

Photograph by Peter Gregoire







If you think about the future of biotechnology, what’s old is becoming new again.

S+B: What do you mean by that?

Now we are back in the same arenas, with a new set of emerging technologies. To give you an idea of the excitement around the use of biotechnology for energy: The Berkeley Center for Synthetic Biology received about US$1 billion in grants in 2007. I’m the chairman of the board of trustees of this group. It was founded and is directed by Jay Keasling, a professor of bio- and chemical engineering at Berkeley and the director of Lawrence Berkeley National Laboratory’s Physical Biosciences Division. About half the energy research money came from BP and the other half came from federal grants. This is only the be­ginning. Biotechnology will be the basis for a whole new petro­leum-free carbon-based economy.

Carbon-neutral Energy Farms

S+B: How would synthetic biology produce energy on a mass scale?


We already know how to effectively create biomass from plants. We grow forests for wood; we have agriculture. With a combination of modern biotechnology techniques we could remove carbon from the air, turn it into a fuel, use that fuel, and return the carbon to the at­mosphere so the whole process is carbon-­neutral with respect to the concentration of carbon dioxide in the atmosphere. Essentially, these techniques would allow us to farm en­ergy, coupling the photosynthetic process with biochemical production of useful hydrocarbons.

Let me take you back in time to think about that for a minute. Before there was life on Earth, it was basically a wet, hot rock. When it cooled down, it was a rock with water. Living organisms arose (we’re not quite sure how), and over the course of several billion years, they transformed rock and water into this beautiful Earth. That’s enormous chemical power, and all of it is locked up in the genes of organisms that proliferate all over the world.



S+B: You mentioned energy farming. What does that look like?
HASELTINE: Many microorganisms grow in the sea, and there are a number of potential ways to use them for energy production. One is to place algae tanks far below the surface, but not so deep that they can’t get sunlight piped down to them. Another is to create a series of saltwater-filled tubes on the surface of a large desert and place algae so that sunlight is absorbed as you pump the water through. There are a number of places in the world where huge deserts are right next to the sea. You don’t want to use arable land, and this gets us away from freshwater, too.

These farms could create a continual atmospheric carbon-neutral production cycle: algae taking sunlight, fixing carbon, and producing useful fuels. As I said earlier, what is old is new again. Humanity used to burn wood for energy. Less than 200 years ago, we started burning fossil fuels. Now we’re returning to the older process, but it’s more efficient with the modern advances of genomics, gene regulation, gene splicing, microbial cultivation, and massive ocean engineering.

S+B: Doesn’t that suggest a reorientation for the energy industry?

Microbial Manufacturing

S+B: How will basic industrial manufacturing processes be changed?

S+B: What is the connection be­tween nanotechnology and biotechnology?
HASELTINE: The fundamental architecture of matter is an atom and a molecule. Something as large as a forest is made of very tiny substances, hooked together. Life and materials sciences are teaching us that we can arrange atoms in precise locations, to self-assemble and form units in small to very large sizes — replicating the manufacturing pro­cesses of nature. The fact that forests grow and that bacteria proliferate shows you that nano-machines work, and can be very efficient. We can build materials that self-assemble, and this means we can reduce the amount of material used in our lives. For example, we don’t have to carve objects out of great masses of metal (and discard the waste), because we can have them assembled, at the molecular or multimolecular level, with every molecule used. Eventually we can make them intelligent so they’ll assemble on command. The basic unit would be a very tiny, submicroscopic unit embodied with the information that says, “connect A, B, C, D.” It will then, in effect, construct itself: We can make a chair, we can make a table, and we can build a house.

This type of construction will probably not be available until the end of this century or the beginning of the next century. Think of it as an intelligent Lego set that you could program so the pieces compose themselves. You could then create a program that says, “Make a candlestick, make a chair, and make a wall.” Ray Kurzweil describes these types of technologies in his book The Age of Intelligent Machines (MIT Press, 1992).

S+B: What are the implications for food production?
Earth’s population is projected to rise to almost 10 billion by 2050. So the need for freshwater and land is acute; we must use our agricultural land more intensively. Genetically modified organisms can help with that. They can produce higher yields and more nutritious foods. They can obviate the need for plowing. Most people don’t understand what plowing is for. It’s really just a weed control technology. You plow over and under the previous year’s crop. But if you have the right combinations of environment-friendly herbicides and the agricultural crops that are resistant to those herbicides, you don’t need to plow. No-plow agriculture saves topsoil and energy. Once you don’t need so much nitrogen fertilizer or complex pesticides, you can get to an agriculture that is much more en­ergy efficient. You can also breed in drought resistance.

People will be healthier as a result. And it will allow us to restore many habitats, because we’ll be using less land to grow food.

S+B: What about the fears about genetically modified foods?
The technology is rapidly spreading, despite the European opposition. It’s spreading in many parts of the world because of its obvious advantages. For example, meat is a highly inefficient source of protein; over the next 20 to 30 years, people will move from meat to plants as a source of protein. I’ve been in Chinese restaurants that serve something that looks like a fish with skin and scales, but it’s entirely made out of soy protein, which is a plant product. You see a chicken that looks like a chicken, it’s carved like a chicken, but it’s not a chicken. You can make foods look and taste very attractive with manipulation, which, in this case, involves a process to spin soy proteins into fibers.

Investment and Infrastructure

S+B: Do you think the bioenergy industry will move ahead faster than the pharmaceutical industry has in the last 20 years in its commercialization of genomic discoveries?
The technology that might justify this amount of investment is finally emerging. Breakthroughs in the last few years have rapidly attracted large sums of investment capital. The Center for Synthetic Biology received its first half-billion-dollar grant less than a year and a half after showing proof of feasibility for the petroleum substitutes. Of course, that’s not how it usually happens. People don’t usu­ally make huge breakthroughs and all of a sudden have a venture capitalist say, “OK, let’s go.” But the volatility of oil prices has made investors realize that this can be very important.

I guarantee you that there are similar programs in constructive biology (though they may not use that name) at all the major chemical and energy companies. They too are looking at making petroleum substitutes. This type of activity doesn’t happen in isolation. When a group puts $1 billion into research, it gets people’s attention.

We also see the rise of very strong scientific communities in this field in other parts of the world. I have been working very closely with the leadership of the government of India. India’s Council of Scientific and Industrial Research, which is one of its major funding agencies, has fostered an alliance between a large group of Indian scientists and our group at Berkeley. We’re planning to [form similar alliances] with scientists in South America and China.

S+B: How challenging will it be to create the infrastructures for producing and distributing bioenergy?
HASELTINE: Constructive biology has the opportunity to produce power and transportation fuels that are fully compatible with our existing infrastructure or system. We might not need as many re­fineries, but we will still need the tankers, pipelines, and transport system.

There are still some major engineering problems. If you’re going to use a marine microorganism as your photosynthetic source of energy, how do you engineer that to be environmentally safe and efficient? We can solve the biology problems pretty quickly. We can make the prototype organisms. But can we build the infrastructure at the large scale that will allow us to produce fuel from them?

I think the engineering problem is going to be solved, but there has to be a business motive to do that, and the motive will depend on the cost of energy and its environmental impacts.

Regenerative Medicine

S+B: Most people, of course, still think of biotech as medical innovation. In that light, what is the significance of personalized medicine?
In my mind, medicine has always been personal, if practiced properly. You are sick and a doctor interacts with you as an individual. This is one of the only times in your life when you have a professional response fully tailored to you as an individual. A good doctor wants to know about you and only you. Maybe he wants to know something about your family members, but that’s because of their relationship to you. If medicine isn’t personal, and isn’t therefore personalized, then it’s not really useful.

When people talk about personalized medicine they tend to focus on genetic inheritance, be­cause it is fascinating to peer into your genetic past and present. But modern genetics, at best, is like looking at your future through a glass darkly. With very few exceptions, such as Huntington’s disease, you can’t say that if you have an inherited trait you’ll get the related disease. In most cases, you have a probability between 10 percent and 0.1 percent of getting the disease; you don’t know when or even if the disease will appear.

Ninety percent of breast cancer seems to have nothing to do with inherited genes. The same is true of prostate cancer in men. There is some role for genetics in predictive medicine, but it’s a much smaller role than people think.

I believe the whole field of what’s called genetic medicine is not really ready for prime time, if it will ever be ready. If I seem negative, it isn’t because I think genetics is unimportant. It is just that genetic inheritance is a very minor aspect of genomics, whereas the applications that I’ve already outlined — energy, agriculture, and materials — are here and important now.




Modern biology has also given doctors more techniques for understanding the disease you have in its current state. Your genes can tell you what you inherited, but they can’t tell you how your cells are behaving now. If you think about a lot of cancer tests, they’re not about what you inherited. They’re about what your cancer is doing today.

S+B: What can you say about the progress of using genomics to create new drugs?
HASELTINE: There is no question that our knowledge has been helpful. But the problem also turned out to be much more complicated than anybody thought. People thought, for example, that maybe they would find a few extra genes that were involved in cancer. It turns out that almost every gene is involved in cancer at some level. And every cancer is genetically different. Even every cell in the cancer is different from every other cell. And maybe 20 or 30 major pathways are in­volved. Does gene re­search help us understand and solve cancer? Maybe it will give us some addi­tional insights. But it isn’t the answer to cancer.

Pharmaceutical Productivity

S+B: Do you think advances in differential diagnosis will improve the pharmaceutical industry’s return on R&D in terms of profits and human health benefits?

HASELTINE: R&D expenses in the pharmaceutical industry have gone up 20-fold in the last 20 years. That’s even in adjusted dollars, per company and per industry. Meanwhile, productivity has de­creased by about a factor of 10. This is probably the biggest productivity collapse the world has ever seen, and it affects the whole industry, biotechnology companies included. When you look at the number of new compounds that are approved, it’s the sum of all the biotechnology, all the universities — the entire world trying to get approval for a new chemical.

So something is wrong, and I don’t believe it is the science, which is moving forward at a pace beyond belief. It must be structural. I’ve been an advisor to many pharmaceutical companies, and I’ve set up several biotech companies, so I have a triangulated view. Size is at the root of a lot of problems. Research and innovation is done best in small groups, but we now have pharmaceutical companies with $70 billion in sales, and they focus only on drugs that can have a broad impact. One product may be worth $5 billion to $7 billion in sales. If a company loses its bet on two or three of these, it’s lost its business.

Typically, marketing people lead these companies. They look over the research results and analyze what might “make” a market. If a drug doesn’t have a chance in the marketplace, they will demand changes to the testing to get a label on the drug to sell it. I call it the reverse Cinderella syndrome — taking a small foot and putting it into a big shoe. What’s the consequence? Drug after drug fails to create a mass market, or a drug gets approved when it shouldn’t and then gets withdrawn because of side effects.

One solution would be to create “virtual” pharmaceutical com­pany structures, where you have many small companies with access to capital and scientists who understand the medical needs. Expenses would be kept minimal through outsourcing. Expertise would be consolidated so it isn’t redundant. Companies would aim their products at smaller markets. It may be a $50 million or $300 million market, but if they don’t invest much, they would make a lot of money.

Some of those drugs will be blockbusters, although you can’t predict which ones. Those drugs will go into the mass market, but you will have drugs selling at a much lower margin. It will be more like cosmetics companies, which aren’t bad businesses. To be an Estée Lauder, you need 4,000 products and 2,000 changes every year.

It’s not going to be easy, but it can be done. A new generation of pharmaceutical executives is rising in the industry, although it will be the next CEO cycle before we see significant change. I predicted that the pharmaceutical price-to-earnings ratio would change from about the mid-20s to the low teens, and [now] I think it’s going to go to the single digits. When it does, people are going to reevaluate how they do research. There will be tremendous opportunities to do things differently and better.

Benefits for the World’s Poorest

S+B: You mentioned the breakthrough in creating an antimalarial drug that will be affordable to populations who need it most. Can we expect the next wave of medical and green genomics to reach more of the two-thirds of the world’s people who live at the “bottom of the pyramid,” in lower-income countries?

S+B: And it’s not just about selling consumer goods to them.


I am working in India now through a foundation I’ve created to deliver high-quality, cost-efficient health care. I believe it’s possible to get equal quality at a cost be­tween 10 and 20 percent below current costs. (See “The Innovation Sandbox,” by C.K. Prahalad, s+b, Autumn 2006.) There are a number of experimental enterprises using technology to create high-quality, af­fordable, low-cost health care for the Indian middle and lower-middle classes. These are self-sustaining, profitable organizations. There is a tremendous amount of experi­mentation. The common theme is, How do you solve the problems of getting high-quality health care at very low cost to very large numbers of people?


S+B: Are you saying that the innovations spawned by biotechnologies can help eliminate the “have” and “have-not” economic extremes?
You’ll never see an end to economic disparity, but you will see unprecedented upward mo­bility in the developing world. We are already seeing something like 35 million to 40 million people a year moving into India’s and China’s middle classes. Think of it as a quarter of the United States’ total pop­ulation joining the middle class each year. Remember, it was middle- to lower-middle-income Amer­­icans, not the upper class, that drove the world economy until very recently.

Mass markets are very powerful, even when the price points are low. So we’re seeing these huge transformations take place, and I think that they can continue, but we need to solve the production problems in order to make these lifestyles sustainable on our planet.

S+B: Can industrial society be sustainable when there are nearly 10 billion people on the planet?
HASELTINE: Yes, if we replace our current generation of wasteful technologies. Biotechnologies will have a significant role in that change. If you look at the full range of what we’ve talked about, we have gone from burning wood to regrowing arteries. That’s a pretty broad span of life sciences, and it’s tremendously exciting.

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William Haseltine: The Thought Leader Interview