‘I JUST HEARD THE PRISON DOOR SHUT BEHIND US.’
I stood with Bob Waterston on the glaring white platform of the little station at Syosset on the Long Island Railroad, waiting for a train to New York. The sun was harsh and bright. We were on our way home from the 1989 Cold Spring Harbor symposium on the biology of the nematode worm. It was always hard for me to go to the worm meetings—to leave behind the lovely softness of an English spring and go to that land of sharp shadows and fierce contrasts. Now I find the transition less acute, but the difference is always there.
The worm meetings had taken place every two years since 1977, but this one had been special. Alan Coulson had unrolled the long scrolls on which we had mapped out the worm genome across the end wall of the Bush lecture theatre. For all three days of the meeting he was besieged by people wanting to check details and add information before they went off on another two-year stint of the real stuff of biology—discovering where and when and how the individual genes direct the production of a fully working worm.
At one point Jim Watson, co-discoverer of the double helix of
DNA and then head of the Human Genome Project, visited the map. ‘You can’t see it without wanting to sequence it, can you?’ he remarked. Our map represented overlapping pieces of worm DNA, lined up in the right order and studded with known landmarks. To sequence it would mean reading every one of the 100 million letters, or bases, in the worm’s genetic code. That would yield the ultimate map: the total of all the information needed to make a worm. In terms of knowing our way around the worm genome, it would be the difference between a school globe and a set of street maps with every house marked.
Later we sat in Jim Watson’s office discussing exactly how we might do this. And we came to an agreement. Bob’s lab in St. Louis and mine in Cambridge would between us sequence the first 3 million bases of the 100 million base genome during the next three years to show that we were capable of doing it. If all went well, we would then apply for the funds to finish the rest.
That much we could plan. We had no inkling that we would soon be enmeshed in the turbulent, contentious but ultimately successful project that resulted in the announcement of the draft human genome sequence in June 2000.
On that May afternoon, as we waited for the New York train under the hot sun, the end was a long way off. Nobody had sequenced more than 250,000 bases before, let alone 3 million or 100 million. Many regarded the very idea as a waste of time and resources. Yet we had committed ourselves to doing it. In the sudden quiet after the bustle of the worm meeting, the realization hit me that there wasn’t any way back: we could only go forward. The clang of the prison door reverberated in my ears. It was one of the most exciting moments in my life.