A synthetic virus could help develop drugs, vaccines, and diagnostic tests but could also be used as a bioweapon.
As countries scramble to contain the novel coronavirus spreading around the world, scientists in Switzerland are intentionally making more of the deadly virus. The only difference is that their version is synthetic.
Behind the doors of a high-security laboratory in a tiny Swiss village, researchers at the University of Bern recreated the coronavirus, formally known as SARS-CoV-2, in just a week using yeast, a published genome, and mail-order DNA. The synthetic virus, which they detail in a new paper posted to the preprint server biorXiv, could help more labs develop drugs, vaccines, and diagnostic tests for the coronavirus. But the ability to quickly make a virus from scratch also raises concerns that the process could be used to make biological weapons.
Scientists typically study a virus by isolating it from a sick patient’s cells and growing it in a lab dish. But researchers have struggled to get their hands on the coronavirus. When an outbreak of a disease happens far away, it can take months for labs to get access to physical samples.
In these situations, researchers might turn to a synthetic version of a virus, also known as an infectious clone, so they can start studying it sooner. Creating a synthetic version can be a more practical option than ordering a dangerous virus through the mail, and it allows researchers to sidestep a lot of regulatory hoops. There are import rules and special permits involved in shipping and acquiring pathogens.
“Collectively, all those things can take a tremendous amount of time,” says David Evans, a virologist at the University of Alberta whose team raised alarm in 2017 for making a synthetic version of the extinct horsepox virus, a relative of the smallpox virus. “If you want to start working with the virus as quickly as possible, it’s sometimes faster and simpler just to make it yourself.”
To make a virus, you need instructions on how to assemble it. On January 10, a Chinese group provided a blueprint of the virus to scientists around the world by publishing a draft of the coronavirus genome on an open-access site. The Swiss team behind the new paper, led by virologist Volker Thiel, immediately got to work. They placed an order of coronavirus DNA with GenScript, a New Jersey-based company that makes and sells synthetic genetic material to researchers. Companies like GenScript print out DNA in short fragments that need to be assembled into a full genome.
Three weeks later, the Swiss team had most of the DNA fragments they needed to start reconstructing the coronavirus genome. Sometimes biologists do this by hand, which can take a lot of time. To speed this up, the team inserted these fragments into brewer’s yeast cells, which assembled the DNA fragments like puzzle pieces using a natural process called recombination. This process formed the coronavirus genome within the yeast.
“It worked perfectly, like a Swiss watch.”
Next, the researchers needed to convert the coronavirus genome from DNA to a related molecule called RNA (coronavirus is an RNA virus, meaning its genetic material is RNA rather than DNA). After that, they made copies of the synthetic virus and found that the virus particles could infect monkey cells — a stand-in for human cells. This showed that the synthetic coronavirus was a faithful copy of the original.
Altogether, the technique took a week after the team got the DNA in the mail.
“It worked perfectly, like a Swiss watch,” says Jörg Jores, an author on the paper and director of the Institute of Veterinary Bacteriology at the University of Bern.
Angela Rasmussen, a virologist at Columbia University’s Mailman School of Public Health, says having a synthetic replica of the virus can help researchers figure out how to stop its spread.
“Having the virus itself is really critical to designing and testing drugs that can potentially ameliorate the viral infection,” she says. Researchers can also use genetic engineering to tweak the virus to see whether certain mutations make it more or less harmful. Having safer versions is particularly helpful so that researchers don’t get infected while studying the virus, says Rasmussen.
Jores says it cost about $30,000 to purchase the DNA fragments, and in a few years, it will probably be even cheaper. DNA synthesizing used to be expensive and laborious, but companies like GenScript, Integrated DNA Technology, and Twist Bioscience have automated the process.
The ability to quickly and cheaply synthesize DNA has led to fears that scientists could brew up genetically engineered pathogens, which could escape from the lab and infect the public. Rasmussen, however, says people shouldn’t worry too much about that possibility because research to make a virus more dangerous, known as gain of function research, is highly regulated. Thiel’s team had special permission from the Swiss government to carry out its research in a high-containment lab that has specific safety requirements.
“It’s not like somebody could go into their lab one day and say, ‘I’m going to modify this virus clone to make it more transmissible,’” she says.
In 2014, the U.S. government suspended similar research after lab workers at the Centers for Disease Control and Prevention were potentially exposed to live anthrax and employees at the Food and Drug Administration came across forgotten vials of the smallpox vaccine. A few years before, two research groups announced that they had made the H5N1 bird flu more contagious in ferrets. In 2017, the government released new guidelines for these types of experiments. Now, scientists proposing such research must go through an extensive review to get approval.
Such gain of function research could help public health experts take measures to prevent and react to pandemics. Scientists first made a synthetic virus in 2002, when they reconstructed a live polio virus using chemicals and publicly available genetic information. That work was actually funded by the Pentagon as part of a program to develop biowarfare countermeasures.
With the rise of unregulated do-it-yourself biology and citizen science labs, some worry that inventive biohackers could cook up deadly pathogens in their garages and accidentally or intentionally release them. But Evans doesn’t think that’s likely.
“It’s still not technically that easy,” he says. “It takes a lot of experimental skill, which is not obvious from reading these papers.” He’s more concerned that a state actor would use synthetic biology to create a bioweapon in the lab and release it to an enemy population. “A government or a government laboratory well-equipped with knowledgeable scientists could replicate all of this stuff.” As of now, there is no evidence that the current outbreak is the result of weaponization.
Companies that print and sell DNA provide one check for potential bad actors. DNA synthesis companies have come together to establish some ground rules on who they sell DNA to and what sequences of DNA they sell. They screen customers and vet gene orders so that sequences of dangerous pathogens don’t end up in the wrong hands. Only authorized labs are able to obtain DNA to make the most lethal ones.
But as making DNA gets increasingly easier, faster, and cheaper, many labs could soon have the ability to print DNA in-house, making the possibility of creating pathogens a lot more feasible.