This executive summary of a white paper was prepared for the Institute for Progress. For the full white paper, download the PDF.
Introduction
Synthetic DNA is now fundamental to much life sciences research, and will likely contribute to important advances in biological sciences, medicine, information technology, and environmental preservation.
As with most powerful tools, synthetic DNA also has the potential to cause harm, whether by accident or intention. The potential for harm through the release of synthesized pathogens is a key reason for concern. It is possible to synthesize a viral genome and boot it up to be a living virus. Thousands of people have this capacity and this number is expected to grow.
The synthetic DNA industry has long been aware of the risk its product poses, and many companies have voluntarily implemented a screening system to mitigate risk. Synthetic DNA providers verify customers’ identities and monitor orders to ensure sequences that could cause harm aren’t released inappropriately. However, screening is inconsistent across the industry. As costs of DNA synthesis fall, screening will make up a greater proportion of companies’ costs, making it harder for companies that screen to remain competitive with those who don’t.
Technological advances will pose other challenges. Benchtop DNA synthesizers have recently come to market. Without regulation, these could allow users to synthesize any sequence, regardless of its risks. Knowledge of pathogens and other harmful sequences is advancing, which means that databases of sequences of concern should be updated regularly. New computational tools may allow design of novel dangerous sequences. Mitigating the risk of novel sequences will require a change to the current paradigm of screening.
Rather than relying on the goodwill of industry to mitigate these threats, the United States (US) Government should proactively protect American citizens from the risks of synthetic biology. The US is a global leader in synthetic biology, accounting for roughly 40% of the global market. This puts the US in a powerful position to set industry standards, setting the bar for typical practice in, such that companies failing to meet this standard can be found liable for negligence. This market dominance enables the US to take leadership that should prompt action in other countries with growing synthetic biology industries.
Recommendations
To mitigate the risk of synthetic DNA, we make the following recommendations:
1. As a matter of urgency, introduce legal requirements for the manufacture and sale of benchtop DNA synthesizers.
Regulations should require that:
- Benchtop synthesizers are only sold to entities with a legitimate reason to synthesize DNA, have adequate biosafety and biosecurity training and facilities, and are not on any security watchlists;
- Before printing, machines compare all requested sequences against a database of sequences of concern, which is promptly updated as new hazardous sequences are identified;
- Potentially hazardous sequences are only synthesized for users who have authorization to work with the sequence;
- Machines require authentication of individual users;
- Strict penalties apply for sale of machines without these safeguards and for the unauthorized synthesis of hazardous sequences.
The Federal Select Agent Regulations govern the possession, use and transfer of a list of pathogens that pose a threat to human and animal health. Without the interventions recommended above, manufacturers of benchtop synthesizers may not be abiding by these regulations. As new hazardous sequences are discovered, regulations may need to be updated to include them.
2. Introduce a legal requirement for providers of synthetic DNA to conduct screening of customers and orders. If this is not possible, require that research funded by the federal government strictly use synthetic DNA from providers that participate in screening.
Requiring all companies to conduct screening to an agreed-upon standard is the best pathway to minimize risks from synthetic DNA. New tools promise to remove many of the financial and operational barriers to screening, such that it is accessible even to small providers.
If a mandate is politically infeasible, an alternative would be requiring all research funded by the US Government to use providers that meet a minimum screening standard. The US Government is a major funder of life sciences research, and synthetic DNA companies have a strong incentive to ensure that they can supply this market. A requirement would result in many companies ensuring that they reach the required standard of screening.
Either version of this legislation should develop a screening standard and a system for verifying compliance with that standard. At a minimum this standard should include screening for pathogens on the Federal Select Agent Program (FSAP) list and the Commerce Control List (CCL). However, as understanding of hazardous DNA sequences develops, the requirements should expand to include this new knowledge.
3. Investigate mechanisms to facilitate the process of customer screening.
The time and resources spent to investigate prospective customers and flagged orders are major components of screening costs to providers and likely pose a major barrier to many companies, particularly smaller companies, conducting screening. We recommend working with industry partners to investigate options for facilitating this process and thereby reducing the cost of screening. Options may include a licensing program or centralized database where prospective customers would register their details, including information on research, publications, biosafety at their facility, and link them to approvals to work with certain pathogens (e.g. FSAP). This system should be developed in a manner that protects the privacy of those using synthetic DNA.
4. Support international efforts to develop screening processes, and engage with other countries with major synthetic biology industries.
As the synthetic DNA industry is international, the US must engage with and support efforts to promote screening. This includes collaborating with international initiatives that aim to simplify and standardize screening, including the International Gene Synthesis Consortium and the International Biosecurity and Biosafety Initiative for Science. The Department of Health and Human Services (HHS) has significant expertise in developing safe screening protocols. By sharing this expertise, HHS can help to develop international screening guidelines that meet US standards and create international consistency in screening.
Similarly, international groups developing automated screening systems, such as the Nuclear Threat Initiative and SecureDNA, may need the cooperation of governments to incorporate approvals to work with certain pathogens into these automated systems. HHS, which oversees the FSAP, and the Department of Commerce, which oversees the CCL, should cooperate with these groups to enable the efficient development of these systems. Input from HHS would also help these groups ensure that their systems meet US standards.
Consistent international screening standards will reduce risks, promote international trade, and minimize the risk of harm to American industry from inconsistent regulation. Along with cooperating with international groups, diplomatic engagement with other nations that host major synthetic gene industries will be vital in building a global regulatory structure that encourages safe scientific advancement.
5. Investigate options to adapt screening processes to the changing technology landscape.
Current screening approaches use DNA sequences from known pathogens and toxins. Evolving knowledge of these pathogens means all screening systems require prompt updating. Application of artificial intelligence to the life sciences may soon allow the design of de novo dangerous DNA sequences. The US Government should investigate how to address this coming challenge to current screening approaches.
However, it is important that any government efforts not inadvertently contribute to these risks by advancing functional prediction capacities. Rather than funding research into sequence functional prediction, the government should work with relevant companies and researchers to reduce these risks. This may involve restricting access to models that could be used to generate dangerous de novo sequences, and/or ensuring that the developers of these models work with groups producing synthetic DNA screening platforms to develop mechanisms to screen for dangerous sequences that may be generated by models.
