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The Indiana Jones of Genomes
Tears of the Cheetah and Other Tales from the Genetic Frontier
by Stephen J. O’Brien

Reviewed by
Patricia Thomas

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Not many molecular geneticists belong to the Explorer’s Club, where the exploits of daredevil balloonists and solo circumnavigators are celebrated with single malt Scotch and termite hors d’oeuvres.

Stephen J. O’Brien is a member in good standing, however, because he can tell stories that begin like this: “Our treacherous climb lasted six hours, slipping and sliding in the cold drizzle up the steep and muddy game path. Lugging our backpacks, in thermal undergarments and Gore-Tex hiking boots, we meandered through thick bamboo forest, over numerous precipices, by loggers’ camps, past towering waterfalls.” O’Brien slogs ever upward, dragging a bit due to “jet lag, Montezuma’s revenge, and a mild hangover,” into the mountainous area set aside for China’s giant pandas. There, he holds a puppy-sized cub while a hair is plucked from its rump.

DNA samples from wild and captive pandas were analyzed at the National Cancer Institute’s Laboratory of Genetic Diversity, which O’Brien has led since 1986. There, his team used comparative genetics to settle an old debate: Is the giant panda truly a bear, or is it an enormous raccoon?

Many lab tests later, O’Brien’s molecular investigations confirmed what old-fashioned taxonomists and millions of children already believed: The panda is a bear. He also was able to show that the main threat to giant pandas is not inbreeding, which imperils Florida panthers and other endangered species, but the destruction of their habitat by China’s burgeoning population.

Over the past 20 years, O’Brien has collected wildlife DNA samples in remote mountain ranges, sweltering savannahs, leech-infested rivers, and even on the high seas. His memoir about his life in science, Tears of the Cheetah And Other Tales From the Genetic Frontier, is packed with so many suspenseful and hair-raising yarns that it could have been entitled Indiana Jones and the Double Helix.

Despite the out-of-the-way places O’Brien has been, much of his work is mainstream biology. When the 1970s War on Cancer pumped unprecedented sums into the study of cancer-causing viruses in animals, O’Brien was one of numerous young biologists who chose cats as a model for trying to understand possible connections between retrovirus infection and cancer. Over the years, he became fascinated with host-pathogen interactions, especially evolutionary adaptations that protect their lucky carriers against infections or cancer.

O’Brien went from studying housecats to cheetahs, whose vulnerability to a lethal immune system virus he traced to a loss of genetic diversity. It appears that few cheetahs escaped the great mammal die-off at the end of the Pleistocene, and that subsequent inbreeding left them with a narrow range of immune responses to infection. O’Brien published evidence for this in Science, which made him a celebrity in the world of conservation biology.

Soon he and his colleagues were invited to study the genetics of lions in India and Africa, panthers in Florida, orangutans in Borneo and Sumatra, pandas in China, and humpback whales in the Caribbean. They analyzed why some species suffer reproductive troubles while others fall prey to infectious diseases, providing information that governments and conservation groups have used to keep various species and populations alive.

Skeptics have sometimes challenged the relevance of all this to O’Brien’s day job at the National Cancer Institute, which presumably is interested in research that will someday help alleviate human suffering. O’Brien argues that analyzing the genomes of species that narrowly escaped extinction enables him to pinpoint resistance or susceptibility genes that may have counterparts in humans. These genes, in turn, may prove useful targets for drugs or gene therapy.

Only in the last three chapters of Tears of the Cheetah does O’Brien tell us that he is the co-discoverer of a really important human gene: CCR5-Δ32 was the first human gene variant found to protect against HIV infection. People with two copies of this mutation are immune to most strains of HIV, because one of the doorways that the virus needs to enter human cells is blocked. (People with one copy can be infected but become sick very slowly.)

O’Brien had found viral restriction genes in animals, and after his only brother died from AIDS in the early eighties, he spent more than a decade searching for genes that interfered with HIV infection. This quest was long and costly, and he credits NCI with backing his hunch until it paid off. O’Brien’s lab has subsequently identified about a dozen gene variations that limit HIV infection or disease progression, and drug companies are working to develop medicines based on these findings.

In the end, Tears of the Cheetah is a collection of rollicking adventure stories that O’Brien uses to make a larger point: Nature has performed countless experiments and inscribed the results in the genomes of every species. Now high-speed gene sequencing and the rapid proliferation of complete animal genomes will fuel unprecedented advances in medicine and conservation alike. The book lags a bit when O’Brien bogs down in the politics of wild animal conservation, and there is an oddball chapter about how he used feline genetics to solve a murder mystery. But these are minor annoyances. And if O’Brien sometimes seems as satisfied with himself as a tomcat with cream on his whiskers, well, he’s earned the right to preen a bit.

. . .

Boston-based science writer Patricia Thomas is the author of Big Shot: Passion, Politics, and the Struggle for an AIDS Vaccine.

O’Brien, Stephen J. Tears of the Cheetah and Other Tales from the Genetic Frontier. Thomas Dunne Books, New York. 2003.

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