Most of us have found ourselves ordering something off the internet before. And, in the world of online retail, virtually anything you could want can be sent to your doorstep at the click of a button. But, what about a do-it-yourself gene therapy kit? Despite probably not being the first thing that comes to mind, a growing subculture of people are on a mission to change this.
The process of scientifically altering your body at home, or ‘biohacking’ as it is known, has been gaining traction over the past few years. It has garnered a lot of media attention, too, and with good reason. One self-professed biohacker injected himself with an untested herpes treatment live on stage, with another administering an equivalent attempt against HIV whilst sat on his sofa. The man who started this trend of stunts, Josiah Zeyner, was livestreamed dosing himself with homemade DNA intended to genetically enlarge his muscles. You can even buy this concoction yourself from his website at a cost of twenty dollars.
Controversy aside, biohacking could well be a glimpse of how gene therapy will fit into future society. Is it really conceivable that we could one day live in a world where this self-administered genetic modification is available at the drop of a hat? Where a whole host of debilitating and currently incurable disorders could be eliminated by means of a simple injection? Clearly, this is a massive oversimplification of the matter, and an optimistic one at that. In order to really understand why this utopia isn’t yet a reality, we need to take a look at the science behind biohacking.
In Zeyner’s case, the target of his creation is the gene for a protein called myostatin. Myostatin acts on muscle cells to prevent their growth, to ensure that they don’t become too large. It does this through two methods of action. The first is by acting on immature muscle cells, known as myoblasts, to prevent them from fully developing. The second is by inhibiting an enzyme called protein kinase B, disrupting a sequence of protein synthesis reactions that would otherwise lead to increased muscle size.
If there is a genetic mutation preventing the production of myostatin, both muscle mass and strength are greatly increased. This is what the gene replacement was aiming to emulate.
The technology used to create the therapy is an adaptation of bacteria’s natural defence against viruses, rather cumbersomely named CRISPR-Cas9. There are two key elements involved in this highly effective and versatile method of genetic manipulation: guide RNA and Cas9.
Cas9 is an enzyme with the ability to cut DNA, like a pair of molecular scissors. Guide RNA tells the Cas9 the exact point along the DNA strand that it should cut. The cell’s own repair machinery then recognises that the DNA is damaged, and so is able to make changes to the DNA at this point in the genome. It can be said that CRISPR is akin to a biological Swiss army knife – it can add genetic material, delete it, or replace a given DNA segment with a customised one.
Unfortunately for Zeyner, his injection doesn’t appear to have delivered any observable results. See, there are several hurdles which have prevented human CRISPR from achieving success as of yet. CRISPR complexes such as his are often not taken up by cells, and when they are, success rates are highly variable. Inhibiting myostatin production in a small number of muscle cells isn’t going to have a singnificant effect when millions more are still producing the protein. Cas9 can also make cuts at points in the DNA where it isn’t supposed to, which has the potential to cause cancer.
However, if developed properly, the potential benefits of human CRISPR are enormous. Zeyner’s myostatin-inhibiting therapy could even serve a much more medically significant purpose than just being a shortcut to a bodybuilder’s physique. Cachexia, which refers to the involuntary wasting away of the body, is a common and often devastating problem in the advanced stages of cancer. Wei et al observed that mice with cancer cachexia treated with myostatin knock-out CRISPR had an increased grip strength and a visible alleviation of muscle wasting. Similar problems such as sarcopenia, which describes muscle wasting with age, and genetic disorders such as muscular dystrophy are some other potential targets of myostatin inhibition. This array of benefits could all come from the alteration of just one, single gene – MSTN. Given that current estimates place the number of protein-coding genes in humans at 19,000, the enormous therapeutic potential CRISPR is put into perspective.
Of course, this is all a far stretch away from the novel creations of today’s biohackers. Perhaps their actions do have some use for the future of science, though. Amongst the general public, there does exist an undertone of mistrust towards gene therapy. It is often viewed as a morally dubious practice resigned to top secret labs, with sensationalist headlines about ‘designer babies’ doing nothing to help tackle the issue. However, is the complete opposite approach of unregulated DIY biohacking a better alternative? Probably not. But, as misguided as many biohackers may be, the transparency and accessibility of their livestreams and blog posts might just serve to bridge the gap between the lab and the average person. And who knows – maybe one day in the distant future, gene therapy will be as simple as a quick injection.
Ezkurdia I, et al. Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes. Human Molecular Genetics. 2014;23(22):5866–78.
Glass DJ. PI3 Kinase Regulation of Skeletal Muscle Hypertrophy and Atrophy. Curr Top in Microbiol and Immunol. 2010;346:267–78.
Wei Y, et al. Prevention of Muscle Wasting by CRISPR/Cas9-mediated Disruption of Myostatin In Vivo. Molecular Therapy. 2016;24(11):1889–91.
Zhang S. A Biohacker Regrets Publicly Injecting Himself With CRISPR [Internet]. The Atlantic. Atlantic Media Company; 2018 [Accessed 2018Aug6]. Available from: https://www.theatlantic.com/science/archive/2018/02/biohacking-stunts-crispr/553511/
By Olivia Greatbatch
Medical Student; University College London