(ischemia) ~85% of the time!

By Mike Darwin

Foreplay

It has taken me roughly 30 years to learn that having the technological capability to achieve some marvelous end is only a small part of the battle to actually achieving it.  This is profoundly true in the world of biology and medicine because, unlike as was the case with “free speech” and “private life,” there was no Martin Luther and no Thomas Paine to definitively divorce these areas of human endeavor from the grasp of the religious moralists, the secular ethicists, and the social busybodies of the earth. The life sciences have yet to have their Martin Luther’s 95 theses nailed to the doors of the places in which this culture’s moral tyrants currently reside. The separation of Church from private life which began with Luther, and of private life from state, which began with the Magna Carta and the US Declaration of Independence, could take us only so far.

Now, we are in an interesting place and time, because never before have potentially lifesaving technologies been being generated at such a phenomenal rate. And yet, they remain outside our grasp as surely and solidly as if there were an impenetrable Prespex wall between them and us. We can look, but we can’t touch.

Beyond our physical inability – or seeming physical inability – to access those lifesaving capabilities, we also pay a heavy price in a different way. Our vision and perspective becomes warped. We literally become unable to see how we might help ourselves, because we have been conditioned to be dis-empowered. We lose the ability to think outside the box and we begin endlessly replaying the failed or marginal strategies that the existing system does allow us to pursue.

However, a close look at our predicament will reveal that that Perspex wall works mostly for the masses – for them – and not for us. If we are careful and clever, we can reach through it and extract much of the technological benefit sitting there. We can do this, but they can’t. Once we understand that, it has the potential to change our perspective on everything in terms of our chances for survival, and for our chances of living productively and in comfort, while much of the rest of world may well pursue a very different path.

That’s what this article, and the ones that follow it, are about. This article is preparatory, it’s a kind of foreplay to prepare you for the powerful penetration of the ideas that are to follow.

Of  Singularities & Hams

Figure 1: Jamón ibérico de bellota is a gourmet ham made from black Iberian pigs fed only acorns during the months prior to their slaughter.

 The first few times it happened, I hardly noticed, and I can’t remember the specifics. But when it really began to annoy me I can  remember, quite clearly, perhaps because I was already in a foul mood and the surroundings were extraordinary. We had been taken out earlier in the day to see the pigs from which the jamón ibérico de bellota is made. The vile, dusty, slobbering and altogether horrid beasts are fed nothing but acorns so that their flesh is rendered especially succulent and flavorful after elaborate smoking and aging. They were moving about with indifferent belligerence, unaware that their kin were to  be on the supper menu late that afternoon. The visit to their quarters made me thankful I did not eat land vertebrates and reminded me uncomfortably of some of my compadres at the Hacienda; the several “Mr. Bigs” who had gathered to discuss the creation of a new cryonics enterprise.

As we sat down to dinner in the courtyard of the Hacienda that evening, I was seated at a table with several middle aged cryonicists and two older ones, (sadly, including myself). It wasn’t long before I was bombarded with the question I would soon find irritating, and eventually come to loathe: “Have you had genomics testing done?”

Figure 2: The courtyard of the Hacienda where my dinner companions assailed me over my lack of diligence in having my genotype analyzed to determine my disease risks.

“And why would I have that done, I asked?” My questioner, an enthusiastic thirty-something, leaned forward a bit and explained to me how rapidly the cost of sequencing DNA base pairs was dropping, and that it was now possible to tell all kinds of things about an individual’s risk for diseases by genotypic analysis.

“It costs only  $200 US; I just had mine done.”

Others began to chime in. Since it was an international crowd, the stories were fascinating and I was content to listen. Some had discovered they had Neanderthal lineage, others had discovered less exotic, but no less unexpected genetic heritage. Finally, the conversation returned to me, the apparent elder statesman and, presumably, the example setting cryonicist at the table: why hadn’t I had my genotype evaluated, and much more importantly, why didn’t I have any plans to do so?

“Look, ” I said, “I think genomics  technology is going to be incredibly valuable. I think its most immediate value is going to be in pharmacogenomics – in determining which drugs work for which individual people and which drugs don’t work, or are actually dangerous for given individuals. A bit later, this technology will likely have real prognostic value. But not now, and not for me. I’m in my early-50s. My relatives are already sick, dying or dead of illnesses that are genetically mediated. I know what my genetic risks are. In fact, from my family history alone, I’ve known what those risks are for roughly 20 years now. Both my parents are now in their 80s, and I have a very good idea of what they are going to die of. And if they don’t die of those things, well, it will be from an accident, an infection or something not likely to be readable in the tea leaves of my genome.

 Figure 3: The Hacienda on the arid Spanish countryside outside Madrid where we took our repast and discussed singularities, past, present and future.

Interestingly, my parents have had every single disease that has also killed their parents, their aunts and their uncles: cancer, hypertension, atherosclerosis, alcoholism, type II diabetes, and Alzheimer’s Disease (AD). I’m pretty sure that AD is going to claim my mother’s life, and I’d say it is probably down to atherosclerosis, and possibly cancer or emphysema, in the case of my father. With the help of modern medicine, my folks have so far dodged all of the other genetically mediated bullets that have been shot at them. So, I know my genetic risks  (and to those I’d add the risk of some peculiar autoimmune diseases in late life are present in my maternal bloodline).

But by far my biggest risks, which would not yet (to my knowledge) show up on any genotypic test are Bipolar-2 Disorder and homosexuality, both of which have a devastating impact on longevity, dramatically increasing the risk of a broad range of pathologies, including cardiovascular disease, cancer, dementia, substance abuse, other mental illness, and all cause mortality. My point is that in most cases where genes influence destiny, you’re best clue is the evolved or evolving fate of your kin – unless you are an anonymous orphan, that is.”

Still, they wouldn’t give up. The implication was that I must have genomic testing. And, truth to tell, I had, and have, no objection to it. It’s not like I am opposed on religious grounds, as if it were fortune telling. “In fact, I think it’s a nifty conversation piece and personally interesting in the bargain. It’s just that I’d have a lot higher priority uses for my $200 in terms of the dramatic medical advantages it could buy me as a cryonicist, if I had $200 to spend on such things! It would make a wonderful Newton Day gift, the kind of thing you’d like, but would never buy for yourself.”

Now that, that statement really set them off! I had thrown gasoline on a fire. Didn’t I know that the exponential decrease in the cost of DNA sequencing constituted a Singularity in biomedicine, one that was, even as were sitting there that very moment, revolutionizing medicine? “Sure.” I said, “But  there are singularities happening all the time. The thing is, most singularities in medicine unfold over a period of decades, and very few individual patients gain benefit from them on the basis of special, unique, or insider knowledge.”

But, I had lost them. They were having none of it, and I wouldn’t be the least bit surprised if I’ve lost you as well. I was irritated and frustrated and I had already lost my temper badly earlier that day. So, I decided to bite my tongue and proceed in relative silence with the rest of the meal. But what I really wanted to say to those gentleman was that, “you wouldn’t know what to do if a medical singularity were to come right up here and bite you in the ass, because it already has!”

One of the (many) reasons the meeting had crumbled was the intransigence of one of the Mr. Bigs, who wanted cryonics with the stipulation that there be essentially no ischemic time. He had his approach to solving the problem which was, well, this meeting was some years ago, and I wonder if Mr. Big is still alive?

It was a strange situation. Mr. Big was clearly not a well man and he knew this to be the case. What I suggested was straightforward, involved nothing either exotic nor illegal and was something that I knew would work, based on the sorry experience of seeing it not work with men exactly like him. I tried to explain to Mr. Big that it was now possible to “simply” look inside of him, from top to bottom, and get a fairly accurate assessment of what his risks were for deanimating in the near future. Given his medical history, which he shared with me,  I also suggested that he have a condition treated which would, probably sooner rather than later, cost him his life, or leave him profoundly disabled. He was having none of that, either!

Instead, a few hours later, here we were seated together at dinner and Mr. Big was extolling the virtues of genomic testing as a way of avoiding premature cryopreservation-  to me.  A true, nearly unalloyed medical singularity had arrived for cryonicists, and for the previous two days they had snuffled and shuffled around each other with same indifferent belligerence of the hogs in the pen nearby who were awaiting their conversion to jamón and their journey away from the Hacienda in someone’s belly. It is at moments like this, which come with increasing frequency, that I sneak a quick look out of the corners of my eyes to see if I can catch a glimpse of some dimple or ripple in the fabric of reality that will clue me into the fact that my life has really been just a joke in very poor taste  – on me.

I’ve struggled mightily with how to effectively communicate the idea that for cryonicists, a singularity of truly incredible magnitude has arrived and that it is one which, in theory, should be available for use by us now. I’m reasonably sure I’ll fail in that task and that no matter how I might have framed the argument, or presented the evidence, the outcome will remain the same. And therein probably lies yet another powerful lesson about why Singularities, wherein everything is transformed in the blink of an eye, never really happen.

How ‘Fast’ are Most Medical Singularities?

Medicine, ironically  much more so than entertainment or warfare, is bound up with the sensitive issues of ethics and morality, which have historically complicated and often slowed the propagation of paradigm changing, or so called “singularity events” within its confines.  Vaccination, contraception, anesthesia, organ transplantation, mechanical life support, resuscitation medicine, in vitro fertilization and embryo and gamete cryopreservation have all been slowed or blocked altogether as a result of religious or ethical concerns. (1,2,3) Indeed, surf the net or turn on TV today and you will see hordes of angry people decrying vaccination, contraception, and arguing furiously over life support. Support for vaccination, ~212 years after Jenner, is even eroding in the nation that spawned it!

The idea that wound infections – sepsis – were caused by a contact-transmissible agent was definitely proved by 1848, in the form of the exhaustive statistical work documenting the effectiveness of antisepsis conducted by Semmelweis. By 1860, the theoretical grounding for the basis of that transmissible agent, germ theory, was in place. Scattered throughout Europe there were a few men who understood the new paradigm and could no doubt foresee many of its practical implications in medicine. These men must have been as frustrated as cryonicists in the middle of this last( 20th) century – men like Pasteur and Koch. If ever there was a singularity in medicine, this was it. And yet, what happened?

Figure 4: President (then General) Robert E. Lee of the Confederate States of America receiving his critical Magic Lantern briefing on the revolutionary, but heretofore unappreciated work of the Hungarian physician Dr. Ignaz Phillip Semmelweis, concerning the importance of antisepsis for the control of infections in battlefield and surgical wounds. The information proved of a vital strategic advantage in helping the Confederacy to successfully prosecute the war against Union forces. Lee is seen here in the sitting room of his home in Arlington, Virginia in this classic painting by John Elder.

Perhaps it might be more instructive if we ask ourselves what should have happened according to the Singulatarian, or even according to the “popular” model of how  powerful, beneficial ideas with virtually no downsides spread through the culture. For instance, one of the most popular “what if” questions in the realm of alternate history is, what if this or that had been different that would have altered the outcome of the United States Civil War?(4) Military historians all have their favorite “what ifs” in this regard, but mine, well mine wouldn’t be military at all, but would come down to a long, drawn out Magic Lantern (PowerPoint) presentation given to a very receptive General Robert E. Lee, on the eve of the Secession. The subject of that presentation would be the revolutionary findings of two maverick Europeans; Dr. Ignaz Philipp Semmelweis, and  Dr. Louis Pasteur, as they apply to battlefield medicine and the recovery and survival of injured troops in the conflict to come.  The Confederacy lost the war for many reasons, but in the end it came down to a lack of manpower and the disproportionately draining and depressing effect that combat related sepsis had on the South. [At least, that's my story and I'm sticking to it ;-).]

Lee would listen, his military surgeons would be briefed on the Confederacy’s “secret weapon” and the tide of history would be turned. Wild and playful imaginings? Yes, but they constitute a considerably more reasonable scenario for the rapid adoption of asepsis in the US (or even half of it!) than just about any other you are likely to come up with, because the reality of what happened is almost incomprehensibly tragic.

Figure 5: In his magnificent painting entitled The Gross Clinic, Thomas Eakins graphically captures the state of surgery in the US during the decades following the US Civil War. These grotesquely unsanitary conditions had by this time to a large extent become a thing of the past in surgical theaters through much of Europe.

Figure 6: Even 14 years later, when Eakins revisits the them of the operating theater in his painting The Agnew Clinic, full adoption of asespsis and antisepsis had not occurred in the US.

Semmelweis’ work had already been published and disseminated around Europe by 1848, and by 1861, the year the American Civil War was opening, Lister was reprising Semmelweis’ discovery of antisepsis in Scotland, not with chlorine, but with carbolic acid. The sad reality was that the Americans (North and South) were so pigheaded regarding germ theory and the value of asepsis and antisepsis to medicine, that it would not be until well into the 19th century before that particular singularity fully took hold of the United States.(5)

Indeed, Lister made an “evangelical” tour of US medical schools in 1876 to little avail.(6)  Whilst the Listerian revolution was well underway in Europe by then, the situation in the US was to remain, as it was so vividly portrayed by Thomas Eakins in his magnificent oil, The Gross Clinic, which was painted the year before Lister’s missionary visit to the germ loving heathens across the pond. Fourteen years later, when Eakins painted The Agnew Clinic, we can see the beginnings of asepsis just starting to take root in the form of basic cleanliness being imposed in theatre. Clearly, antisepsis/asepsis are an example of a technological singularity in medicine, albeit one that took onto a century to fully unfold!

The Problem of Bite Back

But beyond these arguably irrational roadblocks slowing the progress of technological singularities in medicine, there are two others: the very real problems of their rational management on both the macro and the individual (patient) scale.

Figure 5: Edward Tenner’s excellent book, Why Things Bite Back explores many examples and a number of reasons why technological advances often fail to reach their expected potential, and in fact, not infrequently turn out to be self limiting, or even self defeating.

Some of the technological singularities just listed, vaccination, for instance, can have very serious practical, economic and societal consequences. Rapid and widespread introduction of vaccination into equatorial Africa by Christian missionaries, absent the concurrent introduction of agricultural and other infrastructure, resulted in a population explosion and mass famine which has not abated to this day. Oral contraception has resulted in huge demographic and social changes occurring within a single human generation; a heretofore unprecedented event in the history of our species.

While medical advances are usually perceived as an unalloyed good for the patients who will benefit from them, this is rarely, if ever the case. The discovery of x-rays opened the interior of the human body to non-invasive examination, but it also exposed the patients so viewed to initially unsuspected exposure to damaging radiation – a problem that persists in radiologic medicine through the present. Beyond the problem of unforeseen or unknown dangers, there is also the problem of technological bite back, or what Edward Tenner has called the “revenge of unintended consequences.”(7) This is a major adverse effect of technological singularities, and one which often robs them of much of their anticipated bounty – not just for societies, but for individuals as well.

As I’ve just pointed out,  new medical technologies are sharply constrained in their utility at their start due to our inexperience with their bite back potential, and with the possibility of unknown  direct adverse affects of the technology  itself. However, every great once in awhile there are peculiar exceptions, and it just so happens that cryonicists are ideally positioned to enjoy just such an exception, starting now.

References

1. Fasouliotis, Sozos J, Schenker, Joseph G, TI, Cryopreservation of embryos: Medical, ethical, and legal issues. Journal of Assisted Reproduction and Genetics. 13:10 56-76;1996.

2. Simmons , RG, Fulton , J, Fulton, RF. The Prospective Organ Transplant Donor: Problems and Prospects of Medical Innovation. OMEGA–Journal of Death and Dying. 3:4;319-339:1972

3. Carrell. JL, The Speckled Monster: A Historical Tale of Battling the Smallpox Epidemic, Dutton, 2003, ISBN-10: 0525947361.

4. McKinlay, Kantor, If The South Had Won The Civil War, Forge Books, 2001, ISBN-10: 0312869495.

5. Murphy, FP, “Ignaz Philipp Semmelweis (1818–1865): An Annotated Bibliography,” Bulletin of the History of Medicine 20(1946), 653-707: 654f.

6. Herr, HWJ, Ignorance is bliss: the Listerian revolution and  the education of American surgeons. Urology;177:457-60,2007.

7. Tenner, EW, Why Things Bite Back: The Revenge of Unintended Consequences, Vintage, 1997, ISBN-10: 0679747567.