When I say "amyloid," of course, almost everyone thinks of beta-amyloid protein (also called "amyloid beta"), which accumulates as the waxy "senile plaques" that cluster around the brain cells of people with Alzheimer's disease.
--Aubrey de Grey, Ending Aging: The Rejuvenation Breakthroughs
That Could Reverse Human Aging in Our Lifetime, p. 134
Aubrey de Grey is so deep into geek biogerontology that using "almost everyone thinks of" in the sentence quoted above does not strike him as rather generous. In reality, most of us are thinking "amyloid...amyloid...you're talking about the singer, right? No, no...what am I saying...Wasn't she the actress in that movie...?"
Four years ago, I reported that de Grey foresees a not-too-distant future in which humans can reverse the effects of aging, raising the possibility of living healthy lives for hundreds of years. He has not backed away from that position, and this book, written by de Grey and his research associate Michael Rae, represents an update from his perspective. In brief, he says that
- The latest scientific research indicates no flaws in the theory that aging can be eradicated.
- However, getting the required techniques developed will require institutional changes relative to our current system for conducting medical research.
As an economist, I am most interested--and most qualified to form an opinion about--the second point.
De Grey makes state-of-the-art scientific issues accessible to an intelligent layman. He uses metaphors, as when he describes the role of mitichondria in terms of a power plant analogy (p. 53).
But while hydroelectric dams are (for the most part) environmentally benign, mitochondria are in one key aspect more like conventional power sources [in that they] create toxic wastes during the conversion of energy from one form to another...oxygen is also the sink for the electrons that are not fumbled--that are properly processed by the mitochondria--but that process loads four electrons onto each oxygen molecule...Adding one electron, by contrast, transforms benevolent oxygen into a particularly important free radical, superoxide. With your mitochondria generating ATP day and night continually, the ongoing formation of superoxide is like having a constant stream of low-grade nuclear waste leaking out of your local reactor.
De Grey's overarching metaphor is that the body is like a machine that, if properly maintained, can be kept running forever (p. 21).
we have hundred-year-old cars and (in Europe anyway!) thousand-year-old buildings still functioning as well as when they were built--despite the fact that they were not designed to last even a fraction of that length of time...the precedent of cars and houses gives cause for cautious optimism that aging can be postponed indefinitely by sufficiently thorough and frequent maintenance.
However, maintenance of a car or a building often consists of replacement of components at a macro level. You replace whole tires and lightbulbs. You rip out a transmission or a kitchen and put in a new one.
What de Grey is talking about for humans is not macro replacement--giving you new organs or giving your cardiovascular system the equivalent of a transmission overhaul. Instead, he is talking about maintenance at a molecular level. For a car, it would be like having nanobots that repair corroded parts by reversing rust molecule by molecule. For a house, it would be like having shingles that when damaged by wind or wear are able to grow back to their original shape.
Internal Evolution at Work
De Grey sees aging as a byproduct of an evolutionary process that takes place within the body. Mutations occur over time within your cells, sometimes randomly and sometimes stimulated by external events. This evolutionary process changes the balance between what I might call "good stuff" and "bad stuff" (here I am taking the technical caliber of the scientific exposition down several levels). Sometimes, the "good stuff" gets stronger, as when we develop an immunity to a disease. More often, however, the "good stuff" gets weaker and the "bad stuff" (like arterial plaque or pre-cancerous cells) gets stronger. It is this shift in the balance that leads to the symptoms of aging, including susceptibility to disease, which ultimately proves fatal.
Because aging is a natural outcome of the body's internal evolutionary processes, de Grey argues that the standard paradigm for fighting the diseases of aging one by one is flawed. Prevention of one disease, in the form of slowing the processes that cause it, is a doomed strategy.
First, there is the fact that the processes that cause disease are the very processes that make life possible and enjoyable. The prevention paradigm amounts to lengthening the life of a car by keeping it in a dry, climate-controlled garage forever without ever driving it.
Second, there is the fact that if one age-related disease does not get you, then another one will. In my research into the causes of rising health care spending, I learned the sad truth that as we have achieved success in the battle against heart disease, we are increasing the chances that people will die of diseases like Parkinson's or Alzheimer's, with the result that expenditures on institutional care and full-time home care are soaring.
Only Seven Types of Damage
De Grey argues that there are only about seven generic forms of damage, in which our body's evolutionary processes cause it to lose "good stuff" or produce more "bad stuff" (again, those are my dumbed-down expressions). De Grey's approach to reversing aging is to stimulate the body to throw out the bad stuff and grow more good stuff, maintaining a youthful balance.
For example, his approach to eradicate cancer is particularly radical. Cancer consists of "bad stuff" that has won the evolutionary battle and is now reproducing like gangbusters. He wants to make it impossible for any type of cell to take over the internal ecosystem, so his proposal amounts to programming all cells to self-destruct after they reach an expiration date. Obviously, this creates a problem in that we need some of our cells to be able to last longer, or we will run out of "good stuff." His solution is to use periodic stem cell implants to replenish our inventory of "good stuff." Along the way, he makes a clear and compelling case that we need embryonic stem cell research.
(As an aside, I did not find his argument against the conventional cancer-fighting paradigm fully convincing. I find it more appealing to hope that there is a way to give every cell a "suicide pill" that it takes only if it recognizes that it is about to be captured by the cancer-enemy. Instead, killing off every cell, good or bad, and then trying to add new good cells strikes me as inelegant.
De Grey expresses the concern that when a conventional therapy goes after cancer (and the approach that appeals to me is more conventional), the laws of evolution suggest that a few cancer cells are likely to mutate and survive. Those that survive will be drug-resistant and therefore much more dangerous. However, I think that this is not like the mutation of germs, where a drug-resistant bacteria or virus can get started in one person's body and continue to evolve somewhere else. The fact that a cancer cell evolves in my body to evade a particular drug does not make that drug any less effective in your body. If your body is going to develop a drug-resistant form of that cancer, it is going to have to start from scratch. As a result, there may be a limited number of such mutations, and therefore we may need only a finite set of anti-cancer drugs. Of course, I have absolutely no expertise in this area. It is more likely that I misunderstand de Grey's argument than that he is wrong.)
A Crash Course
Too often, academics use their credentials to spit out biased polemics dressed up as science. Ending Aging is the opposite. It is a crash course in state-of-the-art science dressed up as a polemic. De Grey wears his passion for undertaking a war on aging on his sleeve, yet most of the book consists of scientific analysis that, although simplified to enable a layman to follow, is conscientious in reporting doubts and objections to the author's point of view.
I would recommend giving Ending Aging to any scientifically-inclined youngster. It gives a sense of the possibilities, drama, and frustration of scientific inquiry. Also, it might inspire some young geniuses to undertake the sort of investigations and experiments that de Grey thinks will help win the war against aging.
The polemical component of de Grey's book is aimed primarily at the institutions and incentives that currently govern the medical research process. Some of the changes that he proposes are radical, and some are subtle.
The first institutional problem, from de Grey's perspective, is that the incentives lead researchers to focus on specific diseases rather than on general-purpose technologies to fix cell damage. In scientific research, the usual distinction is between "basic" research and "applied" research. Almost everything that De Grey is talking about is in the "applied" arena. We can always use more basic research, but I think he would regard the basic research that we have today as sufficient in many respects.
The distinction between disease-specific and general-purpose fits under applied research. Within the category of applied medical research, there are discoveries that attempt to treat specific diseases, such as prostate cancer or Parkinson's. However, the technologies that de Grey advocates developing might reverse the processes that are implicated in many diseases.
Today, the incentives to experiment with general-purpose anti-aging technologies are limited. Only if a technique can be demonstrated as helping to treat a specific disease can its development be funded and its efficacy tested in humans. Of course, many of the techniques necessary to achieve de Grey's vision can be shoehorned into a disease-fighting agenda somewhere, which is why he can report results that justify his belief in the potential to conquer aging. However, there remains the fact that the current system gives too much incentive to find stopgap solutions to specific diseases and too little incentive to develop general-purpose anti-aging technologies.
The second institutional barrier is risk aversion, which is hard-coded into regulations pertaining to research and to clinical trials. De Grey writes (p. 323-324),
Regulation of experimental drugs and therapies...is based on one abiding principle above all others: the minimization of risk that the therapy might make the patient worse...
I take the view, quite simply, that Hippocrates has had his day...the psychological effect of possibly causing harm...skews the objective cost-benefit analysis of a given treatment...I believe that the 10:1 (at least) ratio of lives lost through slow approval of safe drugs to lives lost through hasty approval of unsafe drugs is no longer acceptable.
...[Laws and regulations will change.] People will die as a result; the 10:1 ratio mentioned above will probably be reduced to 2:1. And people will be happy about this change, because they'll know it's wartime, and the first priority--even justifying considerable loss of life in the short term--is to end the slaughter as soon as humanly possible.
What de Grey is saying is that today's cautious approach to experimental medical testing significantly slows the rate of progress, which means that many people will suffer and die unnecessarily. However, those people are unseen and unknown, whereas those who suffer and die as a result of medical experiments are identifiable and visible. I think that trying to sell people on the idea of taking more risks in order to advance medical progress is not as straightforward as de Grey makes it sound.
As an economist, I immediately think in terms of paying people to undergo risky therapies. For better or worse, this might appeal more to people who are very poor--perhaps even people living in other countries. However, those citizens who are squeamish about de Grey's proposal to expose more people to harm now in order to reduce harm to others in the near future probably would not feel any less squeamish just because those who undergo the experiments are well paid.
At a more subtle level, de Grey wants institutional changes that wrest control of the research agenda from the medical establishment, which is vested in the existing paradigm. Here, the fact that so much medical research is under government auspices makes the outlook discouraging, in my view. If there is one thing that you can count on government to do, it is to protect incumbents and move with great reluctance to support upstarts and innovators.
My guess is that de Grey will have better luck if he tries to mobilize wealthy philanthropists. If instead of donating buildings to universities our billionaires would donate money for prizes that reward general-purpose medical technologies, we might not have to wait for government research to adopt a paradigm shift, which is almost surely not going to happen. Wealthy (and not-so-wealthy) philanthropists who are reading this should check out de Grey's organization SENS and look for ways to contribute both to his institute and to a prize fund.
Let me give de Grey the last word (p.328-329):
Just as people were wrong for centuries about how hard it was to fly but eventually cracked it, we've been wrong since time immemorial about how hard aging is to combat, but we'll eventually crack it, too. But just as people have been pretty reliably correct about how to make better and better aircraft once they had the first one, we can expect to be pretty reliably correct about how to repair the damage of aging more and more comprehensively once we can do it a little.