Biohackers are pirating a cheap version of a million-dollar gene therapy

Citing the tremendous cost of new drugs, an international group of biohackers say they are creating a knockoff of a million-dollar gene therapy.

The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a price tag of $1 million per treatment. Glybera was the first gene therapy ever approved to treat an inherited disease.

Now a band of independent and amateur biologists say they have engineered a prototype of a simpler, low-cost version of Glybera, and they plan to call on university and corporate scientists to help them check, improve, and test it on animals.

The group says it will start sharing the materials and describe their activities this weekend at Biohack the Planet, a conference in Las Vegas that hosts citizen scientists, journalists, and researchers for two days of presentations on body implants, biosafety, and hallucinogens.

“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.

Experts briefed on the biohacking project were divided, with some calling it misguided and unlikely to work. Others say the excessive cost of genetic treatments has left patients without options and created an incentive to pirate genetic breakthroughs.

“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”

This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.

Disrupting the narrative

The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment. 

Andreas Stürmer, a biotechnologist and environmental engineer who is based in Linz, Austria, says that after the idea of reverse-engineering the treatment occurred to him, he brought the concept to Licina. Their collaboration, which took place through Facebook messages and Skype calls, included help from David Ishee, a biohacker in Mississippi.

In another recent example of copycat gene therapy, in 2018, a biohacker in Florida produced and ate an oral gene therapy for lactose intolerance using a 20-year-old scientific paper as a recipe. 

“It’s about disrupting the narrative,” says Licina, also the cofounder of SciHouse, a community biotechnology lab in Indiana. “It was like, ‘Well, why the f*ck not?’”

One reason not to is that copying and selling the drug could infringe on UniQure’s intellectual property. Tom Malone, a spokesperson for UniQure, says the company had not been informed of the biohacking attempt. He says it still owns a patent on the drug but does not believe there is strong demand for the treatment. “To that end, a ‘knockoff’ version of Glybera would likely face significant regulatory and commercial hurdles,” says Malone.

Also, the US Food and Drug Administration has said it is illegal to sell do-it-yourself gene-therapy supplies. Still, some biohackers feel confident grabbing information from published papers, even if some of it has been patented. “This thing is protected 10 different ways,” says Ishee. “I don’t care. Because I’m not selling it.”

Get the job done

To make their knockoff, the biohackers checked the original Glybera papers for the information about the genetic sequence of the gene that patients require corrected copies of. They placed an order with a gene synthesis company for a copy of the DNA, which was added to a circular genetic construct called a “minicircle.” When added to a cell, the mincircle will begin manufacturing small amounts of the lipoprotein lipase enzyme.

That is an important difference from the original Glybera, which employed an injection of viruses into the leg muscle to deliver the gene. Viral delivery is a complex undertaking, but it is the most commonly used strategy in gene therapy. The biohackers don’t have access to viruses because of their high cost, but they say minicircles can potentially be injected, too.

Robert Kotin, an expert in gene-therapy production, calls the minicircle technology controversial and says it has shown contradictory results. While minicircles, unlike viruses, could possibly be readministered time and again, they are not as efficient in getting cells to follow genetic instructions.

“It’s not the same, [but] it can get the job done. It’s just less efficient,” says Ishee of the minicircles, which are based on his design. He thinks they could be injected over a period of half a year. “It’s like if you wanted to dig a swimming pool or a pond—you could buy a backhoe and dig it in a day, or you could do it with a shovel at no cost over several months.”

Biohacking claims

This isn’t the group’s first time making a splash with genetic tinkering claims. Ishee has tried (unsuccessfully) to modify the DNA of dogs, and Licina and Stürmer were involved with a startup company called Ascendance Biomedical whose CEO, Aaron Traywick, injected himself with an untested herpes vaccine in 2018, prompting a wave of criticism.

Traywick was later found dead in a flotation tank. His drowning was ruled accidental and not related to his gene experiments.

This time, the team is taking steps to show that their genetic invention, which they are calling “Slybera,” should be taken seriously. At the Las Vegas event this weekend, they will be calling for help to test their version of the treatment on animals, something they say is too expensive to do themselves.

“I’m not saying that we have a completed gene therapy,” says Licina. “Only that we have one piece.” Currently, the group says Slybera is not ready for patients and needs further development.

Painful disease

Since Glybera was pulled from the European market two years ago, patients with the fat-storage disease it treats, known by the abbreviation LPLD, have not had many options.

Usually diagnosed in childhood, LPLD is characterized by the presence of fat particles in the blood, making it look creamy white. Patients face a lifetime of strict diets and must abstain from alcohol and sugar or face side effects like excruciating pain from pancreatitis. Many female patients are unable to have children. 

“These severe dietary restrictions are very isolating,” says Jill  Prawer, the founder of LPLD Alliance, a patient advocacy group in the United Kingdom. “I was hugely disappointed when Glybera was taken off the market … but I don’t know enough about biohacking, especially about its safety and efficacy—or its legality.”

Prawer wonders “how central the patient’s safety, welfare, and well-being” would be to the biohackers, who all work on biotechnology as a hobby, “and what safeguards would be in place if something went wrong.”

Social justice 

Daniel Gaudet, a doctor in Montreal who treats patients suffering from the deficiency (19 of whom received Glybera in clinical trials), believes the biohackers’ plan is naive. While he agrees Glybera was too expensive, he thinks developing a gene therapy is too complex and risky for amateurs to undertake.

“Access and affordability are real challenges,” says Gaudet. “We must be creative, but biohacking is not the solution.” 

Others aren’t as sure that the biohackers should be written off. Geneticist Michael Hayden led the original Glybera research team at the University of British Columbia. He recalls the thrill when the treatment worked on animals and the hope he felt that patients might be helped. To show that, a company called AMT (which later became UniQure) was formed to run a definitive study on patients.

That’s when the problems started, Hayden says. “As the clinician scientists, we lost control of the project completely ... They decided that they were going to charge a million dollars a shot. In 2012, in Europe, this was outrageous.”

“The right to access medicine is a social-justice issue,” Hayden says.  “Any way to provide potential benefits to patients is entirely meaningful, and I would never stand in the way [of biohackers].” In fact, he says he would be interested in being connected to the team trying to pirate his drug.

“We’d love to learn more,” he says.