To Live Much Longer, We’ll Need Dangerous, Ethically Troubling Clinical Trials

What's to come?
Jan. 26 2012 7:10 AM

The High Price of Long Life

If anti-aging drugs are possible, they will require dangerous—and ethically troubling—clinical trials.

Wanted: Healthy volunteers to participate in clinical trials of experimental therapies designed to radically extend the human life span. The therapies being tested may alter your brain and body at the cellular level.

Sad elderly woman.
What are the considerations of designing medical treatments that regard aging itself as a disease?

Photo by Eduardo Jose Bernardino/iStockphoto.

How long before we see notices like this? Recent media stories suggest that anti-aging medicine may soon change from fantasy into a scientifically realistic prospect. Here I address the dangerous consequences of a widespread belief that human aging could be halted or reversed. If anti-aging medicine is to become a reality, then the various theories about how to halt or reverse the aging process will require testing on human subjects. Carrying out such tests will place unprecedented pressure on the rules protecting human participants in clinical trials, which are already routinely ignored.

There are currently two types of anti-aging research. The traditional approach focuses on diseases of aging, like Alzheimer’s, atherosclerosis, type 2 diabetes, cancer, and other life-shortening ailments that become more common as we grow older. If we can vanquish them, says this school of thought, we can age more healthfully—and perhaps live longer.

Then there’s the more ambitious approach, which sets as its target aging as a disease. The busiest person in this area is Aubrey de Grey, founder of the Strategies for Engineered Negligible Senescence Foundation, or SENS. De Grey aspires to a future in which we become negligibly senescent: People will no longer experience advancing decrepitude ending inevitably in death. De Grey envisages therapies that will intervene in the aging process in more extensive and profound ways than any drug that shrinks Alzheimer’s plaques or helps people with diabetes to better regulate their blood sugar. (In 2010, de Grey described his ideas for “Rejuvenation Biotech” in Slate.

De Grey’s critics call him a snake oil salesman. But this is unfair, mainly because he’s not selling oil or anything else that can be bottled. De Grey’s selling an idea—the idea of agelessness as a realistic goal. If an end or serious delay to aging is achievable—and there’s no reason to think it impossible, though it’s certainly going to be an enormous challenge—then the sooner we start looking for it in earnest, the sooner we’re likely to find it. To hurry this process, de Grey helped set up the Methuselah Foundation, which offers cash prizes to researchers who break records in mouse longevity. (The record as of January 2012 is 1,819 days—not bad for an animal with a life expectancy in the wild of under a year.) Unusually long-lived mice could awaken people to the possibility of radically extending human life spans in much the same way that Dolly the sheep inspired fears and hopes for human cloning.

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At some point, people will have to test any therapies that have successfully extended the life spans of mice. Methuselah mice may be effective as proofs of concept—demonstrations that the life expectancies of mammal species including humans can be dramatically extended. But they certainly won’t show that any particular anti-aging therapy is safe. There are many biological differences between mice and humans; a therapy that carries a mouse to its 3,000th day could swiftly kill a human. It’s in the area of testing that there are serious differences between research on diseases of aging and research on aging as a disease.

It’s not too difficult to entice those suffering from diseases of aging into clinical trials. For example, people with Alzheimer’s recognize that they have a terrible illness. They understand that many experimental drugs don’t work—that some may actually make them sicker. They view such risks as warranted.

Human trials of experimental therapies for aging as a disease are a different matter. The potential benefits may be huge, but so, too, are the risks. Furthermore, to prove that new therapies can extend the life spans of people free of any significant disease of aging, researchers will need to carry out tests on similar people—that is, experiencing healthy aging. Convincing such people to undertake risky treatment will be challenging.

Consider de Grey’s proposed cure for cancer, which is the deal-breaker for would-be life extenders. Its incidence significantly increases with age, meaning that those who make it to 150 before there is a cure or at least a very effective treatment would be advised to cultivate a taste for chemotherapy. De Grey is a proponent of WILT, or whole-body interdiction of the lengthening of telomeres, which are the protective sequences of DNA at the end of chromosomes. This “cure” involves excising the telomerase gene from every cell in the human body. Many cancers acquire the capacity to grow without limit by hijacking this gene. De Grey’s cure for cancer comes with a significant cost; the telomerase gene is there for a reason. Many parts of the human body churn through cells at a pretty rapid rate. Without a well-functioning telomerase gene, we’d soon run out of red blood cells, white blood cells, and platelets. De Grey proposes regular bouts of stem cell therapy to supply the missing cells. Now, I don’t mean to say that WILT could not work or that, if it doesn’t, it couldn’t lead to hypotheses that actually do. It’s just that I would rather not be the first to test it after they’re done with the mice and monkeys.

I suspect that people interested in SENS are likely to be especially averse to the kinds of risks involved in clinical trials. They are, after all, being enticed by the promise of millennial life spans. Why would they sign up for dangerous clinical trials for anti-aging therapies when there’s another option—paying others to do their dirty work? Unlike in some fictional portrayals, there won’t be a single “cure” for aging that, once discovered, can be safely given to anyone who wants and can pay for it. Scientists will develop multiple therapies targeting distinct types of age-related damage. Each will need extensive testing, and there will inevitably be many false turns and disappointments along the way. Anti-aging researchers will need to be well-supplied with healthy human test subjects. A general recognition of the scientific possibility of radically extending human life spans will bring a sense of urgency. Human trials must happen ASAP if safe anti-aging therapies are to arrive in time to arrest the death spiral of biological decay awaiting today’s 40-year-old supporters of SENS.

I suspect, then, that human guinea pigs for anti-aging trials will come disproportionately from the poor and disempowered. A recent report by the Presidential Commission for the Study of Bioethical Issues called for stronger protections for participants in clinical trials. It seeks to block Big Pharma’s old practice of finding jurisdictions less finicky about their subjects’ rights in respect of clinical trials. (For instance, American doctors purposely infected more than 700 Guatemalans with syphilis in the 1940s.) The prospect of a cure for aging will create more powerful desires than did the prospect of a better treatment for syphilis. The rich and powerful will be looking to do away with rules that they perceive as denying them millennial life spans. 

This article arises from Future Tense, a collaboration among Arizona State University, the New America Foundation, and Slate. Future Tense explores the ways emerging technologies affect society, policy, and culture. To read more, visit the Future Tense blog and the Future Tense home page. You can also follow us on Twitter.

Nicholas Agar is an associate professor at Victoria University of Wellington in New Zealand. He is the author, among other things, of Humanity's End: Why We Should Reject Radical Enhancement(2010) and Liberal Eugenics: In Defense of Human Enhancement (2004).

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