Last December, DISCOVER celebrated three researchers for the remarkable ways they were changing the world and our place in it. We named Jay Keasling, a pioneer in synthetic biology, our Scientist of the Year; neuroscientist John Donoghue and geneticist Svante Pääbo were runners-up. When we recently checked back with them, each had already pushed his work into new, even bolder territory.

Jay Keasling When he received his DISCOVER award, Keasling was rejiggering microbes’ DNA to manufacture a cheap, effective treatment for malaria. Now the Department of Energy has given Keasling another world-rescuing task: Engineer similar microbes to spit out environmentally friendly fuel. As director of the new DOE Joint BioEnergy Institute at the Lawrence Berkeley National Laboratory in California—one of three upcoming national Bioenergy Research Centers—Keasling will head the institute’s efforts to support President Bush’s goal of reducing U.S. gasoline consumption by 20 percent within 10 years. “We can use the technology that we’ve developed already in my lab to produce something akin to the gasoline that you pump into your tanks right now,” Keasling says, “only produce it from a renewable source.”

It took millions of years of unrelenting heat and pressure to turn buried decomposing organic matter into fuel, but Keas­ling hopes to accomplish the same basic feat within a few hours in a fermentation tank. All he needs is the right mix of matter and microbes. At his institute, agronomists will work on identifying or creating the fuel crop of the future, while bio-prospectors will hunt for enzymes that quickly convert tough, indigestible cellulose into sugar. Keasling’s contribution to the work is to engineer microbes so they can turn that sugar into transportation fuel. He can already make some molecules—like alkanes and long-chain alcohols—that look as if they might work well as components of a good gasoline substitute.

Meanwhile, Keasling’s fight against malaria continues unabated. Last year his team found that yeast is more efficient than E. coli as a microbial chemical factory to churn out artemisinin, a potent antimalarial drug. Keasling is now sorting through proposals from pharmaceutical companies that want to make the drug using the new technology. The winning partner will forgo the lab’s shaker flasks and hot plates in favor of giant vats. One studio-apartment-size fermentor running 24/7 could make enough artemisinin to treat the entire world.

John Donoghue | Image courtesy of Brown University

John Donoghue In 2005, with the help of a Donoghue-devised brain chip, a quadriplegic man used a robotic arm to pick up a piece of candy. The chip was the most sophisticated brain-computer interface ever tested in humans. In 2007 the device is on the way to going wireless. No more will a chip-assisted patient have a fat black cable sticking out of his skull and running to an amplifier the size of a cigar box. At Donoghue’s Brown University spin-off, Cyberkinetics Neurotechnology Systems, engineers have shrunk the amplifier to the size of a thick postage stamp and will implant it under the scalp. The amplifier translates electrical impulses of the brain into flashes of light that shine through the scalp, where they are picked up by a tiny magnetically attached receiver.

Donoghue is also using the chip to detect brain signals that give him detailed information about brain function. By sticking the chip into different spots on patients’ heads while they are having unrelated neurosurgery, he is eavesdropping on brain activity, looking for clues such as what might precede an epileptic seizure. He dreams of minuscule drug pumps or implanted electrodes that could tickle the brain back into shape before a seizure occurs.

Svante Pääbo Last year Pääbo announced a plan to sequence the entire Neanderthal genome by 2008 and compare our extinct relative’s genes with the genes of chimpanzees and humans. But doing biology on a 40,000-year-old is difficult. A lab tech’s sneeze could contaminate the caveman’s DNA, making our genomes look falsely alike. Long-buried genes could decompose, making our genomes look falsely different. From the Max Planck Institute for Evolutionary Anthropology in Germany, Pääbo reports progress on both fronts.

Over the past year, archaeologists in protective suits, gloves, and face masks have begun collecting DNA straight from a fossil excavation site in Spain, drastically reducing the possibility of contamination. And back at the lab, Pääbo has found that the Neanderthal genetic material has degraded only at the edges of the DNA, so distinguishing evolutionary changes from physical damage really is possible. In May the team—36 scientists from 12 groups in the United States and Europe—assembled at Cold Spring Harbor Laboratory in New York. To date, they have sequenced 30 million base pairs, up from one million last year. That still leaves 2.97 billion base pairs to go. Will they finish before next year is out? Well, Pääbo says, “a rough draft.”