Why does biology take so long to make commercial products? A Job for BOB

May 25, 2016 |

The profusion of government-based Three-Letter Acronyms got so out of hand at one stage that the Navy’s Director of Operational Energy Chris Tindal began a meeting not long ago with a slide that said, simply, EYA. Explain Your Acronym.

But there’s one TLA that was so friendly and promising that it forms the exception to the rule, and that was BOB.

Yep, Bob. The Berkeley Open BioFoundry. Only it’s not BOB anymore. It’s the Syn Bio Foundry. Pronounced Sybfff, one supposes.

What is SBF and why?

“PDO by DuPont and Tate & Lyle was a big success in the end,” Keasling told us, “but took $130M and the development took 15 years.

“The construction of the artemisinin-producing yeast required $25 million in funding and 150 person-years of work, 10 years in all, typical of similar-sized bioengineering projects,” Keasling added. “New synthetic biology and computational technologies are needed to accelerate the development of productive biological systems and  reduce their costs, and industry needs access to them if traditional manufacturing is to be transformed by biomanufacturing.”

So, the aim is to integrate tools and technologies with process analysis and scale-up for more efficient biological engineering. It’s an EERE sponsored effort to build consortium of nine national labs (LBNL, Ames, Argonne, Idaho, Los Alamos, NREL, Oak Ridge, Pacific Northwest, and Sandia).

Initial targets will be molecule/organism combinations that allow us to integrate and stand up the SBF

The workshop all about it

There’s an industry workshop for feedback on the vision — June 14, 2016 in DC. Here’s where you find out all about that.

It raises the question, why is so biology so challenging?

“It’s partly how we have done it. We sort through the research, then we design, and then we spend a lot of time in the lab pipetting liquids, then finally write down the data. But the next cycle of design is not all that improved. Overall, biological engineering is very artisanal.”

Why don’t companies simply partner up and share resources?

“Hosts and tools are not shared, companies who rarely share their tech and they consider it part of their corporate DNA. So the timelines for development don’t fall as fast they could . And these development costs and timeframes and challenges limit start-ups. I’ve seen this up close and over and over again.”

True enough. Although biomanufacturing generates more than $190B per year in the US — and California scoops up around $50B of that, complexity and cost are huge issues.

So, a foundry answers this?

“Wouldn’t it be great if you could just design on a computer, and then some biofoundry, possibly out in the middle of nowhere and with completely different timelines and costs than you would have as a start-up building your own foundry, builds your organism remotely and then you work with it.”

In short, as Berkeley Lab put it back in 2014, “the engineering of biological systems to produce valuable molecules on a commercial scale. In short, what the Molecular Foundry does for nanomaterials.”

Making the usual suspects in molecules?

“It might be completely new chemicals, new platforms,” said Keasling. “Basically, a whole range of materials that you see all around you come from petroleum. Not because they were the best materials, but because those were convenient at the time, because petroleum was what we had that was cheap.”

So, biomass offers alternatives to the same-old?

“Now that we have biomass coming along, and waste materials as a feedstock, we might use computational tools for predicting material properties for monomer chemistry, or make polymers directly. Some companies are focused on proteins as materials. If we can put the design focus first — keep our eye on the properties we want, then we’ll decide later whether to go for a monomer or polymer; we might use biology alone, or biology in combination with chemistry.”

So, letting the performance dictate the design, rather than what the raw material can easily do?

“Yes,” Keasling said, “it’s not the push-in of “here, we have biomass,” let’s make things from that. But let’s figure out what we could make things from, and what the ideal materials and platforms and molecules might be. So we design, and then use biology to build them.”

As envisioned, it could work in 3 ways.

“Help us build the foundry, and then take your designs home,” Keasling explained. “Or, hire the foundry to build an organism for you, pay the full cost and take IP home with you. Or, work with the foundry hand in hand and get favorable IP terms on the organisms created although it wouldn’t be exclusive.

Is this all based on e.coli and yeast?

“E.coli and yeast? That’s been done,” Keasling explained. “It’s clear from our listening sessions that we need organisms that are industrially robust and live in the temperatures and pressures we need for manufacturing, and high PH. Let’s look at organisms that have great properties but where we haven’t worked out the genetics — and we’ll build those out.”

“This center of excellence would be a biofoundry of unprecedented scale, encompassing sophisticated design, build, test and learn tools, and a world-class team of scientific leaders in metabolic pathway design, DNA synthesis and sequence validation, microbial strain construction and testing, and systems biology,” Keasling said. “As an open facility, this center of excellence will serve not only industry but the nation as a whole.”

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