“WE WOULDN’T have a genome at all if we hadn’t carried on with the public
effort,” says John Sulston, the former head of the Sanger Centre in
Cambridge.
In 1998, six years after the Human Genome Project began, the effort to
sequence the genome turned into a race when Craig Venter announced that his
company, Celera, would finish it by 2001 using the “whole genome shotgun”
method. That led some people to question whether the public effort was a waste
of taxpayers’ money. Now Celera is claiming victory. “The whole genome assembly
has been an unqualified success,” Eugene Myers of Celera said on Monday.
But the public project was essential to prevent the genome being
“privatised”, Sulston says. He also rejects the claim that Celera won the race.
“Now that the papers from the two teams can be inspected, we can for the first
time judge the relative strengths of the two versions,” he says. “To get their
sequence, they relied very heavily on the work we put in.” Over half the data in
Celera’s final version came from the Human Genome Project, Sulston says
(see graphic).
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Despite this, Sulston thinks Celera’s version is not greatly superior to the
HGP’s draft version. “Remarkably, his product is very similar to ours. I would
have thought it would be much better. Far from ‘winning the race’, as they have
claimed, their methodology has been found wanting.”
The HGP’s method involves mapping the genome, by identifying “signposts”
along each chromosome, and then sequencing it region by region. Venter claimed
that the pure shotgun method, in which the entire genome is randomly cut into
pieces, sequenced and then assembled by computers, was much faster and more
efficient.
But Sulston says the version Celera produced using this method is inferior to
the HGP’s draft. “It fails badly both in sequence continuity and long-range
order.” To get its final version, Celera had to resort to a “compartmentalised
shotgun” method. This relies on the public project’s map information, and is
really a variation on the HGP’s method, Sulston says. “We can say today that we
were right.”
Sulston says that while Celera’s final version has more gaps, the local
ordering of many of its fragments is more accurate. But this is what you’d
expect, he says, given that Celera had access to the HGP’s data as well as its
own.
“It’s hard to understand where these claims come from,” Venter says. “The
whole genome sequencing technique gave a wonderful reconstruction of the
Դdz.”
“We found that 3 to 5 per cent of the public map was completely
misassembled,” he says. “What adding the [public] data did was make some gaps
smaller and show where some bits were too long. But it didn’t change the
assembly as a whole.”
Both groups still have a lot of work to do, however. Only 33 per cent of the
HGP’s sequence has been finalised. It will take up to two years to finish. “Ours
is not a draft,” Venter insists. “It has some gaps but it’s a highly accurate
sequence with all the pieces in the right order.”
“It’s very plainly a draft,” retorts Sulston. “It’s got a very large number
of gaps.”
Controversy also surrounds the decision by the journal Science to
publish Celera’s papers on the genome even though researchers won’t be given
unrestricted access to its sequence. “If you publish a paper that depends on a
DNA sequence, you put it into one of the public databases,” Sulston says. This
is why the HGP published its papers in a separate journal, Nature,
rather than jointly with Celera, he says.
Venter denies access is restricted. “Ours is accessible, but through
subscription. From 10 am on Monday, it [has been] available free of charge on
the Internet to any academic for any science they want to do. The one
restriction is that they can’t take the data we’ve produced and give it to a
commercial competitor that wants to sell it.”
However, among various other restrictions, researchers will only be allowed
to download one million bases a week. “I hope this unusual thing, where a major
journal has downgraded publication rules to accommodate the whim of a particular
company, does not create a precedent for the future,” says Martin Bobrow, a
geneticist at Cambridge University.