集半導體技術,高階運算能理力與材料科技的IBM正試圖以此項研發跨足生醫產業。近來有兩則IBM的新聞,一則是IBM要加入個人基因組序列的方法研究,一則是IBM的mainframe的生意正接受美國司法部anti-trust的調查。Mainframe是現在的主力產品,而生醫產業是明日之星。
人類於2001年排出了第一個基因序列,花了約十億美元。但隨著科技計的進步,過去四、五年來排出基因序列的成本以每年降為十分之一的速率下降。目前人類基因排序的成本約是在5,000到50,000美元之間,而IBM的目標是將成本降到100美元。
IBM使用的是奈米孔(nanopore)的技術,雖然到目前為止使用這項技術的研發成果都不盡理想,但是IBM似乎胸有成竹,不然也不會做這種宣示才是。
I.B.M. Joins Pursuit of $1,000 Personal Genome
J. Michael Loughran
GENETICS An I.B.M. simulation of the “DNA transistor” it hopes will sequence genomes by reading DNA pulled through an atomic-size hole.
By JOHN MARKOFF
Published: October 5, 2009
One of the oldest names in computing is joining the race to sequence the genome for $1,000. On Tuesday, I.B.M. plans to give technical details of its effort to reach and surpass that goal, ultimately bringing the cost to as low as $100, making a personal genome cheaper than a ticket to a Broadway play.
The project places I.B.M. squarely in the middle of an international race to drive down the cost of gene sequencing to help move toward an era of personalized medicine. The hope is that tailored genomic medicine would offer significant improvements in diagnosis and treatment.
I.B.M. already has a wide range of scientific and commercial efforts in fields like manufacturing supercomputers designed specifically for modeling biological processes. The company’s researchers and executives hope to use its expertise in semiconductor manufacturing, computing and material science to design an integrated sequencing machine that will offer advances both in accuracy and speed, and will lower the cost.
“More and more of biology is becoming an information science, which is very much a business for I.B.M.,” said Ajay Royyuru, senior manager for I.B.M.’s computational biology center at its Thomas J. Watson Laboratory in Yorktown Heights, N.Y.
DNA sequencing began at academic research centers in the 1970s, and the original Human Genome Project successfully sequenced the first genome in 2001 and cost roughly $1 billion.
Since then, the field has accelerated. In the last four to five years, the cost of sequencing has been falling at a rate of tenfold annually, according to George M. Church, a Harvard geneticist. In a recent presentation in Los Angeles, Dr. Church said he expected the industry to stay on that curve, or some fraction of that improvement rate, for the foreseeable future.
At least 17 startup and existing companies are in the sequencing race, pursuing a range of third-generation technologies. Sequencing the human genome now costs $5,000 to $50,000, although Dr. Church emphasized that none of the efforts so far had been completely successful and no research group had yet sequenced the entire genome of a single individual.
The I.B.M. approach is based on what the company describes as a “DNA transistor,” which it hopes will be capable of reading individual nucleotides in a single strand of DNA as it is pulled through an atomic-size hole known as a nanopore. A complete system would consist of two fluid reservoirs separated by a silicon membrane containing an array of up to a million nanopores, making it possible to sequence vast quantities of DNA at once.
nucleotide n. 核苷酸 由磷酸基,糖,和有機氮鹼基構成的核酸的基礎次單位
The company said the goal of the research was to build a machine that would have the capacity to sequence an individual genome of up to three billion bases, or nucleotides, “in several hours.” A system with this power and speed is essential if progress is to be made toward personalized medicine, I.B.M. researchers said.At the heart of the I.B.M. system is a novel mechanism, something like nanoscale electric tweezers. This mechanism repeatedly pauses a strand of DNA, which is naturally negatively charged, as an electric field pulls the strand through a nanopore, an opening just three nanometers in diameter. A nanometer, one one-billionth of a meter, is approximately one eighty-thousandth the width of a human hair.The I.B.M. researchers said they had successfully used a transmission electron microscope to drill a hole through a semiconductor device that was intended to “ratchet” the DNA strand through the opening and then stop for perhaps a millisecond to determine the order of four nucleotide bases — adenine, guanine, cytosine or thymine — that make up the DNA molecule. The I.B.M. team said that the project, which began in 2007, could now reliably pull DNA strands through nanopore holes but that sensing technology to control the rate of movement and to read the specific bases had yet to be demonstrated.Despite the optimism of the I.B.M. researchers, an independent scientist noted that various approaches to nanopore-based sequencing had been tried for years, with only limited success.“DNA strands seem to have a mind of their own,” said Elaine R. Mardis, co-director of the genome center at Washington University in St. Louis, noting that DNA often takes a number of formations other than a straight rod as it passes through a nanopore.Dr. Mardis also said previous efforts to create uniform silicon-based nanopore sensors had been disappointing.One of the crucial advances needed to improve the quality of DNA analysis is to be able to read longer sequences. Current technology is generally in the range of 30 to 800 nucleotides, while the goal is to be able to read sequences of as long as one million bases, according to Dr. Church, who spoke in July at a forum sponsored by Edge.org, a nonprofit online science forum.Other approaches to faster, cheaper sequencing include a biological nanopore approach being pursued by Oxford Nanopore Technologies, a start-up based in England, and an electron microscopy-based system being designed by Halcyon Molecular, a low-profile Silicon Valley start-up that has developed a technique for stretching single strands of DNA laid out on a thin carbon film. The company may be able to image strands as long as one million base pairs, said Dr. Church, who is an adviser to the company, and to several others.“To bring about an era of personalized medicine, it isn’t enough to know the DNA of an average person,” said Gustavo Stolovitzky, an I.B.M. biophysicist, who is one of the researchers who conceived of the I.B.M. project. “As a community, it became clear we need to make efforts to sequence in a way that is fast and cheap.”Next Article in Science (6 of 29) » A version of this article appeared in print on October 6, 2009, on page D2 of the New York edition.http://www.nytimes.com/2009/10/06/science/06dna.html?_r=1&ref=science
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