You arrived at Berkeley in 1992 with training as both a chemical engineer and a biologist. What did you hope to do?

I came with the idea that we could make drugs and chemicals inside microbes. If you want to produce a drug, it may take a huge number of chemical steps—so many that it's not economically feasible using just chemistry. And I thought, gosh, we could be doing a lot of this chemistry inside the cell, using enzymes. Enzymes can do in one step what might take many steps using synthetic organic chemistry. What's more, we could start with something cheap like sugar and end up with something valuable. Once you get one microbe to do it, you can grow that microbe at any scale from a 10-milliliter test tube up to a 100,000-liter fermenter. Unfortunately, when I started we didn't have a lot of tools to manipulate chemistry inside the cell.

Why hadn't anybody tried to engineer cells that way before?

The biotech industry was based on producing a single protein in a cell. For instance, with human growth hormone and human insulin, the first ones to be made by a recombinant DNA, you take one gene, put it into E. coli, express it at an extremely high level, and produce your protein of interest. That's your drug, and you're finished. You break the cells open and you get your drug out. But something like Taxol [a cancer drug] takes many genes to be expressed. You need very fine control of gene expression. When you're producing human growth hormone, you don't need fine control because you just want to fill up the cells with proteins and then break them open.


What made you think that kind of approach was possible?


The Berkeley West Biocenter houses the world's first synthetic biology department, where biological systems are designed.

Courtesy of Roy Kaltschmidt, LBNL

Take bacteria, for instance. When they experience a big shift in temperature, they change the genes that are expressed in the cell. They have control systems that do this, just as in your house when the temperature goes down, the thermostat kicks the furnace on. If you understand these controls, you can make the cell do something that it wouldn't necessarily want to do. That's really where I started thinking about this integration of engineering and biology—not to build tanks to grow microbes but actually to go in and reengineer the cell as a chemical reactor. That's how we treat the cell in my lab: It's a chemical reactor. It takes in something very simple and spits out something complicated and valuable.

When did synthetic biology become a part of your life?

I first heard about the area of synthetic biology about three years ago. I had been doing it all along. It just didn't have a name.

How did you get involved in your antimalaria project?

I became acquainted with a group of natural products called isoprenoids. There's a lot of chemistry there, a huge number of valuable products. It just seemed like a great area in which to be doing research. So we started with a focus of building up the basic pathways needed to make those chemicals, and we thought, what are we going to use this pathway for? We could produce menthol. We could produce beta-carotene. And then a graduate student came to me with an article reporting that the first gene in the pathway for the production of artemisinin had been cloned. I didn't even know what artemisinin was at the time. We thought, gosh, this sounds like a great thing to be working on.

Other than pharmaceuticals, what do you see as some of the most promising near-term developments in synthetic biology?

I think we're going to see it used for fuels. I think that kind of product is not so far off. Unlike pharmaceuticals, it would not have to get FDA approval. I think energy is going to be a really great area. ­DuPont is making an effort to produce propane diol, which is a precursor to carpet fibers, and they're producing it in E. coli that have been genetically engineered. Every year it gets easier and easier to do this stuff because more tools become available, particularly if we have a vibrant synthetic biology industry—or at least a group of people working in this research area producing tools.

What else are you working on in your lab?

Artemisinin is a hydrocarbon, and we have a huge need for hydrocarbons in the fuels area. So while we're still focused on artemisinin, we are starting biofuels projects in the lab that will ramp up even more once the artemisinin project is completed.

So essentially you'd be creating fuels out of sugar?

That's right. Hopefully cellulose.