James Clement is the president of Betterhumans, a Florida anti-aging research organization, and the former executive director of the World Transhumanist Association (now Humanity+). He and his small team have been running human trials on compounds that might slow the aging process.
In the MIT Technology Review, longevity enthusiast Bill Faloon said that you “will do a study for $50,000 that a drug company will spend $10 million on. It’s easy to write [you] a check.” Can you really do studies for less than one percent of what a pharma company would budget?
Lots of doctors and researchers conduct small pilot studies, which cost tens of thousands of dollars rather than tens of millions, but it’s really like “apples and oranges” when it comes to comparing what we do to pharmaceutical-company studies to get a new drug approved. You wouldn’t want to see new drugs approved that had only been tested on dozens of people or for terribly short periods of time.
Our human studies usually focus on testing compounds that have already been tested in numerous other model organisms. They generally involve already-approved drugs or GRAS compounds excluded from such testing because of their historical usage. Since most of our clinical trials so far have only been as “proof of concept” whether something is safe and effective for some age-related disease, especially where our target is an objective measurement of blood chemistry or of gene-expression or protein levels, then in such cases even having a separate placebo control group might not be necessary. This obviously makes the studies much less expensive, while hopefully allowing us enough data to determine whether deeper inquiry is warranted. That said, many of the pilot studies we did early that showed promising results have now led to clinical trials that will have control groups, since in those we’ll be looking for changes that occur over time, rather than just immediately, and we’ll need a comparison group rather than just using the baseline measurement from the subjects.
If all of our studies were long-term, large studies, we could waste many hundreds of thousands of dollars per study, perhaps only finding treatments that barely exceeded “statistical significance.” Small pilot studies are thus our version of a high-throughput, low-cost process of eliminating ineffective treatments from our focus, because their effects aren’t strong enough for us to waste more money or time on. Since we have no profit motive (only the desire to find anti-aging therapies that we can share with physicians and the public), we can stop pursuing particular treatments at the drop of a hat, and pivot to another potential treatment on our list.
A few months ago, there was a study showing that a combination of metformin, DHEA and HGH could reverse epigenetic aging markers. However, this study only had nine participants. How would you weigh the cost advantages of doing a small-N trial, against the noise and uncertainty that comes from not having a larger sample size?
I’m familiar with this project and the researcher in question, Dr. Greg Fahy, had done the experiment on himself (n=1) with good results. The year-long study he then conducted, without placebo controls, was a pilot study, like the ones we do. Like us, he wanted to increase the size of his study group just large enough to meet statistical requirements but not too much so as to waste funds excessively if it didn’t pan out. I’m sure Greg will pursue larger studies now that the proof-of-concept has justified such, and we’ll learn even more from these larger, longer studies.
Many authors have written about how it’s become more and more expensive to bring new drugs to market. Some have dubbed this Eroom’s Law, the opposite of Moore’s Law, where new technology in biomedicine has a higher cost every year. How much of this cost increase do you think comes from human trials getting more expensive to run?
From what I read, pharmaceutical and biotech companies are among the most profitable publicly traded companies, at a level comparable to investment banks. Doesn’t that tell you something about why drugs are so expensive? They used to be run by physicians and scientists, now they’re run by suits.
Your LinkedIn profile says that you used to be a lawyer. How did you transition from doing legal work to doing biotechnology research, especially without an MD or other specialized degree?
I don’t think one’s education or training define who that person is, or what they’re capable of. I read Durk Pearson and Sandy Shaw’s Life Extension book in my third year of law school (1982), and knew this was something I wanted to eventually be involved in. I started the transition in the early 2000s, going to conferences and reading more and more books on microbiology, just as Aubrey de Grey and others starting promoting anti-aging research via online forums, books, videos, and scientific conferences. Over the past eight years I’ve read over 18,000 papers (as of 2019), and taken extensive notes about compounds and therapies which seemed to hold promise for humans. Luckily, I’ve managed to meet and set up collaborations with talented research collaborators and a few skilled physicians, who also help me move things along.
Some people have speculated that, to reduce costs, overhead, and delays, it might be best to run clinical trials “outside the system”, or in a new location without the FDA’s strict regulatory framework. However, it looks like all of your trials have been done in the US, with formal IRB approval. How did you go through the American approval process without a large administrative staff and legal team?
The nature of the small pilot studies we’ve been engaging in, and will continue to run for the foreseeable future, where the treatments consist of the off-label use of already approved drugs or GRAS compounds has allowed me to keep our costs down. However, we have several projects in the works which will involve seeking IND (investigational new drug) status, and we will have to go through more time-consuming and expensive steps than before. Most of these steps are designed to minimize the risk to the subjects and to show that the intended benefit is worth whatever risks are involved; this doesn’t and shouldn’t change merely because one goes offshore. Since we’re doing all of this as a nonprofit whose aim is to speedily identify promising therapies, we can also drop something quickly and pivot to another promising approach without worrying about how this will look to our investors or the market.