'Constructive Biology' Will Reshape Biotech

Last Monday, a group of New Yorkers assembled for a dinner at my apartment to hear Professor Jay Keasling share his vision for the future. Dr. Keasling is a professor of chemical engineering and bioengineering, and the founder of the synthetic biology department at the University of California at Berkeley. He is also the CEO of the Joint BioEnergy Institute in nearby Emeryville, and the director of the physical biosciences division of the Lawrence Berkeley National Laboratory, where he is temporarily filling in for Dr. Steven Chu, now the Secretary of Energy. At my apartment, he unveiled a new and surprising vision, both for the pharmaceutical industry and renewable energy.

Dr. Keasling's group has an innovative approach: rather than solving one problem at a time, they seek to create a set of genetic tools that can be used as interchangeable genetic switches to regulate genes. This approach is very much like that of the electronics industry: using standardized components to build diverse products, A small group of like-minded scientists, working at other universities including MIT and Stanford, have since dubbed this new field "synthetic biology." I prefer the less threatening and more descriptive name "constructive biology."

When I first met Dr. Keasling, he was undertaking his first practical application of these methods. I was a trustee of the not-for-profit organization One World Health, and our group was administering a $42 million grant Dr. Keasling had received from The Gates Foundation to produce the life-saving malaria drug artemisinin.

The story of artemisinin is itself remarkable. The healing properties of the artemesia--or sweet wormwood--plant were first recognized by the Chinese 2000 years ago who prescribed a tea made from its leaves as a cure for recurrent fevers and other maladies. In the 1960s, Chinese scientists isolated and characterized the active ingredient. Artemisinin and other closely related compounds soon became the best available treatment for malaria. The organisms that cause the disease have developed resistance to all other effective therapies, including quinine and chloroquine.
 
The idea Dr. Keasling proposed was straightforward: to transfer the process the artemesia plant uses to make the drug to an organism that is simple to grow in large, reproducible batches. Ultimately, the single-cell organism yeast was chosen, as it has been used for many years to produce ethanol for drinking and for fuel.  Yeast is also a favorite of scientists. The sequence of its entire genome is known, and genes can be added and subtracted at will.

In cells, complex molecules such as artemisinin are assembled one step at a time from simpler components. The problem, therefore, was to find a set of enzymes that would act in tandem to convert chemicals found in yeast to artemisinin. Most of the genes for these enzymes were quickly identified in the artemesia genome itself. Each gene was isolated and inserted into the yeast genome. In all, twelve genes were needed, each expressed in just the right amount.

The initial stages of the work were done in Dr. Keasling's university laboratories. The concluding steps were done by his biotechnology company, Amyris. The final product was a strain of yeast that produced large amounts of a pure compound that required only one final chemical modification to yield pure artemisinin. The entire project was completed in four years.

The artemisinin-producing yeast was then transferred to the French pharmaceutical giant Sanofi-Aventis. Under the terms of the agreement, Sanofi-Aventis will provide the drug to poor countries at its manufacturing cost. The company may sell the drug to the international traveler's market and in developed countries at a higher price, provided the profit is used to subsidize the cost of the drug for poorer countries. It is expected that over time the cost of artemisinin will be reduced tenfold. Moreover, constant supply of high quality artemisinin will be available. Those who receive the drug must pledge to use it only in approved combinations to reduce the likelihood of resistance.

Success emboldened Dr. Keasling and his Berkeley colleagues to apply the technology to other problems. Their newest initiative is to create microorganisms that efficiently convert cellulose to diesel, jet fuel, and gasoline. In the early planning stages of this project, I worked with Dr. Keasling to assemble a board of trustees for a new Institute of Synthetic Biology, a group I now chair. Dr. Keasling and his colleagues at Berkeley and other universities and research centers received a U.S. Department of Energy grant for $134 million spread over five years, as well as a British Petroleum grant for $500 million spread over 10 years.

Presented by

William Haseltine is a former professor at Harvard Medical School, where he researched cancer and HIV/AIDS. He is the founder of Human Genome Sciences, where he served as chairman and CEO, and the president of the William A Haseltine Foundation for Medical Sciences and the Arts. He lives in Washington, D.C.

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