God in a kit: the perils and possibilities of a tool called CRISPR
You may have heard of CRISPR, for all the wrong reasons. You could, for example, have seen a Hollywood monster flick called Rampage that shows you things the gene-editing technology certainly can’t do: make very big versions of a gorilla, a wolf and a crocodile that terrorise humans.
Alternatively, you might have read the far scarier and by all accounts true story of Chinese researcher He Jiankui.
He Jiankui claims he helped make the world’s first genetically edited babies: twin girls whose DNA he said he altered.Credit:AP
That kerfuffle and the near God-like power of CRISPR to reshape the genes of just about any species you can name, from bacteria to butterflies and indeed human babies, brings us to a rather awkward fact: Anybody can now do CRISPR at home.
Simply point your cursor at the website of The ODIN and you’ll be directed to a kit that, for $US159 ($222.50), will furnish you with everything you need from pipette tips, test tubes and the various DNA-splicing proteins that allow you to genetically engineer a version of the E. coli bacterium that is antibiotic-resistant.
You could be forgiven for wondering if placing this kind of kit in public hands is a good thing. After all, former US director of national intelligence James Clapper included genome editing on his 2016 list of global threats on the back of concerns that hostile states could use it to make bioweapons or even engineer Hulk-like supersoldiers.
In 2016, then US intelligence chief James Clapper pointed to gene editing as a major security issue.Credit:AP
As it turns out, there are people who think it might be just fine.
Biohackers at Sydney’s citizen science lab BioFoundry are developing their own home CRISPR kit that will let punters create glow-in-the-dark bacteria. Alex Kelly, BioFoundry’s 26-year-old lab manager and a UNSW graduate with a double degree in commerce and biotech, explains why.
“I’d like to envision a world where things like genetic engineering are more democratised and available to the general public. At the same time I also want to be able to educate people on the risks involved."
Kelly compares biotech to the birth of the computer, once cloistered in big corporations, now at everyone’s fingertips. Upskill the people in biotech, Kelly believes, and you’ll get disruption writ large, with a potentially massive payoff for the most disadvantaged.
Take Big Pharma, where billions of dollars are pumped into blockbuster drugs, while so-called “orphan drugs” for rare diseases never get to market because there are simply too few sufferers to make them profitable.
“There has been a steady and almost cliff-like decrease in the cost of research and development in this space,” says Kelly, pointing out that gene sequencing once costing thousands of dollars now costs $20.
Meow-Ludo Meow-Meow of Biofoundry.Credit:Dallas Kilponen
Those scaled-down economics mean it is now possible, almost unbelievably, to make a medicine in a community science lab in inner Sydney.
As part of the Open Insulin Project, Kelly’s team has synthesised a new analogue of insulin which, if it can pass the regulatory gauntlet laid down by the US Food and Drug Administration, could one day challenge Big Pharma’s monopoly and bring down insulin prices for nearly half a billion diabetics worldwide.
Gilbert’s “Atomic Energy Lab” toy from the 1950s contained actual uranium.
BioFoundry’s flamboyant founder is Meow-Ludo Meow-Meow, a fellow UNSW alumnus with a degree in molecular genetics currently famous for implanting Sydney’s Opal public transport card on a chip under the skin of his hand.
Meow-Meow tells me about other philanthropic BioFoundry projects. One involves engineering a palm oil substitute with the aim of preserving orangutan habitat in Indonesia. Another explores the use of the freshwater fern Azolla to facilitate carbon capture and mitigate global warming.
Lofty aims, no doubt. But they’ll get no closer if young people think science is on the nose, a key reason why Meow-Meow wants the public engaged.
“The benefit is that you get to inspire passion in people … they had science uranium kits in the ’50s, I love this,” says Meow-Meow, who is dismissive of the current benchmark in kid’s chemistry kits: the plastic volcano that explodes courtesy of baking soda and vinegar.
“It’s so sanitised [that] the kids don’t ever get to understand why science is fun.”
No one is suggesting kids start mucking around with radioactivity, but getting them interested in science, technology, engineering and mathematics (STEM) has been flagged as critically important under the Australian government’s National Innovation and Science Agenda.
Melbourne-based Andrew Gray is a director of the Phoenix School Program, a small volunteer-run charity that promotes STEM in schools by donating equipment sourced from research organisations.
“We’re basically like Robin Hood for science equipment, except we don’t steal or wear tights,” he says.
Gray is also a director of DIY bio space BioQuisitive and I’ve come for a visit to see what a citizen science lab actually looks like. His is nestled between a brewery and an ice-cream supplier on the bearded side of Melbourne’s hipster-proof fence in Brunswick.
Despite the location, Gray fronts up clean shaven, with a military-style close crop haircut. Which makes sense when he tells me, across a plain wooden table in the warehouse that houses the lab, that he is ex-US Navy.
Andrew Gray in his shipping container genetic research lab in Brunswick. Credit:Justin McManus
Gray’s trajectory into science took in a year-long tour of duty in Afghanistan, where he faced bombs driving convoys and was embedded as a trainer with the Afghan military. But he also used the internet to take a course in biology, fell in love with it, and came back to Australia to complete a science degree at Monash University.
One of the educational workshops he has run at BioQuisitive uses CRISPR to knock out a hangover-inducing gene in brewer’s yeast.
“Theoretically you could then use this yeast to brew a ‘hangover-free’ beer,” says Gray. For interested parties, none has been brewed to date.
Gray shows me the lab. It’s a shipping container with a sliding door, through which I see lights glimmering on sleek lab benches, like an elongated Tardis for molecular biology buffs. It also bears a very important certificate which reads: “PC1 certified facility.” That means the lab is registered “physical containment” compliant by Australia’s Office of the Gene Technology Regulator (OGTR). In short, you’re good to genetically modify a range of the least dangerous organisms right there.
PC1 certification is no mean feat, requiring box-ticking on everything from how the container is sealed to electrical wiring, biohazard disposal and staff training. I’m wearing sandals and Gray won’t let me inside until I put closed shoes on.
“We teach people about how DNA is this universal language that we all have in common with all life on Earth,” says Gray. One workshop he runs has people extract DNA from random plants they bring in, sequence it, then identify the plant from the DNA database GenBank.
It sounds cool, but Gray has a gripe.
“It’s unfortunate when an entire community of people that are focused on education and responsible access to this technology have to go up against headlines like ‘biohacker does —–',” he says.
“Then people don’t care about us helping out school kids … they care about the scary stuff.”
A biohacker that regularly “does —–” is Josiah Zayner, the body-pierced bete noire of DIY bio who made headlines in 2017 when he injected himself on Facebook Live with a CRISPR concoction designed to knock out the muscle inhibitor myostatin. Chinese researchers made extra-muscly beagles with the same tech in 2015. Zayner, it seems, wished to become similarly ripped.
Josiah Zayner, a former NASA scientist turned biohacker, assembles genetic engineering kits for his biotech company, The Odin, in Oakland, California.Credit:New York Times
But in so doing, the American unleashed a firestorm of criticism from his own DIY bio community.
“His self-experimentation with genetics has done damage to the community and done damage worldwide,” says Meow-Meow. “[It] isn’t the message we should be sending … you can kill yourself.”
As it happens Zayner is also the proprietor of The ODIN and his devil-may-care antics raise questions about their products. Just how safe are the kits anyway? Could, for example, an antibiotic-resistant bug escape into the wild and infect humans?
In 2017 Germany slapped a ban on The Odin kits after analysing them and finding pathogenic bacteria. But these were, apparently, contaminants.
Meow-Meow, moreover, points out that creating antibiotic-resistant bugs is common in gene editing; resistance is often inserted with other genetic changes as a marker that modification was successful.
“It is kind of like saying a carpenter couldn’t have access to a saw because they could use it to kill somebody. If you made it so that scientists couldn’t create antibiotic-resistant bacteria, they couldn’t do any work,” says Meow-Meow.
The ODIN sticker.
If symbolism on a sticker from The ODIN is any guide, Zayner’s enterprise is as much about spreading knowledge as it is commercial. He explains that the “O” contains Yggdrasil, the tree of life in Norse mythology, and the ravens are Huginn (Thought) and Muninn (Memory), who circle the world each day retrieving information for Odin, patriarch of the Norse gods. The "worm" they pass between their beaks is a strand of DNA.
Which raises the question of whether it is even legal in Australia to do The Odin’s CRISPR experiment outside a PC1 lab, say, in your kitchen or garage?
“Kits like the one sold on the ODIN website generally use bacteria that have a long history of safe use in schools, university teaching laboratories and research and are on the OGTR’s ‘exempt dealings’ list. As such, people can import and use the kit without further authorisation under the Gene Technology Act 2000 (GT Act),” a spokesperson for the Department of Health said.
CRISPR at home, then, is officially a thing in Australia.
One of Zayner’s other offerings, however, is less likely to find its way into Aussie garages. “Frog Genetic Engineering Kit: Learn to Genetically Modify Animals” will set you back $US299 and comes with six green tree frogs and a brew of insulin-like growth factor 1 that The Odin claims will make them 25 per cent bigger.
I asked Christopher Gyngell, an ethicist at Melbourne’s Murdoch Children’s Research Institute (MCRI), if he had concerns about the kit.
“I’ve got a million concerns … frogs are sentient creatures with a nervous system. When I look at ethical issues one of the first things to think about is who can be harmed, who can feel pain,” he says.
Ethical questions: genetic engineering kits for sale on the website of The Odin, complete with live frogs.Credit:www.the-odin.com
The capacity of frogs to suffer, says Gyngell, means the experiment may fall foul of animal cruelty laws, while unnecessary experimentation on animals breaches the tenets of animal testing guidelines.
“There has to be a strong goal that you are trying to achieve and you can’t achieve that goal in any way without using an animal,” he says.
And if you’re thinking of ordering one, don’t. I asked the Department of Health if it would be legal to import and use the kit in a typical Australian home.
“[It] cannot be used in Australia without further authorisation under the GT Act,” said the spokesperson. Which is perhaps why The ODIN doesn’t ship that kit to Australia.
So where does the establishment sit on the question of editing genes at home? Sara Howden is joint director of the gene editing facility at the MCRI and an authority on CRISPR.
Howden took me on a tour of her lab, a sprawling state-of-the-art space that seems as expansive as the Royal Park acreage it overlooks. Andrew Gray’s shipping container would fit neatly in a corner and there are no donated goods in sight. Rather, Howden shows off a 3D bioprinter, the first of its type in Australia, recently launched by Federal Health Minister Greg Hunt.
Howden’s team takes stem cells from patients with genetic disorders such as polycystic kidney disease and uses CRISPR to try and correct the defect. By directing the stem cells to form mini-kidneys in a dish, Howden can see if the gene therapy worked; the new bioprinter makes those replica kidneys even more accurate.
A decade ago Howden was using pre-CRISPR tech to correct gene mutations causing retinal disease. It took years.
“Where CRISPR has changed things is now we can do that kind of study, now we can correct that mutation, in a few weeks,” she says.
I asked Howden about Zayner’s myostatin experiment. She cited plenty of reasons why it was unlikely to work, a big one being DNA that doesn’t hitch a ride on a “viral vector” would reach very few muscle cells.
That explanation came with a salutary warning: using viruses to deliver DNA can have catastrophic results, including cancer and something called “cytokine storm”, a massive and often deadly immune reaction.
“If we start getting biohackers that are making large quantities of genetically modified viruses in their backyards, then it becomes next-level scary,” says Howden.
How likely is it, then, that a major discovery could ever come from a citizen science lab? Howden doesn’t know, but she can list the hurdles.
“It’s expensive. That is a major obstacle. And training and collaboration,” she says.
“We have experts across many different fields that collaborate on huge teams and that’s reflected in the publications that you see today. You don’t really make major breakthroughs when you’re working in a silo, let alone in your back yard.”
A 2015 physics paper, for example, lists more than 5000 authors. On that note, Howden extends an invitation.
“The odds are against them in that environment, but I love the passion. Bring those people this way, you know, let’s work together.”
Is she fair dinkum? “Absolutely,” says Howden.
As for whether anyone takes up the offer, you’ll just have to watch this bio space.
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