The case for cryonics

The biology-of-aging blog Ouroboros has posted a skeptical post about cryonics that is highly representative of how most biological scientists respond to questions about cryonics. The discussion of cryonics is largely reduced to a discussion of the technical feasibility of suspended animation and resuscitation requirements. But suspended animation is not cryonics. Cryonics should be discussed in the broader context of decision making under uncertainty. People who have made cryonics arrangements are more than aware that contemporary science is not able to vitrify and resuscitate a complex organism. To them the central question is whether we can reasonably expect that future technologies will be able to repair the injury that is produced by contemporary cryopreservation technologies and rejuvenate the patient. That is the “probabilistic” side of the issue. On the utility side of the equation is nothing less than personal survival.

This does not mean that cryonics should be approached as a form of Pascal’s Wager in a vacuum. Experimental evidence from fields such as cryobiology, biogerontology and nanotechnology plays an important role in shaping our expectations about the technical feasibility of the resuscitation of cryonics patients. Many biologists, however, feel confident that they can make a case against cryonics without even bothering to examine the current state of the field. For example, how many biologists know that the latest generation of vitrification agents have low enough toxicity to permit vitrification of animal brain slices with retention of electrical activity?

The author writes:

The field could take a lesson from the dawn of modern biogerontology back in the early 1990s: Acknowledge the mind-bending complexity of the challenge. Create model systems for cryonics, using the best tools from the vast edifice of modern biological knowledge.

But that is exactly what the cryonics field has done. Millions of dollars have been devoted to identify low-toxicity vitrification agents and protocols to preserve viability after pronouncement of legal death.  Progress in the cryopreservation of complex organs (including the brain) has been so successful that the vitrification agent that is currently used by the Alcor Life Extension Foundation, 21st Century Medicine’s M22, is the least toxic vitrification agent in the peer reviewed cryobiology literature to date.

The author is correct that the project of cryonics is of “mind-bending complexity.” One major reason for this is that the resuscitation of most cryonics patients will require successful rejuvenation. As a result, cryonics advocates are quite interested in anti-aging research. But whereas modern biogerontology, not unlike macroeconomics, is still plagued by ongoing (technical) debates about even the most basic definitions employed in the field, or engaged in discussions about what constitutes the most effective approach to pursue rejuvenation, the cryonics field has moved from the practice of the crude freezing of patients to the pursuit of long term care at cryogenic temperatures without ice formation and minimal ischemic injury.

Perhaps there is good reason for this difference in success rate. As mathematician and cryonics advocate Thomas Donaldson pointed out, anti-aging research faces conceptual and methodological challenges that cryobiology research does not. Perhaps the time scale to develop and validate effective anti-aging strategies is similar to that of developing a mature technology that can manipulate matter at the molecular level. If this is the case, rejuvenation research could benefit from being pursued as a broader evolutionary bio-nanotechnology research program.

The discussion of cryonics is most fruitful where logic and empirical science meet.  We need to employ the tools of logic to guide coherent decision making and we need the results of experimental science to provide empirical weight to guide those decisions. In a world where knowledge is recognized as probabilistic, and where death is recognized as a biological process that can be halted through the use of low temperatures, the decision to make cryonics arrangements can be rational and life-affirming.

The healthy skeptic

Consumers are constantly bombarded with advice about health. Lower your cholesterol, avoid carbs, take dietary supplements, avoid Teflon, get a full body scan, etc. Such advice does not fall on deaf ears. Who does not want to remain healthy, look good, and extend life? Two other factors contribute to our eagerness to consume and follow health advice. First, the accelerating growth of knowledge in fields such as biology and biochemistry. Second, a reasonable assumption that if some chemicals and behaviors can harm us,  there must be chemicals and changes in behavior that can confer great benefits.

The role science plays in contemporary thinking about health is a double edged sword. On the one hand, it can be used to debunk grandiose claims about health by subjecting these claims to rigorous scientific investigation. On the other hand, the authority of  scientists can can be abused to support products or lifestyle changes for which there is little evidence. For many people and journalists, the phrase that “research proves” something is often enough to act on health recommendations, regardless of the nature and quality of the evidence. But it does make a lot of difference whether “research proves” means a small number of experiments in a test tube or a multi-country randomized human trial.

And that is where Robert J. Davis’ book The Healthy Skeptic: Cutting through the Hype about Your Health comes into play. What makes Davis’ book stand out over other books debunking contemporary health claims is that he gives the reader a set of solid guidelines to evaluate scientific statements about health in general. Another major strength is that the author does not single out one group of health hustlers but argues quite persuasively that misinformation about health is not confined to pharmaceutical companies or sellers of dietary supplements, but is rampant among government, non-profit organizations, and consumer activists as well. For example, as  the author writes about consumer activists:

Simply because they’re looking out for our welfare doesn’t necessarily mean that the public interest groups always tell us the truth. Rather than helping us, they can sometimes cause harm by frightening us unnecessarily and diverting our attention from risks that are far more important. As healthy skeptics, we need to apply the same scrutiny to their advice as we give to that from the industry-funded groups or anyone else.

The most “timeless” aspect of the book is the chapter where the author discusses the use and abuse of science in health. Before drawing our wallet or changing our diet, we can ask ourselves the following eight questions:

1. What kind of study is it (laboratory research, short-term human studies, randomized clinical trials etc.)
2. How big is the effect?
3. Could the findings be a fluke?
4. Who was studied?
5. Is there a good explanation?
6. Who paid for the research?
7. Was it peer reviewed?
8.  How does it square with other studies?

As should be clear from those questions, behind the phrase “research proves” are many shades of grey. As the author points out, the question of how a study squares with other studies is perhaps the most crucial question. There is so much (poor) research being published that almost any claim about health can be supported by scientific studies. Sellers of dietary supplements often exploit this by presenting only studies that “support” their recommendations. If health advice does not come with qualifications and/or opposing research conclusions are not mentioned at all, one should be very wary.

Perhaps the most important chapters for life extentionists are those on dietary supplements and “anti-aging doctors.” Davis gives a number of useful recommendations to evaluate claims about supplements:

– Verify “clinically proven” claims
– Don’t assume that “natural” means safe
– Be skeptical of claims that a souped-up or specifically targeted vitamin or mineral supplement is better than an ordinary one
– Don’t be swayed by weasel words (such as “maintains heart health” or “provides immune support”)
– Be wary of organizations or individuals who provide information about supplements and also sell them

When all is said and done, the book does not recommend any radical interventions to improve health or prolong life and sticks to the usual recommendations (don’t smoke, exercise, moderation in eating and drinking, etc.) This is not because of cynicism, but because the more radical claims are just not backed up by contemporary science.

Life extensionists and futurists may believe that they are mostly immune to wishful thinking and the marketing of snake oil but  they may be less immune to more subtle psychological (deadly) traps such as the belief that “this time, things are different,” or the naive assumption that all problems can be solved, given enough time and knowledge. Although progress in science can benefit from scientists that are committed to achieve  important goals like increasing the maximum life span or even defeating death altogether, in reality it is often hard to tell the difference between being motivated by such desires and simply assuming that they will be satisfied, and thus crossing the line into meliorist dogmatic belief.

An interview with the author can be found on the Amazon page for the book.

Nanotechnology: The message matters

A recently conducted study brings a warning to technophiles who think that the facts are all that matter when informing a group of people about a new technology. The fact of the matter is that the message matters more.

In their article “What drives acceptance of nanotechnology?” (Nature Nanotechnology), the Cultural Cognition Project and the Project on Emerging Nanotechnologies reported that, when presented with balanced information about the benefits and risks of nanotechnology, a diverse sample of 1500 people who were largely unfamiliar with nanotechnology became deeply divided regarding its safety as compared to a group not shown such information.

The dividing line was cultural: “People who had more individualistic, pro-commerce values, tended to infer that nanotechnology is safe,” said Kahan, the lead author of the study, “while people who are more worried about economic inequality read the same information as implying that nanotechnology is likely to be dangerous.”

Seeing that people respond so differently to the same information has caused many experts in the field to call for risk-communication strategies that take these findings into account. In this way, they hope to prevent a nanotechnology “culture war”:

“The message matters,” said David Rejeski, director of the Project on Emerging Nanotechnologies. “How information about nanotechnology is presented to the vast majority of the public who still know little about it can either make or break this technology.

Gender differences in stroke treatment and prevention

Over the years, experimental science has developed a standard protocol for the testing of medical hypotheses using animal models which calls for the use of males only. Why? Because no laboratory scientist wants to deal with those pesky female hormones. Female hormone fluctuations are viewed as just another variable to be controlled (generally by excluding females altogether) — all the better for making interpretation of results simple and straightforward.

But, as common sense might dictate, it turns out that results from male-only animal models often give a less-than-accurate view of the whole picture when this research is translated and applied to treatment of disease in humans. Why? Because, as most people without a doctorate in physiology can tell you, physiological gender differences exist. Is it any surprise, then, that disease treatment and prevention should also be prescribed with these physiological differences in mind?

And so the buzz for the past few years in the medical community is the astonishing fact that stroke treatment and prevention are not the same in men and women. In labs that have recently begun to investigate these differences, drugs that were found to protect male brains against stroke in animal models did nothing to protect female brains. The major message behind all this press: doctors cannot continue to apply one-size-fits-all prescriptions for stroke prevention and treatment.

The real fact is that it is even more complicated than a “simple” physiological difference. Traditionally, cardiovascular disease has been viewed as a “man’s disease” (men have about a 19 percent greater chance of stroke than women). Accordingly, studies have found that women are less likely to receive prescriptions for blood pressure medications or be advised to take aspirin, both of which have been shown to reduce stroke risk. Strangely, women are less often treated after having a stroke, even though they appear to respond better to acute stroke treatment (such as tissue plasminogen activator) than men. So while men do indeed have more strokes, women are still more likely to die from stroke.

Women are also at increased risk if they take birth control pills, use hormone replacement therapy, have a thick waist and high triglycerides, or are migraine sufferers. And, contrary to anecdotal evidence, women appear to be less likely to go to the hospital at the first sign of stroke symptoms.

Oregon Health and Science University is at the forefront of research into gender differences in medicine, having developed the first research institute of its kind, the OHSU Research Center for Gender-Based Medicine. Given that Oregon recently ranked 46th out of 50 states for incidence of stroke deaths among women (as reported by Making the Grade on Women’s Health: A National and State-by-State Report Card, 2007), there is obviously a need for gender-based medical research to save the lives of women at increased risk of cardiovascular and other disease.

Lindbergh and Carrel's quest to live forever

It’s difficult to follow up a best-selling book about the cultural history of the penis, but David M. Friedman has a knack for engaging readers in topics that others find difficult to broach. This time he tackles the touchy subject of death by relating the intertwined biographies of Charles Lindbergh and Alexis Carrel in his new book, “The Immortalists: Charles Lindbergh, Alexis Carrel, and Their Daring Quest to Live Forever.”

Like most people, I had only heard of Charles Lindbergh as an aviator and in the context of his first child having been kidnapped and murdered. Imagine my surprise, then, when I happened upon a passage in Cardiopulmonary Bypass: Principles and Practice outlining Lindbergh’s contributions to Alexis Carrel’s isolated organ perfusion research in the 1930s – contributions which, for the first time, “permitted sterile, pulsatile perfusion at variable ‘pulse rates’ and variable perfusion pressures.”

Wait a moment. How did the world’s most famous aviator become involved in organ perfusion? Although much information about Lindbergh and Carrel’s work exists online, Friedman’s book provides a much more personal history of these two accomplished men.

Lindbergh’s overnight catapult into fame and adulation as the first man to fly across the Atlantic ultimately culminated in his loathing the press and greatly valuing privacy. A few years after his groundbreaking flight from New York to Paris in the Spirit of St. Louis, Lindbergh began thinking about things other than aviation. In particular, he wondered why people should have to die. Always an ambitious person, he decided to enter the realm of biology in order to seek the solution to eternal life. Once he made his quest known, it was not long before he was introduced to Alexis Carrel.

Carrel, a French scientist working at the Rockefeller Institute in New York, had already been awarded the Nobel Prize in medicine in 1912 and was far along in his own personal quest for immortality when Lindbergh came along. Convinced that the body was little more than a machine with replaceable parts, Carrel had begun his research by culturing cells from animals and keeping them alive indefinitely after the animal had died, thus “proving” the immortality of man and inviting him to move on to the next step: culturing entire organs. So far, Carrel had been successful at keeping the organs alive outside of the body for a few hours by perfusing them with a nutrient medium, but infection invariably set in and caused the organs to fail.

Lindbergh tackled the problem of creating a better perfusion pump with gusto. Using his engineering expertise and an innate sense for biology he eventually developed a pump that kept the perfusate sterile, thus allowing organs to be kept alive for several days or even weeks. Carrel and Lindbergh published their preliminary results in Science (“The Culture of Whole Organs,” July 21, 1935) and Lindbergh described the perfusion pump in a separate article published later (“An Apparatus for the Culture of Whole Organs,” September 1935, Journal of Experimental Medicine). The entire effort was then written up for publication as a book (“The Culture of Organs”) in 1938. As a team, it was obvious that Carrel and Lindbergh were made for one another.

That was true in more ways than one. Carrel was a eugenicist through and through, and often expounded on his ideas and philosophies with Lindbergh when they weren’t in the lab. Lindbergh had long considered himself superior to the masses of people he sought to avoid (especially journalists), and Carrel’s theories provided him justification for his opinion of himself and other “great men.” Eventually, Lindbergh became so enamored with eugenics that he developed a profound respect for Nazi Germany, much to his protégé’s dismay. Eugenicist or not, Carrel (like most Frenchmen who lived through World War I) hated the Germans and cautioned Lindbergh against speaking too loudly in their favor.

But speak loudly Lindbergh did. In fact, he abandoned the laboratory altogether in order to promote his new cause: non-interventionism. Becoming the spokesman for the America First Committee, he toured the U.S. speaking against America’s involvement in World War II, arguing that we should instead allow the situation in Europe to play out on its own accord. But while he believed that America should not involve itself in foreign wars, he also said that he would be the first to defend his country if it were attacked.

When Japan bombed Pearl Harbor, Lindbergh tried to make good on his promise. However, having thoroughly irritated the Roosevelt administration with his anti-war rallies, he was prevented from serving his country as anything but a civilian. To prove his patriotism Lindbergh fought in the South Pacific, providing cover for American bombers and pilots and eventually shooting down a Japanese plane himself, with the knowledge that if he were caught he would receive no aid from the U.S. and would stand alone.

Carrel, meanwhile, returned to occupied France after retirement from the Rockefeller Institute and tried to create an organization of the brightest thinkers in France to create policies to guide and govern the common people and return his country to glory. Ultimately this project failed and Carrel died ostracized and under house arrest.

When the war was over, Lindbergh visited the concentration camps in Germany and saw the horror and devastation perpetrated in the name of supposed science. He was beside himself and couldn’t believe that the “neat” and “organized” Germans that he had admired would commit such atrocities. He returned to the U.S. to examine his life – and came to the conclusion that he, too, had allowed science to dominate his perspective. He documented his monumental change in attitude in a book called “Of Flight and Life” in 1948. Friedman documents:

“…Lindbergh was urging Americans to break free from the “grip of scientific materialism,” lest it lead them, shackled and helpless, to “the end of our civilization.” The choice facing America, Lindbergh wrote, was as simple as it was stark: “If we do not control our science by a higher moral force, it will destroy us.”

This about-face led Lindbergh to an even greater revelation: that he was no longer an immortalist. After spending time in Africa and coming to appreciate the beauty of nature, Lindbergh dedicated the remaining years of his life to environmentalism. Friedman writes that “The person who once tried to save the world by saving white civilization would now try to save the world from white civilization.” Lindbergh wrote:

“When I watch wild animals on an African plain, my civilized [method] of measuring time gives way to a timeless vision in which life embraces the necessity of death.” I see individual animals as mortal manifestations of immortal life streams; and so I begin to see myself. I am not only one, I am also many, a man and his species. In death, then, is the eternal life which men have sought so blindly for centuries, not realizing they had it as a birthright.”

When faced with a cancer diagnosis in 1974, Charles Lindbergh had already made his peace with death, believing now that it was only through death that man may become immortal. With the same determination that he had done everything in his life, he planned his funeral down to the last detail. When the time came, he flew to his home in Maui and reminisced with his wife and children about his life – one of the most accomplished lives of the 20th century. Then, the man who was the first to fly solo across the Atlantic, who made the “Model T” of perfusion pumps, and who became a great political activist turned environmentalist, finally abandoned science…or, as he told the doctors who wished to continue treating his cancer in its last stages, “no, science has abandoned me.

BioTime's quest to defeat aging

Unless you are a long-time cryonicist or a surgeon, you may not have heard of BioTime before. This company, recently profiled for its innovative stem cell research in Life Extension Magazine, is best known for producing the blood-volume expander Hextend, which was initially developed by Trans Time, an early cryonics company performing ultra-profound hypothermia research. Realizing the potential for Hextend’s conventional medical applications, BioTime was formed and, as they say, the rest is history.

These days, BioTime does its best to distance itself from its early history. As documented in this 2004 WIRED magazine article, BioTime prefers to downplay its (prior) relationship with Trans Time even though the association is well documented. Furthermore, their development of products like Hextend and its modification HetaCool, which can be used as a blood substitute to allow cooling to ultra-profound hypothermic temperatures for heart and brain surgery, as well as newly-developed HetaFreeze, a cryoprotectant solution used for long-term tissue and organ preservation at sub-zero temperatures, point to their cryonics past.

But things are changing at BioTime. Under the direction of CEO Dr. Michael West, and capitalizing on the highly successful sales of Hextend and related products, the company is now heading in a new direction: regenerative medicine. Dr. West, who received his Ph.D. from Baylor College of Medicine in 1989 concentrating on the biology of cellular aging, is pushing the envelope of aging research by developing new forms of stem cells that can be used to reverse cellular aging, perhaps eventually leading to the ability to reverse aging of the entire human body.

In “Regenerative Medicine Breakthroughs: Will BioTime Reset the Clock of Aging?” (November 2008), Life Extension Magazine documents Dr. West’s mission — to understand how to make somatic (i.e., body) cells immortal and then apply this technology to the treatment of aging and aging-related diseases. BioTime is now driven by the potential for stem cell therapy to repair and regenerate organs and tissues and, if possible, to radically extend human lives.

To understand the problem of cellular aging, we must first know what happens to cells as they age. One of the most important contributions in this field was first made by Alexy Olovnikov in the early 1970s, who proposed that the DNA sequence at the ends of each chromosome (called a telomere) shortened each time a cell replicated. Once the telomeres “ran out,” the cell stopped dividing. Olovnikov also theorized that germ (i.e., reproductive) cells, whose telomeres never shorten, do not age due to the production of an “immortalizing enyzme.”  Dr. West became so convinced of Olovnikov’s theory that he formed a company called Geron to investigate it further. As reported by Life Extension Magazine:

“Forty million dollars later,” West recalls, “the gamble paid off.” West’s group had in fact produced Olovnikov’s mysterious enzyme, now known as telemorase, because of its ability to continuously spin out the vital strands of telomere DNA that keep germ cells immortal.

However, getting telemorase into aging cells is easier said than done. Instead of attempting what basically amounted to gene therapy, Dr. West decided to take another route to cell immortalization: stem cell therapy. Because embryonic stem cell research has been so controversial, Dr. West and his team at BioTime are using a technique developed by researchers at Kyoto University to create stem cells from aged somatic cells. In this procedure, transcription factors are removed from egg cells and placed in somatic cells, which transform back into colonies of stem cells over a few weeks’ time, effectively reversing the aging clock in those cells. These cells are then called induced pluripotent stem cells (iPS). They function exactly like embryonic stem cells, but do not come from an embryo.

“And since numerous papers on iPS have now shown switching on the telemorase gene in these cells,” continues Dr. West, “I believe that within the next 12 months, the scientific community will have documented, for the first time ever, the reversal of aging of a human cell.”

Dr. West’s team at BioTime still has a long way to go, however. For starters, they are trying to figure out how those stem cells “decide”  what type of cell to become. With this information, the researchers can better direct stem cells in regenerative therapies to the correct tissue or organ needing repair. Reversal of aging of distinct cell populations could lead to reversal of aging of the entire human body.

Of course it should be noted that one of the many scientific feats cryonics depends upon to succeed is regenerative medicine: it would not be ethical or practical to revive an aged cryonics patient to live in a frail and diminished state. So it seems that BioTime may eventaully be reunited with its roots….

PLAC blood test for sudden cardiac arrest and stroke risk

Life Extension Foundation (LEF) unveiled a new blood test in an article in this month’s Life Extension Magazine (November 2008). Unlike cholesterol testing, which simply gives a measurement of high-density (HDL) and low-density (LDL) lipoprotein levels and provides little information about acute risk of stroke or heart attack, the PLAC® blood test “can accurately identify artherosclerotic plaque that is vulnerable to rupture,” essentially providing a direct assessment of sudden heart attack and stroke risk.

The PLAC® test, developed by diaDexus, Inc., provides this assessment by measuring levels of lipoprotein phospholipase A2 (Lp-PLA2), an enzyme that is directly involved in endothelial dysfunction leading to atherosclerosis (an inflammatory response of the blood vessel wall), plaque accumulation (build-up of lipid deposits inside blood vessels), and rupture (breaking loose of plaque which can then block a blood vessel, causing heart attack or stroke). The PLAC® test specifically measures Lp-PLA2 associated with oxidized LDL particles. In research studies, high levels of Lp-PLA2 have been determined to be highly specific for plaque inflammation: an elevated PLAC® test indicates an increased amount of inflamed atherosclerotic plaques and thus a higher risk of plaque rupture.

Because of the sensitivity and high specificity of the PLAC® test for such inflammation, the predictive value of the test for risk of cardiac arrest and/or stroke is higher than other markers for the prediction of acute events. Furthermore, the PLAC® test is inexpensive and convenient in comparison to CT and other imaging procedures since it involves only the collection of a blood sample.

In general, the PLAC® test is appropriate for those known to be at high risk for cardiovascular disease and stroke, and LEF recommends that it should be performed once a year in persons who are obese or are regular smokers, those with high blood pressure or cholesterol, type 2 diabetes, or a family history of stroke and coronary heart disease. The PLAC® test can be used to guide patient treatment options: from their article, the LEF panel “recommends that patients with high Lp-PLA2 levels be upgraded from moderate risk to high risk, or from high risk to very high risk. In these patients, a suitable goal is to lower LDL to 100 mg/dL in high-risk patients and to 70 mg/dL in very high-risk patients.”

The PLAC® test is currently the only blood test approved by the FDA to assess atherosclerotic risk for coronary heart disease and stroke. While this is useful for guiding patients in their use of known treatment options, it is not known whether lowering Lp-PLA2 itself will result in a reduction of this risk. A large study (IBIS-2 trial) is now underway to shed more light on this topic. In the meantime,  LEF claims that the PLAC® test is by far the most reliable, convenient, and inexpensive method for determining one’s risk of acute ischemic cardiovascular events and is undoubtedly a beneficial tool for helping patients to keep tabs on their risk level and to implement a more aggressive treatment strategy if indicated.

-=Get the PLAC® blood test=-

The hostile wife phenomenon in cryonics

On August 23, Chana and Aschwin de Wolf drafted a blog entry on the phenomenon of partners who are hostile to cryonics. We sent our draft for review to a number of high profile cryonicists and received a message from Mike Darwin telling us that he still had an unpublished article on this topic. Because Darwin’s experience and observations resembled our own, and we believed there was a lot of value to his analysis, we decided to integrate our observations and his article to produce an even more comprehensive piece on the topic. The resulting draft  was distributed again to other cryonics activists and produced some additional text that was added as an appendix to the original article.

Although we do not have any illusions that the problem of hostile partners, and hostile female partners in particular, will be disappearing anytime soon, we believe it is important that this matter of life and death is documented. We also hope that this article will be of help to cryonicists, or people who want to make cryonics arrangements, who have hostile family members.

Michael Darwin, Chana de Wolf, Aschwin de Wolf – Is That What Love is? The Hostile Wife Phenomenon in Cryonics.

The article is also available as a PDF file with images and appendixes

Serendipity and drug discovery

The blog Soft Machines writes about a new opinion piece in the Financial Times by David Shaywitz and Nassim Nicholas Taleb on biomedical science and drug discovery. The molecular revolution in biology was supposed to substitute rational design of drugs for trial and error and handwaving. So why do pharmaceutical companies have so little to show for their efforts?

The answer, we suggest, is the mismeasure of uncertainty, as academic researchers underestimated the fragility of their scientific knowledge while pharmaceuticals executives overestimated their ability to domesticate scientific research…So intent are managers on maintaining focus that important opportunities for novel discovery are lost, as is the intellectual space for tinkering and capitalizing on the chance observations and unexpected directions so important in medical research.

As Taleb, author of the brilliant book “Fooled by Randomness”, and more recently, “The Black Swan”, mentions in an article about him in the same paper:

There is a lot more randomness in biotechnology and any form of medical discovery. The role of design is overestimated. Every time we plan on trying to find a drug we don’t because it closes our mind. How are we discovering drugs? From the side-effects of other drugs.

Selection bias and dietary supplements

One problem in assessing the merits of taking a specific dietary supplement (ranging from vitamins to  exotic multi-ingredient compounds) is widespread selection bias in the documentation that is supposed to support the use of the supplement in question.  The sheer number of scientific studies combined with variation in research methodologies virtually guarantees that for every supplement a supporting study can be found. For example, the recent issue of Life Extension Magazine (August 2008) has an article on the multiple health benefits of melatonin with 81 references. All these studies discuss either the biochemical properties of melatonin or show beneficial effects. This is what is what is seen. What is not seen are the studies in which melatonin is not effective or has adverse effects.  Or the studies that never got published as a result of “publication bias.” Granted, melatonin seems to be a remarkably effective agent for a diverse number of conditions, including its use as a neuroprotective agent in stroke, but such selective presentation of biomedical research seems to be a mainstay in the marketing of dietary supplements.

Another limitation of such documentation is that the studies that are used to recommend the taking of a supplement often solely address the (short-term) effects of that compound on the medical condition in question. Although it would not be practical to report on all the studies that investigate (chronic)  administration of the compound on other systems in the body, such unrelated adverse effects should not be ruled out when considering prolonged use. It is a major leap from demonstrating beneficial effects of a compound in rodents and preliminarily studies in humans to “recommending” the use of that compound for prolonged use in humans. And it is a giant leap to go from such studies to combining different effective compounds in very high dosages in a single product.

Promoting the use of supplements with a hodgepodge of  encouraging in-vitro studies, small animal studies, and observations in humans is not necessarily wrong, nor constitutes deliberate selection bias. Human biochemistry is extremely complex, and rigorous  research would require enormous resources and longitudinal experiments.  In real life there is a need to make informed decisions based on the evidence at hand. Still, our current state of knowledge and our ignorance about how all that we know adds up for specific individuals should induce modesty and, perhaps, moderation. For those who take supplements as a means to radical life extension, making cryonics arrangements remains the irreplaceable  cornerstone of such a program because it increases the odds to reach a time where truly meaningful (molecular) life extension technologies will be available, aside from the protection cryonics offers against most “lethal” accidents.