Biohacking and DIY Gene Therapy: Revolution or Hi-tech Snake Oil?

Do you want bigger muscles? Want to make those brown eyes blue? Does your memory resemble a slice of Swiss cheese? Well, step right up and let me tell you about biohacking! Lend me your ears…and I’ll tell you how to improve them! With our new do-it-yourself genetic engineering kits, you can change whatever genes you want!

Bio-savvy entrepreneurs are determined to make biohacking a mainstream activity. Companies are emerging that promote DIY gene therapy, so now anyone with an opposable thumb can pipet DNA changes into their bodies, their pesky little sister, pets, or just about any living creature they encounter.

Wouldn’t you like to be a biohacker too? Or is biohacking just the latest incarnation of snake oil?

Josiah Zayner, who earned his Ph.D. in biophysics in 2013 at the University of Chicago, is founder and CEO of a company called The ODIN. The main objective of the company “is to make biological engineering and genetic design accessible and available to everyone.” Some of the products on the site look downright cool. One kit allows users to produce bioluminescent bacteria. Another kit makes fluorescent brewer’s yeast (which can then be used to brew beer that glows under blacklight).

Those products seem benign compared to Zayner’s ultimate objective: selling genetic engineering tools to the masses so they can modify their own genes, or those of other living creatures, in whatever way they want without any oversight or regulatory approval. Zayner has already initiated experiments on himself and encourages others to join him on this wild ride. In the rambling presentation below, Zayner explains over shots of scotch and F-bombs that he wants to crowdsource genetic engineering because he believes it will facilitate innovation. Why let professional scientists have all the fun? Zayner demonstrated how easy biohacking your genome can be by injecting the reagents into his arm during the presentation and distributing free samples for the audience to take home.

Let’s take a closer look at his idea. Zayner is using CRISPR/Cas9, a powerful new tool for gene editing, to disable his myostatin gene (learn about the basics of CRISPR/Cas9 and its application in gene therapy). Cas9 is a DNA-cutting enzyme that is directed to a specific site in DNA by a guide sequence. Myostatin stops muscles from growing, so his plan is to knockout this gene in his muscle cells in hopes that it will make them grow once again. Given his affinity for scotch, a more useful experiment might have been to enhance his alcohol dehydrogenase genes.

There is evidence linking the depletion of myostatin to muscle growth. Mice engineered to lack myostatin have double their normal skeletal muscle mass. CRISPR/Cas9 has been specifically used to knockout myostatin in animal embryos, such as rabbits, and the genetically modified animals grew to have more muscle mass. Moreover, when humans are born with mutations that lead to less functional myostatin, they also have more muscle mass (or, in less pleasant-sounding medical terms, “gross muscle hypertrophy”).

CRISPR has already been used to successfully modify human embryos (none were implanted), but to date, no one has tried CRISPR/Cas9 in a living adult. Zayner’s strategy is to simply inject plasmid DNA that contains the Cas9 gene along with the guide sequence that directs it to the myostatin gene.

Importantly, he’s produced no evidence yet to show that these reagents work in human cells. Ideally, we’d like to see confirmation of the gene modification in a muscle biopsy from Zayner, or proof that his approach works in an adult animal model. At the very least, it would be useful to know whether his system alters the gene in cultured cells.

So, can this really work? There are some formidable obstacles and shortcomings. First, the injected plasmid DNA has to get into the muscle cells. Many would argue that the DNA is likely to be degraded or damaged along the way. There is scarce evidence that intramuscular injection of DNA works, but I did find one study done in mice from 1993 suggesting it is possible, although expression levels of the gene injected in this mouse study varied. Variations in the levels of Cas9 or the guide sequence would certainly affect the outcome.

Nevertheless, let’s pretend some of it gets into a few muscle cells and they make the Cas9 protein and its guide sequence. The next big assumption we have to make is that the guide sequence used actually cuts the myostatin gene. Multiple guide sequences usually have to be tried to find one that works and, as mentioned above, I’ve seen no evidence that this particular guide sequence operates as it should in human cells.

Additionally, you have two copies (alleles) of myostatin, one from mom and one from dad. To knockout myostatin completely, Cas9 would have to cut both alleles. Let’s assume we get that far and both alleles of myostatin are cut. Sometimes cells can repair the DNA cut without incident. For myostatin to be disabled, the cell would have to make a mistake when repairing the severed DNA (which they do, but not all the time). Assuming we jump all these hurdles, that one cell or handful of cells is not likely to produce any noticeable change in muscle mass, especially if only one allele was disabled. Zayner claims repeated injections might overcome this issue, but given the sheer number of cells that would need to be altered to produce a visible effect, the claim seems to be on very shaky ground.

Despite all the caveats, disrupting a gene is actually the easiest application of CRISPR/Cas9. To add or change a genetic sequence, an additional fragment of DNA needs to be incorporated where Cas9 made the incision. And if you wanted to use CRISPR/Cas9 to give yourself wings or eyes in the back of your head, you can forget about that. We are nowhere close to knowing how to do such things.

More alarming, there is risk of dangerous side-effects. While the loss of myostatin will increase muscle size as well as bone mineral density and bone mass, it also leads to spinal disc degeneration and spinal osteoarthritis. Second, there is a risk of infection or an allergic reaction to the injections. Third, CRISPR/Cas9 has been reported to produce so-called “off-target” effects. In other words, the guide sequence sometimes escorts Cas9 to other places in the genome, where it may introduce cuts in genes that were not intended to be destroyed—a genetic equivalent of friendly fire.

There’s also the possibility that the CRISPR/Cas9 plasmid itself could integrate into the genome, again possibly disrupting critical genes. One study showed that DNA injected into mouse muscles persisted for life, cranking out the protein constantly. What would happen if Cas9 continues to be produced in Zayner’s cells for the rest of his life? In the worst-case scenario, it would continue to cut up his DNA indiscriminately. There’s also a study in mice suggesting that DNA injection can accelerate autoimmune responses. Finally, unlike injecting an embryo in which all cells have a high probability of being modified, Zayner’s approach is going to produce mosaic effects. In other words, some cells will be edited, but others will not, which could result in a disfigured arm. Zayner dismisses all of these risks with disquieting nonchalance.

If you don’t want to risk modifying your genome to kill your myostatin gene, you can always buy inflatable muscles to wear under your shirt.

Zayner not only advocates genetic modification of your body, but he also encourages biohacking all of nature. He paints a world where you and your buddies decide to order a pizza one night and, what the hell, genetically engineer a puffin to look like a porg. Eschewing the substantial ethical concerns, he is understating the difficulties surrounding genetic modification of complex animals and the sophisticated equipment and training needed to do it. Below is an excellent TED Talk by Ellen Jorgensen that examines the hyped-up claim that CRISPR/Cas9 is cheap and easy.

There’s no product currently available from The ODIN that could bring on the apocalypse, but it is the principle that concerns many people, scientists and non-scientists alike. Even the most avid science enthusiasts are likely to take issue with providing potential crackpots the tools to screw with the recipe of life. Genetic engineering is exciting and promising, but must be explored with great caution by well-trained professionals following reasonable regulations because there is no way to unscramble this egg.

Biohacking has been banned in several countries, and on November 21, 2017 the FDA updated their web site to state that self-administration of gene therapy is against the law. It seems that Zayner, a self-professed fan of the TV show Survivor, just had his torch snuffed out by government regulators chanting, “The tribe has spoken.”

Contributed by:  Bill Sullivan

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The author thanks Colin Sullivan for research assistance and helpful discussions, and Jason Organ for editing and helpful suggestions.