The diminishing returns of reactive medicine

In an article for Slate, Jay Olshansky argues in favor of a position that one would expect to be common sense at this point:

While we can extend life in aging bodies through behavioral improvements and medical treatments, the time has arrived to acknowledge that our current model of reactive medicine, of trying to treat each separate disease of old age as it occurs, is reaching a point of diminishing returns.

So what is the reason why vast amounts of money are spent on research to treat age-associated diseases but so little on eliminating or mitigating aging as such? Why is this “one-disease-at-a-time model” so dominant? One reason might be that most people believe that overcoming one specific manifestation of aging is easier to do than overcoming aging itself. Not surprisingly, most academic and commercial research is shaped by short term ambitions or short-term financial interests.

Many people who deal with serious age-associated diseases hope that a cure can be found within their lifetime.  This is not so strange if you consider that many people who do advocate meaningful rejuvenation research are technological optimists who think the same thing about overcoming aging. In that sense, people show little interest in supporting research that has little personal benefit to them or close relatives. This is further evidenced by the fact that people are more inclined to contribute to anti-aging efforts that promise benefits in their lifetime. This in turn provokes criticism from mainstream scientists of not being realistic, which further discredits the field.

But as Olshansky indicates, the diminishing returns of the approach to just fight the symptoms of aging should force people to change perspective. Olshansky also observes  that “manufacturing survival time in the absence of decelerated aging” can produce a lot of hardship and suffering in old age:

It’s important to acknowledge the fundamental differences between disease and aging. Although age-associated changes in the body produce an increased risk of disease, the reverse is not true. That is, reducing the risk of disease has no influence on biological aging. Thus, if a population is preserved with increasing efficiency by advances in technology that reduce the risk of disease, those saved will live into increasingly later sections of the lifespan where aging takes a greater toll on body and mind. Life extension achieved in this way could extend old age by exposing survivors to the high-risk conditions of frailty that are common, and largely immutable, near the end of life—the very outcome that medicine and public health practitioners are trying to avoid.

For people who have made cryonics arrangements, there is another danger; the possibility of life extension at the price of increased vulnerability to identity-destroying diseases.  There is no shortage of cryonics patients with Alzheimer’s or impaired brain function. As much as we would like to deny it, there could be a disturbing trade-off between life extension and true personal survival as long as treatments for neurodegenerative diseases are not available.

The science of personal survival

There are various competing strategies how to achieve meaningful life extension or rejuvenation, including , but not limited to, genetic manipulation, periodical elimination of damage, caloric restriction,  molecular nanotechnology and mind uploading. A useful review of these strategies has been published in the book The Scientific Conquest of Death: Essays on Infinite Lifespans (2004) by the Immortality Institute. Most people will recognize that these strategies are not mutually exclusive. Some of them can be practiced right now (e.g., caloric restriction) and others ( e.g., periodical elimination of damage) could serve as a bridge to more comprehensive interventions such as a comprehensive genetic overhaul of human biology. As has often been recognized on this website, cryonics holds a special place among life extension strategies because it enables one to benefit from progress in the biomedical sciences that may not occur during one’s lifetime. We would like to think we can escape death by jumping from one successful biomedical innovation to another and that, of course, all the good things will happen in our lifetime, but reality often interferes with such optimism.

One thing that might greatly accelerate the pace of progress in the field of longevity science is the development of an integrated framework that studies the logical and empirical relationships among all these strategies. For example, a recent blog entry on the technical challenges surrounding chemopreservation of the brain triggered a meaningful private exchange about issues concerning the perfusion of ischemic tissue, empirical criteria for information-theoretic death, and the options for histological validation of cryonics technologies.  Such overlapping areas of investigation are plentiful and it would be helpful to explicate them.

Too much focus on “the big picture” can interfere with the identification of original ideas and rapid progress. Too little attention to the adverse effects of compartmentalization risks the waste of resources, which is not a trivial concern in the still poorly funded life extension community.

Reducing compartmentalization can have other sobering effects as well. For example, it is not unusual to see a group of researchers advocating a new approach to their field that is routine in other areas of investigation. For example, the idea that anti-aging research could benefit from less emphasis on illuminating the exact molecular mechanisms of aging and simply treat the observable manifestations of aging is no news to researchers in the field of cerebral ischemia. The pathophysiology of stroke is so complex that greater progress could be achieved by identifying clear targets for pharmacological intervention. But after decades of research it has become abundantly clear that such a paradigm change is no guarantee for more rapid progress. Despite this goal-oriented approach not one single neuroprotective agent has survived clinical trials.  This does not mean that such pragmatic approaches should be abandoned. It does mean, however, that research ideas should be evaluated on their empirical success and not just on their logical merits.

There are obvious examples where the claims in one field seem to make the claims in another field redundant. The most obvious example is the case of molecular nanotechnology. The projected timescales that are envisioned for this technology are not much different from the timescales that are envisioned by some anti-aging researchers to develop meaningful rejuvenation. In that case one could argue that (exclusive) preference should be given to those research programs that allow for the most comprehensive manipulation of biology. For example, a mature nanotechnology would be able to rejuvenate people, resuscitate cryonics patients, and alter the human endoskeleton to make us far less prone to fatal accidents. Such an argument would be a logical extension of the argument against devoting too much time to find treatments for specific age-related diseases instead of tackling aging itself.  Similar reasoning can be employed against anti-aging research. If accelerated change will bring the prospect of general molecular control within reach in the next few decades it makes little sense to spend vast amounts of time agonizing over specific anti-aging interventions. Why not just launch a “Manhattan Project” to pursue the much more comprehensive vision of molecular nanotechnology?

From a logical point of view, this is a persuasive argument. The limitations of such a perspective should now be obvious too.  We do not have certainty about the future of technological progress, let alone its specifics. As a matter of fact, in such matters it is not even evident how we should think about statistical or inductive probabilities.  To some people, the progress in one field is indicative of the progress we are going to observe in other fields, including fields in which there has been little progress to date. The problem with such naive inductivism is that it can just as well be used to  make the opposite case if a different reference class is chosen.

The logical empiricist philosopher Rudolf Carnap once wrote:

The acceptance or rejection of abstract linguistic forms, just as the acceptance or rejection of any other linguistic forms in any branch of science, will finally be decided by their efficiency as instruments, the ratio of the results achieved to the amount and complexity of the efforts required. To decree dogmatic prohibitions of certain linguistic forms instead of testing them by their success or failure in practical use, is worse than futile; it is positively harmful because it may obstruct scientific progress.

A related argument can be made about the science of personal survival. We should be cautious about privileging any line of research on  “logical” grounds. The fate of competing visions should be decided through empirical investigation.  This position should not be interpreted as saying that there is no place for logic in choosing research programs.  Logic has a central place in research design and interpretation of experimental observation but it cannot be solely relied upon a guide for decision making. Empirical observation disciplines thinking and ample room should be left for the unexpected. As Nassim Nicholas Taleb has pointed out:

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.

Many experimental researchers have had the experience of engaging in research to find a solution to one problem but to discover the solution to another problem instead. Researchers who have recognized and embraced this phenomenon by becoming less fond of their own ideas and more open to run with such unexpected discoveries have reaped great benefits.

Peter Thiel: Utopian Pessimist

Peter Thiel, one of the few original minds in the life extension and accelerating-technological-change community, is featured in a short interview at Wired. Thiel seems to be aware of the limitations of extrapolation of trends:

We’ve been living in a unique period of accelerating technological progress. We’ve gone from horses to cars to planes to rockets to computers to the Internet in a very short time. It’s not automatic that that continues.

In a 2008 essay for the Hoover Institute, Thiel writes:

Thought experiments are notoriously misleading. Unlike more rigorous forms of scientific investigation, there are no empirical means to falsify these mental exercises. The optimistic thought experiment exists largely in the mind. The vistas of the mind are not always the same as reality. One could do worse than to ignore Milton ’s seductive promise: “The mind is its own place, and in itself, can make a heaven of hell, a hell of heaven.

As has been argued on this website before, the life extension movement suffers from an abundance of individuals who engage in thought experiments and organize conferences to talk to other people who engage in thought experiments.  But the fight against aging  cannot be won through speculation and wishful thinking alone but is in serious need of an “empirical turn”  that will unleash an avalanche of experimental research (for example, such as envisioned by the newly formed non-profit company Livly).

Further reading: 2008 Reason Interview with Peter Thiel

Thomas Donaldson on cryonics and anti-aging

Just a superficial look at the history of the life extension movement will suffice  to show the rise and fall of numerous fads and trends in ideas about the mechanisms and “treatment” of aging.  Psychological meliorism and simplistic visions of biochemistry create overly optimistic expectations about extending the maximum human lifespan.  But how can we know if a treatment is able to extend the maximum lifespan of humans without giving it to them and waiting….

In his article “Why Cryonics Will Probably Help You More Than Antiaging” (2004), cryonics activist Thomas Donaldson contrasts cryonics with antiaging as a means to life extension and argues that a major advantage of cryonics is that cryobiology research can move at a much faster pace than anti-aging research, especially as it pertains to humans:

The best possible proof that a treatment will indefinitely prolong the lives of human beings must come from a demonstration of its effects on human beings. Not fruit flies, worms, mice, or rats, but human beings. Yet there’s a small problem here: we are human beings ourselves, and a proof that a treatment prolongs the lifespan of people will take … at least the lifespan of some people…cryobiology can progress much faster than antiaging. Not only that, but its progress almost totally lacks the problems of proving that an advance has happened. The state of a brain, or even a section of brain, after vitrification and rewarming to normal temperature, shows directly whether or not the method used improved on previous methods.

What about treatments that have been shown to extend the maximum lifespan in small mammals? Or using  treatments that have been shown in humans to stop or slow down the aging process?

“It takes a long time and the actual reports on clinical use of a drug for physicians to get an idea of the effects of longterm use of that drug.  Very few drugs of any kind get formal tests for the entire lifespan of normal people taking them.”

Even if people are not prevented from experimenting with various life extension technologies, these epistemological and practical problems cannot easily be overcome.

“No matter what some scientists say, a cure for aging involves many problems all of which will need time for their solution. Even now, you may be young and feel that you need not think about cryonics because some means to slow your aging will come before you’ve gotten very old, and from that still other means to slow your aging even more … and so to true agelessness. In this article we have seen why such dreams of a rapid solution to aging cannot come fast for any of us. At the same time, cryonic suspension able at least to preserve our brains in a reversible form, allowing restoration of vital functions, looks likely to come much sooner.”

And as Robert Prehoda pointed out in an old interview, successful treatment of aging will still leave an individual vulnerable to accidents:

Immortality is statistically impossible because accidents would eventually eliminate all individuals in any non-aging population.

Despite these arguments, the life extension and “transhumanist” movement remains many times larger than the people who have made cryonics arrangements.  Some reasons for this are explored in another entry, but the mystery remains.

Aging 2008

Aging: the Disease, the Cure, the Implications

Press Release

Methuselah Foundation Announces Aging 2008 at UCLA
Have you ever dreamed of climbing Mt. Everest – on your 125th birthday?

Los Angeles, CA (May 19, 2008) On Friday June 27th, leading scientists and thinkers in stem cell research and regenerative medicine will gather in Los Angeles at UCLA for Aging 2008 to explain how their work can combat human aging, and the sociological implications of developing rejuvenation therapies.

Aging 2008 is free, with advance registration required at:
http://www.mfoundation.org/Aging2008/.

Dr. Aubrey de Grey, chairman and chief science officer of the Methuselah Foundation, said “Our organization has raised over $10 million to crack open the logjams in longevity science. With the two-armed strategy of direct investments into key research projects, and a competitive prize to spur on scientists racing to break rejuvenation and longevity records in lab mice, the Foundation is actively accelerating the drive toward a future free of age-related degeneration.” The Methuselah Foundation has been covered by 60 Minutes, Popular Science, The Wall Street Journal, and other top-flight media outlets.

The State of California is a frontrunner in regenerative medicine and stem cell research. On November 2, 2004, more than seven million Californians voted to pass Proposition 71, establishing the California Institute for Regenerative Medicine, and allocating $3 billion over ten years to fund stem cell research. Proposition 71 was a rare instance of voters directly authorizing funding for scientific research.

The speakers at Aging 2008 will argue that the near-term consequences of intense research into regenerative medicine could be the development of therapies that extend healthy human life by decades, even if the therapies are applied in middle age. Peter Thiel, president of Clarium Capital, initial investor in Facebook, and lead sponsor of Aging 2008, said, “The time has come to challenge the inevitability of aging. This forum will provide an excellent opportunity to look at the scientific barriers that must be overcome to substantially extend healthy human life, as well as the ethical implications of doing so.”

Aging 2008 also serves as the free opening session for the technically focused Understanding Aging Conference, which will run at UCLA on June 28th and 29th.

What: Aging: The Disease, The Cure, The Implications, hosted by Methuselah Foundation When: Friday, June 27, 2008, Drinks 4pm, Presentations 5pm, Dinner 8pm Where: Royce Hall, 405 Hilgard Ave, Los Angeles, CA 90024 Who:

  • Dr. Bruce Ames, Professor of Biochemistry and Molecular Biology at UC Berkeley
  • G. Steven Burrill, Chairman of Pharmasset and Chairman of Campaign for Medical Research
  • Dr. Aubrey de Grey, Chairman and CSO of Methuselah Foundation and author of Ending Aging
  • Dr. William Haseltine, Chairman of Haseltine Global Health
  • Daniel Perry, Executive Director of Alliance for Aging Research
  • Bernard Siegel, Executive Director of Genetics Policy Institute
  • Dr. Gregory Stock, Director of Program on Medicine, Technology & Society at UCLA School of Medicine
  • Dr. Michael West, CEO of BioTime and Adjunct Professor of Bioengineering at UC Berkeley
About Methuselah Foundation

The Methuselah Foundation is a 501(c)(3) nonprofit organization dedicated to extending the healthy human lifespan. Founded in 2002 by entrepreneur David Gobel and gerontologist Dr. Aubrey de Grey, the Methuselah Foundation funds two major projects: the Mprize, a multimillion dollar research prize, and SENS, a detailed engineering plan to repair aging-related damage. Learn more at http://mfoundation.org.

Media Contact: Maria Entraigues, 310-242-3660, maria@mfoundation.org