DNA cops who ensure that the deadliest viruses in the world are not rebuilt

Genetic engineering could help produce more resilient crops and more effective vaccines. Some fear that it could also be used to make a biological weapon.

In January, a small research team from the University of Alberta devised a cousin of the lethal smallpox virus called horsepox, using strands of DNA that they received by the post office. The body they built was not a threat to humans.

But when scientists published their results in the scientific journal PLOS ONE, a tumult ensues.

The publication of the study "crosses a red line in the field of biosafety," writes Gregory Koblentz, professor in the biodefense department of George Mason University, in a public comment to the journal. "The horse pox virus synthesis brings the world closer to the reappearance of smallpox as a threat to global health security."

Smallpox was eradicated in 1980 after generations of research and vaccination; many Americans born before 1972 have smallpox vaccination scars. The disease, which has already killed nearly a third of infected people, is considered so dangerous that only two laboratories in the world – one at the Centers for Disease Control in Atlanta and the United States. other in Siberia – are authorized by the World Health Organization samples of it.

For years, bioethicists and security experts have wondered whether these carefully guarded samples should be destroyed. But the widespread availability of basic elements of online life means that bad actors do not need to enter a remote lab and steal a sample of smallpox virus to trigger a devastating act of biological terrorism. They may be able to assemble it themselves.

To help reduce the threat, the US intelligence community, which has tracked the potential of new biological technologies to be used for ill-fated purposes for years, is working with a Boston-based company, Ginkgo Bioworks, which manufactures some of the most innovative genetic products in the world to help prevent the construction of a new class of biohazardous weapons.

"We worried about artificial pathogens in the 1990s," said Andy Weber, former deputy secretary of defense for nuclear, chemical and biological defense programs in the Obama administration. He now advises the private sector, including Ginkgo. "Frankly, science has caught up with these concepts."

Using a technology called synthetic biology, a marriage of biology and engineering that allows researchers to build genes in a laboratory, a scientist could theoretically make current diseases more virulent or drug-resistant, or relaunch diseases long eradicated like bubonic plague or Spanish flu. The fear is, without adequate supervision, that this can be done using genetic material acquired online. This has made it easier for people who are watching emerging security threats to come back and see each other. They fear that such innovations could be used to make a biological weapon.

Certainly, the awakening of dormant diseases currently requires significant scientific expertise and laboratory resources. According to security experts, only state actors have been led to use such techniques. However, the pace of innovation is accelerating: many companies can now adapt DNA strands in ways that revolutionize the fields of agriculture, perfumes, medicine and the deepest sense of the word. dangerous in the wrong hands.

In June 2017, Iarpa (Intelligence Advanced Research Projects Activity), a technology research agency within the Office of the Director of National Intelligence, launched a program that, she hopes, will help keep biological technologies alive. advanced in the shelter of the bad actors.

Preventing a potential attack is not as simple as monitoring a list of prohibited pathogens, which would be reported by current screening methods. It is possible to order smaller components of a longer genetic sequence, then reassemble them in a laboratory to build a harmful biological agent, either by design or by accident. There is also concern that new sequences may mimic the functions of harmful pathogens, but this may be out of step with current methods.

The episode of horsepox "suggests that there are risks that are present today," said Jason Matheny, director of Iarpa. "If someone is technically sophisticated and dedicated, someone could do a lot of damage."

To improve screening, IARPA officials have initiated a program with researchers at the Battelle Memorial Institute, a research group based in Columbus, Ohio, Harvard University, Virginia Tech, and others in order to create advanced algorithms. .

In order to understand which genetic combinations could be harmful before being made in the laboratory, the program led by Iarpa introduced Ginkgo, which will develop algorithms that can predict which genetic sequences, even unknown ones, could potentially cause damage. Called Fun GCAT, an acronym for Functional Genomic and Computational Assessment of Threats, the program seeks to create algorithms that would predict how genetic sequences are supposed to work before they are ordered, even if the studied combination is new and not visible in nature.

Ginkgo designs organisms using genetic data, coding them in the same way that computers are programmed. The company is designing microbes capable of living on plant roots and producing nitrogen, thus reducing the need for chemical fertilizers in some crops. He also works on the coding of microbes that produce rose oils for perfumes, no roses needed.

Working from a large loft-style office overlooking Boston Harbor, Ginkgo says he achieves about 40% of the world's gene printing, a form of synthetic biology that creates organisms producing compounds used in common manufacturing processes. the the compounds include rose oil or nitrogen fertilizer.

Synthetic biology has progressed rapidly. Ginkgo CEO Jason Kelly, 37, said that when he was a graduate student in bioengineering at the Massachusetts Institute of Technology in the mid-2000s, he designed about 50,000 base pairs – the designating term the two corresponding DNA units. a rung of the genetic ladder.

Now, says Kelly, his company can design about 50 million pairs a month, thanks to faster and cheaper sequencing techniques. Being able to generate as much genetic material can mean being able to quickly develop vaccines to respond to new pathogens or prototype experimental drugs more quickly, according to the company.

"The rate you can learn is just a lot higher, there's just no comparison," he said.

Gingko quickly saw the potential security risks in his work. He began working with Weber, the former Obama administration official, in 2016 for advice on how best to preserve national security.

"We're doing more genetic engineering than anyone, we think we're going to improve on that, so we have a responsibility to watch both sides of the coin," Kelly said. "How can we protect and defend against this while protecting our ability to achieve all the positive results of biotechnology?"

Asha George, executive director of the Blue Ribbon Study Group on Biodefense, said it's a good sign that Iarpa involves it before synthetic biology technology becomes more prevalent. She said that biosecurity issues are not receiving the attention and resources they deserve.

"The efforts we are still making to address the nuclear threat, chemical threat and incendiary threat are far more important than the US government or any government, in fact, does," she said. "Biological threats do not receive the same level of attention as other threats."

George said that it is not possible or desirable to go back. To do this, she says, this would amount to calling for a ban on computers because of the risks posed by viruses.

"It would be like saying that the industrial revolution could make machines that would produce a lot of pollution, so we will not commit ourselves," she said. "Can you imagine where we would be as a country if we did that?"

Security experts hope that synthetic biology could also counter the threats of emerging diseases by providing a faster way to find and produce vaccines. Drug manufacturers generally conduct less research on infectious diseases than other regions, and even in areas for which vaccines exist, some strains, such as last winter's flu, may be more commonplace. 39, to be resistant to treatment.

Weber hopes that this vaccine research could ultimately take months, rather than decades, with the help of synthetic biology. But if he considers the Iarpa program as a step forward in general, he feels that overall, the country is not prepared.

"[Are] the US government and other governments invest enough against this threat? I think the answer is a categorical no, "he said." Whether it's preparation against the next Spanish flu pandemic or against biological weapons, we are under-invested as a country in the fight against these threats. "