Josiah Zayner took a swig from his beer and squinted into the spotlight. He was already kind of drunk. He also hadn't bothered to write a speech. Tattooed and heavily pierced with a shock of blue-grey hair, he shuffled around uneasily on stage. But 150-odd people had flown in from around the US to hear him speak - the mad pirate-king of biotech.
"It all is coming from my heart," he said, choking up a little. "Everything you're going to hear today is me to the core."
Zayner's audience sat in the fashionably decaying ballroom of an old garbage collectors' social club in Oakland. They had come from universities, startups and do-it-yourself garage biolabs, united if not by a love of citizen science then by a curiosity as to what it is exactly that Zayner is up to. A computer nerd turned NASA scientist turned establishment-science cynic, Zayner is something like the self-appointed leader of a small but burgeoning biohacking movement. He presides over a loose coterie of professional and self-taught scientists who believe that ground-breaking science does not require either a fancy lab or degree.
Zayner was about to talk about his attempts to genetically modify his own body, an endeavour likely to raise at least a couple of eyebrows, including the US federal government's.
But first, he was going to talk about his soul and the sanctity of science. The audience listened with rapt attention.
"This is our world now, the world of the base pair and the amino acid, the beauty of the protein," he began, extolling the dawn of an era defined by synthetic biology and its advancements in understanding the underpinnings of life. He projected the 1986 Hacker Manifesto onto a towering screen behind him. Zayner frequently draws parallels between early computer hackers and today's DIY biologists: Tools such as genetic engineering are poised to drastically reshape our world, and he believes that biohackers could be the ones to free them from the ivory tower. He began to read aloud from the manifesto as if delivering a scientific sermon, swaying back and forth, possessed by the weight of the words. His voice grew closer to a shout with every line.
"We explore and you call us criminals," he read, quoting the manifesto. "We exist without skin colour, without nationality, without religious bias, and you call us criminals. You build atomic bombs, you wage war, you murder, cheat, lie to us and try to make us believe it's for our own good, yet we're the criminals."
At the time, no one had actually called him a criminal, but months later, a warning issued by the FDA would give his reading more meaning.
He turned to the crowd for a dramatic finish.
"Yes I am a criminal," he read. "And my crime is that of curiosity."
Applause erupted. Zayner took another gulp from his beer.
"This literally says 'Not for use in humans.'"
That was August. A few months earlier, I sat at a workbench in Zayner's nowhere-near-sterile headquarters and lab in West Oakland as he ripped dead skin cells off his forearm with duct tape in preparation for an experiment. He wanted to genetically modify his body's skin cells to turn them a darker colour - not his whole body, but a small, circular patch of skin that would wind up looking like a henna tattoo if it actually worked.
First step: Assault himself with duct tape. Next, he would spread a DNA plasmid containing the enzyme tyrosinase over his skin in order to spur his body's production of melanin and (fingers crossed) persuade a small patch of skin on his left forearm to turn a slightly darker shade of pasty-pale. At least theoretically, the plasmid should sink into his skin, penetrate his skin cells, and cause the cells to begin overexpressing the tyrosinase gene, increasing the amount of skin colour-causing melanin in that one circle-shaped spot. He was riffing off a paper he'd read in which scientists used a similar topical gene delivery method to give a different gene to mice.
"The interesting thing is, if it works, will it last?" Zayner told me, a GoPro strapped to his head and a Hell or High Watermelon beer on the table as he filled a pipette with the DNA mixture to spread over his skin. "Or will it be like a suntan and it will just fade away?"
Zayner, 36, has a PhD in biochemistry and biophysics from the University of Chicago, but a few years ago he decided to quit the scientific establishment - and a fellowship at NASA - to devote his time to selling inexpensive DIY bio supplies online, seeding the biohacking revolution one made-in-China pipette sale at a time. Hawking kits for DIY genetic engineering and basic science supplies to both hobbyists and schools, Zayner says that this year his company, The Odin, pulled in about $US500,000 ($658,900) in gross revenue.
When the genetic engineering technology CRISPR arrived on the scene in 2012, promising to make genetic engineering simpler, faster and cheaper, it galvanised an already simmering hobbyist niche of DIY scientists who sought to try their hands at genetically modifying plants, insects, animals and even humans. Zayner views genetics as the ultimate equaliser: He dreams that one day we will no longer be bound by the DNA we are born with, every person free to hack their own genome to augment their intelligence, change their eye colour, or even cure the diseases that ail them with the same ease as, say, building a Squarespace website. That future is still more than a little way off. But recent years have seen enough scientific progress to make Zayner's dream feel more mildly crazy than full-scale wacko. This year, the US Food and Drug Administration approved what it called the "first gene therapy", a treatment for childhood leukaemia that works by genetically modifying a patient's own blood cells. And in November 2017, in a major feat, researchers genetically altered a man's cells while they were still inside his body. In the meantime, Zayner is doing what he can to help a future of recreational CRISPRing arrive by experimenting on himself.
Each experiment has gotten increasingly bolder, the risk higher.
Last year, he made headlines for undertaking his own DIY faecal transplant in an attempt to treat stomach issues that had for years been giving him hell. At the time, experts said the chance that it would do anything other than make him seriously ill was essentially zero. Zayner says it worked. Independent lab sequencing done after the procedure found that the bacterial makeup of his own faecal matter had become more similar to that of his donor, and the state of his bowel movements drastically improved. But, as with most things Zayner does, his experiment lacked the rigour typical of scientific research. There were not multiple study participants or control groups or even a perfectly sterile environment, making it hard to draw any firm conclusions about the experiment, or deduce how it might work out long-term.
Then earlier this year, he infused his skin cells with green fluorescent protein from a jellyfish in an attempt to make his skin glow. The experiment failed to successfully turn him into a living nightlight, but a skin biopsy revealed that at least briefly the protein was replicating within his body, making him in all likelihood the first human-jellyfish hybrid. The experiment I was there to witness was even more extreme.
"Green fluorescent protein doesn't really interact with anything in your cells, it just goes in there and fluoresces," he told me. "The crazy thing about this one is it's actually going to modify the metabolism of my cells a little bit, which is a little scary."
He held up the vial containing the DNA and winced. "Oh god, this literally says 'not for use in humans,'" he said.
The gene Zayner was about to put into his skin cells sometimes occurs in abundance in dark moles that can become cancerous. "They found no association between it and cancer, but they found it as a marker for cancer. It's present at the scene of the crime," he said.
Presence at the scene of the crime was not enough to sway him: "I trust the science that's out there, and I think it will be mostly OK," he said. Even if his auto-experimentation did wind up giving him cancer, he rationalised that it would be possible for a doctor to treat. He was only applying the DNA topically to a small patch of skin, and felt it was likely that unwanted side-effects would be isolated to that patch of skin as well.
"If something goes wrong, I can just chop off that part of the skin," he said.
But really, when you're doing something that's never been done before, it's impossible to predict what could go wrong.
Zayner had originally planned to inject himself with a new gene using the buzzy CRISPR-Cas9 gene-editing system, but decided at the time that it was too risky.
"Once you inject it, then it will start to go into your bloodstream and that might be a little more dangerous," Zayner said as he spread the DNA on his arm, then dried it on his skin using a soldering tool. "I thought, if this works and I get cancer, will I think to myself, 'Well, this was totally worth it to get and die of cancer?' The answer was no."
Apparently, he changed his mind. Five months later, I sat in the audience at a biotech conference as Zayner jabbed a needle containing CRISPR-Cas9 and a gene to promote muscle growth into his left forearm.
CRISPR is a nascent technology compared to other genome engineering strategies, and the scientific literature has suggested that using it sometimes produces unintended effects.
"I kind of have this motto now that if everyone believes something, then I should research the opposite," he explained to me later. Once, he told me, he too had believed that using CRISPR was too dangerous because it could result in too many unintended effects. Then he dug into the research. He said the data he found persuaded him that the potential off-target effects of CRISPR had been over-hyped. How numerous or severe those unintended edits are has been a subject of significant scientific debate, and some scientists share his opinion that fears have been overstated. Still, injecting yourself with CRISPR when there's even any debate about whether it might give you cancer sounds like a terrible idea.
Zayner disagrees. He used to smoke, a habit with a well-documented risk of cancer. He imagines the odds of giving himself cancer with CRISPR are probably lower. (We really do not know if that could be true.) He wonders why smoking is relatively socially acceptable but genetically engineering yourself for fun is not.
Genetic engineering still isn't exactly easy - it's more complicated than pouring some stuff into a test tube and mixing. But anyone can use software such as DeskGen to design custom DNA sequences and then order that DNA on the internet. Places such as eBay now sell used lab equipment for a few hundred dollars instead of many thousands. For $US159 ($210), The Odin sells a kit containing everything you need to make your own glowing yeast. For $US382 ($503), another company, Amino, sells a table-top lab called the DNA Playground that looks like a Fisher Price toy, but enables anyone to "engineer bacteria like a professional".
The garage in Burlingame that was The Odin's home before it moved to Oakland. Image: Courtesy Josiah Zayner
Zayner isn't the only one hoping to spur a DIY bio craze. The number of community science labs in the US has grown at a rapid pace - starting with the opening of Genspace in Brooklyn in 2010 - creating formal hacker spaces to gather and learn new science. Zayner isn't even the first person to undertake unregulated genetic engineering. Last year, BioViva CEO Liz Parish turned herself into patient zero for an anti-ageing therapy her company is researching. And microbiologist Brian Hanley gained attention earlier this year for attempting gene therapy to strengthen his body.
But few have pushed the boundaries of biohacking as consistently - or as publicly - as Zayner. He has helped terminal cancer patients attempt to create their own personalised treatments based on experimental research (though it's a longshot that those treatments will work). Along with injecting himself with CRISPR, he published a "DIY Human CRISPR Guide" online and began selling the same DNA that promotes muscle growth he had injected into himself for $US20 ($26). (The FDA would not comment on the legality of any specific products.) He has sparred with German regulators trying to ban his CRISPR kits from Germany and FDA regulators trying to ban a kit to make glowing yeast in the US. He rails on Twitter and Facebook about what he sees as the failures of science as practised in the exclusive, closed-off laboratories of industry and academia.
"All my friends right now are working postdoc jobs earning $40,000 [$AU52,712] a year with their PhD. It's this cultish system and the idea that one day they could have their own lab holds them in it," he told me nearly two years ago, when I met him for the first time. Just maybe, he hopes, building a strong do-it-yourself community can begin to chip away at the patina of exclusivity and democratise science for all. "I'm just like fuck the system," he said. "Science is a classist thing. DIYbio can break that down."
Zayner has unsurprisingly cultivated a fair number of detractors. The FDA cracked down on kits Zayner sells to brew glowing beer and, while there aren't specific US laws to prevent someone from experimenting on themselves, the agency generally frowns upon anyone doing anything to their body that has not been thoroughly tested and agency-approved. Just this month, the agency issued a stern warning clearly intended to dissuade do-it-yourselfers.
"FDA is aware that gene therapy products intended for self-administration and 'do it yourself' kits to produce gene therapies for self-administration are being made available to the public," the agency said. "The sale of these products is against the law. FDA is concerned about the safety risks involved." (When asked to comment on Zayner specifically, the agency declined and referred me to its statement.)
The German government also sparred with Zayner, placing an import ban on supplies from his company after it claimed to find a pathogen contaminated one of his kits. (Zayner believes the contamination did not originate in his lab. He says sequencing other samples from his lab revealed nothing problematic.)
"Josiah is a good entertainer and performance artist but not a good bio supplier," one European biohacker told me.
Zayner is a showman, and not everyone in the DIY science community is a fan of his tendency toward flash. After his recent CRISPR self-injection stunt, one critic in a Google group for DIYbio called Zayner a "moron".
"He grossly misrepresents the technical difficulty of (DIY) human CRISPR, apparently for the sake of a 'cool' narrative," another biohacker wrote. "I know it's an easy trap to fall into in the world of DIYBio, but I'm not a fan of that kind of thing. I find it dishonest."
Another told me the whole thing "didn't leave a very positive impression".
But surprisingly, Zayner has also garnered a fair amount of respect within the scientific establishment - more than you would expect for a guy whose main mission is to knock the establishment down a peg. The famous Harvard geneticist George Church recently signed on as an adviser to Zayner's company.
"I'm very big on citizen science and DIY bio," Church told me. With all of the ethical quandaries sophisticated science is sure to bring about in the near future, Church hopes people such as Zayner can help make science more accessible to the general public.
"He's doing us a service," Church said. "Which doesn't necessarily mean nothing will go wrong."
Tao Pan, a professor of biochemistry and molecular biology at University of Chicago who was close to Zayner as a grad student and sat on his thesis committee, told me he thought the path Zayner's career has taken is "totally cool" and praised him for "always thinking outside the box". He had seen a YouTube video of one of Zayner's genetic modification experiments, and said he wasn't particularly concerned by it.
"People will do things because they can," Pan said. The bigger question though, is not whether you can, but whether you should.
Shock at what a self-taught scientist can accomplish with just a few hundred dollars of lab equipment has caused some to wonder whether DIY biology should require licensing and regulation, or perhaps be stopped altogether. Zayner has welcomed the discussion. At the second installation of his biohacker conference this winter, Zayner invited Stanford biosecurity expert Megan Palmer to give a talk on biohacking safely and scheduled a discussion between a prominent biohacker named David Ishee and Stanford bioethicist Hank Greely (disclosure: I moderated that discussion).
Greely told me later via email that he found Zayner "surprisingly interesting and enjoyable to talk with - and surprisingly reasonable. Ish."
Zayner's willingness to engage has gradually won over many of his critics, at least in part. Still, said Greely, he thinks Zayner's commitment to DIY science is fundamentally misguided, both because DIY bio is "unlikely to become important" and because if it did, it is "likely to cause more harm than good".
"I could be wrong, he could be right, but my hope is that his strong and subtle mind will eventually become less attached to DIY and instead turn to designing an ecosystem for bioscience development that is safer than DIY, but more democratic and open than the status quo," Greely said.
He added: "I'd much rather be working with him than against him."
Zayner may present publicly as a daredevil hacker with zero limits, but over time his views have drifted more toward the centre. Recently, he took out some of his piercings and dyed a previously blue stripe of hair grey, thinking it might help him look just a bit more, well, mainstream. He hopes that, one day, the movement will become robust enough that he can quit drawing attention to it by experimenting on himself. While trying to give himself a genetic tattoo, initially he had planned to use a machine that delivers an electric shock in order to help the new DNA make its way into his own cells. He decided against it, realising he needed to run tests to figure out how to do it without accidentally, say, shocking his heart.
"Don't tell people I'm not crazy," he told me.
He's critical of his two predecessors in DIY genetic modification because he says they did it in such a way that there's no real way to verify whether their experiment worked. And when last month a fourth person genetically engineered themselves, injecting themselves with a vaccine meant to suppress HIV on Facebook Live, Zayner shook his head at the unscientific approach. For starters, he said, the gene they were using had never been tested in humans, it appeared no one had read the paper the experiment was based on, and they hadn't consulted experts, putting them in dangers of creating a treatment that could seriously hurt someone.
"I mean don't get me wrong I think this is awesome," he added in a conversation over Facebook Messenger. "Like fuck, Monday night and a random live stream of DIY gene therapy. What's next? I am excited."
On a recent visit to his lab, he showed me some other things he's been working on, including culturing his own cheek cells in a non-sterile environment. If he grows enough of them, he told me, he could spin the cells down in a PCR machine to create a more solid mass, fry them up and basically have human meat. A Google doc titled "Ideas" that Zayner shared had many pages more of decidedly outside-the-box ideas including creating an organism from scratch to make it "more optimal", "protein from bacteria for humans to consume", "make crops grow as tall as a tree", and one idea that simply read "dragon skin".
"So now the fun begins."
After five or six applications, his skin colour-engineering project seems to have failed. It's still unclear whether his CRISPR experiment will work. There's a good chance it won't.
"Fail hard and fast so you can figure out what it takes to succeed," he told me. "Sounds like something some Silicon Valley arsehole would say, but it's true."
For Zayner that isn't exactly the point anyway. His real undertaking has been to expand the reach and popularity of garage biology, in part of turning himself into the figurehead of it. The genetic engineering revolution is still early days. Biohacking's Bill Gates or Steve Jobs have yet to emerge. It's still 1957 and hobbyists are making computer memory by wrapping magnetic tape around a copper wire. We have a long way to go before anyone's building biohacking's equivalent of the Apple I in their garage.
Since the infamous biotech conference in which Zayner injected himself with CRISPR in front of an audience, he claims he's received "literally hundreds" of emails wanting to give it a try.
"The barrier of possibility is broken," he said, "So now the fun begins."
Before that, Zayner told me he had ordered the follistatin gene and was simply planning to put it in syringes and pass it around. He was betting that would probably be shocking enough.
His workshop at SynBioBeta - provocatively titled "A Step-By-Step Guide To Genetically Modifying Yourself with CRISPR" - was in a small room that was packed shoulder-to-shoulder, the crowd spilling out into the hallway. One of the documentary crews that seem to perpetually follow Zayner around was there. As people entered, he passed out shot glasses that said "biohack the planet" filled with shots of scotch. CRISPR-filled tubes of DNA were on the table, along with printed how-to guides for genetically modifying a human. True to form, Zayner began his talk with a gulp from a copper-coloured flask.
"I created this DNA in five minutes. If that doesn't blow your mind, I don't know what does," Zayner said, gesturing to the syringes. "I have this really bad snaggletooth. What happens if I could change that? We just tell people that they lost the genetic lottery. Meanwhile, we use the most terrible genetic engineering of all time: Sex."
Zayner rambled well over his allotted half-hour about the work he had been doing, the DIY CRISPR guide, and his fantastical vision for a world when anyone could create their own genetic destiny.
"What's stopping us from all putting this in our scotch and getting jacked right now," he said, gesturing again to the syringe full of muscle-boosting DNA.
A woman in the audience, an EPA employee, asked Zayner what was holding him back from trying his instructions out himself. Zayner accepted the challenge. (He later told me, "I was still scared and nervous when I injected myself. I almost didn't do it.") He picked up the syringe and jabbed it into his arm.
"I'll let you know how it turns out," he said.