Gene-Mining

Genes in chocolate trees, cancers, and sea water are confirming Darwin and changing the world.

I knew genomics had come of age when I heard they were sequencing the chocolate genome-or the tree chocolate comes from, anyway. That’s Theobroma (“food of the gods”) cacao, which is so beset by diseases that the world’s chocolate addicts, me included, could lose our fix.

The Maya believed the gods discovered cacao and gave it to them; they and other Native American cultures cultivated it, used it to appease those gods, and took delight in it. Columbus noticed it, Cortez was served it by the Aztecs, and from the mid-1500s it spread from Spain through Europe and the world. Yum.

Now, its source is endangered by funguses, so the Mars candy people got together with the Agricultural Research Service and IBM-they need Blue Gene, the supercomputer, to do the math-to analyze cacao for genes that boost resistance. Could it also lead to synthetic chocolate-maybe an equally tasty but less addictive kind? Who knows? No limits in the genomics era.

Of course, thousands of labs do human genomics, and almost every New England Journal of Medicine reports news from them. Just this week it revealed a new statistical approach to the known genes for breast cancer, the disease that killed my wife and countless others.

While each one raises risk only slightly, putting 14 of them together in a large sample of women can point to those most at risk. This could make the difference for my daughters. The accompanying editorial was called “From Darwin’s Finches to Canaries in the Coal Mine-Mining the Genome for New Biology.”

The title alone contains an evolutionary reference and two metaphors. Darwin’s finches are mentioned because they helped him see the relationship between phenotypes and underlying hereditary variation. The genes for breast cancer, weak though they are individually, can be timely warnings.

But the mining-the-genome metaphor caught my attention. This kind of survey genomics might be derided by some as a fishing expedition. As the authors say, “Genetic mapping turns hypothesis-driven research on its head.” Since Francis Bacon scientists have been under pressure to form hypotheses first.

But that can be too much of a good thing, and in truth much of science is description–a task renewed with every advance in instrumentation. The microscope revealed new worlds in miniature, the telescope on a grand scale; no one derides Leeuwenhoek for going fishing for new animalcules. Genome sequencing has done the same for genes.

The human genome itself is proving a gold mine for explorers, including medical ones. A whole other approach involves sequencing tumors themselves, and this will gradually result in a new classification of cancers predicting their behavior far better than the crude methods we use now.

In a more abstract realm, I get excited about the platypus genome, because it can help us identify what is uniquely mammalian and uniquely human. The latest issue of Nature reveals the genome of amphioxus-a tiny fish-like creature known as the lancelet-which does the same for vertebrates. These are more abstract contributions than sequencing tumors, but they will be at least equally important. And it gets better.

J. Craig Venter, the enfant terrible of human genomics who accelerated the sequencing of our own genome with privately-funded competition for the government initiative, recently sailed around the world on a fishing expedition-scientific fishing. An avid sailor, he followed the path of a 19th century expedition charting life in the seas.

Every 200 nautical miles he stopped and scooped up a cubic meter of sea water. And when he got back home he sequenced the genes of every living thing in it. The organisms differed in every sample, and had different genes. Every 200 miles, 85 percent of the sequences and species were unique. The biodiversity just under the surface of the sea is astounding.

So in the end Venter and his team expect to find millions of new genes-a far cry from the paltry twenty or twenty-five thousand humans have. Just between Halifax and the Galapagos, where Darwin’s finches were, they doubled the number of known families of genes-among them, thousands of new proteins acting as photoreceptors to detect and respond to different hues of filtered sunlight.

Venter estimates that we know perhaps one percent of the life on our planet. He calls the millions of new genes “the design components of the future.” Any one of them could result in a new manufacturing process that could change the world.

Last month it was revealed that the sea floor, where life may have begun, is teeming with unheard-of microbes, and they will no doubt supply millions of other unknown genes, which could be the building blocks of future medicines and nanotechnologies no one alive today can think of.

Darwin saw things 150 years ago that we will be confirming for centuries to come. His work seemed abstract then, but it is yielding discoveries of the utmost practical value.

He must–metaphorically speaking, of course–be resting easily, and smiling.

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