Which scientist had the greatest impact in the past year? Mike Brown of Caltech forced astronomers to rethink what a planet is. Neil Shubin of the University of Chicago found a key fossil showing how life moved onto land. Emma Whitelaw of the Queensland Institute of Medical Research documented how heredity extends beyond genes. NASA's James Hansen bolstered the case for global warming and spoke out against government censorship. And these were just some of our finalists.
In the end we zeroed in on one researcher whose work stands out even in this illustrious company. We are pleased to announce Jay Keasling as the winner of DISCOVER's first Scientist of the Year award.
2006 Scientist of the year: Jay Keasling
Chemical engineer at the University of California at Berkeley
It's easy to be amazed by 21st-century feats of genetic engineering. Genes can be moved from one species to another, creating, say, goats that secrete drugs in their milk or bacteria that make human insulin. But that's not enough for Jay Keasling. Instead of the simple manipulation of single genes, he wants to engineer many genes to work together, like transistors wired in a circuit.
This new approach to manipulating life—along with explorations of artificial DNA, the creation of novel amino acids, and controlled evolution in the lab—has been dubbed synthetic biology, and Keasling, 42, is one of its chief engineers. As a nascent science, synthetic biology must prove itself through practical application, and Keasling is now close to providing just that: He is attempting to integrate genes from different species into a microbe to fabricate a drug for malaria. It is not just a technical tour de force but a humanitarian one. Keasling's microbes will churn out the drug for a fraction of its current cost, making it accessible to much more of the world. Properly harnessed, these microbes could save millions of lives.
Keasling spent his childhood immersed in the practical end of biology, chemistry, and engineering—he was raised on a farm. This background eventually led him to the burgeoning field of biotechnology. In the early 1980s, genetic engineering had just made the leap from the laboratory to the boardroom, as corporations made small fortunes inserting genes into Escherichia coli to produce insulin, growth hormones, and other valuable molecules. In Keasling's eyes, however, genetic engineering hadn't harnessed the full power of cells. Scientists had simply inserted a single gene into bacteria and coaxed them into churning out as many copies of the same protein as possible.
Often the production of molecules isn't so simple; it requires a complex of several genes. One gene encodes a protein, which then must be reworked by other proteins. Keasling wanted to invent the tools that would allow him to engineer these kinds of genetic assembly lines. So he pursued his Ph.D. not in biology but in chemical engineering. What goes on in a cell, Keasling surmised, is a lot like what goes on in a chemical plant: Petroleum goes in, and after a whole chain of reactions, plastic comes out.
Keasling spent his first decade at the University of California at Berkeley building the new tools he would need to turn cells into chemical plants. He studied plasmids, tiny ringlets of DNA that genetic engineers use to insert foreign genes into bacteria. He also found ways to coax microbes into producing abundant copies of a particular protein, and he invented powerful chemical switches that allowed him to trigger protein production.
Meanwhile, other scientists were similarly borrowing techniques from engineering and figuring out how to manipulate microbes, an effort they came to call synthetic biology. In 2003 the first synthetic biology conference took place at MIT, and by 2006 the field had become a media darling. The Economist heralded it as "Life 2.0"; Forbes wrote about the potential "regenesis" of life.
Behind the dazzle lies the tedious reality: Synthetic biology requires a lot of work to do relatively simple things. Take, for example, the bacterial camera. In 2005 scientists from the University of Texas and the University of California at San Francisco reported that they had created a strain of E. coli that could produce a photograph-like image. They inserted genes for sensing light and producing pigments into the bacteria and then engineered the microbes so that the genes would work together—striking proof of the principles of synthetic biology, but in practice a very clumsy substitute for a digital camera.
After years of perfecting his biological tool kit, Keasling wanted to find a real-world use for it. In 2002 he learned of the dire need for synthetic artemisinin, a compound derived from the sweet wormwood plant, which is 90 percent effective against the parasite that causes malaria and has few side effects (malaria kills some 3 million people a year). However, extracting the drug from sweet wormwood is a slow and expensive process that drives up the cost to as much as 20 times the price of other antimalarial drugs.
Keasling figured he could engineer microbes to pump out artemisinin for a lot less. Rather than wait months for sweet wormwood to grow on farms or try to cobble the drug together with artificial chemistry, Keasling wanted to create it simply by pouring sugar in a tank, then using engineered microbes to make the drug via a chemical pathway of his own creation. In 2003 Keasling's team published its first success, the production of a precursor to artemisinin. That result was impressive enough to garner $43 million from the Bill and Melinda Gates Foundation. To transform the precursor into the real deal, Keasling had to abandon biological manipulations of bacteria and work instead with yeast. Last April his team reported that they had pieced together bacterial, yeast, and wormwood genes and converted yeast into a chemical factory, yielding artemisinic acid.
The final step for Keasling is to figure out how to mass-manufacture artemisinin. Compared with fast-growing bacteria, yeast do a poor job of producing enzymes. So Keasling has two teams of students in a race. One is looking for a way to create the new chemical pathway in E. coli; the other, to scale up the production of artemisinic acid in yeast. Keasling is optimistic that one of the routes will work. If it does, he expects to drive down the cost of artemisinin production from a dollar per gram to just 10 cents.
Fighting malaria is just one part of Keasling's larger agenda to explore the staggering potential of synthetic biology. In his laboratory, students are engineering microbes to break down pesticides, make biodegradable plastics, and create ethanol and other fuels from plants. For his achievements, DISCOVER has named Keasling Scientist of the Year. We took the occasion to talk to him about his work and about the future of synthetic biology.