TR Editors' blog

Sequencing Haiti's Cholera Epidemic

Rapid DNA sequencing identifies the origins of the cholera outbreak.

Emily Singer 12/10/2010

According to the most detailed genetic analysis yet of the strain of cholera bacteria infecting people in Haiti, the pathogen most likely originated in South Asia rather than the Caribbean or Latin America. While scientists still don't know exactly how the bacteria made its way to Haiti, the findings suggest it must have been introduced by human activity. They also lend new urgency to public health efforts; the South Asian strain is both more virulent and more resistant to antibiotic drugs than those currently circulating in Latin America. Since the outbreak began in October, 93,000 people have become sick and more than 2,000 have died.

Eric Schadt and collaborators at Pacific Biosciences, a sequencing company that has developed a novel method for rapidly reading single molecules of DNA, sequenced and analyzed the microbes' DNA in just two days. The ability to quickly analyze pathogens is essential if it is to aid public health responses.

According to a release from Pacific Biosciences, which raised $200 million in an initial public offering last month, researchers sequenced five different cholera strains sent from Harvard Medical School: two samples from the current Haiti outbreak, two samples from South Asia (Bangladeshi isolates from 1971 and 2008), and one sample from Latin America (a 1991 Peruvian isolate). The team then compared this high resolution whole genome sequence information to DNA sequence information available in public databases for 23 diverse strains of V. cholerae. The research was published online this week in the New England Journal of Medicine.

According to a commentary in the NEJM,

The implications of the appearance of this strain are worrisome: as compared with many cholera strains, it is associated with increased virulence, enhanced ability to survive in the environment and in a human host, and increased antibiotic resistance. These factors have substantial epidemiologic ramifications for the entire region and implications for optimal public health approaches to arresting the epidemic's spread.

Ozzy Osbourne's Genome

Genome sequencing makes its move into pop culture.

Emily Singer 10/25/2010

The "Godfather of heavy metal," "the Prince of Darkness," the man who made himself famous by biting the heads off small animals--Ozzy Osbourne--has had his genome sequenced.

The former frontman for Black Sabbath and reality show star recently became one of only a few hundred people in the world who have had their entire genetic code deciphered and analyzed. Osbourne, 61, wrote about his experience in a column in The Times of London on Sunday. He says he was initially skeptical of the idea--"The only Gene I know anything about is the one in Kiss"--but quickly came around when the originator of the project, identified only as Chris, convinced him the results could help explain how he survived 40 years of intense drug and alcohol abuse and all the ill-advised antics that go along with it. As Osbourne notes in his column;

"Look," said Chris, "you've said it yourself: you're a medical miracle. You went on a drink and-drugs bender for 40 years. You broke your neck on a quad bike. You died twice in a chemically induced coma. You walked away from your tour bus without a scratch after it was hit by a plane. Your immune system was so compromised by your lifestyle, you got a positive HIV test for 24 hours, until they proved it was wrong. Yet here you are, alive and well."

Osbourne's blood sample was collected in early July and sent to Cofactor Genomics, a company in St. Louis, Missouri, that sequences DNA. The DNA sequence results were then sent to Knome, a startup based in Cambridge that analyzes human genomes.

Researchers will present the research in more detail later this week at the TED Med conference in San Diego, where Osbourne and his wife, Sharon, will participate in a roundtable discussion. But Jorge Conde, Knome's chief executive officer and a former TR35 winner, shared some of the results with me this morning.

According to the analysis, Osbourne has about 300,000 novel variants, a figure similar to that of other newly sequenced genomes. (The number of novel variants discovered per genome will fall as more people are sequenced.) Analysis of his mitochondrial DNA, inherited from his mother, revealed that Osbourne shared a common ancestor with Stephen Colbert about 1,000 years ago.

The rocker also learned that, like most people of European descent, he has some some DNA segments inherited from Neandertals. "For fun, we did the same analysis for George Church," says Conde. Church, a pioneer in DNA sequencing, Harvard professor, and one of Knome's cofounders, "had three times as much Neandertal DNA."

Given his infamous history, researchers also analyzed a number of genes involved in drug metabolism and addiction. Knome's director of research, Nathan Pearson, aka Dr. Nathan, embarked to England earlier this month to explain the findings to Osbourne.

Bearing in mind what Dr. Nathan said about those odds being dodgy, here are some other interesting things he told me: I'm 6.13 times more likely than the average person to have alcohol dependency or alcohol cravings (er... yeah); 1.31 times more likely to have a cocaine addiction (this must be bollocks, because anyone who takes coke as much as I did gets hooked); and 2.6 times more likely to have hallucinations while taking cannabis (makes sense, although I was usually loaded on so many different things at the same time, it was hard to know what was doing what).

..."One of the unusual things we found in your genome was a spelling in the regulatory segment of your ADH4 gene, which metabolises alcohol," said Dr Nathan. "It could make you more able to break down alcohol than the average person. Or less able." I used to drink four bottles of cognac a day. I'm not sure I need a Harvard scientist to get to the bottom of that mystery.

In my mind, the findings best demonstrate how easy it is to create a narrative out of a genome, especially one belonging to someone with as colorful a personality as Ozzy's. But Dr. Nathan got it right when he explained his own theory for how the musician has survived thus far.

"Look, Mr. Osbourne, after studying your history, taking your blood, extracting your genes from the white cells, making them readable, sequencing them, analysing and interpreting the data using some of the most advanced technology available in the world today--and of course comparing your DNA against all the current research in the US National Library of Medicine, not to mention the 18th revision of the public human reference genome--I think I can say with a good deal of confidence why you're still alive."

I looked at him. He looked at me.

"Go on, then," I said. "Spit it out."

"Sharon," he replied.

Bringing Genome Sequencing into Cancer Care

Life Technologies announces plans to sequence cancer patients' genomes.

Emily Singer 06/03/2010

Cancer treatment is broadly considered to be the frontrunner on the road to personalized medicine. A number of genetic tests exist to determine whether patients with different types of cancers are likely to respond to different drugs, and more examples are being discovered every day. Pharmaceutical companies are developing drugs targeted to some of these mutations, creating companion diagnostic tests to go along with the drugs.

Life Technologies, a global biotechnology tools company, aims to take this one step further. At the Consumer Genetics conference in Boston today, the company announced plans to sequence the genomes of cancer patients who have failed to respond to different drugs and use the results to shape treatment. For example, the tumor of a patient with ovarian cancer might possess a mutation that renders the cancer susceptible to a certain drug that is most commonly found in lung cancer. Physicians could then prescribe that drug, normally used only for lung cancer, off-label.

"This is a groundbreaking initiative for oncologists and their patients that should demonstrate how whole-genome sequencing with analytics and counseling can identify a treatment plan customized specifically for each seriously ill patient," said Paul Billings, director and chief scientific officer of the Genomic Medicine Institute at El Camino Hospital, in a statement from Life Technologies. Billings will serve as the project's chief medical officer. "There is an urgent need to define and validate a complete medical workflow for genomic-based cancer care." Life Technologies, which was created by the combination of Invitrogen Corporation and Applied Biosystems, sells one of the most popular DNA sequencers on the market. The new study, called the Genomic Cancer Care Alliance, is a collaboration between Fox Chase Cancer Center, the Translational Genomics Institute, and others.

According to the statement:

As currently envisioned, patients enrolled in the study will have both tumor and normal tissue sequenced by TGen, Scripps, and other organizations, using Life Technologies' Applied Biosystems SOLiDT System to identify mutations...

The results will be validated by a CLIA-certified lab and interpreted by TGen and Omicia Inc, a personalized medicine company focused on interpreting genome sequences for clinical applications. A centralized tumor board for the study, composed of physicians from Fox Chase Cancer Center, TGen, Scripps and El Camino Hospital's Genomic Medicine Institute, will study the results and consult with patients' oncologists regarding how to use the test results to develop personalized care plans. Scripps Genomic Medicine, a program of the nationally renowned Scripps Health organization, is focused on using genetic information to create individual treatment plans.

Similar, more limited efforts are underway at individual hospitals around the country. Massachusetts General Hospital, for example, tests lung cancer and colorectal cancer patients for a number of mutations, using the information to select treatments or to enroll patients in clinical trials of experimental drugs.

Scientists have sequenced hundreds of cancer genomes in the last year, though only a handful have been published to date. One difficulty has been distinguishing the so-called driver mutations, which enable cells to become cancerous, from mutations that have no impact on the cell. The number of mutations found in different cancers appears to vary widely.

The project follows a more focused pilot project sponsored by Life Technologies announced a couple of months ago, which involves sequencing the genomes of 14 patients with triple-negative breast cancer, an especially serious form of the disease that is resistant to some of the most successful drugs. They will use the genome to guide treatment and then determine if that improves outcomes compared to 14 breast cancer patients who did not have their genomes sequenced.

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