Science Editor

Science Magazine kicked off the year-end roundups last week, announcing its annual list of the top 10 Breakthroughs of the Year in its Dec. 17, 2010, issue. The list ranged from the most high-tech of advances – the creation of a purportedly synthetic bacterium – to decidedly more low-tech, but more immediately useful advances in HIV prophylaxis.

Both synthetic life and HIV prophylaxis are good reminders that most breakthroughs take years or decades to become overnight sensations. The quest to create a synthetic bacterium began 15 years ago, with the sequencing of Mycoplasma genitalium, which has the smallest genome of any known organism.

The team, J. Craig Venter related at a May press conference announcing their synthetic bacterium, immediately wondered whether this was the smallest possible genome, and decided that the way to find out was to create artificial genomes to determine the minimal genome necessary for life.

Over the years, Venter's group developed sequencing methods that allowed them to sequence fairly large chunks of DNA to create a minimal genome, as well as methods to transplant an artificial genome into an existing cell to see whether it could replace that cell's DNA with its own.

And in May, the team members claimed success. They synthesized the genome of one bacterial species, M. mycoides, deleting 14 genes and adding what they termed "watermarks" to be able to distinguish their creation from a natural genome.

They then transplanted the genome into the cytoplasm of a closely related bacterium, M. capricolum. The M. mycoides genome was able to take over, "rebooting" the cell to produce proteins from M. mycoides only. (See BioWorld Today, May 21, 2010.)

Some scientists disputed that Venter's group had truly created life, noting that the cytoplasm used to start the cell line came from a regular, living bacterium. Venter said that he did not consider the synthetic cell to be "life created from scratch," but did consider it "synthetic life."

"We call it synthetic," he clarified, "because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer."

If the creation of life is the year's most high-tech breakthrough, the successful clinical trials of two forms of HIV prophylaxis are probably the most low-tech ones.

Here, too, success was a long time coming; When the CAPRISA 004 trial results showed in July that a vaginal gel containing 1 percent tenofovir (Viread, Gilead Sciences Inc.) reduced the risk of contracting HIV by an average of nearly 40 percent. It was the 12th such trial. Collectively the trials had tested six different microbicides.

And in November, results from the Phase III Chemoprophylaxis for HIV Prevention in Men (iPrEx) study showed that a daily pre-exposure prophylactic dose of Truvada (emtricitabine and tenofovir disoproxil fumarate, Gilead Sciences Inc.) cut the risk of HIV infection by 44 percent in men and male-to-female transsexuals who have sex with men.

Neither method has anywhere near the efficacy of a vaccine, and the pre-exposure prophylaxis trial showed some hints that resistance might become a problem; researchers are awaiting the results of another trial to shed more light on that possibility. But a commentary published along with the iPrEx trial expressed the hope that "these data are likely to place another arrow in the quiver for HIV prevention."

Media attention is one way to gauge breakthroughs, but the attention of fellow scientists is another.

The post-publication peer review website Faculty of 1000 published several lists of top papers last week, including the top five in all of biology. More specific than those named as breakthroughs in Science, the papers picked by the site's reviewers may herald medical advances of tomorrow. One example is the insight, published in January, that platelets may contribute to autoimmune disease, specifically in rheumatoid arthritis. (See BioWorld Today, Jan. 29, 2010.)

Finally, the Dec. 19, 2010, online edition of Nature Methods is dedicated to optogenetics as "Method of the Year."

For optogenetic experiments, a light-sensitive channel, which is usually expressed in algae and causes them to swim toward light, is engineered into cells of interest via gene therapy.

Researchers can then stimulate the engineered cells by delivering light pulses directly onto them via optic fibers. The method was originally developed by Stanford University's Karl Deisseroth and put to use for neuroscience experiments. (See BioWorld Today, Oct. 18, 2007.)

But since its original development, the method has become much more precise – going, in the words of neuroscience researchers Simon Peron and Karel Svoboda, "from cudgel to scalpel." Its use has expanded from neurons into cardiac cells. Other scientists have used the method to activate specific cell signaling circuits, by fusing or anchoring a light-controlled protein to a signaling molecule, which allows researchers to control when a signaling cascade will be set off.

The greatest advantage of optogenetics, Deisseroth wrote in Nature Methods, is the technique's ability to move information across spatial scales. Using optogentics approach allows scientists to control small circuits or populations of neurons "while these populations still remain embedded and functioning within larger intact-tissue systems."

This ability, he wrote, paves the way for a fundamentally changed way of thinking about the brain: "Rather than conceptualizing the brain as a mix of neurotransmitters," he said, the method enables researchers "to move toward a circuit-engineering approach, in which devastating symptoms of disease are understood to causally result from specific . . . patterns of aberrant circuit activity [in] specific neuronal populations."