Monkeying around with myostatin: on the road to healthier humans or human hulks?

The Hulk in Avengers The myostatin gene has been getting quite a bit of attention lately.

The buzz surrounds the idea of inhibiting myostatin either through gene therapy or via germline human genetic modification.

In this way, some hope to create people with more muscle. Myostatin, which also goes by the acronym MSTN, has an inhibitory function on muscle. Inhibit and inhibitor of muscle and you should get more muscle, right?

Data backs it up.

Animals including humans with spontaneous mutations in myostatin have unusual musculature including increases in muscle. This NEJM case report on a boy with a myostatin mutation describes a remarkable phenotype of drastically increased muscle and reduced fat. No clear pathology was associated with the condition, which is referred to as myostatin-related muscle hypertrophy. More on that condition more generally here.

Pop culture is fascinated with the idea of genetically modifying people to artificially create this kind of super-muscle condition. Would they be like superheroes? Just last week came the first report of a person, Liz Parrish, supposedly doing a DIY gene therapy to target myostatin.

Scientists have recently reported a string of super-muscled animals created through genetic modification including GM dogs and pigs.

If this kind of trend continues and increasingly involves people, what might go wrong? One possibility is that GM people who have had the myostatin pathway targeted could have other phenotypes or even diseases that we cannot anticipate.

Claim of risky DIY gene therapy linked to unlicensed stem cell clinic

Elizabeth ParrishIn a strange, but fascinating tale recounted by Antonio Regalado in an article over at MIT Tech Review, we hear the first claim of a do-it-yourself (DIY) gene therapy.

The owner of a small biotech called BioViva, Elizabeth “Liz” Parrish, reportedly traveled from her home in Seattle to get an unapproved, experimental gene therapy in another country.

The article pointed to a Reddit AMA that Parrish recently did where she discussed these events in the context of her interest in anti-aging efforts.

Regalado is fairly blunt about his view of the anti-aging crowd, describing it this way:

“The field of anti-aging research is known for attracting a mix of serious scientists, vitamin entrepreneurs, futurists, and cranks peddling various paths to immortality, including brain freezing.”

In the introduction to the AMA, Parrish is described as, “”the woman who wants to genetically engineer you.” You can read more about her here on her LinkedIn profile.

Below is a video of Parrish discussing anti-aging therapy. She’s clearly very articulate and bright. In the talk she claims that the doctor that she works with at BioViva received an anti-heart disease gene therapy five years ago and is doing well. It’s an extraordinary claim.

She also talks about stem cells and cures for a variety of serious and even fatal diseases such as ALS.

Apparently Parrish’s DIY “therapy” involved two components.

One effort targeted muscle through introduction (presumably through injections of virus?) of the follastatin gene into her muscle. The rationale seems to be that it would inhibit myostatin and give her big muscles. The second intervention reportedly was an IV of “viruses that express telomerase”.

The second one sounds particularly risky given the association between elevated telomerase and cancer. Many things can go wrong with gene therapy and when you combine that with DIY administration it gets even scarier.

Who knows the possible consequences of either of these gene therapies? Even tightly-regulated, experimental gene therapies in the past given as parts of controlled clinical trials have led to deaths. I hope that doesn’t happen here, but if true this situation sounds radical and possibly dangerous.

Still BioViva has had some impressive scientists on board. One, George Martin of the UW, has terminated his link to the company after these recent events. Harvard geneticist George Church, a transhumanist and at times a proponent of human genetic modification, apparently remains on board with BioViva.

By getting an unapproved and potentially dangerous gene therapy abroad, Regalado reports that Parrish was intentionally circumventing the FDA:

“Parrish said in an interview she chose to bypass the U.S. Food and Drug Administration by trying the procedure overseas. The FDA requires costly trials, and aging itself is not generally recognized as a disease that can be addressed by drugs. “What we did is we moved forward to try to treat biological aging,” Parrish says. “We are attempting to reverse aging at a biological level.”

This sidestepping of the FDA was not viewed positively by Church, but he indicated he was inclined to believe that the gene therapy intervention was real. He also has at other times recently been enthusiastic about the concept of a telomerase intervention in people as an approach to aging:

“Church, the Harvard professor, says he thinks targeted DNA changes could in fact extend the normal human life span, which has a maximum length of about 120 years. Earlier this month, at a meeting of the National Academy of Sciences organized to weigh policy on genetic interventions, Church proposed telomerase as one bearing serious consideration. “I think we are very close. I think the world is close, so long as we don’t have a setback,” he says. “The extension of life span is quite dramatic in model organisms … it would be amazing in humans.”

Again, to me the cancer connection with telomerase makes this a dangerous shot in the dark.

This tale gets more puzzling as Regalado points out the involvement of Jason Williams, who is more well-known in the stem cell world for his dubious stem cell clinic (Precision StemCell) that had been located here in the US. He has since moved that abroad after a situation with the FDA. Apparently Williams is also the co-owner of BioViva and he indicated to Regalado that Parrish’s DIY gene therapy took place in Colombia, but not at his clinic.

Parrish seems to espouse a very libertarian view of biomedicine and bioethics:

“We as a company have our own ethics,” she says, referring to what she calls the need for inexpensive gene therapy treatments. “I am certainly not going to ask someone’s permission to potentially create new industries and cures.”

This sounds reminiscent of transhumanism and disruptive technological innovation, but sure seems extremely risky.

It also could set a dangerous precedent for DIY interventions or encourage others to follow this uncertain path. Is this a one-time thing or the start of a larger trend in the world of genetic interventions?