Essays on Science and SocietyGenome-Sequencing Anniversary

The Accelerator

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Science  25 Feb 2011:
Vol. 331, Issue 6020, pp. 1024
DOI: 10.1126/science.1204037

When the Human Genome Project (HGP) was proposed some 25 years ago, the notion was so foreign to biology that commentators had to resort to metaphors from physics. The HGP was biology's Manhattan Project, biology's Moon Shot, biology's Superconducting Supercollider particle accelerator.

To some, the project seemed like mindless drudgework aimed at a dubious goal. (Sydney Brenner waggishly suggested that the HGP be conducted in penal institutions, by “inmates sentenced to 20 megabases—with time off for accuracy.”) In reality, of course, it was the human genetics research of that early era that was marked by tedium (10 years to clone the gene for Huntington's disease!). What smart young student would want to be an ant in an army scaling a linkage peak?

Ultimately, the HGP yielded discoveries as remarkable as any atom-smasher or deep-space telescope. It revealed that the spectrum of protein-coding genes is far smaller than imagined, that physiology depends on a vast universe of regulatory controls and noncoding RNAs, that diseases arise from many unsuspected genes and pathways, that so-called junk DNA may be the mother of much invention.

In the end, though, the HGP might indeed best be viewed as a “high-energy accelerator”—not of particles, but of scientific work and scientific imagination. Individual investigators, the drivers of biomedical progress, can today carry out projects that once required legions: They can readily assay thousands of genes, millions of genetic markers, billions of nucleotides; they can interpret their findings in the context of public data sets representing tens of thousands of experiments worldwide and billions of years of evolutionary information. These capabilities have liberated them to think creatively and boldly about important biomedical challenges. Once seen as “big science,” the HGP has proved to be the most powerful enabler of “small science.”


Robert F. Kennedy famously said, “Some men see things as they are and say ‘Why?’ I dream things that never were and say ‘Why not?’” Increasingly, young biomedical scientists are bringing this same attitude to their work. They are impatient with technological limits that stand in the way of knowledge. They transcend disciplinary boundaries, fusing experimental, computational, and clinical science into a new biology. They roll up their sleeves to create vast data sets, comprehensive reagent collections, and powerful new methods—and they share them freely. They are not afraid to work in teams, if by working together they can change the world.

In the past week, I have attended three scientific meetings, where I heard young scientists brimming with vision about predicting all the ways in which tumors can become resistant to a therapy, unraveling the molecular basis of psychiatric diseases, characterizing the entire human immune response to stimuli, mapping the complete genomic landscape of all transcription factors through development, creating a comprehensive catalog of all cellular circuitry, and devising general methods to speed the development of new therapeutics.

If I had been asked to pick out a present to celebrate the 10th anniversary of the HGP, I could not have chosen better.

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