Supercomputers Track Human Genome
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"PASADENA,
Calif. -- Kwang-I
Yu, president of
Paracel Inc., will not
say which secretive
government agency
buys his company's
specialized
supercomputers. "We
sell to the federal
government," he
demurs.
But J. Craig Venter, the president of Celera Genomics,
is less circumspect. Paracel's machines, he said, are
used by the National Security Agency, the
code-breaking unit that eavesdrops on other nations.
And Dr. Venter should know. Celera Genomics, the
company that mapped the human genome, acquired
Paracel for nearly $250 million in stock in June.
Paracel's machines are designed to sift documents
rapidly for particular words, phrases or strings of
letters -- an ability of obvious use to those filtering
communications for important nuggets.
But what attracted Celera is that Paracel's technology is
also good for breaking another code -- the genetic one.
The machines are being snapped up to sift the blizzard
of data being generated by the Human Genome Project
and various private genomics efforts. "They're all
character strings," said Dr. Yu, comparing the gene
sequence to a text message.
The need for Paracel's machines stems from biology's
shift from a "wet" science performed in test tubes to at
least partly a "dry" one, in which much of the crucial
analysis is done on computers. This has given rise to a
field called bioinformatics, the use of computer science
in life science.
And bioinformatics must handle volumes of data so
huge they could bring ordinary computers to their
knees. The human genome is comprised of three
billion chemical units represented by the letters A, C,
T, and G -- a string that would stretch from Boston to
London if written in letters of the size in this article. A
scientist studying a particular sequence of DNA might
search through the entire human genome, as well as
those of other animals and bacteria, to find similar
sequences. And genomics companies might want to do
thousands of such searches a day.
"There's a class of algorithms that would take forever
on a regular computer," said Edward Kiruluta, vice
president for research and development at
DoubleTwist, a bioinformatics company in Oakland,
Calif. Even with its Paracel machine, he said, some
analyses take weeks. On regular computers, they would
take months. And speed is of the essence, especially in
analyzing data from the publicly financed Human
Genome Project, which makes new sequences
available each day to everyone at the same time.
"As the genome data comes out, you want to analyze it
as fast as you can, make the discoveries first and
protect the intellectual property," said Martin D. Leach,
director for bioinformatics at CuraGen, which uses
genomics to develop drugs.
Computers, of course, are doubling in speed for a given
cost every 18 months or so, according to Moore's Law,
named after Intel's co-founder, Gordon Moore. But the
volume of genomic data is growing even faster, owing
to automated DNA-sequencing machines. GenBank, the
government-run public domain database of DNA
sequences, more than doubled in size the last six
months to more than 8.6 billion chemical units.
I.B.M. estimates that the market for hardware and
software for life sciences will grow from $3.5 billion
now to more than $9 billion by 2002. Carolyn Kovac,
who heads a newly formed life sciences division at
I.B.M., said biologists had replaced physicists as the
main scientific users of supercomputers.
Sun Microsystems and Compaq Computer are also
trying to develop products for the life sciences, with
either supercomputers or servers linked together in big
clusters. And start-ups like Parabon Computation of
Fairfax, Va., and Entropia of San Diego, are trying to
harness tens of thousands of home and business
computers to work on genomics when they would
otherwise be idle by distributing portions of the tasks to
these computers over the Internet.
Paracel's GeneMatcher machine, however, is
especially built for genomic searchers. It has 7,000
processors arranged in a way best suited to matching
character strings. Dr. Yu likened the process to having
each letter of the sequence being studied in a separate
processor strung along the inside of a hose. The
database to be searched flows over these letters like
water through a hose, at the rate of 30 million
characters a second, and each processor sees whether it
has a match as each letter flows by.
With a list price of $360,000, GeneMatcher would be
too much for general-purpose computing. But for the
task for which it was designed, it can be up to 1,000
times as fast as a Pentium-based computer, making it
cost-effective, Dr. Yu said.
The market for machines like GeneMatcher, which are
called genomics accelerators, is tiny. Paracel sells only
one or two a month, so few in fact that it assembles its
machines by hand in one room of a high-rise office
here.
It says it has more than 30 customers, including drug
companies like Novartis, Bayer and AstraZeneca, as
well as some biotechnology and bioinformatics
companies. No customer has more than two machines,
other than Celera, which bought four last year.
But sales are growing. Paracel, which was privately
held before its acquisition by Celera, had sales of
$14.2 million in 1999, up from $5.9 million the year
before. Dr. Yu said Paracel was not profitable because
of investments but had been in the past.
GeneMatcher accounted for $5.2 million of Paracel's
1999 sales, and genomics software $1 million.
Textfinder machines, used by the government agency
and a few other customers to search text databases,
accounted for $8 million.
Paracel's main competitor, TimeLogic, based in Incline
Village, Nev., had sales of $3 million in 1999 and was
profitable, according to its chief executive, James W.
Lindelien. Sales of its DeCypher accelerator rose 350
percent in 1999 and should rise 50 percent this year, he
said.
Compugen, an Israeli company that just went public,
also sells an accelerator but is de-emphasizing that
business.
Some experts think that conventional server farms can
do the job less expensively than genomics accelerators
can and can also be used for other tasks. The National
Center for Biotechnology Information, which runs
GenBank, uses about 140 conventional computers that
are tied together. It is possible, said one expert, to
define the problem so that you don't have to compare
everything with everything else in the entire database.
Indeed, history is not on the side of dedicated
hardware. Machines designed for artificial intelligence,
computer-aided design, database storage and graphics
were all eventually replaced by general-purpose
computers, which became fast enough to handle those
jobs and cost less because of their huge production
volumes. The large sales volumes of general-purpose
computers also generate more money for research and
development at the companies that produce them,
allowing them to improve their machines faster than
companies that design specialized computers.
Paracel's acquisition by Celera will give the company
more financial resources to help it keep up. But some
experts were shocked that Celera would spend so much
money for such a tiny, niche company.
But Dr. Venter of Celera said the Paracel machines
would be important. "There's no university or
pharmaceutical company that has the compute
capability they need to deal with our data or anyone
else's genomic data," he said.
Celera must persuade companies to pay for its genomic
data when GenBank offers much of the same human
genome data free. One way to compete is to offer more
and better data. But another, Dr. Venter said, is to use
the Paracel machines to offer Celera customers faster
searches than they could get using GenBank.
Paracel technology can also be used to compare the
sequence of amino acids that make up a protein and
could become part of a protein analysis machine that is
being designed by Applied Biosystems, Celera's sister
company. Both Celera and Applied Bio, formerly
known as PE Biosystems, are subsidiaries of the PE
Corporation. Celera has one of the largest computer
centers in the world, costing more than $50 million, and
made up mainly of Compaq servers. By May, Celera
had bought only $1.9 million of Paracel machines. But
Dr. Venter said that while the Compaq machines were
used to assemble the genome sequence in the correct
order, the Paracel machines would be used to search
the database.
PE and Paracel have long been partners. In 1996 PE
bought a 14 percent stake in Paracel for $4.5 million.
Dr. Yu himself owned about 17 percent of Paracel,
giving him Celera stock worth about $35 million when
the the acquisition closed in June.
Dr. Yu, 50, grew up in Hong Kong, Taiwan and
Malaysia and came to the United States for college.
After earning his doctorate in computer science from
the California Institute of Technology, he joined TRW,
the defense contractor, where he worked on
development of the text-searching chip. In 1992 TRW
spun out Paracel to commercialize the technology and
before the buyout held 13 percent of the company.
The acquisition by Celera will benefit Paracel, but it
could also cause genomics companies that compete
with Celera to avoid buying from Paracel. TimeLogic
is already playing up this factor in its sales pitch. And
to counter Paracel's alliance with Celera, TimeLogic is
expected to announce soon that its machines will be
distributed by Sun Microsystems.
Dr. Yu said he did not think customers would desert
Paracel. And Paracel will obtain information from
Celera that could help it design better machines.
"I really want to be part of something that's the
definitive provider of tools to mine that information,"
he said. "I can get there faster by merging with Celera." |
