American Chemical Society AMA: Hi Reddit! My name is Megan J. Palmer, of the Center for International Security and Cooperation (CISAC) at Stanford University. Ask me anything about synthetic biology and the responsible development of biotechnology!

Abstract

Hi Reddit! I’m Megan J. Palmer, a Senior Research Scholar at the Center for International Security and Cooperation (CISAC) at Stanford University. I lead a research program focused on governing risk in biotechnology and other emerging technologies. Before moving to Stanford, I served for 5 years as the Deputy Director of the policy-related research program of the multi-university Synthetic Biology Engineering Research Center (Synberc). I was also previously a research scientist at the California Center for Quantitative Bioscience at UC Berkeley, and an affiliate of Lawrence Berkeley National Labs.

I believe that getting diverse communities working in biotechnology more involved in policy discussions is vital to developing the quickly advancing field responsibly and building global leadership to prepare for and respond to inevitable surprise. I founded and serve as Executive Director of the Synthetic Biology Leadership Excellence Accelerator Program (LEAP), which is an international fellowship program in responsible biotechnology leadership. I also lead programs in safety and responsible innovation (which we call ‘Human Practices’) for the international Genetically Engineered Machine (iGEM) competition. I advise various organizations on their approach to biotechnology policy, including serving on the board of the synthetic biology program of the U.S. Department of Energy’s Joint Genomics Institute (JGI).

Before moving into policy I trained as a scientist and engineer. My Ph.D. is in in Biological Engineering from MIT, and I was a postdoctoral scholar in the Bioengineering Department at Stanford University. I received a B.Sc.E. in Engineering Chemistry from Queen’s University, in Kingston, Canada.

Ask me anything about synthetic biology and the responsible development of biotechnology!

Hi Reddit! I'll be online for the next hour (10-11am PT) to answer your questions!

These are great questions - I'll stick around until 11:30 PT to answer a few more.

I'll be back online later this afternoon so feel free to keep asking away! (~2:30 PT)

Thanks Reddit for all our your great questions. I wish I had been able to get to them all! I hope some of the information and resources I've linked to will keep you engaged in this exciting area of work. Until next time! Cheers - Megan

To be honest, I could use a brief synopsis of what synthetic biology currently is. What does your work entail? What goals does your 'industry' have in mind?

ACleverRedditorName

This is a broad, multi-part question – perhaps a good place to start!

What is synthetic biology? You can come across many definitions of synthetic biology. Synthetic biology often refers broadly to the development of foundational tools enabling biotechnology. A slightly more involved definition is that synthetic biology is the deliberate design and construction of biological systems to perform new or improved functions. One guiding philosophy of the field is that taking an engineering approach to biology, including learning by doing, is a powerful way to explore and use living systems. Synthetic biology applications areas are far-reaching –health and medicine, energy, environment, materials production, and more.

I was involved with a project called ‘Building with Biology’ that developed some introductory materials on synthetic biology. You can check them out at www.buildingwithbiology.org.

What does my work entail? My work spans a number of activities and topics at the intersection of synthetic biology and society. As deputy director of the policy-related effort of Synberc, I worked on a wide variety of education, research, and public engagement (including policy engagement) projects. Some of the topic areas we worked on were safety, security, intellectual property, and community organization and governance.

Lately, my work has focused on biological safety and security. I’m interested in how we design and adapt processes to ensure that the technologies we develop overwhelmingly help rather than harm. In some cases technology can quickly outpace policy, and a key challenge is how to equip practitioners working in the field to identify potential issues, and work effectively with policy makers to develop appropriate regulations. This work has involved developing training and educational programs, researching the effectiveness of new policies, and working with policy makers and managers in the US and internationally to update policies and policy-making processes.

What are the goals of the ‘industry’? It’s probably more useful to talk about the community or field rather than a single industry, as biotechnology impacts many industry sectors. Moreover, the specific goals of the community can be just as diverse as the people involved. One goal of the field is to develop more sustainable approaches to production of existing and new materials. For instance, developing platforms for bio-based plastics, or engineering cells to produce and tailor super strong materials like spider-silk. Another goals is to harness the ability of biological systems to perform functions more effectively or efficiently than what you can achieve using non-biological systems. Some of these efforts involve engineering cellular systems to fight disease within the body, or developing biological systems outside the body to test new drugs. Other interesting applications use biological parts – such as using DNA as an efficient data storage tool

Biology is an amazing partner to make and do a huge diversity of things – which is one reason why I think it is such an exciting field to work in.


Hi Dr. Palmer! What are your thoughts on the use of gene drives for eliminating an entire species of mosquito that transmits human disease?

Is it too risky of a ecological decision to purposefully eliminate such a widespread species?

da6id

For those of you not familiar with the concept of gene drive, it refers to a phenomena whereby DNA is inherited more frequently than normal (i.e. closer to 100% than the normal 50%) – “driving” heritable traits through populations over successive generations. While gene drive occurs in nature, only recently have scientists shown they can use gene editing tools to harness these systems and introduce them into new systems.

The possibility of using gene drives has brought a lot of excitement and concerns. On one hand, it could be used to help eliminate disease vectors such as mosquitoes spreading malaria. On the other, it may allow ecosystem-level alterations through the release of a single organisms from a single lab that could have unanticipated effects.

I think that gene drive is a useful approach to continue developing in the laboratory - with extra caution and safeguards - especially as it may allow a new approach to countering diseases that are massive public health problems. However, we have not yet fully determined how to conduct tests (inside and outside of the laboratory) to determine its effects upon wider release. There are a lot of smart people now thinking about how to test gene drive systems and improve our regulatory processes to assess risks both before and potentially after their use. A recent National Academies study explored some of these issues: http://nas-sites.org/gene-drives/.

This is a great example of where new tools and discoveries are creating a need for innovations in policy including how we collectively agree to proceed. My hope is that we spend just as much – if not more – in building these policy tools and approaches as we do the technology tools.


Hi Dr. Palmer, thank you for doing this AMA. What exactly constitutes "responsible biotechnology" and how are the boundaries for safe synthetic biology established? What are some projects that might be pushing the limits of what is considered appropriate?

shiruken

What constitutes “responsible biotechnology” is a difficult question – and is the subject of my research. My work tries to understand the processes by which norms and standards in the field are being developed and promulgated in practice. A number of my colleagues working in areas such as ‘science and technology studies’ and ‘responsible research and innovation’ are also looking at these issues.

While the details may differ with each case, the overarching way I think about responsibility in biotechnology development is when practitioners establish processes that allow active, regular reflection on the goals and means of their work. These processes should be designed to achieve a number of goals including accountability, transparency and deliberation.

In practice, it has been over 40 years since the advent of modern molecular biology, and many norms and standards established by the field’s founders persist today. For instance, the way we classify the risk levels of biological experiments, and the safeguards used to mitigate risks, were developed in the 70s. While scientists helped to develop those standards, government agencies (including regulatory and funding agencies) have been critical in formalizing, promulgating and updating those rules. The precedent that scientists have a responsibility to take an active role in governance continues to be one of the most important safeguards as the field advances. This means scientific societies (which often operate internationally) have a critical role in shaping was is and is not acceptable.

On the commercial side, the framework developed to regulate biotechnology products in the US was first developed in the 80s, and remains largely the same today. The US government recently undertook a revision of this framework (https://www.whitehouse.gov/sites/default/files/microsites/ostp/modernizing_the_reg_system_for_biotech_products_memo_final.pdf). Among the reasons for the review were that new products not fully anticipated when the framework was first developed were exposing potential gaps, ambiguities and uncertainties on how new products should be categorized and which agencies has authority. The US government developed a series of ‘hypothetical case studies’ on products that may pose ambiguities. You can read about them here: https://www.aphis.usda.gov/biotechnology/downloads/Meetings/cf_mod/cf_case_studies.pdf. The white house has also recently released a strategy for modernizing the regulatory system: https://www.whitehouse.gov/sites/default/files/microsites/ostp/biotech_national_strategy_final.pdf

One key principle underpinning these policies is that the regulation of products instead of processes – in essence, saying thay just because something is made from biotechnology doesn't make it inherently less safe, but that we need to consider products on a case by case basis. One difficultly of this approach is that when we don’t have a precedent for a new product it can take time to figure out how to assess its safety.


Do you think synthetic biology will be an important part of future efforts to address climate change, for example through the development of microbially-produced biofuels?

pensivebadger

I think that synthetic biology could provide some useful strategies to help address climate change. One way is through the development of less carbon-intensive production platforms. Another might be new ways to generate and storage energy that involve biological systems. We still have a ways to go in developing platforms for large-scale production of some things - like fuel - that have large enough margins to make them economically viable. Right now a lot of the focus is on more specialty high-value, low-volume chemicals. In time both new processes and changing economic drivers may change the balance.


Hello Dr. Palmer. Thank you for doing this AMA!

There is a growing concern among the public about the development, possibly accidentally, of "superbug" microorganisms such as drug resistant bacteria, fungi and viruses. I'm hearing a lot of concerns from people that research into treatments for these pathogens might end up making things worse. Could you comment on the sorts of policies that are in place, or coming into place, at both the academic and federal, governmental level, to alleviate some of the risks of working with resistance-developing microorganisms?

Zargyboy

‘Risky research’ is receiving increased attention lately as governments in the US and elsewhere consider whether certain research should not be pursued because it poses unjustifiable risks to public health and safety. These risks could involve accidents and unintended consequences (biosafety) or from intentional misuse (biosecurity).

Biological research is inherently dual use – meaning it has the potential to be used in both beneficial and harmful ways. Increasingly there is recognition that a subset of research may pose special concerns to public health and safety by generating knowledge, products or technologies that could be directly misapplied. This work has come to be referred to a Dual Use Research of Concern (DURC).

The term DURC originated 15 years ago with a US National Academies committee formed to examine dual use concerns after series of experiments raised fears of misuse. Their report, Biotechnology Research in the Age of Terrorism (commonly known as the Fink report) outlined seven classes of experiments that could raise misuse concerns. The committee also recommended creating a National Scientific Advisory Board for Biosecurity (NSABB) to provide guidance to all federal agencies involved in life science research on research oversight and other dual use concerns.

Since that time the NSABB was established as a federal advisory committee (in 2004) and new policies have been developed that aim to address DURC oversight. The US Government Policy for Oversight of Life Sciences DURC was released in March 2012, which focused on government departments reviewing research for potential dual-use issues. Additional details on roles and responsibilities were outlined in the 2014 US Government Policy for Institutional Oversight of Life Sciences DURC, which went into effect September 2015. This policy requires that institutions review the seven classes of concerning research studies. However, this review is currently limited to only 15 biological select agents and toxins deemed to pose the greatest risk of misuse and to work conducted or funded by the federal government, meaning there is still work to do.

DURC has generated controversies amongst scientific and policy communities alike regarding the benefits, risks and effective governance strategies. Recently the discussion has revolved around experiments that developed influenza strains that were more transmissible in mammals. These experiments, referred to as ‘Gain of Function’ (GOF) research, raise concerns that the ‘pandemic potential pathogens’ it may create could escape or be used by terrorists. Proponents claim benefits for surveillance and countermeasure development outweighed risks.

In the summer of 2014, the US government instituted a pause in funding for GOF research and chartered the NSABB to conduct a comprehensive risk benefit assessment and a deliberative process to develop recommendations for a new funding policy. You can read the committee’s final recommendations at the link below, which the US government is currently actively considering.

One take-away from this review was there is a small subset of experiments that are too risky to pursue, but for the vast majority of work the benefits likely outweigh the risks. The other is that we often don’t have sufficient data to make well-informed decisions about what might be too risky. This mean that we have to increase our ability to collect data on risks, take steps to anticipate risks, and also develop ways to respond to inevitable surprises.

Similar conversations are happening in other countries, and oversight of dual use research is an active topic in international efforts like the global health security agenda and in the review of science and technology advances pertinent to the UN biological weapons convention.

Fink report: https://www.nap.edu/catalog/10827/biotechnology-research-in-an-age-of-terrorism

NSABB: http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/nsabb

2012 DURC Policy: http://www.phe.gov/s3/dualuse/documents/us-policy-durc-032812.pdf

2014 DURC Policy: http://www.phe.gov/s3/dualuse/documents/durc-policy.pdf

GOF Research Pause: http://www.phe.gov/s3/dualuse/documents/gain-of-function.pdf

NSABB GOF Recommendations: http://osp.od.nih.gov/sites/default/files/NSABB_Final_Report_Recommendations_Evaluation_Oversight_Proposed_Gain_of_Function_Research.pdf


In your field, would you say there is any one particular issue the general public should be more aware of or try to get involved in?

sciencecalibrations

I don't love the term 'general public' as it often misses out on the wide diversity of publics. I think scientists and engineers could be more engaged in understanding and appreciating how the values and interests of different communities might change what technologies (or social interventions) are most appropriate.

It’s hard to narrow it down to one issue that I wish everyone knew about but I think it’s important that we are all aware of how much biotechnology is already impacting our lives – from medicines, to foods (not just those engineered using modern techniques, but also using breeding, to industrial products. I also would love to see more folks involved in local community biolabs and other public engagement projects that can help to demystify the science and get more folks directly engaged in contributing their ideas to the field.

I also think that beyond utility, I would love everyone to share a sense of awe about biological systems and how much we still have to learn about the world around us.


Hi! Thanks for the AMA. In your opinion, what is the most interesting biotechnological feat you have witnessed while working in the field? Theoretical or physical. Maybe both if you have two favourites.

Tanger68

This is a really difficult question as I’m constantly amazed by work being done in this field. And biological systems already do astonishing things without our intervention.

I think some of the most interesting work is in making genome-scale alterations of biological systems (including the development of tools to make these alterations possible). One fascinating project was work in the Church lab at Harvard involving the systematic replacement of codons in e.coli: http://science.sciencemag.org/content/353/6301/819


Hi Megan! As a member of iGEM HQ, I'm really excited to see you doing an AMA! (And we'll all see you this weekend!)

In your opinion, what are the major safety concerns for synthetic biology in the next 5-10 years? Are researchers taking these concerns seriously? And do you have any general tips for researchers in terms of talking about synthetic biology to a broader audience? (other than this great AMA!)

Traci_at_iGEM

Hey Tracy! I’m excited for the iGEM competition this weekend!

Let’s break up your (great!) questions.

What are the major safety concerns for synthetic biology in the next 5-10 years? This is a difficult question – and I think that in general we need to be prepared to be surprised by safety concerns that may emerge.

One issue is our limited ability to predict the emergence of complex biological functions and phenotypes. This is really a (if not the) central scientific challenge for the field, but the safety aspects relate to predicting the emergence phenotypes that impact human, animal and environmental health (like pathogenicity or transmissibility). Such predictions could help us to ensure we put appropriate safeguards in place. The recent ‘Gain of Function’ discussion revealed a paradox whereby it may be too risky in some cases to do experiments to answer these types of questions.

I think that gene drives, and opening up the possibility of making ecosystem level changes through single organism alterations, poses complex safety challenges.

There are also concerns about the deliberate misuse of advanced biotechnology tools as they become easier and more accessible. However, a lot of experts don’t agree on the scale of the threat. Again, we can anticipate some possibilities but also need to prepare to be surprised.

It is also really important to recognize that synthetic biology can help us better understand and counteract current safety concerns. Biological tools can help us understand what our human interventions have already done to natural environments, and help us decipher the roots of disease. They also offer opportunities to better understand and develop responses to threats such as infectious disease.

Are researchers taking these concerns seriously? My experience is that researchers by and large are genuinely interested in ensuring that their work is conducted safely and is used in the most beneficial ways possible.

However, identifying risks (and opportunities!) in your own work can sometimes be difficult, especially when that type of reflection is not well resourced. mentored or incentivized. That’s why it is critical to keep improving systems that help us check our assumptions. Groups like institutional review boards can provide extra scrutiny and complementary information and expertise to research projects and they may think of scenarios you may not have. Unfortunately when we lose sight of the spirit of these systems of oversight, those systems can start seeking like unnecessary barriers to work.

We rely on scientific and policy leaders alike to lead by example in taking these issues seriously and working together to improve our systems of oversight. I think the synthetic biology community by and large has taken a leadership role on these issues – in no small part due to iGEM and decisions by the NSF and Synberc to treat this area as a long-term research topic. I’m encouraged to see more researchers getting excited about safety as a design challenge – not something that detracts from their work but rather that inspires it.

Do you have any general tips for researchers in terms of talking about synthetic biology to a broader audience? I would again point to some of the resources we have developed with the building with biology (ww.buildingwithbiology.org). Communication with new audiences takes practice, so my first piece of advice is to practice - and start local. One critical thing to remember is to listen to the people you are engaging – their interests and values are important and a great place to start a discussion. The key is to establish a dialogue and not just talk at someone. Your own story of what inspired you to be involved in the field can also be a great place to start. It’s also useful to try and put advances in context and discuss how synthetic biology is another step in the evolution of how we interact with our living world including non-molecular biology approaches like breeding. Because we are talking about engineering the very stuff we’re made of these conversations can often be challenging and emotionally charges - but they can help us all to understand our relationships with nature in new ways.


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