Markus Schmidt on Risks from Novel Biotechnologies

Luke Muehlhauser: I’ll start by giving our readers a quick overview of synthetic biology, the “design and construction of biological devices and systems for useful purposes.” As explained in a 2012 book you edited, major applications of synthetic biology include:

• Biofuels: ethanol, algae-based fuels, bio-hydrogen, microbial fuel cells, etc.
• Bioremediation: wastewater treatment, water desalination, solid waste decomposition, CO₂ recapturing, etc.
• Biomaterials: bioplastics, bulk chemicals, cellulosomes, etc.
• Novel developments: protocells and xenobiology for the production of novel cells and organisms.

But in addition to promoting the useful applications of synthetic biology, you also speak and write extensively about the potential risks of synthetic biology. Which risks from novel biotechnologies are you most concerned about?

Markus Schmidt: It doesn’t come as a surprise that a new and emerging technology that is hallmarked as a game changer for the bioeconomy also has the potential for causing harm.

Traditionally we can see direct risks related to safety and security. Safety deals with potential unintended consequences, such as accidents, while security refer to harm that is caused intentionally, such as bioterrorism. Right now, safety issues of SB are mostly covered by existing regulations and practices developed for genetic engineering (GE). But as SB is developing beyond the scope of GE, first of all it deals with genetic systems rather than a set of one or few genetic elements, second it attempts to apply true engineering principles to biology (such as standardization, modularization, hierarchies of abstraction, and separation of design and fabrication); and third it doesn’t only take what nature provides in terms of biochemical systems but attempts to go beyond that. So one concern is that while right now GE regulations seem to be adequate, in a not so distant future GE risk analysis practices will be outdated and we might run into difficulties to assess the safety risks of SB products. Another risk stems from one of the aims of SB to make biology easier to engineer. While this is predominantly a positive approach, it also brings with it the fact that more and more people outside the elite institutions will be able to use SB, such as amateur biologist. While amateurs have overwhelmingly good intentions, many of them do not have a background or training in biosafety and thus have a higher risk for accidents in their garage labs. A third point is the design of new-to-nature “xenobiological” system where alternative biochemical structures are used to run biological operations, such as additional amino acids, different types of nucleic acids etc. but also novel types of cells or protocells that behave differently than natural cells. The introduction of these alternative systems is of great interest to science, society and industry, but needs a careful assessment in order not to cause unwanted effects.

Security comes with a different set of problems. Some experts believe that terrorists could start to use SB to enhance existing or develop new pathogens, or get hold of them via DNA synthesis.

Apart from these classical risks, we might also see indirect risks in other areas, such as the changes SB could cause to the socioeconomic structure. For example, one might ask if the use of this technology is going to benefit most people or just a few. Questions such as these, however, are not unique to SB but come up in every debate about technologies that promise huge changes.

Luke: One problem for the future of biosecurity is that it seems likely that advanced bioweapons will be cheaper to make and harder to track than nuclear fissile material. Thus, states and terrorists might find it easier to threaten groups of people — or maybe the world — with (say) home-built superviruses than with home-built nuclear weapons. And yet the release of a carefully designed supervirus could be as devastating, or more devastating, than a nuclear detonation. What’s your perspective on this?

Markus: The issue of bioterrorism has been tackled by several high level national security groups, such as the NSABB in the US. While there is a certain, although small risk, of people using biotech for illicit purposes, meassures have been taken to keep that from happening. One major concern, e.g. Was the mail-ordered virus form DNA synthesis companies. Following debates among the companies, governments and other stakeholder, there is now an effective screening mechanism in place to prevent people from ordering pathogenic sequences found on the internet.

Apart from that, it would be extremely difficult to make a new supervirus. The abilities to make new forms of life or viruses is still very limited, and will be for the time being. But the issue is on the agenda for national and international security agencies so that any development and inovations with a dual use potential is monitored (e.g. By the UN and others)

Luke: What seem to be the most important factors in getting regulatory bodies and other policy-makers to produce effective policy for biotechnological risk mitigation?

Markus: Innovations in science and technology tend to outpace the speed by which regulatory bodies operate. In other words policy-makers run the risk to be too slow to react on new challenges to the regulatory system, plus once they react it still takes some time before adapted or new regulations or guidelines are actually in place. In a time where the bioeconomy is believed to hold great potential for Europe or the USA, regulatory bodies cannot afford to hold up research and innovation once the techno-science goes beyond the limits of established regulations. So a real-time and forward looking assessment by policy makers is needed, as demonstrated e.g. by the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) of the European Commission, that is currently analysing the need to update the existing biotech regulation on synthetic biology.¹

Another important point is the acknowledgement of the convergence of different technologies into one. In the case of synthetic biology we see the confluence of biotech, nanotech, IT and other areas into one converging field. So far the biotech and IT regulations come from a very different background with different aims and distinct cultures, and path dependencies tend to lock in the opportunities seen by the regulatory community. Future regulations of synthetic biology must take this convergence into account.

A third aspect is a broader stakeholder consultation, a more participatory form of deriving to conclusions compared to the first genetic engineering rules implemented in the mid 70ies.

Luke: My impression is that government ethics & safety committees like SCENIHR are rarely able to spur policy changes that are implemented quickly enough for regulators to “keep up” with new technological developments. Is that your impression as well? And if it is, is there anything different about SCENIHR that should give us more hope than might usually be justified?

Markus: No. In principle, all the committees that advise governments on new science and technologies face the problem of keeping up to date with the pace of research and innovation. In synthetic biology, quite remarkably, a lot of committees from different countries and with different thematic focuses have taken up synbio as a case study. So all together I think that synbio is reasonably well covered.

Let’s not forget that although synbio has been promised a “game-changer”, the “next industrial revolution” etc, real breakthroughs that impact the market are yet to come. With the few exceptions where a quick response was necessary by governments (such as in DNA synthesis and biosecurity), the “speed kills” argument doesn’t weigh as heavy as the need to provide sustainable medium to long term governance frameworks.

I think it the following statement is ascribed to Bill Gates who said “We always overestimate the change that will occur in the next two years and underestimate the change that will occur in the next ten. Don’t let yourself be lulled into inaction.”

Luke: Interesting. Can you give an example or two of the kind of ethics & safety committee success that you hope for with SCENIHR?

Markus: What I would like to see as an outcome of the SCENIHIR opinion on synbio is a statement regarding where, when and how the risks of synbio will go beyond those of genetically modified organisms. How should risk assessment be adapted or amended so we can continue to have a robust assessment of the risks involved? Also I would like to see an analysis of the potential for novel built-in safety locks (aka. semantic containment², genetic firewall³) and recommendations on how to use them, so policy makers, scientists, funding agencies, and industry have a clear idea for which application built-in safety locks can be used, which additional level of safety can be provided, and which research, innovation and governance gaps have to be filled in order to have a fully operational safety lock available.

Luke: Thanks, Markus!

1. Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) in association with Scientific Committee on Consumer Safety (SCCS), Scientific Committee on Health and Environmental Risks (SCHER). request for a joint scientific opinion: on Synthetic Biology ↩
2. Schmidt M, de Lorenzo V. 2012. Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology. FEBSLetters. Vol. 586: 2199-2206 ↩
3. Schmidt M. 2010. Xenobiology: a new form of life as the ultimate biosafety tool. BioEssays. Vol.32(4): 322-331 ↩