filmmaker by the name of Frank Cole (1954-2000). The commentator remarked on his stupidity for being “killed by bandits in Africa.” I was struck by this remark, because, even more astonishing to me than the discovery that MP3 players existed in 2007, was the discovery of even the possibility that a man like this Frank Cole, could have been a cryonicist. The idea was incomprehensible to me.

It took me quite awhile to find out something of who Frank Cole was, and it was not until I saw his searing final film, Life Without Death, that I think I began to grasp what he was about. But, truth to tell, it was not until I read his former lover, Anne Milligan’s reminiscence of him (see below), that I felt I fully understood him. And that made me very sorry that I had missed the opportunity to know him, because in his work I believe I see the same, almost otherworldly ability to see the culture and the world “we” inhabit from outside, above, below, or beyond it. And in his work I see the exact same vision of the loss of those we love as the penultimate evil, and of death as what it is; the ultimate horror and the ultimate evil.

Figure 13: Frank Cole as a young man.

 I think Cole would have understood when I say that that ability, or practice, if you will, is the perhaps the best psychological preparation possible for recovery from cryopreservation. It is not a place you can ever get to by watching TV, reading books, or otherwise attempting to escape the time stream you inhabit by being distracted from it.

To understand that kind of alienation and isolation, and to taste of its absolute irreversibility requires that you step completely out of the world you inhabit and go to another one that is embedded not just in a different time, but in a different era, and in a different place in space. To do that is, necessarily, to take a horrific risk, because where you will be is not a simulation, and there is no recall from error or mischance, and no opportunity for “a reboot.”

In writing this, I am reminded of one of the songs that was on that discarded MP3 player from the dustbin in London, when it came into my possession. It was by a British pop group called ‘The Enemy.’ It’s lyrics come to mind now, as I think of Frank Cole, the nature, fragility and arbitrariness of life, and how absolutely essential it is that we continue to transcend our accepted experience of it, forever and ever, even for trillions and trillions of years, as the Ancient Egyptians liked to say.

We’ll Live And Die In These Towns

Lyrics by The Enemy

You spend your time in smokey rooms
where haggled old women
with cheap perfume say,
“It never happens for people
like us you know.”
Well nothing ever happened on its own and well,

the toilets smell of desperation
the streets all echo of aggregation
and you wonder
why you can’t get no sleep
when you’ve got nothing to do,
and you’ve had nothing to eat.
Your life’s slipping
and sliding right out of view
and there’s absolutely nothing
that you can do well

We’ll live and die,
we’ll live and die in these towns
don’t let it drag you down
don’t let it drag you down now
we’ll live and die,
we’ll live and die in these towns
don`t let it drag you down
don`t let it drag you down now

Dirty dishes from a TV meal
that went cold from the wind
through a smashed up window
You can’t go out if anybody calls ya
cause you can’t have a bath
when there`s no hot water
and your friends are out
on the town again
and you ask yourself if it will ever end
and it`s all too much for your head to take
just a matter of time
before you break, well

We’ll live and die,
we’ll live and die in these towns
don’t let it drag you down
don’t let it drag you down now
we’ll live and die,
we’ll live and die in these towns
don`t let it drag you down
don`t let it drag you down now

now…
now…

we’ll live and die,
we’ll live and die in these towns
don’t let it drag you down
don’t let it drag you down now
we`ll live and die,
we’ll live and die in these towns
don’t let it drag you down
don’t let it drag you down now

Our critics often say that practical immortality will result in a world of boredom – in a world of eternal sameness inhabited by people making the same choices over and over again. There is merit to this criticism because success, a prerequisite for indefinite survival, breeds complacency. Even with lives as short and turbulent as ours in the developed West are today, it is easily possible to become anesthetized by the time stream we are embedded in. When this happens, we lose all consciousness of the bigger picture, indeed the true picture of reality and we risk losing our ability to transcend the Trivial Timescale and inhabit the Cosmic one, however briefly. Lose that and we lose our ability to survive. Men like Frank Cole remind us that while there is great peril in journeys of transcendence which allow us to step out of our given time stream and cultural imperative. However without them, we face the even greater peril of forgetting, or failing even to understand the complex, challenging and utterly alien nature of the universe as it really exists.

My Life with Frank Cole

October 4, 2009

I delivered this tribute at the Book Launch “Life Beyond Death: The Cinema of Frank Cole” & Film Retrospective sponsored by the Canadian Film Institute at the National Library, Ottawa Oct 3rd, 2009. Frank Cole was a Canadian Documentary Filmmaker who was killed in 2000 by bandits near Mali while crossing the Sahara Desert. Rick Taylor is a Professor at Carleton University, Author and Frank’s best friend.

Dear Rick,

I just finished Life Without Death. I read it in one sitting and was sucked down the rabbit hole. It’s a beautiful book and I especially wanted you to know how much I loved your memoir, Saltwater Road to the Sahara. Your lovingly recreated details brought everything back so vividly It was poignant and bittersweet

And thank you for portraying me with such kindness and especially saying that I loved him whole heartedly because I did, though in truth, I don’t often revisit those memories now, weighed down as they are, with the silent echo of words never spoken, with youth’s uncertainty and unbending pride.

I enjoyed the book immensely but I was sorry that no one had written about Frank from a woman’s perspective because that dynamic informed both his art and life. I don’t think a man, even you Rick, could fully comprehend what it was like to be Frank’s Eve, to be the snake, the seductive field of sleeping poppies. To inherit the complicated push pull of his relationship with his mother. To stand innocent against the charge that intimacy leads to complacency, loss of purpose, and ultimately loss of self.

And so I hope you’ll indulge me while I revisit the piece of Frank’s story that was also mine, through the lens of my sensibilities.

I met Frank in the late 70’s in response to a laundromat ad for a roommate. To say that Frank was different is, of course, an understatement. While it’s true that he seemed remarkably serious and mature for his age, there was something more. His clipped words were punctured with unnerving silences and delivered with an enigmatic assuredness that seemed to announce that he had not only cornered Truth but had it up against the wall by the throat.

The disarming combination of animal magnetism, a rejection of society’s conventions, and a driving intensity body-slammed those he met through their comfort zone. People either loved or hated Frank, they were never indifferent.

In those days he was the enfant terrible in the Algonquin Film program and our apartment became the meeting place of a never-ending parade of Ottawa’s counter culture, drawn by Frank’s aura. It was palpable – Life seemed to be to be more meaningful, more vibrant, and more exciting in his presence. I was captivated and determined. I set out to impress Frank Cole.

Though Frank was not traditionally handsome, there were plenty of women vying for his attention. With his love of the outrageous and the absurd, I sensed that he would be won over by nothing less than a grand gesture.

So one night I placed a small table outside his bedroom and covered it with linen cloth and formal place setting for one. Wearing only a fedora and boots, I perched on the plate and knocked. I can still hear him roar with appreciative laughter as he opened the door… In the morning he took photographs and wrote a terse and clinical account of the night.

That was my introduction to Frank as the outsider. At 24 he had already adopted the practice of precisely and unflinchingly documenting his life with his uncanny ability to be both the observer and the observed,

It isn’t easy to pinpoint the various trajectories that coalesced into Frank’s view of the world. No doubt accompanying his parents to war torn countries, long separations at boarding school, his beloved brother Peter‘s open heart surgery at 8, and later the death of his grandparents, all contributed to his lifelong fear of becoming dependent on anyone or any thing including his own basic needs.

Being in relationship with Frank meant that I too, was expected to engage in this struggle. Work always came first and often our dates started around midnight after Frank had completed a long day of disciplined writing. (Canada Council really got its money’s worth)

He refused to play the role of boyfriend – he wouldn’t meet my parents or socialize with my friends. When we went on trips, he kept a notebook where he meticulously divided expenses down to the last cent. He allowed me to move in with him several times only to kick me out when, as he put in, things got a little too cozy. It was a joke among his friends that when I got sick he would move back home to his mother, and leave me to fend for myself

But just when I’d think that I had his nihilistic angst-ridden, intellectual little ass pigeon-holed, a new aspect of his personality would emerge. Like when he took me to visit the Mountenays. .

The whole family would surround the car whooping “Mamma, it’s Frankie, Mamma, come on out and see Frankie” and he’d smile warmly, laughing wholeheartedly at their childlike jokes and shyly acquiescing to their boisterous wranglings to get him to join this or that team for baseball or cards.

There was nothing patronizing, or condescending in either his personal dealings with them or his affectionate tribute “The Mountenays”. He loved being sucked into the vortex of their exuberance and vitality. And perhaps he also envied their complete lack of self consciousness, and their ability to dissolve into the collective, two things that were totally foreign to his nature.

He was both drawn and repulsed by the rawness of life, the primal power of sex and fascinated by those who clashed with it full on, unencumbered by society and Hallmark sentiments.

After the Mountenays, he considered making a film about the sex trade and we spent endless nights in New York City strip clubs and on Rue St Laurent in Montreal peering into shadowy doorways, and talking to prostitutes.

In light of what was to happen, I still feel a twinge of remorse for telling him that he could never inhabit the desperate world of these people because he had a safety net. Unlike them, he could go home.

Frank wrote his life like a well scripted film. All the action was subservient to the main theme. He told me that he couldn’t marry me or make a home with me and he didn’t want our child to be born.

But in unguarded moments, the dispossessed part of him that yearned for intimacy seeped around the corner of his resolve. One time after being ill with a high fever, he told me that in his delirium he had imagined his body was divided into tiny squares, all of which I had lovingly cared for in turn. “It was great” he admitted wistfully.

Night after night, under the blanket of darkness, I witnessed his agonizing and repeated struggle to conquer his need for connection, and love. No matter that he failed more often than he succeeded.

He told me that I would commit suicide in his film. Sacrifice myself to set him free to force him to be independent, strong and alone. Catching the mirrored reflection of his eyes , I realized he wished it were true.

In the end, the very things that attracted me to Frank made life with him hell. Once, in a heated argument, hurled the most vitriolic insult in his arsenal, predicting with disdain that I would end up a housewife”

keeper of the home, keeper of the heart….

In his world of no compromise, my only option was to disown myself as a woman, to devalue the gifts of the feminine. It broke my heart to choose …me. I ended the relationship.

In October 1988, I received a call from Frank asking to see me. Over the years our paths had crossed mostly at his parents’ home. After dinner we would retreat to the basement, where, drawing up battle lines, we would spar with feigned indifference over such topics as cryogenics and the locus of the self, (Frank insisting on the head, while I argued for the heart), the campaigns of Alexander the Great, the merits of Juan Butler and always his safety in the desert.

But this night was different. His usual bravado was absent- he was drawn and pale. After some time he answered the question I could not ask. He was going to the Sahara in the morning . “Annie “, he said quietly,” don’t leave me alone tonight, don’t go. I’m afraid ”.

That night I held faith on Frank’s behalf, folding him into my body like a child, words spilling like beads of blood, dropping into the confessional of night. In the morning he was gone and when he returned months later, the wall was back . We never spoke of it again.

And now I sit with Frank’s account of that trip open on my knee. I notice the date, Oct 28, 1988, a week since his arrival, a week since the last night we had spent together. He writes that he despairs over how he will ever manage to cross the Sahara. Then he adds “ I rode behind Sid Ahmed toward a bed of sand. He chose it because of it’s softness and because it had a bush that provided shelter from the wind. He checked it for scorpions and snakes and then covered any fallen thorns with sand. He laid down a groundsheet for my sleeping bag… like a father putting a child to bed. This was how,. This….was how. ..with these people’s hearts…, nothing would be impossible.

I read that paragraph again and again, – grief and gratitude flooding me in equal measure.

Frank Cole lived his life with courage. He called it the strength to be free. As for me, I like to remember that in October 1988, in the Sahara Desert, he came to recognize the true meaning of the word. Courage – Avec Coeur- with heart. Because Frank Cole lived his life with heart.

And that is a life well lived

With much affection

Annie

Copyright E. Anne Milligan 2009

Footnotes

Figure 1: Survival of California Adventist men (1980-1988) and other California men (1985) beyond the age of 30 years. The difference between the 2 groups was significant (P,.001). These were non-Hispanic white subjects. Hazards for 1989 are used for non-Adventist Californians older than 94 years (see the “Subjects and Methods” section of the text). AHS indicates Adventist Health Study; CI, confidence interval.

The Seventh-day Adventist Church (SDA) is a Christian denomination that was founded in 1963 as an offshoot of the Millerite movement in the US during the middle part of the 19th century. Ellen White, the principal founder of SDA, advocated a lifestyle incorporating the following five behaviors: not smoking, eating a plant based diet, eating nuts several times per week, engaging in regular exercise and maintaining normal body weight throughout the individual’s lifetime[1] Adventists also typically eschew alcohol (~8% drink), tobacco (~1.8% smoke), butter, strong seasonings (including pepper), caffeine (coffee, tea, cola) and consider the eating of pork, shellfish, and other foods proscribed as “unclean” in Leviticus as especially unwholesome.[2]

Beginning in 1960, two studies were conducted to determine the effects of the SDA lifestyle on all-cause mortality, as well as on disease-specific mortality and morbidity. The first study was conducted in the interval from 1960 to 1965. The Adventist Mortality Study, also known as the Adventist Health Study-1 (AHS-1) was comprised of 22,940 California Adventists and consisted of an intensive 5-year follow-up, and a more informal 25-year follow-up.[3] The AHS-1 found that the mean lifespan for California Adventist men was 6.2 years longer than for non-Adventist California men. The mean lifespan extension achieved by SDA women was more modest; a 3.7-year advantage over their non-SDA counterparts. These statistics were based on life table analyses.[4]

The reduction in disease specific mortality was impressive, with the overall death rate from neoplasms being 60% lower for SDA men and 76% lower for SDA women.[3, 5] The incidence of breast and colorectal cancer were dramatically lower than in the control population with SDA women experiencing 85% less breast cancer [6-8]and SDA men and women experiencing 62% less colorectal cancer.[3, 9, 10]The incidence of coronary heart disease (CHD) was 66% lower for SDA men and 98% lower for SDA women.[11-13] On average Adventist men live 7.3 years longer and Adventist women live 4.4 years longer than other Californians.

The second Adventist Health Study (AHS-2) took place in the time period between 1974 and 1988 and involved approximately 34,000 Californian Adventists over the age of 25. AHS-2 was designed to try to determine which components of the SDA lifestyle provided protection against specific types of disease. The AHS-2 found that the consumption of red and white meat was associated with an increase of colon cancer and that, independent of meat consumption, eating legumes was protective against the disease.[5, 10, 14] The consumption of nuts was found to be inversely related to the incidence of myocardial infarction, and regular consumption of nuts several times a week reduced the incidence of coronary heard disease CHD by ~50%.[15-17] A strong inverse relationship was found between the risk of CHD and the consumption whole grain wheat bread, as opposed to white bread (~45% reduction in CAD).[16] In men, the frequent consumption of tomatoes and of soy milk was associated with a ~60% reduction in the incidence of prostate cancer.[16, 18, 19]

Figure 2: Survival of California Adventist women (1980-1988) and other California women (1985) beyond the age of 30 years. The difference between the 2 groups was significant (P,.001). These were non-Hispanic white subjects. Hazards for 1989 are used for non-Adventist Californians older than 94 years (see the “Subjects and Methods” section of the text). AHS indicates Adventist Health Study; CI, confidence interval.

Unlike the Cretan diet, the dietary practices of the SDAs are less homogenous and typically incorporate foods commonly consumed by Americans (although with more moderation), including many associated with degenerative disease, such as refined sugar and snack foods. Similarly, the SDA diet typically strives to replace traditional American foods with healthier alternatives, while maintaining the flavor, texture and appearance of the original dishes.[20] One way this is done is by using a range of proprietary textured vegetable protein products (TVP) derived from wheat or soy (with corn or soy oil providing the calories from fat) as meat substitutes. There is also a heavy emphasis on the consumption of vegetables, nuts, whole grains and fruits.[21, 22]

Figure 3: Examples of textured vegetable protein products made to resemble commonly eaten meat dishes in the US.

These products have historically been manufactured by companies owned by or closely associated with the SDA church[23] and this was an added factor in their widespread use. Lentils are also often substituted for meat in traditional American recipes, such as meatloaf and soup. The use of TVP meat substitutes increase compliance by making products that allow for the preparation of foods that fill the cultural niche of beef, chicken and turkey. There are even faux-meat hot dogs available (Figure 3). Nuts are also commonly used as an ingredient in TVP dishes to provide added flavor and a more meat-like mouth feel.[20] Examples of commonly used SDA “meatless meat products” (Figure 3) along with their ingredients and nutritional content are available at http://fatsecret.com/calories-nutrition/worthington-loma-linda#Meatless_Foods.

The primary sources of lipids in the SDA diet have historically been from corn and soy oils, and to a lesser extent oils from nuts (corn oil has partly been replaced by canola oil in the contemporary SDA diet). In examining the commonalities between the SDA and the Cretan diet, the following components seem the most likely candidates to explain the reduction in morbidity and mortality observed in both populations:

• No or very low consumption of red meat
• No or low consumption of meat (excluding fish) in general
• Large consumption of fresh fruits and vegetables
• Use of free range hens’ eggs
• No or low consumption of butter
• No or low consumption of unfermented milk products
• Emphasis on legumes in the diet
• Emphasis on the regular consumption of nuts
• Fat intake primarily in the form of polyunsaturated or monounsaturated fats of vegetable origin
• Regular exercise
• Maintenance of near ideal body weight over the lifespan
• Abstention from smoking

Which Diet for a New Lifestyle?

Figure 4: The Greek Food Column and the three critically important lifestyle elements that accompany it; balance, proportionality and regular exercise.

The Lyon Heart Study clearly showed that the diet of Crete can be adhered to over a period of 5 years. Figure 4 is the Greek Column Food Guide based on the diet of Crete. The visualization of this food guide in the form of a Greek column includes the concepts of genetic variation and nutrition and balanced energy intake and energy expenditure; it is based on foods, not food groups. Although it excludes certain foods made with hydrogenated oils, it does not restrict the intake of naturally occurring foods. It also takes into consideration moderation, variety and proportionality. Dietary guidelines shown in Table 1 provide further information on how to implement the diet of Crete.

Table 1.
The seven dietary guidelines of The Cretan Diet
1. Eat foods rich in (n-3) fatty acids such as fatty fish (salmon, tuna,
trout, herring, mackerel), walnuts, canola oil, flaxseeds and green
leafy vegetables. Or, if you prefer, take (n-3) supplements.
2. Use monounsaturated oils such as olive oil and canola oil as your
primary fat.
3. Eat seven or more servings of fruits and vegetables every day.
4. Eat more vegetable protein, including peas, beans and nuts.
5. Avoid saturated fat by choosing lean meat over fatty meat (if you
eat meat) and low fat over full fat milk products.
6. Avoid oils that are high in (n-6) fatty acids, including corn,
safflower, sunflower, soybean, and cottonseed oils.
7. Reduce your intake of trans fatty acids by cutting back on
margarine; vegetable shortening; commercial pastries; deep-fat
fried food; and most prepared snacks, mixes and convenience
food.

Studies on the diets of hunter-gatherers suggest that (n-3) fatty acids were present in practically all foods that humans ate, and present in equal amounts with (n-6) fatty acids (i.e., 1:1 ratio). The depletion of the (n-3) fatty acids in Western diets is the result of the industrialization of farming, and to a lesser extent, the recent emergence of aquaculture. The high ratio of (n-6) to (n-3) fatty acids (16.74:1 instead of 1:1) is a consequence of the inexpensive mass production of vegetable oils and their substitution in much of the diet for saturated fats as a consequence of economic considerations, government policy (corn and soy subsidies) and erroneous health advice by the “experts.” The latter, led by Ancel Keyes,  recommended the indiscriminate substitution of saturated fat and butter with oils high in (n-6) fatty acids to lower serum cholesterol. This effort was successful in reducing the incidence of CVD, however it has not reduced the incidence of other pro-inflammatory diseases, and the mean lifespan has not increased fully commensurate with the decrease in CVD mortality.

The results of the Seven Countries Studies and the Lyon Heart Study based on a modified Cretan diet that is balanced in (n-6) and (n-3) fatty acids, rich in antioxidant micronutrients, and in chemoprotective trace minerals  from fruits, vegetables, wild growing herbs and greens is associated with decreased rates of heart disease and cancer; more so than any other diet, drug intervention, or technique. Indeed, all attempts to date to administer nutrients believed to be protective against disease as supplements have been unsuccessful. Attempts to reduce the incidence of CVD with vitamin C, vitamin E and with folic acid and vitamin B-6 (the latter to achieve reduction in elevated serum homocyeteine levels) have failed, suggesting that the biochemical protection these molecules provide in vitro, and in laboratory animal settings, requires the presence of other molecular species in order to act in vivo.

What appears to be unique about the Cretan (and to a lesser extent the SDA diet) is the content of bioprotective nutrients with a broad range of action, specifically the following: 1) a more balanced intake of essemtial fatty acids (EFAs) from vegetable, animal and marine sources; a ratio of (n-6) to (n-3) fatty acids of ;2:1 instead of the 15:1 in most Western diets (it is 16.74:1 in the US); and 2) a diet rich in antioxidants, i.e., high in vitamin C, vitamin E, b-carotene, glutathione, resveratrol, selenium, phytoestrogens, folate, and other phytochemicals from green leafy vegetables; phenolic compounds from wine and olive oil; high intakes of tomatoes, onions, garlic and herbs, especially oregano, mint, rosemary, parsley and dill, which contain  lycopene, allyl thiosulfinates, salicylates, carotenoids, indoles, onoterpenes, polyphenols, flavonoids and other phytochemicals used in cooking vegetables, meat and fish.

Some Serious Caveats Regarding the Applicability of Historical Data

In asking people about how long they expect to live, I’m often surprised by the high degree of confidence they exhibit based on the longevity of relatives. If you challenge the assumption that because their aunts, uncles or parents lived into their 80s or 90s that they will too, you will likely be met with the vehement assertion that this fact pretty much guarantees a similar outcome for the respondents. This assertion would be more credible if their long lived 1^st or 3^rd degree kin were reared under identical, or at least under similar conditions. And therein lies the rub, because this is usually not the case.

Figure 5: Average weekly hours spent on home production from 1900 to 2000 for two aggregates of the population; those in their productive prime, and those in their declining years.

It must be remembered in making historical comparisons with contemporary Westerners in terms of both life expectancy, and dietary or other interventional lifespan studies, that 20th century Cretans and Adventists were, of necessity, far less sedentary than is the average 21st century Westerner today. In this cohort of people housework (household production) involved a considerable amount of exercise, and often no small amount of hard physical labor. Until the middle of the 20th century in the US, laundry was done by hand, in whole or in part, and clothing was hung up to dry, taken down and ironed. Even operating automobiles involved clutching, shifting gears and manual operation of windows – small things by themselves, but cumulatively important.

Figure 6: Between 1950 and 2000 there was a ~ 20% reduction in the types of work classified as “high activity.” What is neither shown nor known is the degree to which both high and low activity jobs have become less strenuous. [24]

Meal preparation in 1965 required ~ 16.5 hours per week and the total numbers of hours spent in home production was on the order of 51.8 hours at that time. [25] As can be seen in Figure 5, time spent on home production decreased significantly beginning around 1960. Beyond the decrease in total hours spent on housework, there was a much larger decrease in the amount of physical effort required. Washing machines and clothes dryers, prepared meal components and entire prepared meals, as well as countless other “labor saving” devices, goods and services have markedly decreased fitness. The same has been true of strenuous physical activity in the work place where the overall number of high activity jobs have decreased by ~ 20% from 1970-2000.[26, 27]  There has also been a large shift in the workplace demographic since the mid-2oth century. Life expectancy increased from 47.3[28] years in 1900 to 77.8 years today, a consequence of which (in part) was the exodus of teens from the workforce. In 1920, ~20% of the US labor force was comprised of males aged 15 to 18 years of age.[28] Today, very few teenagers work full time jobs, and the number of teens employed in summer jobs has decreased from ~60% in 1994, to ~40% in 2008.[29] Of those teens who do find summer employment very few are in physically demanding (and consequently usually hazardous) areas of work, such as construction or agriculture. This change, coupled with increased TV viewing and other sedentary activities, translates into reduced fitness in the age 15-30 demographic.

Figure 7: The graph above shows the distribution of the Body Mass Index between the 1971–1975 and 1988–1994 surveys. Over this time, median BMI increased by 0.9; the 75th percentile increased by 1.5; and the 95th percentile increased by 2.7.[238]

In their article, “Why Have Americans Become More Obese?” Cutler, et al., take the contrary position and argue that it is not reduced energy expenditure (or fitness) in the the population, but rather, the reduced investment required in terms of time per calorie consumed, that has been the primary cause of the change in US, and increasingly Western European eating habits (and thus is responsible for the current epidemic of obesity and type II diabetes).[30] Superior food packaging and preservation have cut not just meal preparation time dramatically, but also cleanup time. The mess generated in the preparation of multiple elements of a meal is now confined to the factory and the cleanup is included in the price of the food. It is also no longer necessary to spend as much time cooking, or even heating food, because it can be rapidly prepared and be made ready to eat in a matter of minutes from refrigerator or cupboard by the use of the microwave oven. These technological changes have thus reduced the threshold for eating formerly time consuming and messy to prepare dishes to the point of almost no effort or expenditure of time at all. It is now almost as easy to eat a piece of cake or pie, a brownie, or complex entree as it once was to eat an apple. All the mess and time involved in baking a cake or a pie from scratch is gone.

Regardless of the cause, we are most certainly not our parents or our grandparents, and as the current epidemic of obesity and type II diabetes attests, we are not likely to age or die as they did, either. Any doubts about the difference between “us” and “them” (or even “us then” and “us now”) should be laid to rest by a careful perusal of Figure 7.

The generations who participated in the AHS and Seven Countries Study were also fed differently. In Europe, they were subjected to nearly a decade of reduced calorie consumption, and even in the US, the relatively high cost of calories (in time, if nothing else) combined with less leisure time and fewer options for sedentary work, no doubt acted to limit calorie consumption, compared to today. This reduced calorie consumption may have been protective, and might have served to add years to life even in the presence or the absence of a more optimal diet. These generations of people were also fed on agricultural products derived mostly from small farms where crops and livestock had the opportunity to acquire a broad range of micro-nutrients and phytochemicals that are now less abundant in the food supply.

How Square is Curve Already?

Figure 8: The death rate from cardiovascular disease in the US has plummeted since the turn of century in part due to the replacement of saturated fats with of polyunsaturated fats in the diet.[31]

It should also be pointed out that data from longitudinal studies like the AHS-1&2 and the Seven Countries Study reach us as light does from a distant star. When we point and look at the star in the crook of the handle of the Big Dipper we say, “Look, there’s Alcor!” But of course that isn’t the Alcors we are looking at, but rather the light that shows what they looked like 83 years ago. Similarly, all of the data in AHS-1&2 and Seven Countries Study is a generation or two (or three!) old by the time we have it. The participants in those studies are mostly dead now, as indeed they would have to be in order for us to be able to plot lifespan curves for them. Thus, it is easy to make the mistake of saying, “If I adopt this diet I can expect 7 additional years of life, or 10 additional years of life, because that’s what the study participants experienced.

At least one problem with that assumption is that some of the benefits from both studies have very likely already been realized in the form of the switch from saturated to poly- and monounsaturated fats in the diet, which began in the early 1960s and continues through the present. The most significant benefit from both the Seven Countries Cretan diet and the Adventist Vegetarian diet has been the reduction in mortality (and morbidity) from CVD that has been ongoing since ~1968 in the US. The death rate from CVD has been halved since 1960 when both of these studies were undertaken (Figure 8). To those who vilify Ancel Keys for not getting it just right, I can only say, “Look at (Figure 8) and try to tell me that you could have done better.” So, we’ve undoubtedly used up some of benefit from these dietary interventions in terms of mean lifespan extension.

Figure 9: These curves show the best case extension of mean lifespan that can be anticipated with the Adventist Vegetarian diet or the Cretan Diet.

Finally, it is critically important to understand that both the Cretan and the Adventist Vegetarian diets are really not “diets” at all, but rather lifestyles. Both lifestyles have in common a strong emphasis on low impact exercise and a non-sedentary way of life. Both lifestyles were a product of a time without televisions or computers, and both lifestyles required then, and will require now, considerably greater time for food preparation and cleanup. The upside of that is that we should also eat less, if Cutler et al., are correct. That is important to consider as well, because, leaving aside whether fats, carbohydrates or protein should comprise X- percentage of a given diet’s calories, one thing both these diets have in common is modest to moderate calorie restriction.  Five, or possibly even 10 extra years of healthy, productive life should hopefully make the practical costs worthwhile.

The Caveman Diet, or Just How Credulous Are You?

“There are races of people who are all slim, who are stronger and faster than us. They all have straight teeth and perfect eyesight. Arthritis, diabetes, hypertension, heart disease, stroke, depression, schizophrenia and cancer are absolute rarities for them. These people are the last 84 tribes of hunter-gatherers in the world. They share a secret that is over 2 million years old. Their secret is their diet- a diet that has changed little from that of the first humans 2 million years ago, and their predecessors up to 7 million years ago. Theirs is the diet that man evolved on, the diet that is coded for in our genes. It has some major differences to the diet of “civilization”. You are in for a few big surprises.

The basic principles of the Paleolithic Diet are so simple that most high school students can understand them. Within 15 minutes from now you will grasp the major elements. At the technical level, Paleolithic Diet Theory has a depth and breadth that is unmatched by all other dietary theories.” – Dr. Ben Balzer, M.D.

The ideas underlying the Cretan Diet and the SDA Vegetarian diet are complex and do not admit of easy reduction to a catchphrase. The actual foods permitted and consumed in both diets differ markedly – one proscribing all meat, the other urging fish consumption, one obtaining most of the dietary fat calories from PUFAs, and the other from monounsaturated olive oil… It is these differences in the face of the common outcome of greatly improved health and moderate extension of the mean lifespan that are, in fact, key, because they tell us about the likely underlying common mechanisms and thus possibly of their action. They also offer us the opportunity for more choice, and therefore for more flexibility and the likelihood of greater compliance.

The Paleo Diet: A diet so unscientific, only a caveman would do it.

That is not, however, how people make a quick buck. Neither diet is particularly ‘sexy.’ And both diets require an understanding of the underlying biology that makes them work in order to be credible. It’s not possible, or at least not as easy to offer up a one sentence explanation for the feeble minded, such as, “This is a healthy diet that will extend lifespan because it is the natural human diet that our ancestors were evolved to eat.”[32-34] That sounds great because it is simple, easy to understand and “seems right” to a lot of uninformed, ignorant and fearful people. It also speaks to that deep and abiding suspicion that our health (and our other woes) is an artifact of our having lost our way – either from the primordial Garden of Eden, or from our biologically appropriate evolutionary ground state (i.e., before we embarked on agriculture). In fact, the emphasis on a 1:1 or 2:1 ratio of (n-6) to (n-3) fatty acids was derived from observations of contemporary hunter gatherer populations who have a low incidence of inflammatory and age-associated degenerative disease compared to that seen in post-agricultural populations. That was a useful insight that was subsequently validated in many human studies, the best of which extended over a period of decades. That’s the heart and soul of Level 1, Evidence Based Medicine.

In 1988, S. Boyd Eaton, Marjorie Shostak and Melvin Konner published a book entitled The Paleolithic Prescription: A Program of Diet & Exercise and a Design for Living[32] advocating a diet based on what the authors hypothesized the primordial pre-agricultural human diet was like. Subsequently, well over a dozen books have been published advocating variations on this diet based on arm chair hypothesizing from findings in the scientific and ethnographic literature.  The diet (depending upon the version you come across) is low (10-15% energy) or moderate in fat , low in carbohydrate (20–40% energy), and  high in protein diet (19–35% energy) which provides 55–65% of total calories from meat, 35–45% of calories from non-grain and low glycemic index vegetable sources with a primarily saturated fat intake (10%–58% energy) similar to or higher than that found in Western diets.[35-37]

The first problem with this approach is that the diet is not validated; the AHS and the Seven Counties studies had the considerable advantage of being able to study actual, living human beings under real world conditions, and then apply those insights to other populations, including populations already suffering from CVD. Indeed, that is where so many of the insights, as well as so many of the unresolved questions regarding these diets/lifestyles come from (i.e., the data are complex and robust). Late Paleolithic people are not only long dead and gone, they are really long dead and gone, and contemporary hunter gatherers – the few that remain – cannot be considered equivalent. Ironically, most of the data cited on the relationship between CVD and diet by the originators of the Paleolithic diet are from the Seven Countries Study![32, 37]

Even more to the point, there is present in the hypothesis of Eaton, Konner et al.,[32, 33] the notion that 10,000 years of agriculture is evolutionarily insignificant. In essence, they posit that human evolution with respect to diet stopped 10,000 years ago.[32, 35] At first glance this might seem to be credible, because human evolution has occurred over a period of millions years and it would seem that any changes that would occur in population genetics over a mere 10,000 years must be trivial. However, this is not the case for several reasons. First, the rate of evolution is a function of a complex interplay of multiple factors, including environmental change and selection pressure. It is only necessary to look at the various breeds of dogs, or pigeons created by artificial selection to understand that evolutionary change can be swift.

The introduction of agriculture was a watershed event and it would be astonishing if it was not accompanied by significant evolutionary adaptations to the dietary changes that resulted.  To understand that this is so it is only necessary to examine the strong natural selection for the gene that controls lactase production.[38] Human populations with a long history of cattle herding and milk consumption can metabolize lactose present in cow’s milk throughout adulthood, whereas populations that did not domesticate cattle cannot. Natural selection for the heterozygous carriers of the sickle-cell gene to maintain sickle-cell trait in populations exposed to malaria is another post-advent of agriculture evolutionary adaptation. This adaptation was selected for as a direct result of an agriculture-induced alteration to the environment; the clearance of the tropical forests in central Africa, which in turn led to the explosion in the population of the Anopheles mosquitoes that are the vectors for the Plasmodium parasite that causes malaria.

Recently developed techniques for measuring genetic variability now allow for the determination of selection operating in the human genome.[39] Directional selection has been identified in the glucose-6-phosphate dehydrogenase (G6PD) gene, which confers resistance to malaria.[40] What is more, G6PD resistance has evolved not once, but twice in humans, in both Africa and in the Americas.[41] Similarly, the genes expressing chemokine receptor 5 (CCR5) among Europeans, which confers resistance to the human immunodeficiency virus (HIV) are likely to have been selected for within this population over a period of several hundred years in response to Yersinia pestis (bubonic plague) and tuberculosis, both of which use the CCR5 receptor as an entry portal into the host.[42]  Numerous other studies have also provided evidence for the recent operation of natural selection on the human genome as a result of very recently developed techniques that allow for comparisons over long sections of DNA.[43-46]

In addition to the conservation of lactase production into adulthood, there is substantial evidence of evolutionary adaptation to the high carbohydrate diet that was a product of agriculture. The incidence of obesity that occurs upon exposure to high calorie “affluence diets” is known to vary greatly by ethnicity. The Pima people (or Akimel O’odham) are a racial group of Amerindians living in central and southern Arizona. One-half of adult Pima Indians have diabetes and 95% of those with diabetes are overweight or obese.

Obesity is thought to be 50-90% heritable. Genome scans in obesity studies are highly reproducible and, despite ethnic and environmental differences, the loci at chromosomes 2 and 10 are generally confirmed as the source of the phenotype. Obesity is “oligogenic,” with expression modulated by “polygenic modifier genes” interacting with the environment in food choices, physical activity, and smoking.[38] Prior to their introduction to the “American” diet after WWII the Pima were not obese and diabetes was extremely rare.[39-41] The diet of the Pima was a very low fat, high carbohydrate diet consistent with the subsistence agriculture of the desert southwest.[42, 43]  Some variations in the ectonucleotide pyrophosphatase phosphodiesterase gene-1 (ENPP1) are associated with a 50% increase in the risk of morbid obesity in adults and a 69% increased risk of childhood obesity. An ENPP1 mutation, for example, which is known to protect against obesity and type II diabetes, is present in about 90 percent of non-Africans, but nearly absent in Africans and, not coincidentally, in the Pima. Human evolution in response to environmental change and in response to dietary change is both ongoing and dynamic.[47][44]

Of course, the Paleolithic diet may be the best diet yet conceived. I could give many reasons why I believe this is not so, but absent hard data gleaned from human trials, I can’t prove much. And that is my final and most important point. I did a Pubmed search using the keywords “Paleolithic diet” and I got 67 hits. Of those 67 hits only 9 were papers that involved actual human or animal application of the diet, or even discussion of same. I’ve copied all of the cites for these studies below:

1: Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010 Dec;25(6):594-602. PubMed PMID: 21139123.

2: Jönsson T, Granfeldt Y, Erlanson-Albertsson C, Ahrén B, Lindeberg S. Apaleolithic diet is more satiating per calorie than a Mediterranean-like diet in  individuals with ischemic heart disease. Nutr Metab (Lond). 2010 Nov 30;7:85. PubMed PMID: 21118562; PubMed Central PMCID: PMC3009971.

3: Klonoff DC. The beneficial effects of a Paleolithic diet on type 2 diabetes and other risk factors for cardiovascular disease. J Diabetes Sci Technol. 2009 Nov 1;3(6):1229-32. PubMed PMID: 20144375; PubMed Central PMCID: PMC2787021.

4: Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic[corrected] nutrition, and evolutionary health promotion. Am J Clin Nutr. 2010 Feb;91(2):295-7. Epub 2009 Dec 30. Erratum in: Am J Clin Nutr. 2010 Apr;91(4):1072. PubMed PMID: 20042522.

5: Jönsson T, Granfeldt Y, Ahrén B, Branell UC, Pålsson G, Hansson A, Söderström  M, Lindeberg S. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol. 2009 Jul 16;8:35. PubMed PMID: 19604407; PubMed Central PMCID: PMC2724493.

6: Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC Jr, Sebastian A. Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. Eur J Clin Nutr. 2009 Aug;63(8):947-55. Epub 2009 Feb  11. PubMed PMID: 19209185.

7: Osterdahl M, Kocturk T, Koochek A, Wändell PE. Effects of a short-term intervention with a paleolithic diet in healthy volunteers. Eur J Clin Nutr. 2008 May;62(5):682-5. Epub 2007 May 16. PubMed PMID: 17522610.

8: Jönsson T, Ahrén B, Pacini G, Sundler F, Wierup N, Steen S, Sjöberg T, Ugander M, Frostegård J, Göransson L, Lindeberg S. A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs. Nutr Metab (Lond). 2006 Nov 2;3:39. PubMed PMID: 17081292; PubMed Central PMCID: PMC1635051.

9: Eaton SB, Eaton SB 3rd. Paleolithic vs. modern diets—selected pathophysiological implications. Eur J Nutr. 2000 Apr;39(2):67-70. PubMed PMID: 10918987.

If I enter the keywords “Mediterranean diet” I get 2,269 hits, of which 225 are reports of clinical trials. I will not copy those here!

That’s it. Nine papers of poor quality and not a single clinical trial demonstrating reduced morbidity or mortality – even in CHD or type II diabetes.  Sixty-seven papers of hypothesizing 25 years after this diet was put forth. That is dismal science and it is inexcusable to take a position advocating such an intervention in the complete absence of any evidence that it will actually extend the human (or the laboratory animal) lifespan when there is a large body of high quality data that supports far less extreme, and far more practical dietary and lifestyle interventions that will accomplish those ends.

I have no problem with people coming up with a hypothesis, however kooky or sane, and then proceeding to try it out – even on people – as long as those people have informed consent and the data they are given is accurate. In looking over the various books and the countless media articles on the Paleolithic diet, I was struck by how much the Paleolithic Diet’s hype reminded me of the Pritikin diet hype, and even more so of the Pearson & Shaw Life Extension Revolution circus from 30 years ago. “Live to be 100!” “Feel great! Experience all day energy every day!” “Lose Weight!” Well, at least one of those is very likely true, and that is that most people who undertake any version of the Paleo diets I’ve reviewed will likely lose weight. But as to the other claims? Right now they are preposterous. The sad thing is that for first the time in history we have one diet/lifestyle choice that satisfies EBM-1 criteria, and another that satisfies EBM-2 criteria. Both are “proven” to reduce morbidity from a range of degenerative diseases, and both have been proven to significantly extend mean lifespan…

Max More, CEO Alcor Life Extension Foundation

As I so often say, “You pays your money and you takes your chances.” Still,  it is embarrassing to see cryonicists buy into yet another quick fix cure all, with no appropriate science to back it up. In his article “The Cryo-Paelo Solution”[48] Alcor President Max More advocates the Paleolithic Diet as a life extending add-on to cryonics. This recommendation is supplemented by a web interview.[49] His citations consist these of these popular books on the subject: Loren Cordain, The Paleo Diet; Nora T. Gedgaudas, Primal Body, Primal Mind; Mark Sisson, The Primal Blueprint; Gary Taubes, Why We Get Fat;Gary Taubes, Good Calories, Bad Calories; Arthur de Vany, The New Evolution Diet. The expert More cites as the one to consult for an introduction to Paleo-dieting is Loren Cordain, author of  The Paleo Diet. The quote that open this section on the Paleolithic diet is by Dr. Ben Balzer, M.D., and is from the “Introduction” to Cordrain’s book. Need I say more?

End of Part 3

References

1.            White E: Ministry of Healing: http://books.google.com/books/about/The_Ministry_of_Healing.html?id=2bu2ry223JAC: Kessinger Publishing, LLC; 1905.

2.            Rucker C: The Seventh-Day Diet: A Practical Plan to Apply the Adventist Lifestyle to Live Longer, Healthier, and Slimmer in the 21st Century: Pacific Press Publishing Association 2002.

3.            Mills PK, Beeson WL, Phillips RL, Fraser GE: Cancer incidence among California Seventh-Day Adventists, 1976-1982. Am J Clin Nutr 1994, 59(5 Suppl):1136S-1142S.

4.            Kahn HA, Phillips RL, Snowdon DA, Choi W: Association between reported diet and all-cause mortality. Twenty-one-year follow-up on 27,530 adult Seventh-Day Adventists. Am J Epidemiol 1984, 119(5):775-787.

5.            Grundmann E: Cancer morbidity and mortality in USA Mormons and Seventh-day Adventists. Arch Anat Cytol Pathol 1992, 40(2-3):73-78.

6.            Zollinger TW, Phillips RL, Kuzma JW: Breast cancer survival rates among Seventh-day Adventists and non-Seventh-day Adventists. Am J Epidemiol 1984, 119(4):503-509.

7.            Fraser GE: Diet as primordial prevention in Seventh-Day Adventists. Prev Med 1999, 29(6 Pt 2):S18-23.

8.            Mills PK, Annegers JF, Phillips RL: Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists. Am J Epidemiol 1988, 127(3):440-453.

9.            Mills PK, Beeson WL, Phillips RL, Fraser GE: Bladder cancer in a low risk population: results from the Adventist Health Study. Am J Epidemiol 1991, 133(3):230-239.

10.          Phillips RL, Snowdon DA: Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists. J Natl Cancer Inst 1985, 74(2):307-317.

11.          Fraser GE, Dysinger W, Best C, Chan R: Ischemic heart disease risk factors in middle-aged Seventh-day Adventist men and their neighbors. Am J Epidemiol 1987, 126(4):638-646.

12.          Fraser GE, Lindsted KD, Beeson WL: Effect of risk factor values on lifetime risk of and age at first coronary event. The Adventist Health Study. Am J Epidemiol 1995, 142(7):746-758.

13.          Fraser GE, Shavlik DJ: Risk factors for all-cause and coronary heart disease mortality in the oldest-old. The Adventist Health Study. Arch Intern Med 1997, 157(19):2249-2258.

14.          Giem P, Beeson WL, Fraser GE: The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology 1993, 12(1):28-36.

15.          Fraser GE, Sabate J, Beeson WL, Strahan TM: A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med 1992, 152(7):1416-1424.

16.          Fraser GE: Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr 1999, 70(3 Suppl):532S-538S.

17.          Sabate J: Nut consumption, vegetarian diets, ischemic heart disease risk, and all-cause mortality: evidence from epidemiologic studies. Am J Clin Nutr 1999, 70(3 Suppl):500S-503S.

18.          Willett W: Lessons from dietary studies in Adventists and questions for the future. Am J Clin Nutr 2003, 78(3 Suppl):539S-543S.

19.          Phillips RL, Snowdon DA: Association of meat and coffee use with cancers of the large bowel, breast, and prostate among Seventh-Day Adventists: preliminary results. Cancer Res 1983, 43(5 Suppl):2403s-2408s.

20.          Beck J, Beck, JJ, Jarnes, K.: Adventist Sabbath Dinner Cookbook: Pacific Press Publishing Association; 2001.

21.          Council GCoS-dAN: The Seventh-day Adventist Position Statement on Vegetarian Diets: http://www.sdada.org/position.htm. In.; 2010.

22.          Health LLUSoP: The Vegetarian Food Pyramid: http://www.vegetariannutrition.org/food-pyramid.pdf. In. Loma Linda: Loma Linda University; 2008.

23.          Center S: History of Loma Linda Foods: http://www.soyinfocenter.com/HSS/loma_linda_foods.php. In. Lafayette: Soyinfo Center; 2004.

24.          King G, Fitzhugh, EC, Bassett, DR Jr, McLaughlin, JE, Strath SJ, et al.: Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity. Int J Obes Relat Metab Disord 2001, 25:606-612.

25.          Ramey V: Time Spent in Home Production in the Twentieth-Century United States: New Estimates from Old Data :http://weber.ucsd.edu/~vramey/research/Home_Production_published.pdf. The Journal of Economic History 2009, 59(1).

26.          Borodulin K, Laatikainen, T, Juolevi, A, Jousilahti, P. : Thirty-year trends of physical activity in relation to age, calendar time and birth cohort in Finnish adults. Eur J Public Health 2008, 18(3):339-344.

27.          Brownson R, Boehmer, TK, Luke, DA.: Declining rates of physical activity in the United States: what are the contributors. Annu Rev Public Health 2005, 26(421-43).

28.          Census USBot: U.S. Bureau of the Census, Historical Statistics of the United States, Colonial Times to 1970. 1971.

29.          Camarota S, Jensenius, K. : A Drought of Summer Jobs: Immigration and the Long-Term Decline in Employment Among U.S.-Born Teenagers: http://www.cis.org/articles/2010/teen-study.pdf. In: Backgrounder. Center for Immigration Studies; 2010.

30.          Cutler D, Glaeser, EL, Shapiro, JM.: Why have americans become more obese? Journal of Economic Perspectives 2003 17(3):93-118.

31.          National Heart LaBI: Morbidity & mortality: 1998 chartbook on cardiovascular, lung, and blood diseases. In. Edited by Health UDoHaHSNIo. Rockville, Maryland: US Government Printing Office; 1998.

32.          Eaton S, Shostak, M, Konner, M.: The Paleolithic Prescription: A Program of Diet & Exercise and a Design for Living. New York:: Harper & Row; 1988.

33.          Konner M, Eaton SB: Paleolithic nutrition: twenty-five years later. Nutr Clin Pract, 25(6):594-602.

34.          Lindeberg S: [Paleolithic diet and evolution medicine: the key to diseases of the western world]. Lakartidningen 2005, 102(26-27):1976-1978.

35.          O’Keefe J, Cordain L.: Cardiovascular Disease Resulting From a Diet and Lifestyle at Odds With Our Paleolithic Genome: How to Become a 21st-Century Hunter-Gatherer. Mayo Clin Proc 2004;, 79:101-108.

36.          Cordain L, Eaton SB, Miller JB, Mann N, Hill K: The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr 2002, 56 Suppl 1:S42-52.

37.          Marlowe F: Hunter-gatherers and human evolution. Evolutionary Anthropology 2005, 14:54 -67.

38.          Froguel P, Boutin P: Genetics of pathways regulating body weight in the development of obesity in humans. Exp Biol Med (Maywood) 2001, 226(11):991-996.

39.          Bennett PH, Burch TA, Miller M: Diabetes mellitus in American (Pima) Indians. Lancet 1971, 2(7716):125-128.

40.          Bennett PH, Rushforth NB, Miller M, LeCompte PM: Epidemiologic studies of diabetes in the Pima Indians. Recent Prog Horm Res 1976, 32:333-376.

41.          Zimmet P, Arblaster M, Thoma K: The effect of westernization on native populations. Studies on a Micronesian community with a high diabetes prevalence. Aust N Z J Med 1978, 8(2):141-146.

42.          Ravussin E, Valencia ME, Esparza J, Bennett PH, Schulz LO: Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 1994, 17(9):1067-1074.

43.          Boyce VL, Swinburn BA: The traditional Pima Indian diet. Composition and adaptation for use in a dietary intervention study. Diabetes Care 1993, 16(1):369-371.

44.          Malhotra A, Kobes S, Knowler WC, Baier LJ, Bogardus C, Hanson RL: A Genome-Wide Association Study of BMI in American Indians. Obesity (Silver Spring).

45.          More M: The cryo-paelo solution: http://www.alcor.org/magazine/2011/03/07/the-cryo-paleo-solution/. Cryonics (on line edition) 2011.

46.          Snyder S: Alcor CEO Max More and the paleo diet: http://samsnyder.com/2011/05/22/alcor-ceo-max-more-and-the-paleo-diet/. In: A Blog by Sam Snyder. Sam Snyder; 2011.

Figure 1:

The Seven Countries and Adventist Health Studies

Nathan Pritikin drew his initial conclusions about the effect of dietary change from classified data he was privy to during World War II (WWII) on the patterns of age-associated disease in Europe as a consequence wartime calorie restriction and severe reduction of fat intake due to the severely reduced availability of meat and dairy products.  He also observed that the incidence of age-associated degenerative diseases was  very low in human populations where the diet was very low in fat (~10% of the total caloric intake), contained no refined sugars and consisted mostly of fresh vegetables and fruits  with very little meat being consumed. Similarly, the physiologist Ancel Keys (Figure 1), who was working with the Army Quartermaster Corps in developing K-Rations,[1] became involved in the Army’s program to create scientifically informed re-feeding programs for POWs and civilians suffering from starvation, saw the same kind of data. Unlike Pritikin, Keys had the opportunity to do human experimentation afforded by wartime conditions.[2, 3] Keys working hypothesis was different than Pritkin’s, namely that it was primarily saturated fats in the diet that were responsible for the high incidence of cardiovascular disease (CVD) in the affluent and well-fed West.

This epidemiological approach to identifying patterns of food consumption associated with increased or reduced risk of degenerative disease was also being pursued around this time in the US, by physicians at the Loma Linda Medical Center in Loma Linda, CA. Loma Linda was an almost exclusively Seventh Day Adventist community at that time, and these physicians believed that their patients, who practiced a vegetarian diet in conjunction with abstention from tobacco and alcohol, were considerably healthier than the non-Adventist population in California. They began a study of diet, lifestyle and the incidence of disease and all-cause mortality in 1958; the Adventist Health Study-1 (AHS-1) [4-26]

Keys returned to Europe after the war and began a study of six European countries, which later became the Seven Countries Study. [27-72] The dietary recommendations which emerged from the Seven Countries Study are commonly referred to as the “Mediterranean diet.” However, the use of the words “Mediterranean diet” to describe these recommendations is a misnomer. The countries of the Mediterranean basin have large differences in diet, lifestyle and in their corresponding rates of morbidly and mortality. The country with the lowest death rate  (14.0 – 18.0 per 1000 persons), is Crete, whose death rate has been at this level since at least 1930. [73] The diet of Crete is archetypical of the ‘traditional’ Greek diet before the introduction of continental European and American foods into Greece after ~ 1960.

The Seven Countries Study was the first to generate robust data on the incidence of cardiovascular disease in a range of populations (US, Finland, The Netherlands, Italy, the former Yugoslavia, Japan and Greece) with a fairly broad spectrum of dietary patterns. The study showed differences on the order of 5 to 10-fold in coronary artery disease (CAD) between the populations studied. [36, 50, 74]

Figure 2: The Cretan diet food pyramid.

Both the Seven Countries Study and the AHS-1 demonstrated large reductions in disease-specific morbidly and mortality, as well as in all-cause mortality; primarily as a result of diet and lifestyle differences. In the case of the Seven Countries Study, extensive follow-on research using well designed prospective studies, resulted in the development of a set of dietary guidelines which became known as the “Mediterranean” or more correctly, the “Cretan diet.” The guidelines which constitute the Cretan diet satisfy Level-1 EBM criteria for extension of the mean lifespan by ~10 years, reduction in all cause mortality, high levels of compliance, and very importantly, titratability. In other words, the degree of compliance with the diet is roughly commensurate with the benefit that results. [75-77]

What About Cholesterol?

For thirty years an acrimonious debate has raged in the scientific and medical communities over whether cholesterol, or any molecular species of lipoprotein, “causes heart disease” or other CVD. The causes of the inflammatory events that underlie the start of arterial plaque formations are complex, possibly multifactorial (e.g., genetic, viral, microbial, environmental, etc.) and by no means fully elucidated. Keys, Pritikin and many others mistakenly believed that “elevated” serum cholesterol was the primary cause of CVD. This hypothesis is well supported by the epidemiological data. However, there are many people who have normal or even slightly low levels of total cholesterol, or of the low density lipoprotein (LDL) species whose oxidation is usually cited as the motor of atherogenesis.

However, the observations of Keys and Pritkin extended beyond a cause and effect relationship between cholesterol and CVD. In different ways, both men demonstrated that altering the total serum cholesterol level and/or the ratio between the LDL and high density lipoprotein (HDL) species, they could reduce the incidence of the disease. In Pritkin’s case, he even demonstrated that the disease could be reversed by the expedient of a very low fat diet.[78-80] Pritkin demonstrated his theory on a very small population of people; principally those who read his book, or otherwise followed his dietary advice. Keys, on the other hand, conducted an experiment on a grand scale.

Throughout the 1960s Keys campaigned relentlessly to persuade physicians, public health authorities and the public themselves (directly) to replace the bulk of the calories they consumed in (saturated) fat with polyunsaturated fat. The purpose of this international dietary intervention was to reduce the serum cholesterol of the population, and thus the incidence of CVD. This effort enjoyed unprecedented success and it has resulted a doubling of the proportion of the unsaturated fatty acid, linoleic acid, in the tissues of Americans between 1960 and 1975.[81]  The mortality rate from coronary heart disease (CAD) in the US began to fall, starting in 1968, and it has continued to decline since then. It has been estimated that approximately 50% of the decline in CVD is as a result of dietary and lifestyle changes, exclusive of the reduction in tobacco abuse.[82]

As a scientist, I am acutely interested to understand the details of the pathophysiology of atherosclerosis. As someone who wants to avoid CVD, I am much more concerned with what works, even if the biomechanics are incomplete, or even contradictory. In this case, what works is that on a population basis, blood lipids are highly predictive of the risk of disease. Similarly, for most patients, raising HDL and lowering LDL are protective against both the onset of CVD, and to a lesser extent, its progression. Lipid status is thus a useful screening tool, as well as an instructive guide to the individual patient’s likely response to treatment. It is not necessary to believe that “cholesterol,” or any particular species of lipoprotein “causes” CVD. It is only necessary to understand that they are, at the least, useful biomarkers on a population wide basis and that they are often useful in the intelligent management of individual patients.

 Table 1: Fatty Acids Ratios in Different Diets

From the inception of the AHS-1 in 1958, and the Six Countries Study around the same time,[68, 83] the primary focus of the research, as was the case with Pritikin, was on the possible relationship of the diet to the etiology of CVD, with special emphasis on the fatty acid composition of the diet. The 5-year follow-up in the Seven Countries Study found favorable all-cause death rates in Greece, Italy and Japan, as compared with the other countries, including dramatically lower rates of CVD in Crete, and to a lesser extent in Japan.[84]The diet of Crete has in common with the diet of hunter-gatherers similar quantities of antioxidants, saturated fat, fiber, monounsaturated fat and, very importantly, the ratio of (n-6) to (n-3) fatty acids. [75-77]

One the basis of insights gained from the Seven Countries Study a wide range of epidemiologic investigations,  controlled clinical trials and relevant animal experiments have confirmed the hypotriglyceridemic, anti-inflammatory and antithrombotic aspects of (n-3) fatty acids (28 –35) as well as the criticality of (n-3) fatty acids, particularly Docosahexaenoic (n-3) (DHA) acid in the diet for the normal development of the retina and brain in the human infant. As a consequence of these insights, a study of the (n-3) fatty acid composition of diets that were known to be associated with reduced rates of CVD and cancer was undertaken.[75] The initial conclusion was that the high olive oil intake, which accounts for ~35% of the calories consumed in the Cretan diet, was likely responsible for the low rates of CVD and cancer. However, the Japanese have a similarly low incidence of these diseases and yet only ~11% of their calorie intake is from fat, none of which is from olive oil.

Figure 3: Mortality and morbidity difference between populations of patients with coronary artery disease (CAD) eating the Cretan diet and those on the low fat American Heart Association Step 1 diet[151]

The common factors between the populations of Crete and Japan were that they both consumed large amounts of vegetables (including wild plants), fruits, nuts and legumes, all of which are rich sources of folic acid, glutathione and vitamins E, C and other antioxidants. Wild plants are rich sources of (n-3) fatty acids and antioxidants and their consumption is not confined to humans. Both in Crete and in rural Japan, chickens and other livestock, such as goats and cows, are free ranging and consume wild vegetation in abundance (and in the case of chickens, insects, arachnids and worms) which are rich in (n-3) fatty acids and antioxidants, as well as cytoprotective and vasculoprotective trace minerals which are concentrated in the food chain. The result is poultry, eggs and milk which contain radically different ratios of (n-3) to (n-6) fatty acids and are enriched with selenium. For example, eggs from Crete have a ratio of (n-6) to (n-3) of 1:3, whereas the US ‘battery egg’ has a ratio of 19:4. Of course, the presence of this favorable ratio of lipids in eggs is also reflected in prepared foods which contain eggs (such as noodles, some breads and soups, etc.) and in the flesh of the animals that are slaughtered and eaten.

Analysis of the serum (n-3) fatty acid levels of the populations in Crete and Japan demonstrated that they had had higher concentrations of (n-3) fatty acids than did the other populations in the study, all of whom had a far high incidences of age associated degenerative diseases. The two populations with the lowest CAD in the Seven Countries Study consumed the highest amount of α-linoleic acid (α-LNA) the major sources of which were the wild herb purslane, walnuts and figs. By contrast, the Japanese obtained their α-LNA from canola and soybean oils. Interestingly, the Seventh Day Adventists, who experience an increase in mean lifespan of 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women over that of their non-Adventist cohorts in the US[10], consume a vegetarian diet that is rich in nuts and oils containing α-LNA. The SDAs, like the people of Crete, have not only higher levels of α-LNA, but also lower levels of linoleic acid[9, 85, 86]

Figure 4: The Lyon Diet Heart Study demonstrated a 50 to 70% reduction of the risk of recurrence of myocardial infarction (MI) after four years of follow-up in coronary heart disease (CHD patients. The Lyon diet employed α-LNA as 0.6 to 1% of total daily energy or about 2 g per day in patients who follow a traditional Mediterranean diet. Supplementation with very long chain omega-3 fatty acids (c.1g per day) in patients following a Mediterranean type of diet was shown to decrease the risk of cardiac death by 30% and of sudden cardiac death by 45% in the GISSI trial. [87]

In 1994 de Lorgeril and Renaud published the results of a prospective study to evaluate a diet which contained the types and ratios of essential fatty acids (EFAs) found to be effective at reducing CVD in the Seven Countries Studies. The Lyon Heart Study (LHS), as it came to be known, was a randomized, single-blind secondary prevention trial that combined a modified Cretan diet enriched with α-LNA with that of the Step I American Heart Association diet.[87] The LHS demonstrated a reduction in all-cause mortality of 70% in the experimental population which consumed a diet low in butter and processed meats, but high in fish, nuts, fruits and vegetables (Figure 5).[87] The LHS followed subjects for 5 years after the start of the intervention and examined the reduction of risk for coronary artery disease (CAD) as well as in mortality from all cancers. The reduction in CAD was 56% (P 5 0.03) over that of control subjects, and in cancer mortality it was 61% (P 5 0.05)!

Figure 5: Cardiac morbidity and mortality in the Lyon Diet Heart Study. Of particular importance to cryonicists is the reduction in mortality from sudden cardiac death (SCD). [87]

Olive Oil, or Something Else?

Figure 6: The author has serious questions about whether experiments conducted using industrially prepared laboratory animal chows (right) are representative of the results obtained when fresh fruits and vegetable as well as foods consumed in their native state are used (left).

An initial and obvious conclusion from The Seven Countries Study was that a significant part of the reduction in morbidity and the extension of lifespan due to the Cretan diet was a consequence of the consumption of a large fraction of the calories in the diet in the form of monounsaturated  fats (MUFAs), principally as a result of olive oil consumption. However, recent animal studies have yielded paradoxical results. For instance, experiments in green monkeys have shown that a diet high in MUFAs (olive oil source) causes atherosclerosis equivalent to that observed in animals fed a diet high in saturated fats (SFAs).[88] This effect appears to result from an increased secretion of cholesteryl oleate enriched lipoproteins, as well as due to an increase in the circulating blood levels of chylomicron remnants, which are highly atherogenic lipoproteins. [89-91]

These paradoxical animal results have raised questions amongst epidemiologists and nutritionists about whether MUFAs really have beneficial effects in humans. Green monkeys are metabolically and genetically different than humans and the human data indicate that dietary MUFAs have favorable effects on CHD risk. There is also a significant amount of mechanistic data that indicate that there are molecular species in olive oil that have potent antioxidant and anti-inflammatory properties. In particular, the polyphenolic compounds hydroxytyrosol and oleuropein have been shown to possess these properties both in vitro and in vivo.[92-96] There is also the issue of the way in which olive oil is incorporated into the chow for experimental animals (Figure 6). Olive oil incorporated into a manufactured chow along with other dietary ingredients is not the way in which humans consume it, and this factor should be taken into consideration in future studies.

Figure 7: The titratability of the beneficial effects of the Cretan diet are nicely illustrated in this series of graphs showing all cause mortality over a ten year period with three variations of the Cretan diet; the world Health Organization recommended diet base on the Seven Countries Study, a broadly similar diet, and a carbohydrate restricted version of the Cretan Diet. Kaplan-Meier survival curves for individuals considered adequate reporters of dietary intake, grouped as low-, medium-, or high-adherent individuals to the dietary patterns investigated. Crude hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression analyses with the use of low-adherent individuals as the reference group for each dietary pattern. A: World Health Organization (WHO) dietary guidelines, according to the Healthy Diet Indicator: medium adherent (HR: 0.70; 95% CI: 0.43, 1.15), high adherent (HR: 0.97; 95% CI: 0.45, 2.07). B: Mediterranean-like diet, according to the Mediterranean Diet Score: medium adherent (HR: 0.68; 95% CI: 0.44, 1.04), high adherent (HR: 0.29; 95% CI: 0.12, 0.70. C: Carbohydrate-restricted (CR) diet, according to the CR diet score: medium adherent (HR: 1.92; 95% CI: 1.02, 3.62), high adherent (HR: 2.17; 95% CI: 1.05, 4.45).[148]

Anti-inflammatory and Cytoregulatory Lipids in the Cretan Diet

One proposed resolution to the paradoxical animal findings regarding the atherogenicity of olive oil in the laboratory is the observation that both the high fat MFA diet of the Cretans, and the low fat PFA diet of the Japanese, are rich in (n-3) fatty acids and antioxidants, in particular resveratrol, glutathione, vitamin C, vitamin E, lycopene, b-carotene, polyphenols and polyamines obtained from fruits, vegetables, wild plants, and olive oil. [97] [98-101] Additionally, both diets are enriched in α-LNA and eicosapentaenoic acid [EPA, 20:5 (n-3)] from the consumption of large amounts of fish, relative to the control countries.[159, 171, 174] Because olive oil is high in the monounsaturated fatty acid oleic acid [18:1, (n-9)] and low in saturated (n-6) fatty acids it cannot compete with the endogenous desaturation and elongation of α-LNA, or with the incorporation of α-LNA into the constituent phospholipids of cell membranes. This is particularly important in the case of red blood cell (RBC) and platelet membranes, where they act to increase the deformability of RBCs and decrease the aggreability and adhesions of platelets. [102-108]

The ratio of (n-6) to (n-3) lipids in the Cretan diet is between 2:1 and 1:1, which is very close to the dietary ratio of the Japanese, as that of hunter-gatherer societies. The beneficial effects of such a ratio and their importance in normal growth and development [109, 110] as well as in the reduction of risk for CVD, hypertension, type II diabetes, osteoarthritis and, to a lesser extent cancer, are voluminously documented in the literature.[111] [112-116] The traditional Greek diet is very low in animal fat and thus the saturated fat content is quite low (7–8%). This low intake of SFAs is complemented by the high intake of  (n-6) and (n-3) EFAs which are also rich in phytoestrogens and other phytochemicals  as well α-LNA, vitamin C, vitamin E and glutathione.[117, 118] These molecules have been shown to have hypoglycemic, hypocholesterolemic and antitumor properties in animal experiments.[119-124] Consistent with these findings is the fact that the mortality from breast, prostate, bladder and colorectal cancer is lower in both the Cretan and the AHS populations than is the case for controls. [14, 20, 86, 125-129]

The principal EFA in the US diet is LA, an (n-6) fatty acid which is the precursor to the eicosanoids – molecules which have proinflammatory and cytoproliferative effects. The EFAs are converted to prostaglandins by the cyclooxygenases and to leukotrienes (LT) by the lipoxygenases. Arachidonicacid [(AA); 20:4(n-6)] and EPA, an (n-3) fatty acid, compete for cyclooxygenases and lipoxygenases, resulting in the production of eicosanoids with opposing effects. In general, AA-derived eicosanoids, such as the 2-series prostanoids and 4-series LTs, have pro-inflammatory effects, whereas EPA-derived eicosanoids, such as the 3-series prostanoids and5-series LTs, have anti-inflammatory effects. A focus of recent research has been to understand the importance of the (n-6) to (n-3) ratio, rather than the absolute level of either species of PUFA in cancer prevention.[102, 130]

Figure 8: The major active product of the omega-6 fatty acids is arachadonic acid which is converted to the 2-series prostaglandins and 4-series leukotrienes by the action of cyclooxygenase. The 2-series prostaglandins are pro-inflammatory.  In addition to the AA produced endogenously there are vast supplies available from the diet, most notably in meat, eggs and peanut oil.  In the Western diet there are comparatively few products of omega-3 metabolism to moderate the pro-inflammatory action of excessive dietary omega-6consumption. If the amount of omega-3 fatty acids in the diet is increased, their metabolites (primarily EPA and DHA) compete with arachidonic acid for access to cyclooxygenase resulting increased production of anti-inflammatory mediators as well as a decrease in the pro-inflammatory mediators, thereby significantly reducing the ratio of pro-inflammatory to anti-inflammatory mediators.

In animal studies (rats) LA increases the size and number of tumors, whereas fish oil [containing the (n-3) fatty acids EPA and DHA] decreases the incidence of tumor formation, as well as tumor size.[131] This finding is consistent with other studies in rats that indicate that the potent inhibitors of prostaglandin synthesis, the NSAIDs indomethacin and flurbiprofen are effective at reducing the incidence of spontaneously occurring breast cancer. Epidemiological studies in humans have also indicated a potentially chemoprotective effect as result of long term consumption of NSAID drugs.[132-136] Fish oils have been used to adjust systemic levels of  (n-3) fatty acids in animals models of colon, lung, breast, pancreatic and prostate cancers to reduce prostaglandin synthesis, with resulting chemoprevrention and/or slowed growth and metastases in neoplastic disease in the laboratory setting.[131]

These studies, together with the epidemiologic evidence, appear to confirm the importance of a (n-6) to (n-3) ratio of 2:1 as being chemoprotective in cancer, and raise the possibility that (n-3) fatty acids might be used as adjuvant therapy to reduce the risk of recurrence and metastases of breast cancer in humans following surgery and chemotherapy.[132-136] Epidemiological studies have also consistently shown that fish oil consumption protects against the development of a broad range of cancers, but especially breast and prostate cancer. [137-144] Thus, it is not the absolute level of either (n-3) or (n-6) lipids, but rather their presence in a ratio of 1:1 or 2:1 that chemoprotective against a number of cancers[128, 129, 145, 146] Western diets have a ratio of 10–20:1.[147]

Figure 9: The Cretan diet provides significant protection against Alzheimer’s disease (AD) in patients who have been diagnosed with mild cognitive impairment (MCI). Survival curves based on Cox analysis comparing cumulative AD incidence in subjects with MCI at the first evaluation by Mediterranean diet (MeDi) adherence tertile (P for trend = .02). The figure is derived from a model that is adjusted for cohort, age, sex, ethnicity, education, APOE genotype, caloric intake, body mass index, and time between the first dietary assessment and the first cognitive assessment. Duration of follow-up is truncated at 10 years. Results of log-rank tests for pairwise comparisons are as follows: middle vs low tertile, ² = 4.26, P = .03; low vs high tertile, ² = 1.39, P = .23; and middle vs high tertile, ² = 0.12, P = .72.[148, 149]

Both the Cretan and the Adventist vegetarian diets confer substantial protection against the mild cognitive impairment (MCI) of aging and against Alzheimer’s disease (AD)(Figure 9)[148, 149] Interestingly, the AHS-2 results demonstrate a link between the incidence of dementia and the consumption of all meat products, including fish and poultry. This may account for added benefit of Adventist Vegetarian diet over what would be expected on the basis of its lipid constituents and the presence of some adverse foodstuffs, such as refined sugar. Perhaps meat consumption is associated with adverse effects, per se? The literature is open to interpretation on this point.[150, 151]

The two highest quality studies examining the effect of vegetarian diets on lifespan, as well as morbidity were conducted by Key, et al., and were published in 2009.[152, 153] These studies found no significant difference in lifespan between the control and the vegetarian populations in the study. However, as so often happens in studies of this kind, both the control and the vegetarian group experienced statistically significant lower rates of mortality than the general population (UK). This kind of confounding result may be due to self-selection of on average healthier people within the general population to serve as controls. Another limitation on these studies is that they were barely powered adequately to detect small to moderate differences in mortality. The vegetarian group in this study had a lower body mass index (BMI) and consequently less obesity. The incidence of CVD and cancer were not statistically significant between the groups.

End of Part 2

References

1.            Gottlieb SH: “K-ration”. Diabetes and cardiovascular risk. Diabetes Forecast 2002, 55(2):44-46.

2.            Kalm LM, Semba RD: They starved so that others be better fed: remembering Ancel Keys and the Minnesota experiment. J Nutr 2005, 135(6):1347-1352.

3.            Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E: Coronary Heart Disease among Minnesota Business and Professional Men Followed Fifteen Years. Circulation 1963, 28:381-395.

4.            Skinner JD, Carruth BR, Pope J, Varner L, Goldberg D: Food and nutrient intake of white, pregnant adolescents. J Am Diet Assoc 1992, 92(9):1127-1129.

5.            Grundmann E: Cancer morbidity and mortality in USA Mormons and Seventh-day Adventists. Arch Anat Cytol Pathol 1992, 40(2-3):73-78.

6.            Fraser GE: Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr 1999, 70(3 Suppl):532S-538S.

7.            Fraser GE: Determinants of ischemic heart disease in Seventh-day Adventists: a review. Am J Clin Nutr 1988, 48(3 Suppl):833-836.

8.            Fraser GE, Lindsted KD, Beeson WL: Effect of risk factor values on lifetime risk of and age at first coronary event. The Adventist Health Study. Am J Epidemiol 1995, 142(7):746-758.

9.            Fraser GE, Sabate J, Beeson WL, Strahan TM: A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med 1992, 152(7):1416-1424.

10.          Fraser GE, Shavlik DJ: Ten years of life: Is it a matter of choice? Arch Intern Med 2001, 161(13):1645-1652.

11.          Fraser GE, Shavlik DJ: Risk factors for all-cause and coronary heart disease mortality in the oldest-old. The Adventist Health Study. Arch Intern Med 1997, 157(19):2249-2258.

12.          Giem P, Beeson WL, Fraser GE: The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology 1993, 12(1):28-36.

13.          Mills PK, Beeson WL, Phillips RL, Fraser GE: Cancer incidence among California Seventh-Day Adventists, 1976-1982. Am J Clin Nutr 1994, 59(5 Suppl):1136S-1142S.

14.          Singh PN, Sabate J, Fraser GE: Does low meat consumption increase life expectancy in humans? Am J Clin Nutr 2003, 78(3 Suppl):526S-532S.

15.          Snowdon DA, Phillips RL, Fraser GE: Meat consumption and fatal ischemic heart disease. Prev Med 1984, 13(5):490-500.

16.          Mills PK, Preston-Martin S, Annegers JF, Beeson WL, Phillips RL, Fraser GE: Risk factors for tumors of the brain and cranial meninges in Seventh-Day Adventists. Neuroepidemiology 1989, 8(5):266-275.

17.          Singh N, Graves J, Taylor PD, MacAllister RJ, Singer DR: Effects of a ‘healthy’ diet and of acute and long-term vitamin C on vascular function in healthy older subjects. Cardiovasc Res 2002, 56(1):118-125.

18.          Taylor CB, Allen ES, Mikkelson B, Kang-Jey H: Serum cholesterol levels of Seventh-day Adventists. Paroi Arterielle 1976, 3(4):175-179.

19.          Kahn HA, Phillips RL, Snowdon DA, Choi W: Association between reported diet and all-cause mortality. Twenty-one-year follow-up on 27,530 adult Seventh-Day Adventists. Am J Epidemiol 1984, 119(5):775-787.

20.          Beeson WL, Mills PK, Phillips RL, Andress M, Fraser GE: Chronic disease among Seventh-day Adventists, a low-risk group. Rationale, methodology, and description of the population. Cancer 1989, 64(3):570-581.

21.          Masley SC, Weaver W, Peri G, Phillips SE: Efficacy of lifestyle changes in modifying practical markers of wellness and aging. Altern Ther Health Med 2008, 14(2):24-29.

22.          Mills PK, Annegers JF, Phillips RL: Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists. Am J Epidemiol 1988, 127(3):440-453.

23.          Phillips RL, Garfinkel L, Kuzma JW, Beeson WL, Lotz T, Brin B: Mortality among California Seventh-Day Adventists for selected cancer sites. J Natl Cancer Inst 1980, 65(5):1097-1107.

24.          Phillips RL, Snowdon DA: Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists. J Natl Cancer Inst 1985, 74(2):307-317.

25.          Vang A, Singh PN, Lee JW, Haddad EH, Brinegar CH: Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies. Ann Nutr Metab 2008, 52(2):96-104.

26.          Fonnebo V: The Tromso Heart Study: coronary risk factors in Seventh-Day Adventists. Am J Epidemiol 1985, 122(5):789-793.

27.          Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S et al: Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995, 155(4):381-386.

28.          Coronary heart disease in seven countries. I. The study program and objectives. Circulation 1970, 41(4 Suppl):I1-8.

29.          Twenty-five year incidence and prediction of coronary heart disease in two Italian rural population samples. The Italian Research Group of the Seven Countries Study. Acta Cardiol 1986, 41(4):283-299.

30.          The diet and all-causes death rate in the Seven Countries Study. Lancet 1981, 2(8237):58-61.

31.          Alberti-Fidanza A, Fidanza F, Chiuchiu MP, Verducci G, Fruttini D: Dietary studies on two rural italian population groups of the Seven Countries Study. 3. Trend Of food and nutrient intake from 1960 to 1991. Eur J Clin Nutr 1999, 53(11):854-860.

32.          Alberti-Fidanza A, Paolacci CA, Chiuchiu MP, Coli R, Fruttini D, Verducci G, Fidanza F: Dietary studies on two rural Italian population groups of the Seven Countries Study. 1. Food and nutrient intake at the thirty-first year follow-up in 1991. Eur J Clin Nutr 1994, 48(2):85-91.

33.          Alberti-Fidanza A, Paolacci CA, Chiuchiu MP, Coli R, Parretta MG, Verducci G, Fidanza F: Dietary studies on two rural Italian population groups of the Seven Countries Study. 2. Concurrent validation of protein, fat and carbohydrate intake. Eur J Clin Nutr 1994, 48(2):92-96.

34.          Alonso A, Jacobs DR, Jr., Menotti A, Nissinen A, Dontas A, Kafatos A, Kromhout D: Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study. J Neurol Sci 2009, 280(1-2):79-83.

35.          Alvarez Guisasola F, Mavros P, Nocea G, Alemao E, Alexander CM, Yin D: Glycaemic control among patients with type 2 diabetes mellitus in seven European countries: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study. Diabetes Obes Metab 2008, 10 Suppl 1:8-15.

36.          Cheng TO: Ancel Keys, seven countries study, China connections, and K rations. J Am Diet Assoc 2005, 105(3):349.

37.          de Lorgeril M, Salen P: Mediterranean type of diet for the prevention of coronary heart disease. A global perspective from the seven countries study to the most recent dietary trials. Int J Vitam Nutr Res 2001, 71(3):166-172.

38.          Ducimetiere P, Richard JL, Cambien F, Rakotovao R, Claude JR: Coronary heart disease in middle-aged Frenchmen. Comparisons between Paris Prospective Study, Seven Countries Study, and Pooling Project. Lancet 1980, 1(8182):1346-1350.

39.          Farchi G, Fidanza F, Giampaoli S, Mariotti S, Menotti A: Alcohol and survival in the Italian rural cohorts of the Seven Countries Study. Int J Epidemiol 2000, 29(4):667-671.

40.          Feskens EJ, Tuomilehto J, Stengard JH, Pekkanen J, Nissinen A, Kromhout D: Hypertension and overweight associated with hyperinsulinaemia and glucose tolerance: a longitudinal study of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetologia 1995, 38(7):839-847.

41.          Feskens EJ, Virtanen SM, Rasanen L, Tuomilehto J, Stengard J, Pekkanen J, Nissinen A, Kromhout D: Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetes Care 1995, 18(8):1104-1112.

42.          Fidanza F, Alberti A, Lanti M, Menotti A: Mediterranean diet score: correlation with 25-year mortality from coronary heart disease in the Seven Countries Study. Nutr Metab Cardiovasc Dis 2004, 14(6):397.

43.          Alberti A, Fruttini D, Fidanza F: The Mediterranean Adequacy Index: further confirming results of validity. Nutr Metab Cardiovasc Dis 2009, 19(1):61-66.

44.          Jacobs DR, Jr., Adachi H, Mulder I, Kromhout D, Menotti A, Nissinen A, Blackburn H: Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study. Arch Intern Med 1999, 159(7):733-740.

45.          Jansen DF, Nedeljkovic S, Feskens EJ, Ostojic MC, Grujic MZ, Bloemberg BP, Kromhout D: Coffee consumption, alcohol use, and cigarette smoking as determinants of serum total and HDL cholesterol in two Serbian cohorts of the Seven Countries Study. Arterioscler Thromb Vasc Biol 1995, 15(11):1793-1797.

46.          Jansen MC, Bueno-de-Mesquita HB, Buzina R, Fidanza F, Menotti A, Blackburn H, Nissinen AM, Kok FJ, Kromhout D: Dietary fiber and plant foods in relation to colorectal cancer mortality: the Seven Countries Study. Int J Cancer 1999, 81(2):174-179.

47.          Jansen MC, Bueno-de-Mesquita HB, Rasanen L, Fidanza F, Menotti A, Nissinen A, Feskens EJ, Kok FJ, Kromhout D: Consumption of plant foods and stomach cancer mortality in the seven countries study. Is grain consumption a risk factor? Seven Countries Study Research Group. Nutr Cancer 1999, 34(1):49-55.

48.          Kafatos A, Diacatou A, Voukiklaris G, Nikolakakis N, Vlachonikolis J, Kounali D, Mamalakis G, Dontas AS: Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study. Am J Clin Nutr 1997, 65(6):1882-1886.

49.          Karon JM, Parker RA: Re: “The diet and 15-year death rate in the Seven Countries Study”. Am J Epidemiol 1988, 128(1):238-241.

50.          Keys A, Menotti A, Aravanis C, Blackburn H, Djordevic BS, Buzina R, Dontas AS, Fidanza F, Karvonen MJ, Kimura N et al: The seven countries study: 2,289 deaths in 15 years. Prev Med 1984, 13(2):141-154.

51.          Kromhout D: [The 'Seven Countries Study': 40 years of research in coronary heart diseases in 7 countries]. Ned Tijdschr Geneeskd 1997, 141(1):7-9.

52.          Kromhout D, Bloemberg B, Feskens E, Menotti A, Nissinen A: Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study. Int J Epidemiol 2000, 29(2):260-265.

53.          Kromhout D, Bloemberg B, Seidell JC, Nissinen A, Menotti A: Physical activity and dietary fiber determine population body fat levels: the Seven Countries Study. Int J Obes Relat Metab Disord 2001, 25(3):301-306.

54.          Kromhout D, Katan MB, Menotti A, Keys A, Bloemberg B: Serum cholesterol and long-term death rates from suicide, accidents, or violence. Seven Countries Study Group. Lancet 1992, 340(8814):317.

55.          Kromhout D, Menotti A, Bloemberg B, Aravanis C, Blackburn H, Buzina R, Dontas AS, Fidanza F, Giampaoli S, Jansen A et al: Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med 1995, 24(3):308-315.

56.          Kromhout D, Nedeljkovic SI, Grujic MZ, Ostojic MC, Keys A, Menotti A, Katan MB, van Oostrom MA, Bloemberg BP: Changes in major risk factors for cardiovascular diseases over 25 years in the Serbian cohorts of the Seven Countries Study. Int J Epidemiol 1994, 23(1):5-11.

57.          Lanti M, Menotti A, Nedeljkovic S, Nissinen A, Kafatos A, Kromhout D: Long-term trends in major cardiovascular risk factors in cohorts of aging men in the European cohorts of the Seven Countries Study. Aging Clin Exp Res 2005, 17(4):306-315.

58.          Mamalakis G, Jansen E, Cremers H, Kiriakakis M, Tsibinos G, Kafatos A: Depression and adipose and serum cholesteryl ester polyunsaturated fatty acids in the survivors of the seven countries study population of Crete. Eur J Clin Nutr 2006, 60(8):1016-1023.

59.          Mamalakis G, Kiriakakis M, Tsibinos G, Kafatos A: Depression and adipose polyunsaturated fatty acids in the survivors of the Seven Countries Study population of Crete. Prostaglandins Leukot Essent Fatty Acids 2004, 70(6):495-501.

60.          Mariotti S, Capocaccia R, Farchi G, Menotti A, Verdecchia A, Keys A: Differences in the incidence rate of coronary heart disease between north and south European cohorts of the Seven Countries Study as partially explained by risk factors. Eur Heart J 1982, 3(5):481-487.

61.          Mariotti S, Capocaccia R, Farchi G, Menotti A, Verdecchia A, Keys A: Age, period, cohort and geographical area effects on the relationship between risk factors and coronary heart disease mortality. 15-year follow-up of the European cohorts of the Seven Countries study. J Chronic Dis 1986, 39(3):229-242.

62.          Menotti A: The relationship of total serum cholesterol to coronary heart disease in older men. The Italian rural areas of the Seven Countries Study. Ann Epidemiol 1992, 2(1-2):107-111.

63.          Menotti A, Blackburn H, Kromhout D, Nissinen A, Adachi H, Lanti M: Cardiovascular risk factors as determinants of 25-year all-cause mortality in the seven countries study. Eur J Epidemiol 2001, 17(4):337-346.

64.          Menotti A, Blackburn H, Kromhout D, Nissinen A, Karvonen M, Aravanis C, Dontas A, Fidanza F, Giampaoli S: The inverse relation of average population blood pressure and stroke mortality rates in the seven countries study: a paradox. Eur J Epidemiol 1997, 13(4):379-386.

65.          Menotti A, Blackburn H, Seccareccia F, Kromhout D, Nissinen A, Aravanis C, Giampaoli S, Mohacek I, Nedeljkovic S, Toshima H: The relation of chronic diseases to all-cause mortality risk–the Seven Countries Study. Ann Med 1997, 29(2):135-141.

66.          Menotti A, Conti S, Corradini P, Giampaoli S, Rumi A, Signoretti P: [Incidence and prediction of coronary heart disease in the Italian cohorts of the Seven Countries Study. 10 year experience (author's transl)]. G Ital Cardiol 1980, 10(7):792-806.

67.          Menotti A, Jacobs DR, Jr., Blackburn H, Kromhout D, Nissinen A, Nedeljkovic S, Buzina R, Mohacek I, Seccareccia F, Giampaoli S et al: Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes. Stroke 1996, 27(3):381-387.

68.          Menotti A, Keys A, Aravanis C, Blackburn H, Dontas A, Fidanza F, Karvonen MJ, Kromhout D, Nedeljkovic S, Nissinen A et al: Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Ann Med 1989, 21(3):175-179.

69.          Menotti A, Keys A, Blackburn H, Aravanis C, Dontas A, Fidanza F, Giampaoli S, Karvonen M, Kromhout D, Nedeljkovic S et al: Twenty-year stroke mortality and prediction in twelve cohorts of the Seven Countries Study. Int J Epidemiol 1990, 19(2):309-315.

70.          Menotti A, Keys A, Blackburn H, Karvonen M, Punsar S, Nissinen A, Pekkanen J, Kromhout D, Giampaoli S, Seccareccia F et al: Blood pressure changes as predictors of future mortality in the seven countries study. J Hum Hypertens 1991, 5(3):137-144.

71.          Menotti A, Keys A, Blackburn H, Kromhout D, Karvonen M, Nissinen A, Pekkanen J, Punsar S, Fidanza F, Giampaoli S et al: Comparison of multivariate predictive power of major risk factors for coronary heart diseases in different countries: results from eight nations of the Seven Countries Study, 25-year follow-up. J Cardiovasc Risk 1996, 3(1):69-75.

72.          Menotti A, Keys A, Kromhout D, Blackburn H, Aravanis C, Bloemberg B, Buzina R, Dontas A, Fidanza F, Giampaoli S et al: Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study. Eur J Epidemiol 1993, 9(5):527-536.

73.          Allbaugh L: Crete: A Case Study of an Underdeveloped Area. Princeton, N.J: Princeton University Press; 1953.

74.          Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys MH et al: The diet and 15-year death rate in the seven countries study. Am J Epidemiol 1986, 124(6):903-915.

75.          Simopoulos A, Robinson, J.: The Omega Diet. The Lifesaving Nutritional Program Based on the Diet of the Island of Crete. New York: HarperCollins; 1999.

76.          Simopoulos AP: The traditional diet of Greece and cancer. Eur J Cancer Prev 2004, 13(3):219-230.

77.          Simopoulos AP: What is so special about the diet of Greece? The scientific evidence. World Rev Nutr Diet 2005, 95:80-92.

78.          Ornish D: Can lifestyle changes reverse coronary heart disease? World Rev Nutr Diet 1993, 72:38-48.

79.          Hubbard J, Inkeles, S, Barnard, RJ.: Nathan Pritikin’s Heart. N Engl J Med 1985, 313:52.

80.          Barnard R, Pritikin, R,  Rosenthal, R, et al.: Pritikin Approach to Cardiac Rehabilitation; Rehabilitation Medicine. St. Louis: Mosby Company, ; 1988.

81.          Katan M, Beynen, AC.: Linoleic acid consumption and coronary heart disease  in U.S.A. and U.K. Lancet 1981, 15(2(8242)):371.

82.          Goldman L, Cook, EF.: The decline in ischemic heart disease mortality rates: An analysis of the comparative effects of medical interventions and changes in lifestyle. . Ann Intern Med 1984 101(6)::825-836.

83.          Keys A: Coronary heart disease in seven countries. Circulation

 1970, 41: (suppl.): 1-211

84.          Keyes A: Coronary heart disease in seven countries. Circulation

 1970, 41: (suppl.): 1-211

85.          Sandker GW, Kromhout, D, Aravanis, C, Bloemberg, BP. Mensink, R P, Karalias, N, Katan, MB.: Serum lipids in elderly men in Crete and The Netherlands. . Eur J Clin Nutr 1993, 47:201-208.

86.          Willett W: Lessons from dietary studies in Adventists and questions for the future. Am J Clin Nutr 2003, 78(3 Suppl):539S-543S.

87.          de Lorgeril M, Salen P: The Mediterranean diet in secondary prevention of coronary heart disease. Clin Invest Med 2006, 29(3):154-158.

88.          Rudel L, Parks, JS,  Sawyer, JK.: Compared with dietary monounsaturated and saturated fat, polyunsaturated fat protects african green monkeys from coronary artery atherosclerosis Arteriosclerosis, Thrombosis, and Vascular Biology 1995, 15:2101-2110

89.          Higashi K, Ishikawa, T, Shige H, Tomiyasu, K, Yoshida, H, Ito, T, Nakajima, K, Yonemura, A, Sawada, S, Nakamura, H.: Olive oil increases the magnitude of postprandial chylomicron remnants compared to milk fat and safflower oil. J Am Coll Nutr 1997, 16::429-434.

90.          de Bruin T, Brouwer, CB, van Linde-Sibenius, TM, Erkelens,DW. : Different postprandial metabolism of olive oil and soybean oil: a possible mechanism of the high-density lipoprotein conserving effect of olive oil. Am J Clin Nutr 1993, 58:477-483.

91.          Bray G, Popkin, BM. : Dietary fat intake does affect obesity. Am J Clin Nutr 1998, 68:1157-1173.

92.          Briante R, Febbraio F, Nucci R: Antioxidant properties of low molecular weight phenols present in the mediterranean diet. J Agric Food Chem 2003, 51(24):6975-6981.

93.          Boskou D: Olive oil. World Rev Nutr Diet 2007, 97:180-210.

94.          Konstantinidou V, Covas MI, Munoz-Aguayo D, Khymenets O, de la Torre R, Saez G, Tormos Mdel C, Toledo E, Marti A, Ruiz-Gutierrez V et al: In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J, 24(7):2546-2557.

95.          Wahle KW, Caruso D, Ochoa JJ, Quiles JL: Olive oil and modulation of cell signaling in disease prevention. Lipids 2004, 39(12):1223-1231.

96.          Battino M, Ferreiro MS: Ageing and the Mediterranean diet: a review of the role of dietary fats. Public Health Nutr 2004, 7(7):953-958.

97.          Manios Y, Detopoulou V, Visioli F, Galli C: Mediterranean diet as a nutrition education and dietary guide: misconceptions and the neglected role of locally consumed foods and wild green plants. Forum Nutr 2006, 59:154-170.

98.          Ferro-Luzzi A, James WP, Kafatos A: The high-fat Greek diet: a recipe for all? Eur J Clin Nutr 2002, 56(9):796-809.

99.          Renaud S, de Lorgeril, M., Delaye, J., Guidollet, J., Jacquard, F., Mamelle, N., Martin, J. L., Monjaud, I., Salen, P, Touboul, P.: Cretan

Mediterranean diet for prevention of coronary heart disease. Am J Clin Nutr 1995, 61((suppl.)):1360S-1367S.

100.        Mamelle N: Mediterranean dietary pattern in a randomized trial. Prolonged survival and possible reduced cancer rate. Arch Intern Med 1998, 158:1181-1187.

101.        de Lorgeril M, Salen P: Modified cretan Mediterranean diet in the prevention of coronary heart disease and cancer: An update. World Rev Nutr Diet 2007, 97:1-32.

102.        Simopoulos A: Omega-3 fatty acids in health and disease and in growth and development. m J Clin Nutr 1991(54):438-463.

103.        Freese R, Mutanen M, Valsta LM, Salminen I: Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation. Thromb Haemost 1994, 71(1):73-77.

104.        Valsta LM, Salminen I, Aro A, Mutanen M: Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids. Eur J Clin Nutr 1996, 50(4):229-235.

105.        Sebedio JL, Vermunt SH, Chardigny JM, Beaufrere B, Mensink RP, Armstrong RA, Christie WW, Niemela J, Henon G, Riemersma RA: The effect of dietary trans alpha-linolenic acid on plasma lipids and platelet fatty acid composition: the TransLinE study. Eur J Clin Nutr 2000, 54(2):104-113.

106.        Garcia-Marcos L, Canflanca IM, Garrido JB, Varela AL, Garcia-Hernandez G, Guillen Grima F, Gonzalez-Diaz C, Carvajal-Uruena I, Arnedo-Pena A, Busquets-Monge RM et al: Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren. Thorax 2007, 62(6):503-508.

107.        Burri BJ, Dougherty RM, Kelley DS, Iacono JM: Platelet aggregation in humans is affected by replacement of dietary linoleic acid with oleic acid. Am J Clin Nutr 1991, 54(2):359-362.

108.        Chan JK, McDonald BE, Gerrard JM, Bruce VM, Weaver BJ, Holub BJ: Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 1993, 28(9):811-817.

109.        Birch E, Hoffman, DR, Uauy, R, Birch, DG, Prestidge, C.: Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatr Res 1998, 44: 201-209.

110.        Birch E, Birch, D., Hoffman, D., Hale, L., Everett, M, Uauy, R.: Breast-feeding and optimal visual development Strabismus

  J Pediatr Ophthalmol 1993, 30: 33-38.

111.        Simopoulos A, Kifer, RR, Martin, RE.: Health  effects of polyunsaturated fatty acids in seafoods. Orlando: Academic Press; 1986.

112.        Hamazaki T, Okuyama, H. (ed.): Fatty Acids and Lipids-New Findings: http://content.karger.com/ProdukteDB/produkte.asp?Aktion=showproducts&searchWhat=books&searchParm=toc&ProduktNr=224409. Basel: Karger; 2001.

113.        Leaf A, Weber, PC.: Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988, 318:549-557.

114.        Simopoulos A: Fatty acids in the prevention-management of cardiovascular disease. Can J Physiol Pharmacol 1997, 75:234-239.

115.        Simopoulos A: Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999, 70 ( (suppl.)):560S-569S.

116.        Simopoulos A, Leaf, A, Salem, N., Jr.: Essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Ann Nutr Metabolism 1999, 43:27-130.

117.        Weisburger J: Mechanisms of action in antioxidants as exemplified in vegetables, tomatoes and tea. Food Chem Toxicol 1999, 37(943-948).

118.        Hertog M, Hollman,  PCH, Katan, MB.: Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in The Netherlands. J Agric Food Chem 1992, 40:2379-2383.

119.        Slater T, Block, G,  eds.: Antioxidant vitamins and b-carotene in disease prevention. Am J Clin Nutr 1991, 53( (suppl.)):189S-396S.

120.        Agradi E, Vegeto E, Sozzi A, Fico G, Regondi S, Tome F: Traditional healthy Mediterranean diet: estrogenic activity of plants used as food and flavoring agents. Phytother Res 2006, 20(8):670-675.

121.        Gerber M: Biofactors in the Mediterranean diet. Clin Chem Lab Med 2003, 41(8):999-1004.

122.        Heinrich M, Leonti M, Nebel S, Peschel W: “Local Food – Nutraceuticals”: an example of a multidisciplinary research project on local knowledge. J Physiol Pharmacol 2005, 56 Suppl 1:5-22.

123.        Visioli F, Galli C: Biological properties of olive oil phytochemicals. Crit Rev Food Sci Nutr 2002, 42(3):209-221.

124.        Cristina F: Mediterranean diet health benefits may be due to a synergistic combination of phytochemicals and fatty-acids. BMJ 2005, 331(7508):E366.

125.        Mills PK, Beeson WL, Phillips RL, Fraser GE: Bladder cancer in a low risk population: results from the Adventist Health Study. Am J Epidemiol 1991, 133(3):230-239.

126.        Hirayama T: Mortality in Japanese with life-styles similar to Seventh-Day Adventists: strategy for risk reduction by life-style modification. Natl Cancer Inst Monogr 1985, 69:143-153.

127.        Zollinger TW, Phillips RL, Kuzma JW: Breast cancer survival rates among Seventh-day Adventists and non-Seventh-day Adventists. Am J Epidemiol 1984, 119(4):503-509.

128.        Levi F, La Vecchia, C, Lucchini, F, Negri, E.: Cancer mortalityin Europe. Eur J Cancer Prev 1995, 1990-1992(4):389-417.

129.        Stamatiou K, Alevizos A, Mariolis A, Sofras F: [Mediterranean diet and prostate cancer]. Actas Urol Esp 2006, 30(3):340.

130.        Fernandez E, Gallus S, La Vecchia C: Nutrition and cancer risk: an overview. J Br Menopause Soc 2006, 12(4):139-142.

131.        Cave W, Jr.: Fatty acid diet effects on tumorigenesis in experimental animals. . World Rev Nutr Diet 1991, 3(66):462-476.

132.        Cowing B, Saker, KE.: Polyunsaturated fatty acids and epidermal growth factor receptor/mitogen-activated protein kinase signaling in

mammary cancer. J Nutr 2001, 131::1125-1128.

133.        Schley PD, Brindley DN, Field CJ: (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 2007, 137(3):548-553.

134.        Ge Y, Chen Z, Kang ZB, Cluette-Brown J, Laposata M, Kang JX: Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. Anticancer Res 2002, 22(2A):537-543.

135.        Bardon S, Le MT, Alessandri JM: Metabolic conversion and growth effects of n-6 and n-3 polyunsaturated fatty acids in the T47D breast cancer cell line. Cancer Lett 1996, 99(1):51-58.

136.        Chajes V, Sattler W, Stranzl A, Kostner GM: Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: relationship to peroxides and vitamin-E. Breast Cancer Res Treat 1995, 34(3):199-212.

137.        Nielsen N, Hansen, JPH.: Breast cancer in Greenland-selected epidemiological, clinical and histological features. J Cancer Res Clin Oncol 1980, 98:287-299.

138.        Terry P, Lichtenstein, P, Feychting, M, Ahlbom, A, Wolk, A.: Fatty fish consumption and risk of prostate cancer. Lancet 2001, 357:1764-1766.

139.        Wargovich MJ: Fish oil and colon cancer. Gastroenterology 1992, 103(3):1096-1098.

140.        Caygill CP, Charlett A, Hill MJ: Fat, fish, fish oil and cancer. Br J Cancer 1996, 74(1):159-164.

141.        Lindner MA: A fish oil diet inhibits colon cancer in mice. Nutr Cancer 1991, 15(1):1-11.

142.        Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N: Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun, 402(4):602-607.

143.        Moreira AP, Sabarense CM, Dias CM, Lunz W, Natali AJ, Gloria MB, Peluzio MC: Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats. Braz J Med Biol Res 2009, 42(12):1167-1172.

144.        Chiang KC, Persons KS, Istfan NW, Holick MF, Chen TC: Fish oil enhances the antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 on liver cancer cells. Anticancer Res 2009, 29(9):3591-3596.

145.        Miano L: [Mediterranean diet, micronutrients and prostate carcinoma: a rationale approach to primary prevention of prostate cancer]. Arch Ital Urol Androl 2003, 75(3):166-178.

146.        Yee LD, Young DC, Rosol TJ, Vanbuskirk AM, Clinton SK: Dietary (n-3) polyunsaturated fatty acids inhibit HER-2/neu-induced breast cancer in mice independently of the PPARgamma ligand rosiglitazone. J Nutr 2005, 135(5):983-988.

147.        Simopoulos A: Evolutionary aspects of diet and essential fatty acids. World Rev Nutr Diet 2001, 88:18-27.

148.        Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA: Mediterranean diet and mild cognitive impairment. Arch Neurol 2009, 66(2):216-225.

149.        Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA: Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006, 59(6):912-921.

150.        Appleby PN, Thorogood M, Mann JI, Key TJ: The Oxford Vegetarian Study: an overview. Am J Clin Nutr 1999, 70(3 Suppl):525S-531S.

151.        Key TJ, Appleby PN, Rosell MS: Health effects of vegetarian and vegan diets. Proc Nutr Soc 2006, 65(1):35-41.

152.        Key TJ, Appleby PN, Spencer EA, Travis RC, Roddam AW, Allen NE: Mortality in British vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Am J Clin Nutr 2009, 89(5):1613S-1619S.

153.        Key TJ, Appleby PN, Spencer EA, Travis RC, Roddam AW, Allen NE: Cancer incidence in vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Am J Clin Nutr 2009, 89(5):1620S-1626S.

By Mike Darwin

First, Try to Make it to the Mean

For the past two months I’ve been asking people I encounter in public places[1] the question, “How old do you think you’ll live to be?” The answer I get from non-smokers is usually a number somewhere between 75 and 90, regardless of their age. Occasionally, people will remark that they expect to live to be100, or even 120 because of “medical advances,” but mostly people put their prospects at or above the mean lifespan for people living in the US. This shouldn’t be surprising, because the mean life expectancy in the US for men and women combined is currently 77.8 years. Since nobody (except for smokers) wants to be less than average, the lowest number people volunteer is right around the mean lifespan for the population of the US, at present.

Figure 1: In statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to highest value and picking the middle one. If there are an even number of observations, then there is no single middle value; the median is then usually defined to be the mean of the two middle values. At most, half the population has values less than the median, and, at most, half have values greater than the median. If both groups contain less than half the population, then some of the population is exactly equal to the median. For example, if a < b < c, then the median of the list {a, b, c} is b, and, if a < b < c < d, then the median of the list {a, b, c, d} is the mean of b and c; i.e., it is (b + c)/2.

However, life expectancy is not the same as mean, or average lifespan. Rather, life expectancy constitutes the expected number of years, on average, that a particular cohort of individuals in the population will survive if the rate of mortality remains constant (until the maximum lifespan is reached).[2] Life expectancy is thus the median number of years, at birth, that a population born in a particular year is expected to survive. For instance, based on the most recent data, life expectancy at birth in 2008 was 77.8 years.[1] The good news for people in this cohort is that half of them will live longer than 77.8 years, and the bad news is that half of them will not survive to their 77^th birthday.

Table 1. U.S. Life Expectancy at Birth,

by Sex, in Selected Years

(in years)

 Source: For data through 2002, the Congressional Research Service (CRS) compilation from National Center for Health Statistics (NCHS), United States Life Tables, 2002, National Vital Statistics Reports, vol. 53, no. 6, Nov. 10, 2004. For 2003, NCHS, Deaths: Final Data for 2003, National Vital Statistics Reports, vol. 54, no. 13, Apr. 19, 2006.[3]

It is also the case that the lifespan of all of the individuals in the nation does not necessarily increase along with the reported statistical mean lifespan for the nation’s population as a whole. As an example, I was born in 1955, and if we look at the cohort survival data from that period, the median life expectancy for males from my cohort is ~ 66 years. Of course, this includes all males in my cohort, including those who died at birth, those who died in various wars, those who died as a result of youthful indiscretion (some fraction of deaths by accident, suicide and homicide), and those who died due to “random” accidents. A more precise estimate of my life expectancy (and yours) can be had by consulting the chart in Figure 2, below.

Figure 2: US life expectancy as a function of age (2008 data set).

Most people seem to assume that they are guaranteed survival to whatever the current mean US lifespan is. Unfortunately, that isn’t the case, and in fact half of them will die before reaching the mean lifespan. So, when I hear immortalists talking about living to be 120 (or longer) as a result of one or more dietary and/or pharmacological interventions or another, my first thought is, “Shouldn’t you be sure you can crawl before you try to fly?” I say this because, as the data show, it’s not all that easy to make it to “average;” half of those who try die! And if you think about it, why they died (failed) is likely to be very important; even if it was from seemingly random things like a drunk driver hitting them head on, or because they had the misfortune to have the genetic predisposition to type I diabetes.

Table 2. Age-adjusted Death Rates for Various Causes of Death

(per 100,000 population)

Source: CRS compilation from National Center for Health Statistics (NCHS), Health, United States, 2005 with Chartbook on Trends in the Health of Americans, Table 29.

Of course, most people don’t die from freak accidents; they die from fairly predictable, commonplace and to significant extent avoidable causes, as can be seen in Table 2, above. By far the largest causes of death that prevent people from reaching the statistical mean (or beyond) are cardiovascular disease (CVD) and cancer. To give a better understanding of the percentages, I’ve done a quick and dirty pie chart (Figure 3, below). By far the largest source of theoretically preventable mortality is from cardiovascular disease, and what’s more, interventions that reduce the incidence or severity of CVD also have the potential to reduce the incidence of obesity (in particular, visceral adiposity) and thus the incidence of diabetes. Growing understanding of the biology of atherosclerosis has resulted in dietary interventions, and improved treatment in the form of the statin drugs and coronary revascularization.

Figure 3: Graphic presentation of the leading causes of mortality in the US as a percentage of all deaths.

The first insight into how to prevent, and even reverse atherosclerosis, came in the early 1970s and this insight, and its clinical application have a number of important lessons for today’s ‘do it yourself life extensionists.’

When I arrived in Southern California to work full-time on cryonics in 1974, I stayed for several months with Fred and Linda Chamberlain. I hadn’t been in their home for 24 hours when I was introduced to a book and to a diet that offered the promise of “living to be 100 years old.” The book was titled Live Longer Now and its author, Nathan Pritikin (1915 – 1985), an inventor with no medical background, claimed to have found a diet that would not only prevent atherosclerosis, but also reverse it. I was skeptical at the time, but a decade later I had seen enough firsthand evidence to reconsider Pritkin’s claims. Atherosclerosis most often presents in the form of coronary artery and peripheral artery disease (PAD). While the course is variable in terms of the rate progression, the disease itself is irreversible and by the time it is clinically evident, it has typically been underway for decades.

How not Succeed While Trying: The Pritikin Diet

Figure 4: Nathan Pritikin was the classic outsider to medicine. His background was not even that of an academic, but rather that of a successful inventor who made significant contributions to industrial processes in electronics. He was a consummate scientist: a keen observer with an eye for anomalies in the world around him who generated clever hypotheses, and then hammered them into theory using well designed experiments. He was roundly vilified by the medical and scientific communities of the 1970s thru the late 1980s.  His theory, that reduction of total serum cholesterol to ~120 mg/dl, and in particular LDL cholesterol to ~<80 mg/dl, in combination with a program of weight reduction and modification of the diet to exclude simple carbohydrates, keep fat consumption to ~ 10% of calories and eliminate added salt is now widely accepted in a medicine. [2-15]

I began to see patients with severe coronary artery disease (CAD) and intermittent claudication (PAD) become symptom free and recover excellent levels of exercise tolerance. That prompted me to contact the Pritikin Longevity Center in Santa Barbara, CA in 1982 and to begin closely looking at the data from the clinical study they were doing at the Veterans’ Administration Hospital in Long Beach, CA on patients with well documented CAD and PAD. Their data were unequivocal; the diet was capable of reducing atheromatous plaques in the coronary arteries, as demonstrated by angiography, as well as reversing ST-segment changes associated with myocardial ischemia during exercise (treadmill testing).

Shortly thereafter, I began advocating (as well as personally practicing) the Pritikin diet to Alcor members, and to cryonicists in general, as a way to avoid the catastrophe of Sudden Cardiac Death (SCD), and possibly to live longer, as well.[16, 17] I learned a number of important things from that experience. The first was that very low fat diets were intensely unpleasant for most people, and that even people who were well aware that they were dying from CAD would either not adopt the diet, or became noncompliant after a short while on it.

The first lesson was thus that an intervention that works is of little use (beyond the mechanistic insights it offers) if no one will use it. I also learned that any claims for life span extension, or improved wellbeing and overall health (for any intervention), must be backed up with data demonstrating those claims. In particular, I learned that all-cause mortality was the last and the best word in validating claims of extending lifespan.

The Pritikin diet was, in fact, effective at dramatically reducing morbidity and mortality from CVD and type II diabetes.[2, 13, 14, 18-26] However, because the diet eschewed all fats and restricted the calorie intake in fats to 10-15% of the total calorie intake of the diet, with the emphasis on polyunsaturated fats. As previously noted, it proved almost impossible to persuade Alcor members to adopt the diet,[27] or even to embrace a modified version of it, wherein one day a week was a “diet free day,” during which the individual could eat proscribed foods ad lib, as he chose. Somewhat surprisingly, I am still in contact with all six of the surviving individuals who adopted the Pritikin diet between 1974 and 1985; the maximum period of compliance was 6 years, and none of these individuals is still on the diet. Three of these individuals have been treated for cancer, though I would hasten to add that I do not believe that in any of these cases the Pritikin diet was either causative or contributory.

Near Universal Noncompliance = Failure

The reasons for the noncompliance, and ultimately for abandonment of the Pritikin diet, were not difficult to ascertain. The most pressing and immediate were the near constant cravings for prohibited foods which, contrary to statement from the Pritikin Longevity Center and those present in Pritikin-approved books and publications, did not diminish over time. Hunger, per se, was not a problem, since the bulk amount of food consumed typically increased over baseline, due to the low caloric density of the foods allowed on diet.[28]  Additionally, there were serious problems with mood (irritability and depression), fatigue, reduced ability to concentrate, winter pruritis, binge eating and “constantly feeling cold,” including a much reduced ability to tolerate cool or cold environments when at rest or a low level of activity.[27] There have been no long-term compliance or all-cause mortality studies of the Pritikin diet, however one published study of a nearly identical diet showed very poor compliance at one year.[29]

Since the mid-1980s, a significant amount of evidence has accumulated indicating that the very low serum cholesterol levels required to effect the reversal of atherosclerosis can result in mood disorders leading to increased irritability, and even violence.[30-36] Studies of more modest reductions in dietary fat intake have not shown benefit in reducing morbidity and mortality from CVD or cancer, and there is the suggestion that mortality reductions resulting from decreases in CVD, hypertension, obesity and diabetes may be made up for by increases in the incidence cancer, suicide and homicide.[27, 31, 37] However, the bottom lines is that 30 years later, there is still no evidence indicating that the Pritikin diet reduces all-cause mortality, or that the non-compliance obstacle can be overcome. The absence of effect with moderate (i.e., less extreme) or so called “reduced fat” diets is especially discouraging, because it indicates the likelihood of an “almost all or none” effect with little or benefit obtained from partial compliance.[38-40] This is, in fact, the position that Nathan Pritikin took.[41]

So while the Pritikin diet met Level-1 (Evidence Based Medicine) criteria for reversing atherosclerosis (and in some cases, type II diabetes), it failed to meet the three other claims it made; namely a longer lifespan with the prospect of reaching age 100, greatly reduced incidence of cancer and a healthier happier life as a result of decreased disease burden. Despite its failure as a technique to reduce all-cause mortality,[4] the Pritkin diet was important because it demonstrated for the first time that it was indeed possible not only to prevent or slow atherosclerosis, but to reverse it, as well – and to do so by something as seemingly low technology as dietary intervention. The Pritikin diet was also effective at reversing type II diabetes in many patients, as well as reducing or eliminating the need for antihypertensive medication, especially in patients who were overweight. Despite these formidable advantages, its poor rate of compliance (negligible amongst cryonicists and life extensionists, as well as cardiac patients) and its failure to improve all-cause mortality has made it a practical failure for population-wide application. [5]

Footnotes

- William Shakespeare, Sonnet 29

By Mike Darwin

People support religion because they find it rewarding to do so for many excellent reasons. It provides a community of people with similar beliefs that validate and strengthen each other. It is specifically designed as a crisis resource – somewhere to turn when people are feeling lost, afraid, uncertain or alone. It has powerful pragmatic advantages because it provides people with in-person social networking that is frequently of use in business, child care and as a resource for practical advice and help with many of life’s troubles. Very importantly, religion serves as a source of the dissolution of or absolution from existential guilt. Just by the act of living we compromise or deprive others both of quality life, and of life itself.

It is axiomatic that by forgoing the luxuries we all enjoy we could save others from starvation and disease – and yet we do not. In our daily lives we also injure others, both knowingly and unknowingly, and these things are, to empathetic people, a source of guilt and discomfort – if not outright pain.

Religion offers both forgiveness and concrete ways that we can address these sources of moral ennui in our lives. It is also often a source of very real material and emotional support for those who find themselves down on their luck, sick, old or dying. A good religion takes care of its own and ensures that no member of the flock is turned out on the street to die a beggar. Finally, and perhaps most importantly, religion provides a narrative for peoples’ lives – a story that allows them to make some sense out of what appears to be an otherwise senseless existence,. It doesn’t matter if the narrative is scientifically valid, or if it is especially credible as long as it provides both hope and meaning. Closely related are the promises of an afterlife, not just for the individual, but for his family and community, as well.

Those are excellent reasons to be involved in a religion and to try to believe, even if you don’t. Indeed, all of the “old” religions spend a great deal of time on the subject of “struggling with belief” and an essential ingredient of a saint in Catholicism (Roman and Orthodox) is that the saint have struggled powerfully with doubt – in fact that they be wracked with it. Since sainthood is generally a singularly unrewarding thing in this life, it seems only reasonable that doubt about the wisdom of such a course of action be a material part of the experience. I would be an incredible liar if I said that I do not mock certain specifics of religions, or that I do not, as Curtis Henderson often did, remark, “How can they seriously believe that crap!” But that is not the same as holding religion in contempt, or considering it insane and useless. Religion exists because it meets many deep and abiding needs, including man’s search for meaning – his search for a narrative to make sense of it all. That desire is frequently mocked by people in cryonics and immortalism, and that is both an injustice and a mistake.

Humans are story creatures. We can only understand our world on a daily working basis through narrative. A few of our species can use mathematics to understand the world, but even now there are no maths do not that not require some narrative to relate mathematical insights to the world we inhabit. Most of technology is a result of narrative processes, and the scientific method itself is the essence of a story, in that it has a beginning, a middle and an end: observation, experimentation, hypothesis, experimentation and theory. The scientific method is the (so far) ultimate refinement of the tool of narrative to give us a coherent, and in this case valid understanding of our world. We are also time-creatures, and the essence of a story is what happens over time. We, and the stories we tell, real or imagined, valid or invalid, are thus bound by and included in the Chronosphere.

 The thing that killed far more people in the concentration camps of Hitler, Stalin, Mao and Pol Pot than starvation was hopelessness. Strip away hope and you will soon end life. Emily Dickinson may have been right when she said, “Hope is the thing with feathers that perches in the soul…” However, she was certainly wrong when she went on to say, “Yet, never, in extremity, It asked a crumb of me.” Hope requires lots of feeding and is does best when it is raised up on a diet of rational, responsible caring. Hope must be credible and its manifestations must be real and apparent. People seek meaning and succor in religion because they can both see and personally experience its benefits – not just in a promised afterlife, but here and now. One reason for the failure of cryonics organizations is that they are as cold and unfeeling as the stainless steel dewars and liquid nitrogen they employ in the only visible manifestation of their temporal work. Yes, there is some comfort in that, but you don’t even get to touch it until you’re “dead.”

While you are alive what you get from them is bills and yet more requests for money. You get a newsletter which is about as involved and caring for the narrative of your life, and your experience of it, as is an issue of Scientific American or Wired. In fact, it might be argued that those publications are more concerned with your interest and enjoyment of what is to come, because their articles involve you in the putative futures they discuss, if in no other way than asking questions and giving answers with the words “we” and “you” in them. “Will we discover that there are indeed countless universes…” or “So, someday you may well pull up to the pump and instead of filling your car with petrol, you’ll recharge your recharge your tank, which contains a matrix of complex metal hydride, with hydrogen…”

To take and take and take and not to care, not to really care (or to be able to show it) can in no way compete with what is available at any Kiwanis Club, Moose Lodge, Temple or Church. To leave people without a narrative, without a community, without a sense of overarching purpose and without even the hint of charity, should they be in need, is not a recipe for success.

Cryonics, and indefinitely extended life in youthful good health, which it implies, is a powerful and profoundly good idea which will revolutionize the world and prepare us to spread to other worlds. That is a potent message that is both inspired and inspiring and for which men will lay down their nets (and webs) and go forth and work to make it a reality. But they cannot do that absent the narrative, and they cannot do that absent the community, and they most certainly cannot do that absent both leadership and support. Cryonics will continue to grow slowly, often in ways detrimental to its survival and it will remain weak and divided until, at some point in the interesting times ahead, it comes to the attention of important people. At that point its narrative will be over, and the ending will have been written not by us, but by our enemies – the enemies of life itself.

Calorie Restriction: First You Starve and Then You Die (Horribly)

Figure 1: Supercentenarians in “extreme old age”:  Jeane Calmette, 121; Ingeborg Mestad, 110; Walter Breuning, 114; Marie-Louise Meilleur, 117.

There’s a proven technique in animals for reaching the maximum lifespan; the longest time that animals of a given species have the inherent capacity to survive. It’s called calorie restriction, and there is a large body of animal data in an impressive range of species that says it works. There is even an ongoing project being conducted by the National Institutes of Aging (NIA) to evaluate calorie restriction in primates and it seems to be working in them, too. The calorie restricted Rhesus macaque monkeys have lower death rates, lower rates of age-associated degenerative diseases, and their overall health and activity level are dramatically better than is the case for the control animals, who are fed a diet that simulates the ad lib calorie intake by humans in the Developed World.

There’s just one catch, and that is that calorie restriction, to the extent necessary to get the individual to the maximum end of the lifespan envelope is, for most humans, a miserable experience. It is also one fraught with the potential for malnutrition and the development of eating disorders, such as anorexia nervosa and bulimia. But there’s another problem with calorie restriction in humans, and that’s that the end results are that you end up a blind, debilitated old crone or codger, and then you die.

Having said that, I don’t want to minimize or dismiss the probable very real advantages of calorie restriction in humans and they are that there is likely to be, on average, a 15-25 year extension of the healthy and reasonably productive lifespan, with a large decrease in most of quality of life eroding (and costly) degenerative diseases, such as diabetes, cardiovascular disease, osteoarthritis, dementia and very likely, tooth decay and gum disease. That’s impressive, even if it isn’t very practical for most people without some kind of pharmacological assistance.

There is also ongoing research to discover drugs that mimic the effects of calorie restriction on gene expression so that the benefits of the technique can be had without the attendant suffering and the very real risks of adverse effects on psychology and nutrition.[1] This is a promising area of research, and it will be covered here in considerable detail on an ongoing basis. However, this is not the time to start any discussion of  specific ‘evidence based’ technologies for extending healthy lifespan. Indeed, before we go any further, it is necessary to become familiar with the concept of evidence based medicine (EBM) (Figure 2).

Evidence Based Medicine

Figure 2:  Detailed Diagrammatic representation of the levels of evidence used in Evidence Based Medicine.

Evidence-based medicine (EBM), also called evidence-based practice (EBP) aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments, including the lack of treatment, and diagnostic tests.Evidence quality can range from meta-analyses and systematic reviews of double-blind, placebo-controlled clinical trials at the top of the pyramid (above), to conventional wisdom at the bottom.

The discrete types or levels of evidence I will be using in all my discussions here on Chronosphere are those of the Centre for Evidence Based Medicine (CEBM),  as set out in their “’Levels of Evidence’ Document” which is reproduced, below.

1. A summary of how evidence can be graded.

In simple terms, one way of looking at levels of evidence is as follows (the higher the level, the better the quality; the lower, the greater the bias):

or…

• Category I:  Evidence from at least one properly randomized controlled trial.
• Category II-1: Evidence from well-designed controlled trials without randomization.
• Category II-2: Evidence from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
• Category II-3: Evidence from multiple times series with or without intervention or dramatic results in uncontrolled experiments such as the results of the introduction of penicillin treatment in the 1940s.
• Category III: Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

[Source: Harris, R.P. et al. (2001). Current methods of the U.S. Preventive Services Task Force: a review of the process. American Journal of Preventive Medicine. April 20 (3 Supplement): 21-35.]

Not surprisingly, the place to start in looking for any reliable method(s) of life extension is at the top of the evidence pyramid, which consists of Systematic Reviews (including well designed meta-analyses) and Randomized Double Blind Clinical Studies.

Figure 3: The EBM pyramid made simple.

The majority of “amateur interventive gerontologists,” or active “life extensionists” who are pursuing lifespan extending therapies on themselves are usually both surprised and dismayed when looking at this pyramid (Figure 3). The first reason for this is that either all, or almost all, of the interventions they are using are at the very bottom of the pyramid. The second reason for the shock and dismay (and often disbelief) is that animal and in in vitro research rank below the ideas, editorializing and opinions of medical professionals, instead of at the top of the pyramid, where most activist life extensionists typically feel they should belong.

However, the fact is that very little animal, or in vitro research has any direct clinical applicability to humans.[2-4] This is not because government regulations or “greedy” pharmaceutical companies don’t want people to benefit from disease-curing or life extending drugs, but rather, because the vast majority of that research is either bad (junk) science or it fails to translate to humans.[4-10] Even when animal studies are well designed and carried out in relevant animal models of disease and show strongly positive results, mostly these findings fail to translate to humans. There are many reasons for this, but chief amongst them is that animals, despite their high ‘percentage’ of genetic overlap with humans, are really biochemically sufficiently different that the findings aren’t applicable to humans. The public are bombarded with numbers, such as chimpanzees are 96% to 98% genetically homologous with humans; cats: 90%, dogs: 82%, cows: 80%, rats: 69% and mice: 67% (http://www.ncbi.nlm.nih.gov/homologene).  These numbers get even more impressive when it is noted that 75% of mouse genes have equivalents in humans and 90% of the mouse genome can be matched to a comparable region on the human genome. In fact, recent research indicates that ~ 99% of mouse genes turn out to have analogs in humans.

Figure 4: If we were mice, most cancers would be treatable or cured, there would be effective drugs for stroke and cerebral ischemia, and a wide range of other conditions would have effective therapies. However, we are not mice.

So what’s the problem with the applicability of animal research to humans? Well, consider that at in 3 out of ten patients the drug prescribed for them fails to work. It’s not that the patient is non-compliant or just doesn’t get better; it is that the drug failed to have the anticipated therapeutic effect. Thus, in those patients, the drug was a waste of money and time; and to the extent that it may have adverse effects, a real danger. In fact, there are 2.2 million serious cases of adverse drug reactions (ADRs) and over 100,000 deaths each year in the US. That makes (ADRs) one of the leading causes of hospitalization and death in the US! Most people take ADRs and lack of therapeutic effect in the drugs they are prescribed (or purchase over the counter (OTC)) for granted. “Oh, that doesn’t work for me,” or “I can’t take that because…” are commonplace remarks. And they apply to people who use only “natural” or herbal remedies as much or more as they do those who use “synthetic” drugs.

The reason for these phenomena is very instructive about why animal research turns out to have so little applicability to humans. The cause of the huge variation in responsiveness to drugs in humans is genetic variation between individuals; even identical twins are not genetically identical, due to mutations and to variations in gene activation (epigenetic factors).[11] There are two types of genetic variations known to impact drug metabolism; copy number variation, which results from deletions, inversions, insertions and duplications in genes, and nucleotide variations, or single nucleotide polymorphisms (SNPs). It is estimated that approximately 0.4% of the genomes of unrelated people typically differ with respect to gene copy number. The nucleotide diversity (SNPs) between humans is about 0.1%, which is 1 difference per 1,000 DNA base pairs! Combine these two numbers and human genetic variation is estimated to be at least 0.5% or, if you prefer, 99.5% similarity between individuals.[11-13]

That seemingly trivial amount of genetic variation is responsible for the observed and well documented large disparity in response to therapeutic drugs observed within the human species. Even the SNPs (pronounced “snips”) have a profound effect on the response (or lack thereof) to therapeutic drugs and they are the sources of a major research effort to develop a catalog of SNPs that can be used as a diagnostic tool to predict and individual person’s drug response. This rapidly developing area of research is called pharmacogenomics and it has already seen clinical application in cancer chemotherapy, anticoagulant dosing, the treatment of Hepatitis C and psoriasis, and in seizure disorders.[14-20]

New Drug Development: May I Suggest Roulette, Instead?

A few more words need to be said about the drug development research and success. Leaving animal data aside, most human clinical trials to evaluate refinements of existing (and proven) drugs or therapies either fail, or result in active harm.[2, 21-23] The chances of a novel molecule making it from in vitro or animal testing to clinical use in humans are ~ 1,000 to 1. You’d be much, much better off playing straight-up roulette, where the odds against you are only 37 to 1. Even in studies or clinical trials where there are ample existing theory and prior in vitro, animal research and clinical trials data that were positive and point compellingly to a favorable outcome, trials often fail.

A good example of this with direct relevance to life extensionists is the saga of vitamin E in the treatment and prevention of atherosclerosis, and in particular, coronary artery disease.There are many animal experiments showing that vitamin E reduces or inhibits the development of atherosclerosis. Epidemiological studies in humans provided robust support to these data, since consumption of vitamin E in the diet was inversely associated with mortality from cardiovascular disease.[24, 25] And to the theoreticians and mechanists, there was the perhaps even more compelling fact that the free radical biochemistry implicated as being a primary factor underlying atherogenesis (oxidized low density lipoprotein (LDL)) is favorably impacted by the addition of vitamin E and similar chain breaking antioxidants to the diet in supraphysiological amounts.[26] The free radical theory of aging also supports the idea that vitamin E and other antioxidant molecules might reduce the incidence of degenerative disease, and perhaps retard aging. Further, in accordance with both theory and the animal data, administration of vitamin E to human volunteers reduced the level of lipid peroxidation, and in particular reduced the level of oxidized LDL.[27]

Figure 5:*NHS indicates Nurses’ Health Study; HPS, Health Professionals’ Follow-up Study; EPESE, Established Populations for Epidemiologic Studies of the Elderly; IWHS, Iowa Women’s Health Study; MI, myocardial infarction; and ellipses, none.

Several prospective studies in which vitamin E was given as a supplement, including the US Nurses’ Health Study[28] and the US Health Professionals’ Follow-up Study, found a 34% and 39% reduction (respectively), in the incidence of myocardial infarction, [29] More impressively still, the  Iowa Women’s Health Study found a 47% reduction in cardiac mortality.[30] These were not small studies published in obscure journals. They were very large trials (Figure 5) and they were published in the New England Journal of Medicine. So what’s the problem? The problem was that other researchers could not duplicate the results and so subsequent, carefully designed trials were conducted.

The largest and best designed of these was the a randomized, placebo-controlled Medical Research Council/British Heart Foundation (MRC/BHF) Heart Protection Study in which antioxidant vitamin supplementation was examined in 20,536 individuals with coronary disease, other occlusive arterial disease, or diabetes mellitus. The study participants were randomized to receive vitamin E (600 mg), vitamin C (250 mg), and beta carotene (20 mg) daily or matching placebo. Intention-to-treat comparisons of outcome were conducted among all participants. An advantage to this study was that critics of earlier failed trials pointed out that vitamin E can act as a pro-oxidant in the absence of vitamin C and that it has in vitro pro-oxidant activity in cell membrane lipids under some conditions. In vivo, vitamin C is the molecule which disposes of the water soluble radical species that can be generated by vitamin E and beta carotene was added to scavenge lipid soluble radicals.

The MRC/BHF study found no significant differences between the vitamin and placebo groups in all-cause mortality, or in deaths caused by vascular or nonvascular conditions. Nor were there any significant differences between groups in the incidence of nonfatal myocardial infarction or sudden cardiac death, nonfatal or fatal stroke, or coronary or non-coronary re-vascularization. In fact, the study found that the use of antioxidant vitamins did not produce any significant reductions in 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome, compared with placebo.[31]

Other studies also showed no benefit [32-34] and there was even some suggestion of harm in the form of an apparent increase in mortality and morbidity from gastrointestinal and intracranial bleeding. In 2009, a metanalysis of vitamin E supplementation trials by Dotan, et al., using Markov model analysis showed that the vitamin E supplemented “virtual cohort” had 0.30 decrease in their quality-adjusted life year (QALY) (95%CI 0.21 to 0.39) compared to the non-treated “virtual cohort.”[35] QALY is a statistical measurement tool used to evaluate not just death or discrete injurious events, such as heart attack or hemorrhagic stroke, but rather measure these events, along with all deaths or debilities as a single entity, and report them in terms of how much loss or gain of functional life occurs in a given group. This work supports an earlier metanalysis showing increased all-cause mortality associated with vitamin E doses ~500 mg/day or more. When a metanalysis was done to look specifically for the effects of vitamin E on stroke it was found that vitamin E increased the risk for hemorrhagic stroke by 22% and reduced the risk of ischemic stroke by 10%.[1]

The metanalysis indicating that vitamin E supplementation (≥500 mg q.d.) is associated with an increase in morbidity and mortality is consistent with the known effect of vitamin E in such doses on bleeding time. Supraphysiologic vitamin E antagonizes vitamin K and causes platelet dysfunction resulting in an increased prothrombin time. It is almost axiomatic in medicine that any increase in bleeding time (anticoagulation) is associated with an increased incidence of clinically significant gastrointestinal (GI) and intracranial bleeding. For vitamin E to show benefit, it would be necessary for any increase in adverse effects to be offset by the benefits it conferred. For vitamin E, this was not the case, whereas for aspirin, which also increases bleeding time and causes an increased incidence of GI and intracranial bleeding, shows such strong benefit in the reduction of myocardial infarction that it is worth the associated risk in the appropriate patient population (i.e., those 50 or over and those with known cardiovascular disease).

This kind of “reversal of fortune” happens over and over again in medicine with respect to drugs as as to other treatment interventions and it is one of the well justified reasons why the astute clinician is very skeptical about putative therapies to treat disease that have not been scientifically vetted – preferably repeatedly, internationally and in well designed and executed trials. It is thus an unfortunate reality that no matter how compelling a therapy seems theoretically or in the laboratory, it still must be proven clinically. And it is even truer that the overwhelming majority of putative therapeutic interventions either fail to work, or injure or kill the patient. There is absolutely no reason to think that this will not be the case with putative life extension drugs.

It is also usually the case that taking multiple drugs, or polypharmacy as it is formally known, negatively shifts the risk to benefit ratio (especially in the ill the debilitated or the elderly). This is so because the biochemistry of living systems is not only enormously complex; it is also interdependent and self regulating. The vast majority of drugs, or supraphysiological doses of nutrients, will perturb multiple biochemical pathways and the more molecules administered, the more likely it becomes resulting adverse interactions will occur. It is, as the Taoist maxim cautions, virtually impossible “to do just one thing” when dealing with a complex and dynamic system. Alter one part of the system in a desirable way and there will likely be consequences in other parts of it – and the odds are high that they will not be favorable.[2]

Thus, in making decisions about which putative life extension therapies to use, the most rational course is to start with those where there is Level-1 evidence of benefit. That may not even seem possible, since there are no known lifespan extending drugs or treatments in humans, let alone ones that have undergone extensive, well designed and repeated clinical trials. Or are there? The answer to that question will be the subject of the next article in this series.

Footnotes

 References

1.            Ingram D, Zhu, M, Mamczarz, J, Zou, S, Lane, MA, Roth, GS, deCabo, R.: Calorie restriction mimetics: an emerging research field. Aging Cell 2006, 5(2):97-108.

2.            Ikonomidou C, Turski L: Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 2002, 1(6):383-386.

3.            Ozdemir FN, Akcay A, Elsurer R, Sezer S, Arat Z, Haberal M: Interdialytic weight gain is less with the Mediterranean type of diet in hemodialysis patients. J Ren Nutr 2005, 15(4):371-376.

4.            Whiteside GT, Adedoyin A, Leventhal L: Predictive validity of animal pain models? A comparison of the pharmacokinetic-pharmacodynamic relationship for pain drugs in rats and humans. Neuropharmacology 2008, 54(5):767-775.

5.            Harber LC, Armstrong RB, Ichikawa H: Current status of predictive animal models for drug photoallergy and their correlation with drug photoallergy in humans. J Natl Cancer Inst 1982, 69(1):237-244.

6.            Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W et al: Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 2000, 32(1):56-67.

7.            Pound P, Ebrahim, S, Sandercock, P, Bracken, MB, et al.: Where is the evidence that animal research benefits humans?: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC351856/pdf/bmj32800514.pdf. BMJ 2004, 328:514-517.

8.            Dixit R, Boelsterli UA: Healthy animals and animal models of human disease(s) in safety assessment of human pharmaceuticals, including therapeutic antibodies. Drug Discov Today 2007, 12(7-8):336-342.

9.            Caldwell J: Problems and opportunities in toxicity testing arising from species differences in xenobiotic metabolism. Toxicol Lett 1992, 64-65 Spec No:651-659.

10.          Wilbourn J, Haroun L, Heseltine E, Kaldor J, Partensky C, Vainio H: Response of experimental animals to human carcinogens: an analysis based upon the IARC Monographs programme. Carcinogenesis 1986, 7(11):1853-1863.

11.          Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, Diaz de Stahl T, Menzel U, Sandgren J, von Tell D, Poplawski A et al: Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 2008, 82(3):763-771.

12.          Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL et al: A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001, 409(6822):928-933.

13.          Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N et al: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 1999, 22(3):231-238.

14.          Beaulieu M, de Denus S, Lachaine J: Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics, 11(11):1573-1590.

15.          Beery TA, Smith CR: Genetics/genomics advances to influence care for patients with chronic disease. Rehabil Nurs, 36(2):54-59, 88.

16.          Cacabelos R, Hashimoto R, Takeda M: Pharmacogenomics of antipsychotics efficacy for schizophrenia. Psychiatry Clin Neurosci, 65(1):3-19.

17.          Johnson JA, Liggett SB: Cardiovascular pharmacogenomics of adrenergic receptor signaling: clinical implications and future directions. Clin Pharmacol Ther, 89(3):366-378.

18.          Schwab M, Schaeffeler E, Zanger UM, Brauch H, Kroemer HK: [Pharmacogenomics: hype or hope?]. Dtsch Med Wochenschr, 136(10):461-467.

19.          Kamal SM: Hepatitis C virus genotype 4 therapy: progress and challenges. Liver Int, 31 Suppl 1:45-52.

20.          Yoshida S, Sugawara T, Nishio T, Kaneko S: [Personalized medicine for epilepsy based on the pharmacogenomic testing]. Brain Nerve, 63(4):295-299.

21.          Wiendl H, Neuhaus O, Kappos L, Hohlfeld R: [Multiple sclerosis. Current review of failed and discontinued clinical trials of drug treatment]. Nervenarzt 2000, 71(8):597-610.

22.          Corman LC, Davidson RA: Why clinical trials fail: the hidden assumptions of clinical trials. South Med J 1992, 85(2):117-118.

23.          Krum H, Tonkin A: Why do phase III trials of promising heart failure drugs often fail? The contribution of “regression to the truth”. J Card Fail 2003, 9(5):364-367.

24.          Rimm E, Stampler, MJ, Ascherio, A, Giovannuci, E, Willett, GA, Colditz, WC.: Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993, 328::1450-1455.

25.          Stampfer M, Hennekens, CH, Manson, JE, Colditz, GA, Rosner, B, Willett, WC.: Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993, 328:1444-1449.

26.          Stampfer M, Rimm, EB: Epidemiologic evidence for vitamin E in prevention of cardiovascular disease. Am J Clin Nutr 1995, 62:1365S-1369S.

27.          Reaven P, Witztum JL.: Comparison of supplementation of RRR-alpha-tocopherol and racemic alpha- tocopherol in humans. Effects on lipid levels and lipoprotein susceptibility to oxidation. Arteriosclerosis, Thrombosis, and Vascular Biology 1993, 13:601-608.

28.          Stampfer M, Hennekens, CH, Manson, JE, Colditz, GA, Rosner, B, Willett, WC.: A prospective study of vitamin E consumption and risk of coronary disease in women. N Engl J Med 1993, 328:1444-1449.

29.          Rimm E, Stampfer, MJ, Ascherio, A, Giovannucci, E, Colditz, GA, Willett, WC.: Vitamin E supplementation and the risk of coronary heart disease among men. N Engl J Med 1993, 328:1450-1456.

30.          Kushi L, Folsom, AR, Prineas, RJ, Mink, PJ,Wu,Y, Bostick, RM.: Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 1996, 334:1156-1162.

31.          Aizawa K, Shoemaker JK, Overend TJ, Petrella RJ: Metabolic syndrome, endothelial function and lifestyle modification. Diab Vasc Dis Res 2009, 6(3):181-189.

32.          Yusuf S, Dagenais, G, Pogue, J, Bosch, J, Sleight, P.: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators:  http://content.nejm.org/cgi/content/full/342/3/154. N Engl J Med 2000;, 342(3):154-160.

33.          Lonn E, Bosch, J, Yusuf, S, Sheridan, P, Pogue, J, Arnold, JM, et al.: HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;, 293(11):1338 -1347.

34.          Vivekananthan D, Penn, MS, Sapp, SK, Hsu, A, Topol, EJ.: Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomized trials. Lancet 2003, 1:2017 -2023.

35.          Dotan YP, I. Lichtenberg, D.  Leshno, M.: Decision analysis Supports the paradigm that Indiscriminate supplementation of vitamin E does more harm than good. Arterioscler Thromb Vasc Biol 2009, 29:1304-1309.

Ray Kurzweil with a portrait of his father.

“It’s as if you took a lot of very good food and some dog excrement and blended it all up so that you can’t possibly figure out what’s good or bad. It’s an intimate mixture of rubbish and good ideas, and it’s very hard to disentangle the two, because these are smart people; they’re not stupid.”

– Douglas Hofstadter, author of Gödel, Escher, Bach, on the books of Ray Kurzweil and Hans Moravec. [See Ross, Greg. "An interview with Douglas R. Hofstadter." American Scientist. Retrieved 2011-08-10.]

It is not very often that I see something that simultaneously evokes sympathy, anger and pity. I am a regular viewer of ABC’s “Nightline” program which airs beginning at 2330 in most of the US. It’s part of my ‘wind-down ritual’ at the end of the day. Often, I’m reading, or otherwise engaged while the bits and bytes comprising the program make their way from geosynchronous orbit and chatter out of the television. The introduction to the 09 August program caught my attention, because it was to feature Ray Kurzweil, talking about practical immortality. Of course, I know who Kurzweil is – both of them. There is the maverick Edisonian inventor who brought us the Kurzweil Reader (and thus the CCD flatbed scanner and the text-to-speech synthesizer) and the Kurzweil who transformed digital musical instrumentation with his Kurzweil K250 music synthesizer. And then, well then there is the Ray Kurzweil who brought us the idea of the Singularity, and three books that expound scientifically bankrupt ideas for ‘do it yourself’ interventive gerontology: The 10% Solution for a Healthy Life Fantastic Voyage: Live Long Enough to Live Forever, TRANSCEND: Nine Steps to Living Well Forever.

And last, but by no means least, there is the Ray Kurzweil who made one of the creepiest movies I’ve ever seen, “The Singularity is Near,” which I viewed as a rough cut in a private screening in Europe. That film was the near perfect combination of suggested transgendered autoerotic pedophilia with narcissism of cosmic proportions. I watched it, immobilized as one is when witnessing a public beheading, or the torture of small animals in an Egyptian souk. I was immobilized in a way that only disbelief and shock immobilize you. An extended trailer of his latest documentary, Transcendent Man is available here: http://transcendentman.com/

The “Nightline” segment on Kurzweil opened as follows:

“Ray Kurzweil, a prominent inventor and “futurist” who has long predicted that mind and machine will one day merge, has been making arrangements to talk to his dead father through the help of a computer.

“I will be able to talk to this re-creation,” he explained. “Ultimately, it will be so realistic it will be like talking to my father.”

Kurzweil’s father, an orchestra conductor, has been gone for more than 40 years.
However, the 63-year-old inventor has been gathering boxes of letters, documents and photos in his Newton, Mass., home with the hopes of one day being able to create an avatar, or a virtual computer replica, of his late father. The avatar will be programmed to know everything about Kurzweil’s father’s past, and will think like his father used to, if all goes according to plan.

“You can certainly argue that, philosophically, that is not your father,” Kurzweil said. “That is a replica, but I can actually make a strong case that it would be more like my father than my father would be, were he to live.”
Said to look and sound like Woody Allen’s nerdier younger brother, Kurzweil has been working on predicting the future for decades. At age 17, he was invited to appear on the CBS show “I’ve Got a Secret” to demonstrate how a computer program he invented could compose music.

Kurzweil went on to invent optical scanners, machines that read for the blind and synthesizers. Still inventing today, Kurzweil has developed a reputation for himself from just making predictions, mostly about how fast our technology is advancing.”
The program continued to document Kurzweil’s plan to recreate his father, and he argues that this can be done by using documents, photographs and his own memory of the man. At one point, he even asserts that such an emulation would be “more like my father than my father, had he lived.”

Sympathy? Yes, I felt a great deal of sympathy because I too have lost those I have loved to death, and also suffered, and suffer still, because I lack the power to bring them back to life.

Anger? Yes, a fair bit of anger because what Kurzweil is proposing insults the intelligence of anyone who has even the sketchiest conception of what it is to be human. The idea that a person can be inferred from boxes of paper documents and photographs with technology, extant or foreseeable, let alone in Kurzweil’s possession now, is ludicrous. That Kurzweil’s insight into the nature of personhood, including his own, is so shallow and uni-dimensional goes a long way towards explaining the cluelessness with which he is pursuing his social engineering campaign to make radical life extension, cryonics and uploading socially acceptable.

The “Nightline” program was surprisingly respectful and matter of fact. Kurzwel has superb public relations people and the “Nightline” editors were amply stocked with photos, film clips and in short, a very impressive visual montage to accompany Kurzweil’s modest proposal for resurrection of the dead from letters, news clippings, old photos and presumably rent receipts and cancelled checks documenting visits to the dentist or the haberdasher.

But as even most of the most unreflective and superficial dullards understand, if only emotionally, a person is not and cannot be reconstructed from the empty wrappers of a life long ended. A few bars of melody, a scent, a fragment of a recorded voice, the taste of something long forgotten, all of these can, and do from time to time evoke in reflective and self aware people, streams of memories, and with those memories countless connections, relationships, thoughts sounds, sensations and yes, and very importantly, feelings. One of the things I found so appalling and so narcissistically selfish about the Kurzweil interview is that he is not really interested in having his father live again, rather he is only interested in having his personal experience of his father available for his self-gratification again. It doesn’t matter what his father thinks or feels, it only matters that the Avatar Father makes Kurzweil think and feel that he has been returned to life. The equation of an avatar of the person with the person himself is an utterly repellant thing, because at its root it is the penultimate in dehumanization; and I think that on some level Kurzweil must know this, since he is trying to persuade the rubes that it really is resurrection.

Consider this justifiably oft quoted sentence from Proust’s Remembrance of Things Past:

“And as soon as I had recognized the taste of the piece of madeleine soaked in her decoction of lime-blossom which my aunt used to give me (although I did not yet know and must long postpone the discovery of why this memory made me so happy) immediately the old grey house upon the street, where her room was, rose up like a stage set to attach itself to the little pavilion opening on to the garden which had been built out behind it for my parents (the isolated segment which until that moment had been all that I could see); and with the house the town, from morning to night and in all weathers, the Square where I used to be sent before lunch, the streets along which I used to run errands, the country roads we took when it was fine.”

That is the merest sampling of what a person is. And as beautiful and evocative of the complex tangle of memory, sensation, reaction and the recursion of all those things as that passage is, even a hundred million, or a billion like it would not describe the mind of the dullest human being who moves amongst us.

Actress Marilu Henner was featured on 60 Minutes because it’s a day she’ll never forget — just like every day in her life; pas, present and future.

If you still have any doubts about the staggering volume of information, not to mention the unique wetware on which it is processed, that comprises the human mind, consider the recent scientific verification that people exist who have “superior autobiographical memory,” or hyperthymesia.[1-3] These individuals have essentially complete audiovisual recall of almost every waking moment of their lives. They can “run the movie” of their life experience forward or backward in their head and extract information from what they “re-experience.” As actress Marilu Hennner, one of those identified with this trait remarked on the CBS documentary program “60 Minutes”:”It’s like putting in a DVD and it queues up to a certain place. I’m there again, so I’m looking out from my eyes and seeing things visually as I would have that day.” These are otherwise normal individuals who have no profound cuts in normal cognitive function which might be used to explain the extraordinary storage of such memory minutiae. The “60 Minutes” segment on hyperthymesia is compelling viewing, and it is available on line: http://www.cbsnews.com/video/watch/?id=7166313n

Given the flashes of such recall most of us experience momentarily and erratically in our lives, this phenomenon begs the question: are all of us recording and storing such a broad bandwidth of information? Is it that we are not storing it, or that we cannot, and for good reason, access it with such fidelity at will? The individuals who possess this capability all describe it as burdensome and at times traumatic – memories come unbidden, constantly triggered by cues in the everyday world around them. And with some of those memories come searing emotions. If we need an evolutionary reason for the stoppering-up of such a prodigious memory in dark, amber bottles, to be dispensed only in needful draughts, these people are living examples.

Kurzweil seems to be suffering from an all too common syndrome in highly successful mavericks who have a history of repeatedly proving the experts (as well as their critics) wrong. This course through life is much the same as fame – especially if it brings fortune with it, and thus the ability to surround oneself with people who either share your worldview, or who will (or actually do) agree with any idea or obsession that takes charge. Removed from the tempering focus that reality affords most people, it becomes easy to slip into a world where the line between your dreams and desires, and what is really possible, becomes blurred and then disappears altogether. Kurzweil appears to be well on his way there, if he hasn’t reach that final destination already, and that, well, that is just pitiful.

Many of Kurzweil’s ideas are crazy – a mixture of wishful thinking, inappropriate application of animal data to humans, and in the case of his resurrection scheme, poisonous and dangerous to cryonics on at least two levels. First, it is wrong – people are not scraps of paper, or even whole heaps of them. That is a demeaning idea at best, and a dangerous one at worst, if it is taken seriously. Second, while Kurzweil still commands respect, at some point the men in the media with the butterfly nets will come calling. Kurzweil’s anti-aging program is much more likely to shorten his lifespan and deplete the pocketbook of the average person, upon whom he urges its use, than it is to provide any medical benefit.

This kind of disconnected, narcissistic spiral carried out privately is a thing that evokes pity, and even shame in seeing it. Those of us who have been involved in life extension for 20, 30, or 40 years have seen it before; increasingly desperate and delusion belief that barely suggestively beneficial molecules in animal studies will confer decades of added life, and finally, the decline into frailty and death. As I watched the “Nightline” program, I realized that there is yet another advantage to cryonics that I had not previously considered, and that is the extraordinary dignity and courage with which most cryonicists confront the end of this life cycle. While many were ridiculed for their lack of realism for a lifetime, most were men and women who did what they reasonably could to live as long as possible now, made no exaggerated or unreasonable claims about cryonics – and in fact, regarded it and represented it as what it currently is – a long shot experimental procedure that may well not work, but for them was infinitely better than the alternative.

The extraordinarily accurate, generally matter of fact, and with few exceptions dignified coverage of Bob Ettinger’s passing into cryopreservation is an example. It’s a worthy example and the way we should strive to be seen. Kurzweil reportedly has cryonics arrangements with Alcor. I’m glad to hear that, because I think he is a fundamentally a very good and very decent man who shares our core values. He has improved and enriched the lives of countless people through his scientific and technological innovations. However, as I can tell you from experience, while many disabilities are now tolerated in our society, crazy and creepy are not amongst them.

References

1.            Cahill L, McGaugh JL: Modulation of memory storage. Curr Opin Neurobiol 1996, 6(2):237-242.

2.            Cahill L, McGaugh JL: A novel demonstration of enhanced memory associated with emotional arousal. Conscious Cogn 1995, 4(4):410-421.

3.            Parker ES, Cahill L, McGaugh JL: A case of unusual autobiographical remembering. Neurocase 2006, 12(1):35-49.

Have I got your attention now?

Good.

Most people say my writing here is far too long and not nearly to the point. Today I’ll remedy that. [Though you’ll still have to read this http://wp.me/p1sGcr-1h for what I going to say here to have much credibility. Read, read it carefully, and note when the contents were first published on-line.]

A couple of readers have also noted that I “seem to be in a hurry” with whatever my agenda is. Today, in part, I’ll explain why.

Over the past few days the true state of the global economy has started to be unveiled. It is going to get a lot worse. I’m no prophet or seer; would that I were. Because then, I could quantify it all for you and spoil the ending by telling you how it’s going to turn out; for you, for me, and for everyone else on the planet. But the truth is, I have no crystal ball and no metaphysical “inside track” on the future. I had hoped, fervently, that I might have some more time, that we might have some more time – perhaps as much as a year or two, before this global economic decompensation occurred. Well, no such luck. What is happening now is the beginning of what is going to be a very bad time. I have been back and forth over the skin of this earth these past 6 years, and I can tell you that much of the world has been precariously balanced on a knife’s edge of instability, fear, hopelessness and simmering rage for onto to a decade, now.

When the French Revolution arrived, Louis VI and Marie Antoinette could hardly have been more surprised. Hosni Mubarak, lying in his hospital bed in a cage Cairo, must certainly feel a similar sense of disbelief and disorientation. To be plucked from his villa at Sharm el Sheik, after he surrendered the Presidency? Incredible! The difficulty for many of you reading this (in the Developed World) is that you have lived like Louis, Marie and Hosni for the last few decades – completely out of touch with that segment of the world deemed both untouchable and insignificant. It’s not that you’ve actively avoided them, but rather than you could not even see them, and if you did catch a glimpse of them from time to time, out of the corner of your eye, you not only had no opportunity for discourse with them – you lacked the language – you literally lacked the language – both symbolic and visceral – to communicate. You might more easily have communed with an ant, or an apple tree.

Now, regrettably, many of you are about to join them. Do not worry about any lack of knowledge of their linguistics. The lingua franca of fear and disenfranchisement is one that all but the Doctor Panglosses, and the Wickens Micawbers of the world, learn with astonishing speed. Chances are, you will too.

I don’t know how much ‘play’ there is left in the system. That means I don’t know when the futile and irrational wars the West is currently prosecuting will be replaced with much larger, more costly and absolutely essential conflicts. It means I don’t know exactly when healthcare expenditures are going to decrease from 17.6% of the GDP, to somewhere in the single digits (and all the grim statistics that implies). It also means I can’t tell you exactly when the currency is going to start really inflating – in part, because I don’t know to what extent deflation from lack of demand for major commodities will occur – or when – although I note that oil prices have already dropped.

I am an expert, a bona fide expert at watching things die and observing, in order to understand the mechanics of that process, even to the point where it has proceeded well into decomposition. Human and non-human, I’ve observed so many deaths I long ago lost count. This has made me wise enough to ‘know it when I see it,’ and wiser still, to know that I lack the tools to bring precision to my understanding of the process. I can tell you when it is underway, but I cannot tell you the appointed minute, the appointed hour, or even the appointed week, month, or year of its arrival.

I said I’d keep this bearably short, and I will. We’ve been fucked. It happened quite some time ago, but in the daze of the booze and drugs, we simply didn’t feel it – until now. My message, here and now, is to first be aware that this has happened. You have no time for denial, or for recriminations. Second, neither panic nor abandon hope in the months to come. Third, immediately stop all non-essential expenditures and save everything you can. When you need to convert those savings into non-cash commodities, of one kind or another, will become apparent in due time. If you have modest and manageable debt, pay it off. If you have large debt, begin to position yourself to walk away from it with as little injury to your assets and psyche as possible. Much of the work of doing this in the US is psychological. In other places, more material preparations will likely be required. Finally, if you are a cryonicist and you want to continue to be one, be prepared to relocate. It is very likely that cryonics (biopreservation) is going to require the support of an active, cohesive and geographically united community.

I am sorry for this message. I hoped to have far more time to sieve a working group of good minds, with good hearts, to confront what is now upon us. No such luck.