The Chemistry Of Biology

WOOLLY MAMMOTHS were spectacularly exotic beasts that roamed through the frozen northern reaches of Europe, Asia, and North America for a few million years until they became extinct 8,000 to 10,000 years ago. They coexisted with, and were hunted by, modern humans, who drew pictures of them on cave walls. Although the disappearance of much of their habitat at the end of the last ice age certainly played a role in the extinction of woolly mammoths, predation by humans also contributed to their demise.

Because quite well-preserved mammoth carcasses have been retrieved from the ice in Siberia and elsewhere, people have hoped that it might be possible to re-create mammoths by taking genetic material from a carcass and somehow implanting it in the egg of a modern elephant. This has not proved to be feasible because DNA in even well-preserved specimens has deteriorated into small fragments.

In November, a team of scientists from Pennsylvania State University and a number of other institutions around the world reported the sequencing of about 70% of the nuclear genome of the mammoth (Nature 2008, 456, 387). The team, which was led by Penn State scientists Webb Miller and Stephan C. Schuster, had previously reported the sequence of mammoth mitochondrial DNA.

In a commentary that appears in the same issue of Nature (page 330), Michael Hofreiter of the Max Planck Institute for Evolutionary Anthropology points out that this research tour de force is a product of amazing advances in sequencing technology. "Within the space of less than a decade," Hofreiter writes, "the development of high-throughput technologies has transformed the task of sequencing a mammalian genome from the years-long, multimillion-dollar endeavour it was originally, to a project that can be performed by an individual laboratory within a few months."

The point of the sequencing project is to better understand the evolutionary biology of mammoths, in particular their relationship to present-day elephants. It turns out that mammoth and elephant genomes are about 99.4% identical, according to the Penn State team. The researchers state that completing a "high-fidelity, high-coverage" mammoth genome will be feasible once the entire mammoth genome and the modern elephant genome are sequenced.

Reports on the work in both the New York Times and the Washington Post speculated on whether the sequence of the mammoth genome will enable people to re-create living woolly mammoths. We cannot yet create the 4.7 billion-base-pair mammoth genome synthetically. However, it might be possible to selectively mutate elephant DNA over a number of generations to create a mammoth, the Times report suggests.

This research and the speculation about where it may lead is possible only because, as I have pointed out before on this page, biology has in the past four decades become a chemical science. In his commentary, Hofreiter calls the progress in sequencing technology "breathtaking." The speculation about selectively mutating elephant DNA into mammoth DNA in the Times is based on unpublished work on a technique that can modify 50,000 genomic sites at a time.

This is chemistry, plain and simple. You can call it sequencing technology or genome technology, but it is chemistry applied to key biological questions. Chemistry, the enabling science, has utterly changed biology; it is also utterly changing many of the other disciplines it interfaces with.

The editorial in last week's issue by Managing Editor Ivan Amato discussed another aspect of the chemical transformation of biology, synthetic biology. Despite some qualms, Amato acknowledged that synthetic biology is going to happen.

I have qualms about bringing back woolly mammoths. I hope it doesn't happen because, not only are mammoths extinct, the world they inhabited is extinct, too. There is no place for them, and it seems cruel to bring them back just so we can stare at them.

Instead of resurrecting species our ancestors helped drive to extinction, I think we should be working desperately to curb the mass extinction we ourselves are driving today.

Thanks for reading.

Rudy Baum, Editor-in-chief