Interview with Brian H. Davison

INDUSTRIAL BIOTECHNOLOGY: How do you envision the future landscape of industrial biotechnology unfolding? How will biobased innovation help drive the global bioeconomy?

BRIAN DAVISON: We face a real challenge as we continue to roll out what we call “white biotechnology.” We will continue to use industrial biotechnology in areas in which we have been using it all along–products, chemicals, fuels, pharmaceuticals–but how do we accelerate the mode of bringing it in and find ways to try more ideas and derisk them earlier? It will be interesting to see how we balance the increasing power of our ability to do metabolic engineering and link that back into the process technology side of things, which remains important as we move to scale-up and implementation. That is where industrial biotechnology really works, at the interface between what metabolic engineering, chemistry, and these other new tools allow us to do as a proof-of-concept and the process configurations that allow us to do it better and at scale.

We have seen a swing toward metabolic engineering approaches as the solution to problems. I think the pendulum will continue to swing away from where industrial biotechnology was 25 years ago, which was more process-based solutions–reactors, fermenters, separations, for example. One of the challenges is that even though there have been huge successes with the biology-based approaches, when it comes to being part of a bioeconomy, these have to be tested and put to scale. If you rely only on the metabolic engineering side of things without linking it to the process, separations, and logistics side, you are going to stumble later in the process rather than earlier.

The core of innovation will derive from the ability to manipulate biology. During the next decade more innovations will continue to come from that side, rather than from the process side, although advances in areas such as immobilization and membrane separation, for example, will be essential for implementing the technologies and bringing them into the market.

IND BIOTECH: What would you describe as the main challenges facing the industrial biotechnology community at present? Do the solutions lie mainly in the area of R&D/technology advances, policy, funding, or greater integration and coordination of effort?

BRIAN DAVISON: One important challenge is the need to derisk the technology. One of the challenges we have faced over the past 5 years in biofuels has been the requirement for $100-$300 million of capital to build a cellulosic biorefinery. There were some significant challenges in the last 5 years to raising that much capital for a new technology. The core element of that is risk, which is what the financiers look at. To move things into the bioeconomy, the industry needs to find easier, earlier ways to implement things that have lower risk so they have a better chance of moving forward.

Another thing the industry needs to do is to continue trying a wider number of ideas. Most new ideas do not successfully advance into commercial practice; we know this from the venture capital industry. One of the challenges for industrial biotechnology in this regard is that most of the research dollars come from the government, and the government is increasingly risk-averse. Can you imagine selling to Congress a proposal in which you expect half of the things you are going to try to fail, in the hopes of achieving one huge success, as is the norm in the venture capital industry?

I think one of the main challenges for the industrial biotechnology community remains in the interfaces between the biology side and the process side; between new tools and techniques in genetic engineering, synthetic and systems biology, and computational resources for large data management, and linking that into how it helps you move something forward and succeed. I think we have shown that many of these things can work in principle–we have shown proof of concept–but then moving further across what is sometimes called “the valley of death” remains a challenge. We have learned from the drug and pharma side that we need to be able to identify barriers earlier.

We also face other challenges in the biofuels, bioproducts, and renewables areas in terms of stability. We talked about financing risk, but there is also policy instability, which adds another layer of risk. For example, will the rules on the Renewable Fuels Standard (RFS) change this year, next year, in 2 years, or 5 years? As a community, we need to be realistic about risk and communicate risk, even while remaining optimistic. As researchers, we are supposed to take risks and to try things that have not been tried before.

IND BIOTECH: What would you identify as the greatest positive change in the industrial biotechnology community or overall research environment since you began your career? The biggest negative change?

BRIAN DAVISON: The recognition and the value of team-oriented science has been a big positive change, as well as the support at multiple levels of research centers, whether physical or virtual centers to help people interact and work together. We need to be doing more of that. We need to dig deeper into systems biology and, for example, our expanded understanding across new technologies the past couple of decades has been insightful and powerful in terms of building our fundamental knowledge. There have been some great examples of people and organizations that have built very successful teams. One is DuPont's success with 1,3-propanediol (PDO), in which the company combined multiple strategies of biological understanding, metabolic engineering, and mutagenesis to develop a microbial strain that became their production strain. While accomplishing this, their team was working with biochemical and separations engineers on scale-up and developing a commercial process. The ability to build teams and to exploit new tools across multiple disciplines has been a really powerful phenomenon throughout my career. These successes create a foundation not only of biological models for greater understanding, but also conceptual models for how to work together.

In terms of negatives, one challenge of being in research in this area is the increasing push on publish or perish. Therefore, while industry, national laboratories, and sponsors see the value of “team science,” this is not always recognized in university tenure committees. Another is what I described previously as an increasing aversion to risk, encompassing both the cost and time to try exploratory ideas. I think we need to try more ideas, with the hope of finding something successful or failing early. But either the funding needs to be available to do that, or there needs to be the slack in time and schedules to allow researchers to do that on the side, and there is less and less of that slack in every part of the research system these days.

IND BIOTECH: What are your main research and career interests at present? What are you most passionate about?

BRIAN DAVISON: I am a biochemical engineer and I have been working essentially as an industrial microbiologist. My research interests target renewable bioenergy and bioproducts. I have worked mainly in the area of experimenting with different techniques to work at the interface of biology and multiple phases. For example, linking separations with reactors, immobilization, and solid substrates such as biomass. That has been the main focus of my career—looking at biology in complex systems and how these reactions occur in the cellular, reactor, and natural environment.

I am an advocate for renewable bioenergy and bioproducts, even though there is ongoing debate. Although there are some valid reasons for the debate, my response is that renewable solutions are still better than many of the alternatives. We know there are ways we can grow biofeedstocks unsustainably and there are ways we can grow them more sustainably. With more knowledge we need to help society move forward with good strategies and not let purely economic drivers push things into bad strategies in terms of sustainability and functionality.

I think there is a valid role for GMOs, and we have certainly gotten comfortable with that in the US in terms of the industrial environment for producing drugs and other types of commodity and higher value chemicals, and even in the production of some crops. But again we have to find ways to derisk the technology and to express the risks carefully to the public and to regulators. In one of my roles at Oak Ridge, I chair our Institutional Biosafety Committee, and I get to see and talk about a lot of the issues related to what we are doing and whether we are doing it properly and safely.

IND BIOTECH: How do you see your role in championing industrial biotechnology?

BRIAN DAVISON: My role as Science Coordinator in the BioEnergy Science Center is one of the most important things I do to foster integration and to help champion industrial biotechnology. Part of “championing” is to help tell the story. As scientists, I think we undervalue the power of telling the story and using metaphor to communicate the power and value of science and of how things progress and move forward to our sponsors, to our elected government, to other scientists, and to the public. We all need to find ways to carry out that conversation better at multiple levels of technical density. This often means leaving our comfort zones and communicating what we are doing. I often tell my students and younger colleagues that they need to be able to explain their research to their mothers. They often give me a very blank look. They do not need to present their full dissertation, but to give a 2 to 3 minute version that a nonscientist can understand. That takes practice, but you do get better at it. I give my mother much credit for my ability to be able to explain science—since she would keep asking questions until I explained in a way she could understand.

An important aspect of championing industrial biotechnology is being able to communicate life at the interfaces. I am a good example; I was trained as a chemical engineer, I have essentially been working in microbiology, and now I work with biologists doing various kinds of research and with a large number of other kinds of scientists in this area. Part of this experience is being able to translate and move between these different disciplines.

Another big challenge for industrial biotechnology is in the interfaces of the different scales at which our biology functions: the subcellular, the membrane level, the organization of cells, films and biofilms, how they attach to form substrates and ecosystems, the reactors, and mass transfer between solid, liquid, and gas phases. All of those factors come into these interfaces as well, and you have to be able to move between them and not assume that everything is the same within them.