Goldfish Learn To Drive

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FR
OM T
OP: MA
TTHEW RAK
OLA; NHGRI
Ambitious beginnings
SAEY:
My first memory of the Human Genome Project was 
when I was an undergraduate student at the University of 
Nebraska in Lincoln, and I remember Walter Gilbert, who is 
a Nobel Prize winner, coming and talking about the project. 
He proposed this really audacious idea of sequencing 3 billion 
pairs of bases in the human genome — all of our DNA. After
Gilbert’s talk, I walked back to the lab with a couple of profes-
sors, and they were saying, “This can never happen. It’s going 
to cost way too much money. There’s just no way we can do 
this.” So how did you pull it off?
GREEN:
By the time the genome project started in October
of 1990, I was working in a cutting-edge genomics lab at
Washington University. We were one of the first funded groups 
to participate in the Human Genome Project. We had some 
ideas on how to start, and we had really no idea how we were 
going to pull it off. 
It was the overwhelmingly compelling vision for why this 
was so important that galvanized enthusiasm among not only 
a group of scientists like myself, but also the funding agencies, 
the governments, the private funders from around the world, 
who said, “This seems unimaginable, like putting a person on the 
moon, but it seems so important. We’ll figure it out.” So it was 
one of these circumstances where you just get the right people 
in the right place, get them resourced, get them organized, be 
willing to do things differently, and then figure it out as you go.
SAEY: 
I got to witness this because I was a graduate student at 
Washington University, in a lab sequencing the yeast genome. 
Robert Waterston’s lab, which received one of the first grants 
from the Human Genome Project, was right across the hall. 
They started with C. elegans, the roundworm genome. I 
remember they were starting very methodically, mapping out 
the genes and then sequencing each piece, marching along. 
But then, toward the end of the ’90s, there was this shotgun 
sequencing revolution spearheaded by kind of a controversial 
figure, Craig Venter. You just shred the genome, throw it all in a 
sequencing machine and then put it together in the computer. 
Did that help a lot? 
GREEN: 
There’s no question it sped things up. What Craig suc-
cessfully did was to determine that there were approaches that 
could be used where you didn’t have to do piecemeal sequenc-
ing. The important nuance to point out is the only way you’re 
able to put [the pieces] back together then was by having many 
mapping elements that allow you to hang pieces together and 
organize them. It’s not like it all zipped together 3 billion let-
ters. A lot of the meticulous mapping that had been done, 
painstaking mapping, helped provide organizing guideposts.
The press covered it as a race, and the press covered it as 
option A versus option B. And the truth resided somewhere 
in between. What was driving the change, of course, was
technology advances. If you chart the time since the end of 
TETIANA LAZUNO
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