Science期刊列出2008年十大科學進展，其中與生技相關的進展節錄如下
The first direct detections of exoplanets topped the list of this year's runners-up for Breakthrough of the Year. Other notable discoveries included cancer genes, new high-temperature superconductors, and a new water-splitting catalyst.
http://www.sciencemag.org/cgi/content/summary/322/5909/1768
BREAKTHROUGH OF THE YEAR: Reprogramming Cells (細胞重編程)
Gretchen Vogel (19 December 2008)
Science 322 (5909), 1766. [DOI: 10.1126/science.322.5909.1766]
This year, scientists achieved a long-sought feat of cellular alchemy. They took skin cells from patients suffering from a variety of diseases and reprogrammed them into stem cells. The transformed cells grow and divide in the laboratory, giving researchers new tools to study the cellular processes that underlie the patients' diseases. The achievement could also be an important step on a long path to treating diseases with a patient's own cells.
The feat rests on a genetic trick, first developed in mice and described 2 years ago, in which scientists wipe out a cell's developmental "memory," causing it to return to its pristine embryonic state and then regrow into something else. In 2008, researchers achieved another milestone in cell reprogramming. In an elegant study in live mice, they prompted cells to make the leap directly from one mature cell into another--flouting the usual rule that development of cells is a one-way street. These and other advances in tweaking cells to assume new identities add up to make the now flourishing field of cellular reprogramming Science's Breakthrough of the Year.
http://www.sciencemag.org/cgi/content/full/322/5909/1766
Cancer Genes (癌症基因)
Researchers this year turned a searchlight on the errant DNA that leads tumor cells to grow out of control. These studies are revealing the entire genetic landscape of specific human cancers, providing new avenues for diagnosis and treatment.
Tumor cells are typically riddled with genetic mistakes that disrupt key cell pathways, removing the brakes on cell division. Thanks to the completion of the human genome and cheaper sequencing, researchers can now systematically survey many genes in cancer cells for changes that earlier methods missed. Results from the first of these so-called cancer genome projects came out 2 years ago, and the output ramped up in 2008.
Leading the list were reports on pancreatic cancer and glioblastoma, the deadliest cancers. By sequencing hundreds or thousands of genes, researchers fingered dozens of mutations, both known and new. For example, a new cancer gene called IDH1 appeared in a sizable 12% of samples from glioma brain tumors. A separate glioma study revealed hints as to why some patients' tumors develop drug resistance. Other studies winnowed out abnormal DNA in lung adenocarcinoma tumors and acute myeloid leukemia.
Watching Proteins at Work (觀察蛋白質的工作)
After studying proteins for more than a century, biochemists pushed the boundaries of watching the molecules in action--and received surprises at every turn.
Scientists have long debated how proteins bind to their targets. Most think the shape of a target molecule forces a protein to wiggle into a complementary profile. But it's also possible that proteins in solution wiggle among many slightly different conformations until one finds its target. Computational biologists in Germany and the United States offered bold new support for that upstart idea when they crunched extensive experimental data and showed how one long-studied protein seems to dance among dozens of conformations. In another surprise, a U.S. team tracked individual proteins and found that a single random molecular event can switch a bacterial cell from one metabolic state to another.
Zooming out to the large scale, proteomics researchers in Germany simultaneously monitored the abundance of up to 6000 proteins in yeast cells and quantified how the expression of individual proteins differed between two different cell types. Their technique could lead to new insights into development and disease. Finally, proteomics researchers in Sweden revealed that different tissues in the body likely get their unique characteristics by controlling not which proteins are expressed but how much of each gets made.
The Video Embryo (胚胎發育錄影)
The dance of cells as a fertilized egg becomes an organism is at the center of developmental biology. But most microscopes allow only partial glimpses of the process. This year, scientists observed the ballet in unprecedented detail, recording and analyzing movies that traced the movements of the roughly 16,000 cells that make up the zebrafish embryo by the end of its first day of development.
Researchers in Germany made the movies with a new microscope they designed. It uses a laser beam to scan through a living specimen, capturing real-time images and avoiding the bleaching and light damage that have usually limited such videos to just a few hours. The researchers then used massive computing power to analyze and visualize the recorded movements. They also ran the movies backward to trace the origin of cells that form specific tissues, such as the retina. A movie of a well-known mutant strain of fish revealed for the first time exactly what goes wrong as the embryo develops.
The zebrafish movies are freely available on the Internet, and the developers say they hope the Web site will develop into a full-blown virtual embryo--a sort of developmental biology YouTube with contributions from labs around the world.
Fat of a Different Color (另一種顏色的脂肪)
This year, researchers finally uncovered the mysterious roots of so-called brown fat. Hardly blubber, the energy-using tissue turns out to be one step away from muscle.
Anatomists first noted the distinction between our two fat types more than 400 years ago. White fat is the energy-caching padding that vexes doctors and dieters. If white fat is a quilt, brown fat is an electric blanket. Thanks to plentiful mitochondria, it burns fat molecules to generate heat that warms the body.
Scientists long assumed that both fat varieties developed from the same kind of progenitor cell. Then a team led by U.S. scientists discovered that they could morph brown fat into muscle and vice versa. The researchers knew that the gene PRDM16 spurs specialization of brown fat. So when they turned down PRDM16 in brown-fat precursor cells, they expected white fat cells to result.
Instead, the cells stretched out into tube-shaped muscle cells that could even twitch. Reflecting their altered identity, the cells switched off a raft of genes characteristic of brown fat and switched on genes typical of muscle. Coercing cells that had already begun differentiating into muscle to fashion PRDM16 triggered the reverse transformation, yielding brown fat. Using a technique called lineage tracing, the researchers identified the descendants of the muscle cell clan in mice. They included muscle and brown fat cells but not white fat cells.
The discoveries could mark a step toward antiobesity treatments that melt away bad white fat, either by firing up existing fat-burning brown cells in the body or by transplanting new ones.
Sequencing Bonanza (測序大豐收)
New genome-sequencing technologies that are much faster and cheaper than the approach used to decipher the first human genome are driving a boom in sequencing.
This year, using "sequencing by synthesis" technology from 454 Sequencing, which "grows" fluorescently labeled DNA on microscopic beads, researchers produced the mitochondrial genomes of extinct cave bears and of a Neandertal, and 70% of the genome of a woolly mammoth. A preliminary draft of the full Neandertal genome is in the works. Another new technology, developed by Solexa (now part of Illumina), made its debut in the scientific literature with the descriptions of the first genomes of an Asian, an African, and a cancer patient, shedding new light on early human migrations and candidate genes that may underlie malignancies. Illumina's technology sequences DNA in massively parallel reactions on glass plates. A proof-of-concept paper by Pacific Biosciences, a company that sequences single DNA molecules, provided an exciting glimpse of even faster sequencing. Now the goal is to make it more accurate. Costs continue to drop; at least one company boasts that genomes for $5000 are in reach.