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New Haven: Biotech City?
Ever
since the gun factories left, Yale's host city has been searching
for new economic engines to replace them. A surge in biotechnology
may point the way.
May
2001
by Bruce Fellman
Five
years ago, Jon Soderstrom, then in charge of new business development at Lockheed
Martin Energy Systems Corporation in Oak Ridge, Tennessee, got a
job offer he didn't want to refuse. Greg Gardiner, the Pfizer pharmaceuticals executive who had come out of retirement to take charge of Yale's
Office of Cooperative
Research (OCR), had been given a mandate by President Levin
to raise the profile of the University's efforts to convert its
scientific research into marketable products. Would Soderstrom,
an expert in what is known as technology transfer, be interested
in bringing the OCR to a new level?
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"If
there was ever going to be another Silicon Valley or Route
128, New Haven was as likely a place as any."
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"I looked
around the country and figured that if there was ever going to be
another Silicon Valley or Route 128, New Haven was as likely a place
as any," says Soderstrom. "It was such an untapped community."
It is
untapped no more.
The OCR,
which was established in 1982, had expanded its reach in the mid-1990s
under Gardiner to include the creation of companies, particularly
those that might exploit the University's strengths in the biomedical
sciences. And while naysayers dismissed the notion that biotechnology
might prove the salvation of New Haven's ailing economy, entrepreneurs
and investors didn't share their pessimism.
In the
past few years, the OCR, now directed by Soderstrom (Gardiner retired
in 1998, but remains a consultant) has helped broker deals that
have led to the creation of more than 16 biotech companies in the
Elm City, and there are at least eight new ventures in development.
The phenomenon has produced more than a thousand jobs, and last
year, so much private equity investment arrived in the area—$1.1
billion, according to OCR statistics—that when developers recently
pulled out of the proposed Long Wharf Mall, a controversial project
that had been touted as a cornerstone of New Haven's economic recovery,
Mayor John DeStefano Jr. simply shrugged it off. Biotech, said DeStefano,
would easily make up for any loss.
"That's
a lot of weight to put on our shoulders,"
quips Soderstrom, but recent events suggest that the mayor's vote
of confidence was not misplaced. In addition to a plethora of startups
that are based on discoveries made by Yale scientists, one slightly
more mature New Haven company, Curagen
(founded in 1993 by Jonathan Rothberg '91PhD), signed a $1.4-billion
deal in January with pharmaceutical giant Bayer to collaborate on
the development of drugs aimed at curbing obesity, diabetes, and
other ailments. Genaissance
Pharmaceuticals, launched in 1997 by Gualberto Ruano '92PhD,
'97MD, sold nearly $90 million worth of stock when it went public
last year—a noteworthy achievement because it occurred during
a down year for the stock market.
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"There's
been a complete transformation in the University's attitude
towards cooperating with industry."
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Meanwhile,
the University has helped attract two major real estate developers,
Winstanley Associates and Lyme Properties, LLC, that have experience
in creating laboratory space, a valuable commodity that was in desperately
short supply. Winstanley bought the vacant headquarters of Southern
New England Telephone at the corner of George and College streets
for $27 million and is spending at least that amount to renovate
the building. Lyme, which earlier had developed the highly successful
biotech complex called One Kendall Square in Cambridge, has taken
over the development and management of Science Park, the 80-acre
factory complex that once housed the Winchester firearms plant and
is now home to a number of biotech and high-tech firms, including
Genaissance. A turnaround is clearly under way, for after years
of losing money, the Park announced in March that it expects to
turn a profit of $1 million in 2001.
"New
Haven is becoming a destination resort," says Jeffrey Collinson
'63, a partner in the Stamford-based venture capital firm of Collinson,
Howe, and Lennox LLC. The company specializes in investing in
healthcare firms in the early stages of their development and has
provided funding for half a dozen New Haven-area biotech startups,
beginning with Neurogen in the late 1980s and continuing to the
present with Molecular
Staging, Inc., which was spun off from the research of Yale
geneticist David Ward and his colleagues and now occupies lab space
in the Winstanley building at 300 George Street. "Keeping this technology
close to home is a good thing for the University and the city,"
says Collinson.
There
are many reasons to agree. New Haven tax revenues could rise, perhaps
significantly, and for the University, royalties from licenses it
has granted to companies exploiting patented discoveries made in
Yale research labs have already proven a substantial source of income.
The biotechnology industry is also attracting related services in
such areas as law, public relations, venture capital, and the like.
But not everyone sees biotech as the proper prescription for New Haven's economic ills.
"I think we're overselling this big-time," says Douglas Rae, the
Richard S. Ely Professor of Management at the School of Management
and an expert on urban affairs. "We've already seen that the original
story of Science Park, which was supposed to employ its neighbors,
was hollow. I give biotech two cheers—it may be wonderful for
PhDs, but I don't see it as a replacement for Winchester."
At its
height through both World Wars and into the 1950s, Winchester and
other New Haven factories employed some 38,000 people. The company
was bought by the Olin Corporation in 1981, and much of its business
was moved elsewhere. This, coupled with the general decline in manufacturing
throughout the city, reduced the number of these jobs to only about
5,500 last year. "While there's certainly a multiplier effect to
retaining Yalies and other bright and well-paid people here, biotech
is not going to be a big piece of the answer for the city," says
Rae. "I wince every time I hear how we're going to solve an 80-year-old
problem in 80 or so months."
Biotech
may not be a panacea, but the progress already made has created
a positive buzz about New Haven, including favorable feature coverage
in the New York Times and the Wall
Street Journal—a welcome change for a city that has seen its share of bad
press. "The deeply engrained idea that New Haven can't succeed is
an attitude we're working to overcome," says Soderstrom. "This effort
is all about creating the engine that will get us to a 21st-century economic future."
This
deep involvement in boosting the economy of its host city is striking evidence of the cooperative relationship that now prevails between
Yale and New Haven. But the fact that the University has embraced entrepreneurship at all, let alone with such enthusiasm, is a sign
of what many are calling a fundamental shift in attitudes.
One of
those who have seen the change up close is Genaissance CEO Gualberto
Ruano. In the late 1980s, Ruano was working in the laboratory of
genetics professor Kenneth Kidd, and in the course of his research,
Ruano discovered a rapid method of decoding DNA and the genetic
code. "It never went through my mind that there could be a patent
involved," says Ruano. But a visit to the lab by Dr. Henry Lee,
Connecticut's well-known forensic pathologist, who wanted to set
up a DNA fingerprinting facility, changed his point of view. "I
started thinking that there might be an application for the technique
I had found," says Ruano.
Ruano
worked with then-OCR director Bob Bickerton to secure what became
U.S. patent number 5,427,911 ("a patent that has generated more
money than the University put into training me," says the researcher),
and he began to look for possible applications. Ruano's training
in population genetics had impressed him with the importance of
variations in genes, and his technical expertise enabled him to
study the genetic code that was being read in its entirety by the
Human Genome Project
and tease out the portions which might prove useful in developing
medications.
The problem
was that no University laboratory could afford to invest in the
kind of equipment required for such a task. Each of the gene sequencing
machines used in Ruano's work costs $300,000 and runs nonstop, and
he needed dozens of them.
"I had
to go industrial," he says. Ruano also had to raise vast sums of
money—$195 million to date for a venture he expects will turn
a profit by 2004. But while such efforts have fostered numerous
collaborations with University researchers—Genaissance even sponsors
a lecture series with the School of Medicine—Ruano's entrepreneurship
would probably have garnered the CEO something akin to pariah status
at Yale in an earlier time.
"There's
been a complete transformation in the University's attitude towards
cooperating with industry,"
notes Alan Sartorelli, the Alfred Gilman Professor of Pharmacology.
"More than 30 years ago, when I proposed the first major interaction
with Bristol-Myers, many of my colleagues suggested that any collaboration
would take away from the purity of what we do in academia and maybe even destroy Yale. But corporations are no longer seen as wearing
black hats." And neither are professors who would like to see their
basic research go commercial.
To be
sure, one reason for the change of heart is simply the passage into
history of an era during which corporate America was widely regarded
on many campuses as threatening, if not evil. Another reason is
the Bayh-Dole
Act, a 1980 law that established guidelines for patenting and
licensing discoveries made with federal funds and encouraged technology
transfer as a means of promoting economic growth.
Schools
with strong engineering traditions, such as MIT and Stanford, were
already comfortable using basic science as the source for product
development. But according to University provost Alison Richard, Yale was at first reluctant to take part. No more.
"We live in a society where it is less and less desirable, to say
nothing of tenable, for universities to hide inside their ivory
towers," notes Richard.
Yale's
shift in attitude began in the early 1980s, when
Robert Bickerton headed the OCR and faculty committees were grappling
with conflict-of-interest issues raised by any proposed collaboration.
In 1988 Bickerton shepherded the licensing of a compound called
d4T to the Milford-based Bristol-Myers
Squibb. The substance, discovered by pharmacologist William
Prusoff and medicinal chemist Tai-Shun Lin, was the first of a class
of anti-AIDS drugs known as reverse transcriptase inhibitors. The
medication, marketed under the trade name of Zerit, has generated
more than $100 million in royalties for Yale and helped finance
the Medical School's massive Clinical Research Building, now under
construction at the corner of Congress Avenue and Cedar Street.
(In March, the University ageed to relax the terms of its licensing
agreement so that the drug could be made more easily available in
Africa, where AIDS has reached pandemic proportions. (See "Yale,
Drug Maker Loosen Rein on AIDS Drug in Africa," May
2001.)
"The
world of licensing is a world of jackpots," says Richard. And in
that venue, Yale, despite its relative latecomer status, fares remarkably
well. With annual royalties last year of nearly $41 million from
100 licenses, it is ranked number-three (behind Columbia and Florida
State) among U.S. research universities in licensing income.
The booming economy of the 1990s meant that there were increasing amounts of
capital looking for places to grow, and President Levin embarked
on a partnership with New Haven to boost its economic fortunes.
Gardiner, and, later, Soderstrom and his staff, brought a new energy
and expertise to OCR, but what really made the subsequent surge
possible was a change in the fundamental structure of the pharmaceutical
industry.
The recent
trend has been for giant companies like Pfizer, GlaxoWellcome, and
the like to get even bigger through mergers and acquisitions. In
many cases, however, the outcome of this growth has been an increased emphasis on testing and marketing drugs, and a decrease in the basic
research necessary to discover new medicines.
"What's
moved into this vacuum is the biotech company," says Alan Sartorelli,
the inventor of several promising anticancer drugs being developed
by Vion Pharmaceuticals.
Sartorelli helped start Vion several years ago to bring his work
into the healthcare marketplace, and the company is also refining
a cancer drug delivery system discovered by John Pawelek, a senior
research scientist in dermatology.
Vion
is based in Science Park, which was launched in 1982 by a consortium
made up of Yale, New Haven, the State of Connecticut, and the Olin
Corporation to turn the abandoned and crumbling Winchester factory
complex into a business incubator for technology-driven companies.
But while the Park has been home to some notable success stories
over the years, it never seemed to live up to its promise. "What
was missing was demand," says Bruce Alexander, Yale's vice president for New Haven and state affairs.
"It would have taken a miracle to create a successful Science Park
without demand."
Worse
yet, the public-private group that managed the Park often couldn't
meet the needs of companies that were beginning to succeed and watched
helplessly as they moved to other areas. One high-profile tenant,
Alexion Pharmaceuticals, expanded its operations to a site in Cheshire,
a suburb of New Haven, while another company, Gene Logic, left the
Park and moved to Gaithersburg, Maryland. "There was plenty of venture
capital around, and there was no lack of entrepreneurial management
talent to run these businesses," says Alexander. "The main threat
was the lack of laboratory space in the city."
There
had been talk in the 1990s about developing a biotech park in the
Hill district near Yale–New Haven Hospital. But toward the end of
the last decade when the OCR had companies ready to roll, the proposed
site was still a weedy median strip along Route 34. "If any boom
was going to happen, we needed lab space in a short time frame,"
said Alexander, "and so we turned to existing facilities."
The
former headquarters of the Southern New England Telephone Company
at 300 George Street was empty, and Alexander saw beyond
the peeling paint. The building was structurally sound, equipped
with the heavy-duty floors and air-handling systems required by
biotech firms, and wired for high-speed internet connections. "It
was also close to the Medical School, which was a distinct advantage,"
he explained. "Startups like to be close to the source of their
science."
The reverse
is also true, notes David Ward, professor of genetics and cofounder
of Molecular Staging, Inc. (MSI), whose corporate and research offices
at 300 George Street are a five-minute walk from Ward's lab at the
Medical School. The company had its origins in novel technologies,
particularly one called "rolling
circle amplification," that had been invented by Ward and other
researchers. RCA, as it is known, enables researchers to detect
small molecular abnormalities in genes and proteins that are important
in many diseases. "The RCA technique's sensitivity is orders of
magnitude ahead of everyone else's," says Ward. "It has set a gold
standard for detection tests called immunoassays, and it was of
almost immediate interest to a number of industries."
Deals
have been struck with companies such as Cytocell, Motorola, and
Amersham Pharmacia Biotech to license the proprietary technology,
but while MSI president Torben Christensen saw the advantages of
being close to Ward, he had a problem: The rapidly growing startup
had nowhere to expand. Christensen was eyeing lab space in New Jersey.
So was William Rice,
a cancer researcher and entrepreneur
with a fledgling company, Achillion
Pharmaceuticals, that needed a product to commercialize. Alfred
E. "Buz" Brown, who directs the OCR's medical school branch, brought
a suite of promising antiviral compounds discovered by Yale pharmacologist
Yung-Chi Cheng to Rice's attention, and when the match seemed a
good fit, Brown and his staff were also able to bring together a
quartet of investment groups and lawyers to execute a simultaneous
signing of more than 100 legal agreements required to start commercializing
the drugs. "This is not a venture for the faint-of-heart," says
Brown.
And it
almost didn't happen in New Haven, for Achillion was being heavily
courted by Princeton, which offered first-rate facilities. But then
the SNET building became available. Alexander led a delegation that encouraged Achillion to move to 300 George Street, and the University
helped ensure the success of the project by leasing a substantial
amount of floor space that is being refurbished to house offices
and laboratories that needed to find temporary homes in advance
of Medical School renovations.
The building
is currently 60 percent occupied, and any empty space is not likely
to remain so for long. Science Park is almost filled, and the fact
that Soderstrom reports a steady stream of patentable discoveries
coming into his office means that Lyme Properties need not worry
about having tenants for the one million square feet of laboratory
and office space it is creating in the forbidding shell of the old
Winchester plant's Building 25.
"The
challenge for Yale and the city is dealing with the potential instability
inherent in this industry," says Genaissance CEO Ruano. "But I think
we've reached critical mass." Adds Soderstrom: "We have just begun
to see the fruits of our labors."  |
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