October 22, 2018
Op/ed: Synthetic biology and the new culture of responsibility
In 1980, in one of modern medicine’s crowning achievements, the World Health Organization declared the official eradication of smallpox — a virus that is estimated to have killed more than 300 million people in the 20th century. That’s three times the combined death tolls of all the wars fought during the same period, including WWI and WWII.
Today, scientists hold the tools to resurrect smallpox from scratch. (“The smallpox sequence is published, so you could recover it by synthesis if you had the lab facilities to do that,” said David Baltimore, winner of 1975 Nobel Prize in physiology or medicine.)
In fact, they’ve done just that with several other viruses. Last year, Canadian researchers reconstituted the “extinct” horsepox virus, a cousin of smallpox, for $100,000 using mail-order DNA. That experiment follows others like it, including the assembly of the much smaller poliovirus in 2002 and the resurrection in 2005 of the H1N1 pandemic virus, also known as the “Spanish influenza”, that wiped out 50 million people a century ago. Underlying these scientific milestones and many other contributions to healthcare, environmentally friendly manufacturing, and more, is a field called synthetic biology — and it is gaining speed.
Synthetic biology, or “synbio,” combines principles of engineering and biology to produce products for agriculture, healthcare, foods, materials, and more. During the first week of October, at the SynBioBeta 2018 Conference in San Francisco, California, scientists, engineers, entrepreneurs, policymakers, and venture capitalists from around the world showcased and discussed the latest advances in synbio. These cutting-edge innovations ranged from the storage of digital information (0s and 1s) in DNA molecules, to re-engineering the infamous salmonella bacteria to become a source of vaccine delivery, and rewiring the genetic circuitry of bacteria to make biosensors that can detect environmental pollutants.
Working with and within the synbio community, we see the tremendous power of biotechnology as a force for good. But synthetic biology also presents risks that need to be managed. One such risk stems from the dual-use applications of biotechnology — the possibility that this technology could be diverted to construct toxins and pathogens for use as biological weapons. As the building blocks of synthetic biology become more decentralized, or “democratized,” the risk that these tools will be misused by individuals with sinister intentions goes up accordingly.
Consider DNA synthesis technology. The ability to construct long DNA molecules efficiently and affordably from chemical precursors has been a tremendous benefit to synbio startups and to scientists in universities who can now outsource this tedious task to centralized facilities. But this also opens the door to the possibility that an individual with evil intent will order genes belonging to toxins and pathogens. Once obtained, those genes can be introduced into cells or cell-free extracts where they can be transcribed and subsequently translated into toxins or even disease-causing viruses.
DNA synthesis companies have responded to this risk by undertaking prudent self-regulation under the banner of the International Gene Synthesis Consortium (IGSC). In 2009, the IGSC began to screen the identities of both their customers and any orders of double stranded DNA molecules above 200 base pairs in length. The goal was to ensure that DNA sequences belonging to a list of toxins and pathogens are only provided to researchers specifically authorized to work with those agents.
This framework, which was implemented almost 10 years ago, is still in effect today. It is not, however, without its shortcomings. There are technical challenges to screening shorter oligonucleotides, which can be used to construct bigger DNA molecules. Moreover, IGSC’s membership covers only 80% of the gene synthesis market, leaving a hole that a bad actor could conceivably exploit.
While this framework has been largely static, technology has not. And as synbio accelerates, the risks increase. For instance, companies are hard at work building desktop gene synthesizers that could be sold to laboratories or even individuals. That is going to require a different risk-mitigation framework than the one currently in place at centralized DNA factories. Other companies are working to create novel platforms to generate molecules and modified organisms to treat disease. These same technologies could be used to make novel toxins and pathogenic organisms. Add to this the trend towards robotics automation, new advancements in software and computer assisted biological design (Bio-CAD), and artificial intelligence, and it becomes clear that even a novice without formal scientific training could eventually use these tools, for good or evil.
Where do we go from here?
Clearly, it is in the interest of the synthetic biology community to ensure that its tools are neither used, nor attempted to be used, for nefarious purposes. Either scenario could trigger severe government regulations that would hamper innovation and growth in the sector.
The industry as a whole has an opportunity to build on the initial self-regulation model that has been employed by several pioneering gene synthesis companies. Scientists and engineers who are developing new technologies are well-positioned to think through tailored technical and institutional safeguards to prevent misuse (Dr. Ali Nouri was a fellow in the Johns Hopkins Center for Health Security Conference Fellowship on Biosecurity and Synthetic Biology that was held in conjunction with SynBioBeta 2018). They should build bridges to the policy community to assess risks, develop proposed guidelines, and implement them in such a way as to foster, not impede, further innovation.
For their part, commercial enterprises — including startups, and the private venture capitalists that fund them — could also adopt a culture of proactive vigilance that prioritizes the identification and mitigation of risks. The “move fast and break things” mantra popularized by Mark Zuckerberg has helped spur innovation, but it has also introduced new risks. As seen in the recent Russian interference in U.S. elections, even seemingly harmless technologies like social media, without effective safeguards, can have destructive “dual-use” applications. In the case of synthetic biology, the potential for misuse and need for risk mitigation is even more obvious.
Gene synthesis companies have already demonstrated that academic, commercial and policy communities can work together to safeguard against risks within a dynamic framework that champions process transparency, open channels, interdisciplinary collaboration, and industry standards that must be universally adopted to be truly effective. Synthetic biology is not unique in its dual-use nature; artificial Intelligence, additive manufacturing, and other fledgling fields all carry tremendous benefits as well as risks.
By building on – and going beyond – the existing risk mitigation framework for DNA synthesis, the synbio community can set a powerful example for other sectors to follow.
Dr. Ali Nouri is President of the Federation of American Scientists (@_ali_nouri); Shahram Seyedin-Noor is Founder & General Partner of Civilization Ventures, a venture capital fund that invests in synthetic biology and health technology (@CivilizationVC).