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Featured researches published by Nidhi Subbaraman.
Nature Biotechnology | 2011
Nidhi Subbaraman
Early in November, at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) in Atlanta, researchers from the British company Oxitec disclosed results from the worlds first genetically modified (GM) mosquito field trials aimed at controlling the carrier for dengue fever. After the presentation at the meeting, Science (330, 1030–1031, 2010) published a news story claiming the trials had “strained ties” with Oxitecs collaborator, the Bill and Melinda Gates Foundation. Anthony James, the lead investigator on the Gates team, was also quoted as saying he would “never release GM mosquitoes the way Oxitec has now done in Grand Cayman.” Although some concerns have been raised as to how information about the trial was disseminated, it seems that controversy over the environmental release of a GM organism has been overblown.
Nature Biotechnology | 2011
Laura DeFrancesco; Nidhi Subbaraman
379 Torrent’s (now part of Life Technologies of Carlsbad, California) Personal Genomics Machine—a secondgeneration sequencing platform that they won in a competition—to broaden the reach of their assay. Elsewhere, Levi Garraway of the DanaFarber Cancer Center in Boston has developed the OncoMap assay, which interrogates over 400 distinct mutations in 41 cancer genes (Nat. Genet. 39, 347–351, 2007). With his colleague Matthew Meyerson and the Broad Institute’s Eric Lander and Todd Golub, Garraway co-founded Foundation Medicine, headquartered in Cambridge, Massachusetts. The company is gearing up a sequencing service for oncologists that they believe will provide clinically useful information for as many as 50% of cancer patients. As leading sequencing platform companies continue to drive up accuracy rates, and instrumentation costs plummet, a battle will likely ensue for the genomic medicine market, estimated by a Piper Jaffray report to reap billions of dollars per year (Benzinga, 7 February 2011; http://www.benzinga.com/analyst-ratings/ 11/02/838880/piper-jaffray-provides-color-onilmn-leukemia-tumor-data#). The current standard bearer for secondgeneration sequencing is Illumina of San Diego, whose HiSeq 2000 has been adopted by genome centers around the globe, capturing 70% of the market. Other instruments will soon offer some stiff competition. Ion Torrent’s Personal Genome Machine (PGM), for example, will combine Life Technologies’ marketing might, a lower cost per machine (
Nature Biotechnology | 2011
Nidhi Subbaraman
50K as compared with
Nature Biotechnology | 2010
Nidhi Subbaraman
690K for the HiSeq 2001 released in January), a small footprint, simple chemistry, and lower running costs and turnaround time. Life Technologies has already placed a large number of machines, according to Andy Felton, chief of Life Technologies’ genetics systems division—he won’t say exactly how many— but the company announced publicly that they have 60 orders, a “significant fraction” from A six-year-old boy’s life saved by wholeexome sequencing is a recent example of how sequencing has crossed the threshold into clinical management. The case, reported in March in Genetics in Medicine, baffled physicians at the Medical College of Wisconsin in Milwaukee, Wisconsin. The child was wasting away, despite over 100 surgeries to repair multiple intestinal fistulas. Clinicians could not diagnose the problem, until sequencing revealed the boy had a mutation in XIAP (X-linked inhibitor of apoptosis), which was known to be linked to another pathology remedied by bone marrow transplantation. A transplant saved the boy’s life. In February, Richard Lifton, director of the Yale Center for Human Genetics and Genomics in New Haven, published another triumph of genome sequencing over disease. Using exome sequencing on four individuals with a severe form of hypertension, the Yale group identified a mutation in the gene encoding the potassium ion channel KCNJ5 as driving the development of aldosterone-producing tumors in the adrenal gland. As DNA sequencing gains credence in pathology laboratories, next-generation instrument providers view the trend of solving mystery diseases by sequencing either the total genome or in some cases, all gene coding regions (exome) as an opportunity to expand their customer base beyond the research community. Apart from diagnosing rare genetic disorders, genome sequencing is already popular in pathology laboratories, particularly for cancer testing. Individuals at several major cancer centers have had their tumors profiled for mutations using next-generation sequencing technology. Pathologists John Iafrate and Long Phi Li at Boston’s Massachusetts General Hospital are currently using a multiplexing single nucleotide polymorphisms assay to interrogate over a hundred hot spots in oncogenes and tumor suppressor genes (EMBO Molecular Medicine 2, 146–158, 2011). They are also testing Ion sequencing firms eye pathology labs as next big market opportunity
Nature Biotechnology | 2011
Nidhi Subbaraman
381 A study reporting that the median cost of bringing a new drug to market is as low as
Nature Biotechnology | 2011
Nidhi Subbaraman
59 million has met with considerable controversy. The authors, Donald W. Light of the University of Pennsylvania and the University of Medicine and Dentistry in New Jersey, and Rebecca Warburton, of the University of Victoria in British Columbia, Canada, estimate in the journal BioSocieties (6, 34–50, 2011) that the figures touted by the industry are inflated. Critics retort that although the authors rightly critique the lack of transparency and limited sample of companies used in previous estimates, Light and Warburton wrongly assume that clinical trial and regulatory review times are decreasing and underestimate drug discovery attrition rates and risk. Light and Warburton found that net median corporate R&D costs varied from
Nature Biotechnology | 2011
Nidhi Subbaraman
13 million to
Nature Biotechnology | 2011
Nidhi Subbaraman
204 million, depending on the type of drug. The resulting
Nature Biotechnology | 2011
Nidhi Subbaraman
59.4 million estimate is for the average drug, not just new medical entities, and does not include the cost of discovery, which varies 30-fold. The authors argue that the widely accepted figure from the 2003 study by the Tufts Center for the Study of Drug Development in Boston is inflated. The Tufts economists analyzed cost data for 68 randomly selected drugs from ten pharma companies, and concluded that the average amount spent per drug was
Nature Biotechnology | 2010
Nidhi Subbaraman
802 million in 2000. This gave rise to an adjusted figure of