Meet the Scientists on the Frontlines of Protecting Humanity from a Man-Made Pathogen
From left: Jean Peccoud, Randall Murch, and Neeraj Rao.
Jean Peccoud wasn't expecting an email from the FBI. He definitely wasn't expecting the agency to invite him to a meeting. "My reaction was, 'What did I do wrong to be on the FBI watch list?'" he recalls.
You use those blueprints for white-hat research—which is, indeed, why the open blueprints exist—or you can do the same for a black-hat attack.
He didn't know what the feds could possibly want from him. "I was mostly scared at this point," he says. "I was deeply disturbed by the whole thing."
But he decided to go anyway, and when he traveled to San Francisco for the 2008 gathering, the reason for the e-vite became clear: The FBI was reaching out to researchers like him—scientists interested in synthetic biology—in anticipation of the potential nefarious uses of this technology. "The whole purpose of the meeting was, 'Let's start talking to each other before we actually need to talk to each other,'" says Peccoud, now a professor of chemical and biological engineering at Colorado State University. "'And let's make sure next time you get an email from the FBI, you don't freak out."
Synthetic biology—which Peccoud defines as "the application of engineering methods to biological systems"—holds great power, and with that (as always) comes great responsibility. When you can synthesize genetic material in a lab, you can create new ways of diagnosing and treating people, and even new food ingredients. But you can also "print" the genetic sequence of a virus or virulent bacterium.
And while it's not easy, it's also not as hard as it could be, in part because dangerous sequences have publicly available blueprints. You use those blueprints for white-hat research—which is, indeed, why the open blueprints exist—or you can do the same for a black-hat attack. You could synthesize a dangerous pathogen's code on purpose, or you could unwittingly do so because someone tampered with your digital instructions. Ordering synthetic genes for viral sequences, says Peccoud, would likely be more difficult today than it was a decade ago.
"There is more awareness of the industry, and they are taking this more seriously," he says. "There is no specific regulation, though."
Trying to lock down the interconnected machines that enable synthetic biology, secure its lab processes, and keep dangerous pathogens out of the hands of bad actors is part of a relatively new field: cyberbiosecurity, whose name Peccoud and colleagues introduced in a 2018 paper.
Biological threats feel especially acute right now, during the ongoing pandemic. COVID-19 is a natural pathogen -- not one engineered in a lab. But future outbreaks could start from a bug nature didn't build, if the wrong people get ahold of the right genetic sequences, and put them in the right sequence. Securing the equipment and processes that make synthetic biology possible -- so that doesn't happen -- is part of why the field of cyberbiosecurity was born.
The Origin Story
It is perhaps no coincidence that the FBI pinged Peccoud when it did: soon after a journalist ordered a sequence of smallpox DNA and wrote, for The Guardian, about how easy it was. "That was not good press for anybody," says Peccoud. Previously, in 2002, the Pentagon had funded SUNY Stonybrook researchers to try something similar: They ordered bits of polio DNA piecemeal and, over the course of three years, strung them together.
Although many years have passed since those early gotchas, the current patchwork of regulations still wouldn't necessarily prevent someone from pulling similar tricks now, and the technological systems that synthetic biology runs on are more intertwined — and so perhaps more hackable — than ever. Researchers like Peccoud are working to bring awareness to those potential problems, to promote accountability, and to provide early-detection tools that would catch the whiff of a rotten act before it became one.
Peccoud notes that if someone wants to get access to a specific pathogen, it is probably easier to collect it from the environment or take it from a biodefense lab than to whip it up synthetically. "However, people could use genetic databases to design a system that combines different genes in a way that would make them dangerous together without each of the components being dangerous on its own," he says. "This would be much more difficult to detect."
After his meeting with the FBI, Peccoud grew more interested in these sorts of security questions. So he was paying attention when, in 2010, the Department of Health and Human Services — now helping manage the response to COVID-19 — created guidance for how to screen synthetic biology orders, to make sure suppliers didn't accidentally send bad actors the sequences that make up bad genomes.
Guidance is nice, Peccoud thought, but it's just words. He wanted to turn those words into action: into a computer program. "I didn't know if it was something you can run on a desktop or if you need a supercomputer to run it," he says. So, one summer, he tasked a team of student researchers with poring over the sentences and turning them into scripts. "I let the FBI know," he says, having both learned his lesson and wanting to get in on the game.
Peccoud later joined forces with Randall Murch, a former FBI agent and current Virginia Tech professor, and a team of colleagues from both Virginia Tech and the University of Nebraska-Lincoln, on a prototype project for the Department of Defense. They went into a lab at the University of Nebraska at Lincoln and assessed all its cyberbio-vulnerabilities. The lab develops and produces prototype vaccines, therapeutics, and prophylactic components — exactly the kind of place that you always, and especially right now, want to keep secure.
"We were creating wiki of all these nasty things."
The team found dozens of Achilles' heels, and put them in a private report. Not long after that project, the two and their colleagues wrote the paper that first used the term "cyberbiosecurity." A second paper, led by Murch, came out five months later and provided a proposed definition and more comprehensive perspective on cyberbiosecurity. But although it's now a buzzword, it's the definition, not the jargon, that matters. "Frankly, I don't really care if they call it cyberbiosecurity," says Murch. Call it what you want: Just pay attention to its tenets.
A Database of Scary Sequences
Peccoud and Murch, of course, aren't the only ones working to screen sequences and secure devices. At the nonprofit Battelle Memorial Institute in Columbus, Ohio, for instance, scientists are working on solutions that balance the openness inherent to science and the closure that can stop bad stuff. "There's a challenge there that you want to enable research but you want to make sure that what people are ordering is safe," says the organization's Neeraj Rao.
Rao can't talk about the work Battelle does for the spy agency IARPA, the Intelligence Advanced Research Projects Activity, on a project called Fun GCAT, which aims to use computational tools to deep-screen gene-sequence orders to see if they pose a threat. It can, though, talk about a twin-type internal project: ThreatSEQ (pronounced, of course, "threat seek").
The project started when "a government customer" (as usual, no one will say which) asked Battelle to curate a list of dangerous toxins and pathogens, and their genetic sequences. The researchers even started tagging sequences according to their function — like whether a particular sequence is involved in a germ's virulence or toxicity. That helps if someone is trying to use synthetic biology not to gin up a yawn-inducing old bug but to engineer a totally new one. "How do you essentially predict what the function of a novel sequence is?" says Rao. You look at what other, similar bits of code do.
"We were creating wiki of all these nasty things," says Rao. As they were working, they realized that DNA manufacturers could potentially scan in sequences that people ordered, run them against the database, and see if anything scary matched up. Kind of like that plagiarism software your college professors used.
Battelle began offering their screening capability, as ThreatSEQ. When customers -- like, currently, Twist Bioscience -- throw their sequences in, and get a report back, the manufacturers make the final decision about whether to fulfill a flagged order — whether, in the analogy, to give an F for plagiarism. After all, legitimate researchers do legitimately need to have DNA from legitimately bad organisms.
"Maybe it's the CDC," says Rao. "If things check out, oftentimes [the manufacturers] will fulfill the order." If it's your aggrieved uncle seeking the virulent pathogen, maybe not. But ultimately, no one is stopping the manufacturers from doing so.
Beyond that kind of tampering, though, cyberbiosecurity also includes keeping a lockdown on the machines that make the genetic sequences. "Somebody now doesn't need physical access to infrastructure to tamper with it," says Rao. So it needs the same cyber protections as other internet-connected devices.
Scientists are also now using DNA to store data — encoding information in its bases, rather than into a hard drive. To download the data, you sequence the DNA and read it back into a computer. But if you think like a bad guy, you'd realize that a bad guy could then, for instance, insert a computer virus into the genetic code, and when the researcher went to nab her data, her desktop would crash or infect the others on the network.
Something like that actually happened in 2017 at the USENIX security symposium, an annual programming conference: Researchers from the University of Washington encoded malware into DNA, and when the gene sequencer assembled the DNA, it corrupted the sequencer's software, then the computer that controlled it.
"This vulnerability could be just the opening an adversary needs to compromise an organization's systems," Inspirion Biosciences' J. Craig Reed and Nicolas Dunaway wrote in a paper for Frontiers in Bioengineering and Biotechnology, included in an e-book that Murch edited called Mapping the Cyberbiosecurity Enterprise.
Where We Go From Here
So what to do about all this? That's hard to say, in part because we don't know how big a current problem any of it poses. As noted in Mapping the Cyberbiosecurity Enterprise, "Information about private sector infrastructure vulnerabilities or data breaches is protected from public release by the Protected Critical Infrastructure Information (PCII) Program," if the privateers share the information with the government. "Government sector vulnerabilities or data breaches," meanwhile, "are rarely shared with the public."
"What I think is encouraging right now is the fact that we're even having this discussion."
The regulations that could rein in problems aren't as robust as many would like them to be, and much good behavior is technically voluntary — although guidelines and best practices do exist from organizations like the International Gene Synthesis Consortium and the National Institute of Standards and Technology.
Rao thinks it would be smart if grant-giving agencies like the National Institutes of Health and the National Science Foundation required any scientists who took their money to work with manufacturing companies that screen sequences. But he also still thinks we're on our way to being ahead of the curve, in terms of preventing print-your-own bioproblems: "What I think is encouraging right now is the fact that we're even having this discussion," says Rao.
Peccoud, for his part, has worked to keep such conversations going, including by doing training for the FBI and planning a workshop for students in which they imagine and work to guard against the malicious use of their research. But actually, Peccoud believes that human error, flawed lab processes, and mislabeled samples might be bigger threats than the outside ones. "Way too often, I think that people think of security as, 'Oh, there is a bad guy going after me,' and the main thing you should be worried about is yourself and errors," he says.
Murch thinks we're only at the beginning of understanding where our weak points are, and how many times they've been bruised. Decreasing those contusions, though, won't just take more secure systems. "The answer won't be technical only," he says. It'll be social, political, policy-related, and economic — a cultural revolution all its own.
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.
