HapMap: A Genomic Guide to Disease

In October 2005, scientists in Cambridge, MA and Oxford, U.K. published the first draft of the HapMap, a database of human genetic variation. The map should radically improve scientists’ ability to discover genes involved in cancer, diabetes, and a host of other diseases (see A New Map for Health, November 7).

The massive project, which catalogues more than three million points of genetic variation based on samples from 269 people, also involved advances in technology. The cost of identifying one single nucleotide polymorphism (SNP) dropped from almost a dollar in 2002 to less than one cent in 2005, and efficiency also increased, from hundreds of SNPs identified per day to millions.

The HapMap is expected to help identify genetic markers that predict which individuals will respond to certain drugs. That information could resolve part of the controversy surrounding BiDil, a heart drug approved by the Food and Drug Administration in June that carries the first race-specific prescription guidelines. Critics of the drug have questioned if race is a good proxy for the genetic variations that most likely underlie an individual’s response to the drug (see Race and Medicine, April). “The best we could do in 2005 was use self-reported race; but I hope more and more we’ll have genetic markers instead of phenotypic markers,” says Dr. Steve Nissen, a cardiologist at the Cleveland Clinic in Cleveland, who chaired the FDA advisory panel on BiDil.

A Roller Coaster Ride for Stem Cell Research

This year brought a series of promising highs – and terrible lows – for the field of stem cell research. U.S. researchers continued to struggle with federal funding limitations. Scientists were forced to set up parallel research spaces to their federally supported labs to work on new stem cell lines and to find new funding sources to continue their work (see Braving Medicine’s Frontier, September).

In an attempt to circumvent some of the funding problems and ethical objections that have plagued human embryonic stem cell research, which requires the use of discarded human embryos, two Massachusetts scientists developed new techniques to create the cells. Both techniques eliminated the destruction of human embryos normally required to generate stem cells; however, many conservative ethicists still weren’t satisfied (see A More Moral Stem Cell?, October 18).

Then the field took a big blow this month when stem cell leader Woo Suk Hwang, at Seoul National University in South Korea, announced he wanted to retract a landmark paper published in Science in May. In the paper, Hwang and colleagues said they had efficiently created 11 lines of stem cells perfectly matched to 11 patients with different diseases. The findings were hailed as a huge leap forward for the clinical potential of stem cells.

Those findings came into doubt in December amid allegations of ethical and scientific misconduct. On December 23, an investigative panel from Seoul National University released a preliminary report concluding that Hwang faked at least some of his research. Hwang subsequently resigned his position, but he has maintained that the science behind his work was real. (Technologyreview.com will publish a story in January exploring the implications of this controversy for stem cell research in the United States.)

Cloning Cats and Dogs

In 2005, the cost of a cloned cat dropped from $50,000 to the “bargain” price of $32,000. Genetic Savings and Clone, the world’s first pet cloning company, based in Sausalito, CA, provides this controversial service to people who have lost “an exceptional pet” ’ (see Briefcase: Genetic Savings and Clone: No Pet Project, March). GSC’s early success was up in the air in 2002 – after its first cloned cat turned out to look nothing like her donor, a calico. (Unlike other cats, a calico’s coat color is not entirely genetically determined.) But the company has forged ahead. GSC sold its second cloned kitten, Little Gizmo, in February, and was able to lower the price tag by switching to a more efficient cloning technology. The company assures prospective customers that their two current clients have been satisfied by the likeness of their newly fabricated felines.

Unfortunately, pet owners longing to clone their dogs will have to wait. Canine cloning presents an entirely new set of obstacles: dogs produce eggs infrequently, and those that are produced are too immature to use directly in the cloning process. While GSC had hoped to overcome these challenges and create a cloned dog in 2005, they may – or may not – have been beaten to the punch by Woo Suk Hwang, the same Korean stem cell researcher accused of faking the research behind a Science paper on human stem cell lines (see above). In August, Hwang’s group published a paper in Nature announcing the creation of Snuppy, purportedly the world’s first cloned dog. However, the pooch’s status as a clone is now in serious doubt.

GSC is still working on canine cloning. “We think there’s a reasonably good chance we’ll succeed this coming year,” says Ben Carlson, a company spokesperson.

The Methuselah Debates

Technology Review’s most widely read – and most controversial – story in 2005 was a profile of Aubrey de Grey, an English bioinformaticist and self-educated biogerontologist who has outlined a seven-point plan to cure human aging (see Do You Want to Live Forever?, February). The story provoked reams of criticism, from both de Grey’s supporters and his detractors. The former, who approve of de Grey’s quest to defeat death – known as “strategies for engineered negligible senescence,” or SENS – were outraged by Technology Review’s skeptical tone. At the other end of the spectrum, traditional biogerontologists were annoyed that de Grey’s ideas were getting any press at all.

Prior to the debate in our pages (both print and online), few scientists in the field had come out against de Grey – who has become one of the world’s most quoted anti-aging scientists. After the story, in November 2005, molecular biology journal EMBO reports published a letter signed by approximately 30 scientists explaining why de Grey’s popularity is detrimental to the goals of anti-aging research.

“We as journalists and scientists have a duty to present this in a critical framework,” says Jason Pontin, editor in chief of Technology Review. “Biogerontology matters because geriatrics matters, now more than ever. Anything we can do to create therapies so people can live a long, healthy life until the end – that will be the great accomplishment of biogerontology.” (Also see our Q&A with Leonard Guarente, December 2005/January 2006.)

In September, Pontin issued the SENS challenge, a $20,000 prize to any molecular biologist or group of molecular biologists who could satisfactorily explain why the SENS plan wouldn’t work. Technology Review has received several entries and will announce a winner early next year.

A healthful new year to all our readers.