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.

31. July 2008 · Comments Off on Serendipity and drug discovery · Categories: Science, Society · Tags: , , ,

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.