Since its inception, synthetic biology has inspired new promises but caused some to fear the threat of potential new dangers. Discussions about both the potential benefits and the potential harms of synthetic biology are constantly fed and expanded by the stream of new capabilities and applications it enables. Recent months have seen a slew of controversial discussions around synthetic biology applications in development. Last year, DARPA’s Insect Allies program — designed to develop insects that could spread pathogen-fighting viruses to crops — set off a heated debate about its dual use potential. A month later, He Jiankui sparked international outrage when he claimed to have created the first CRISPR-edited human babies. And this September, UK company Oxitec was facing questions about whether its genetically modified mosquitos — designed to reduce serious public health diseases like malaria — were surviving in the wild longer than expected.
Discussions of biosecurity issues in synthetic biology bring together many different fields and perspectives, including the biotechnology industry, academics, government officials and members of the wider public. This diversity was on display at SynBioBeta’s 2019 breakout panel discussion on biosecurity, which brought together Sarah Carter from Science Policy Consulting, Jason Gammack from Inscripta, Milana Boukhman Trounce from Stanford Medical School, Gabriel Lopez from Synvivia, and Renee Wegrzyn from DARPA.
Sarah Carter kicked off the panel by emphasizing that biosecurity means “a whole lot of different things to a whole lot of different people.” For international organizations such as the WHO and the Biological Weapons Convention, biosecurity is often associated with biological weapons, produced intentionally by state and non-state actors alike. Other organizations think of biosecurity as the misuse of biology on a much smaller scale, like unintentional release of harmful biological agents by biohackers and the DIYBio movement.
In industry, biosecurity is often associated with the need to protect a company’s assets, such as intellectual property and biological materials. Carter shared some of the approaches used by the Defense Threat Reducation Agency (DTRA) to analyze the emerging synthetic biology “ecosystem.” This includes assessing what the most potent capabilities are, both beneficial and harmful, and who has access. Many of the most powerful capabilities currently remained in reach of only a small group of individuals and organizations.
“The most impressive and ambitious capabilities are really not available widely,” said Carter.
Carter also highlighted the increasingly international nature of industrial synthetic biology and its implications for biosecurity. There are now companies all over the world working in the field, and supply chains often stretch across many borders. This makes controls and regulations more challenging to establish. Carter described the work she had been doing to understand what best practices in industry look like, given the rapidly evolving landscape of synthetic biology and biosecurity. Such best practices include robust customer screening, IP and data protection, and cybersecurity. According to Carter, these practices are “both beneficial to the industry but also… help biosecurity more broadly.” Carter also raised the importance of efforts to identify potential risks. Indeed, this last point was a recurring theme in the session, with a clear consensus amongst panelists that doing both is essential but difficult.
“It’s really hard for people to even understand what we’re securing against,” said Carter, with Boukhman later adding: “It’s incredibly difficult to do an accurate assessment of the risk.”
Milana Boukhman took the stage next, sharing her perspective on biosecurity as an emergency doctor by training who had been teaching biosecurity at Stanford for over a decade. She presented three case studies where biotech means were used for dubious ends: the synthesis of Horsepox virus de novo by Canadian researchers, the development of human-transmissible H5N1 in the Netherlands, and the creation of a more virulent Mousepox strain in Australia. All of these projects had been carried out by well-meaning academics, not state-level programs, showing how few resources are needed to make something scary.
Boukhman drew a parallel between the current situation in biosecurity and cybersecurity in the 70s. Much like synthetic biology today, people then were only starting to grasp the full potential of the technology and realising how important cybersecurity was going to be.
“In the 1970s people didn’t really think about cybersecurity,” she said, “and now it’s a really big deal. I feel like that’s where biosecurity is now.”
Renee Wegrzyn then took the floor to talk about her work with DARPA. She introduced DARPA’s Safe Genes Program, one of their flagship biosecurity projects. Wegrzyn explained that DARPA thought of biosecurity not only through the lens of preventing threats to human health, but also considered how to mitigate economic threats. To illustrate the link between biosecurity and economics, she showed how publications about the off-target effects of CRISPR resulted in share devaluations at gene therapy companies equivalent to losses of hundreds of millions of dollars.
As an example of biosecurity done right, Wegrzyn talked about a researcher working for DARPA who had found off-target CRISPR effects in mRNA. Rather than publish these results immediately, the researcher successfully requested that DARPA extend their funding so they could also learn how to prevent these off-target edits. In yet another parallel to cybersecurity — where it is common practice not to reveal a vulnerability until after it has been patched — the researcher published their work showing the “vulnerability” of CRISPR off-target mRNA editing only after they could also show how to “patch” this problem.
Wegrzyn was followed by Gabriel Lopez, who described Synvivia’s take on biosecurity. Synvivia creates protein switches to control GMOs and their functions, including their survival. Like many of the other speakers in the panel, Lopez drew parallels to the tech world, particularly information security. Encryption was once widely used only by governments, but has been adopted en masse in recent years by companies realizing the value of their information. Lopez described how cybersecurity is now driven not by governments but by industry and its needs. He argued that the same would happen to biosecurity. Eventually this would not be driven by government regulators anymore but instead by the biotech industry, once its importance was understood — like data encryption before it.
“Biosecurity is inevitable and will be a market-driven element to the future of the bioeconomy,” Lopez remarked.
Jason Gammack from Inscripta agreed with Lopez about the role of industry in driving biosecurity. “Biosecurity at Inscripta is part of our core DNA,” he said. Inscripta’s philosophy is to tackle biosecurity cooperatively with their customers, to help them make sure they didn’t create dangerous organisms. “This is a partnership.”
Gammack also talked about how often Inscripta had been frustrated by the “silos” they had encountered when trying to promote biosecurity. In their experience, important information and skills that need to be brought to bear are spread across many people and fields. Often, these entities don’t communicate enough, hindering the implementation of robust biosecurity.
In the Q&A, several of the panellists again alluded to the difficulty of identifying and assessing biosecurity threats. The effect of this problem was immediately highlighted by the first question, which asked what the biggest threats to our biosecurity are, and elicited different answers from each of the panelists. It was clear there were no right or wrong answers, just different perspectives based on the background and point of view of each participant.
One worry was about new scientific and technical capabilities to enhance virulence and transmissibility, which could make existing treatments and vaccines useless. Another big issue was the potential for indirect attacks targeting agriculture, water supplies, and the environment more broadly.
The issue of collective responsibility was raising, with Dr. He’s work as an example. This had been supported not only by academics outside of China but also by equipment and reagents supplied to him by US companies. “All of those supplies were freely available,” said one attendee. Gammack described how Inscripta was approaching these issues in part by making their machines “always online.” This ensured they could not be used without reporting back to Inscripta what they were doing, giving the company oversight about what their equipment was being used to do.
The session wrapped up with a discussion between panelists and audience members about how to improve biosecurity. One consensus that emerged: the bedrock for protecting populations from new (or revived) pathogens was to strengthen our ability to respond to ‘conventional’ outbreaks. Preparing for one would prepare us for the other.
“We can’t build a tall enough wall that will ensure that there is no bioterrorism, but what we can build are a series of hurdles,” said Gammack. With enough hurdles, anybody intentionally creating something dangerous would be spotted by tripping over at least one of them.
How could all this be put in place? Panelists agreed that it was never too early for companies to start thinking about this, and that incentives should exist right from the start, including at the investor level.5