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As the field of synthetic biology advances at a rapid pace, it necessarily raises regulatory and ethical questions which must be assessed and addressed. The following is an independent piece presented by Dr. Marc Saner of the Institute for Science, Society and Policy (ISSP) at the University of Ottawa. In it, Dr. Saner offers his take on the benefits of a total field view and a focus on “responsible innovation” in synthetic biology within both Ontario and Canada.

The Benefits of a Total Field View

Dr. Marc Saner
The Institute for Science, Society and Policy (ISSP), University of Ottawa
msaner@uottawa.ca | @MarcSaner

While there is no universally accepted definition for “synthetic biology,” advocates and critics seem to agree that recent advances such as the creation of synthetic genomes, editing genes using CRISPR-Cas9, and engineering yeast to manufacture chemicals differs from traditional biotechnology in important ways. The new label provides an opportunity to emphasize both new hopes and worries that result from faster, cheaper, and more precise biotechnology.

Why is synthetic biology an opportunity for Ontario and Canada? Firstly, Genome Canada has invested over 1 billion Canadian dollars into genomics and biotechnology since 2000 (3 billion when accounting for the required co-funding). As a result, a significant amount of genomics talent, know-how and infrastructure exists in Canada. A relatively small nation like Canada may be well advised to buttress such existing strength—to build on mountains rather than to fill the valleys.

Secondly, we are well situated internationally. CRISPR-Cas9 has been invented in Boston and San Francisco and there is also much innovation taking place in the UK and in China. We are in a good position to work with these international centers linguistically, geographically, and with respect to our immigration history and trends.

Finally, most advocates will point to the promise of synthetic biology to address significant challenges facing humanity today. The applications are in many sectors including health, food, energy, environment and climate change (I refer you to the Ontario Genomics website and the op-ed authored by the Chief Scientist of Québec, Rémi Quirion, Canadian synthetic biology pioneer Vincent Martin, alongside the current and preceding CEOs of Genome Canada in the Hill Times, November 28, 2014).

In the midst of such enthusiasm, good planning requires a total field view, and the GE³LS perspective provides such breadth. With ethics and social implications in mind, we first must ask: what are the up- and downsides of “faster and cheaper”?

Of course, we desperately want solutions to our pressing physical and social problems, but are we confident that society and regulators will keep pace with the innovators? The difference in pace between the innovators and the comparatively slower risk assessors and lawmakers has been labelled the “pacing problem” by regulatory experts. The outpacing of regulatory oversight is not only a concern for society who may worry about under-regulation (the on-going international debate over the labelling of GMOs is a good example here). The pacing problem is also a problem for innovators who find it difficult predicting regulatory requirements and timelines. This problem can easily arise when a company produces a completely innovative product, such as a multi-function product based on converging technologies, where there are no comparator products (with associated known safety data) for risk assessors to use, and it is unclear which regulatory agency is in charge. Understanding diverging viewpoints and developing empathy for all actors and stakeholders will pay dividends here. So will good planning.

Furthermore, it is critical to consider the implications of the diffusion of new capabilities. The decline in cost and complexity of modern biotechnology has made it more accessible to young students and do-it-yourself and makerspace communities. It is truly impressive that high school students can make real inventions and start companies on Kickstarter. And it’s desirable that the promise of a new technology platform does not get monopolized by a small, powerful elite. But the potential of diffusion to facilitate dual-use requires attention as well. The dual-use discussion is often focused on potential terrorist activities, for example the production of pathogens via synthetic biology methods. The increasing ease of both information access and DNA synthesis makes such misuse ever more plausible, year after year. The dual-use of technology also has potential manifestations in the clandestine production of unregulated products including illicit drugs. Considering the term “home-brew opiates” was used in the pages of Nature over two years ago, one is left to wonder the implications of further progress and accessibility that has ensued since. Debate and planning cannot be postponed here.

Last but not least, is the question of whether “total biological novelty” is something we as a society are ready to cope with. We know, for example, that de-extinction, significant health-span extension, and the genetic engineering of humans are now realistic aims. While the purpose behind these technological advances is obvious, it is plausible that our diverse publics will not endorse these innovations without reservation. It would not be the first time that there are spiritual objections, winners and losers, different beneficiaries and risk-bearers. Thus, a debate on risk tolerance, costs and benefits, and moral limits must happen, sooner rather than later. It must demonstrate a transparency and openness in scientific progress, which is essential to build and maintain trust, and would function to inform innovators about market realities, and shine a light on ethics, including decision-making processes. Such knowledge would inform which procedures are most acceptable and which product functions are most needed and wanted. As in any good design, form needs to follow function.

I have a personal wish list when it comes to what we collectively should do. My top wish is a focus on capacity building in multiple ways towards something we can call “responsible innovation” (see www.ricah.ca on this point). We need to create innovation capacities so that we can become direct beneficiaries of this technology platform. We also need regulatory and risk assessment capacities to address the pacing problem. We need societal capacities to discuss complex science and technology issues including costs and benefits, risks and risk tolerances, moral duties and moral limits. We need political capacities to take leadership on technologies that will change the world. Enhanced capacities of this kind should lead to improved upstream engagement (linking innovators to stakeholders), public involvement, foresight and planning, and adaptive management towards shared goals. Arriving at shared goals sounds like a good thing to me.

What is the Genome Project-Write?

Thirty-two years ago, the largest life science project ever conducted, the Human Genome Project (HGP), was proposed to “read” or sequence a human genome. Successfully completed in 2003, this project sparked a revolution in science that has changed the way we understand the human body and the world, and incited the advancement of technology which decreased the costs of sequencing by more than 3-million fold. However, despite this incredible leap forward in knowledge and technology, our understanding of the genome post-HGP is far from complete. For, in the words of Richard Feynman, “what I cannot create, I cannot understand.”

Thus, building on the knowledge and technological advances of the HGP, the Genome Project-Write (GP-Write), which is endeavoring to actively synthesize, or “write,” DNA to build complete complex genomes from scratch, is the natural next step in scientific progress.

To meet its objective of grand scale synthesis and genome editing over the next ten years, GP-Write will necessarily harness the collective power and expertise of the global scientific community to drive the development of the requisite tools, technology, and methods that are, at present, still undiscovered. To date, nearly 200 scientists from 15 countries have expressed interest in participating in the project, spurred on by a $250k seed from Autodesk. In total, the effort is expected to attract over $1B in funding.

What value will GP-Write generate?

The GP-Write will greatly advance and transform fundamental knowledge of the biology of living organisms. It will dramatically advance DNA-synthesis technologies to make the writing of genetic material more precise and the artificial production of genomes easier, faster, and cheaper.

GP-Write will catalyze the pursuit and development of the technology, tools, and expertise needed to synthesize whole genomes. This process alone will generate a wealth of information that will provide insights and answers to fundamental biological questions which have eluded scientific explanation thus far. For instance, relating the sequence of nucleotides in synthesized DNA to physiological properties and functional behaviors will greatly improve our knowledge of the large number of human genes with unknown function. Likewise, it will enable an understanding of the function of non-coding regions that make up the majority of the human genome. These developments will enable incredible insights into human biology and disease, and have the potential to transform our approach to health and illness.

Moreover, just as sequence costs plummeted following the HGP, GP-Write aims to decrease DNA synthesis costs by over 1000-fold. As DNA synthesis is already used as a platform technology in research, increasing accessibility will accelerate research and development across the spectrum of biotechnology, and improve the accessibility, breadth and quality of the research being conducted. For instance, the ability to design and synthesize DNA in a fraction of the time and at the fraction of the cost will largely enable scientists to create custom cell lines and organoids to study disease and discover drugs, and study plant traits such as yield and disease tolerance.

Furthermore, the ability to design custom genomes for industrially relevant organisms like plants and microbes engenders the ability to employ natural biology as a technology. Equipping engineers with the capability to digitally design and rapidly create cells as biological ‘apps’ will make using living cells and their powerful hardware as simple as computer programming. This will not only significantly speed up technical development and reduce time-to-market for existing applications, but will also enable previously unthinkable possibilities, like designing trees to grow in controlled shapes like houses or storing vast amounts of digital data in DNA hard drives. It will drive a transformation in how we produce materials, grow our food, treat disease, and remediate the environment – and usher in an era of using biology as a technology to inform and design solutions for the myriad of global challenges facing humanity today.

How are concerns about safety and ethics being addressed?

In a field centered on engineering and synthetizing entire genomes and creating new organisms, safety and ethical issues must be addressed parallel to technology development. Indeed, progress in technology development will necessarily create new, and often unforeseen, ethical and safety issues that must be analyzed and acted upon as they arise. Therefore, GP-Write is engaging a diverse array of perspectives “including leading experts, but more broadly harnessing the collective wisdom of ordinary members of the public” to consider the “ethical, legal/policy, social, religious, and other impacts” of GP-Write. The project infrastructure will also include the active engagement of the humanities and social sciences, including but not limited to bioethicists and legal scholars, and it will establish robust mechanisms for community engagement to enable inclusive decision-making.

How can Ontario scientists get involved?

GP-Write is still in its infancy, meaning Ontario scientists have the opportunity to make significant contributions to the work of the initiative and this emerging area of research. Here are a few ways to get involved:

Visit the Engineering Biology Center to learn more
Sign up to attend the May 2017 GP-Write Meeting at the New York Genome Centre
Contact co-founder Nancy Kelley to join the consortium
Submit a pilot project proposal

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