From: GBurch1@aol.com
Date: Mon Jul 05 1999 - 09:06:31 MDT
Here's a good overview article about Geron's background, current situation
and the bioethics controversies that may inhibit it's work.
http://www.mercurycenter.com/business/top/004568.htm
Posted at 7:27 p.m. PDT Saturday, July 3, 1999
Biotech pioneer has vision, needs results
BY ARIANA EUNJUNG CHA
Knight Ridder News Service
After achieving a series of scientific breakthroughs that are
reshaping the way we think about life, a daring Menlo Park
biotechnology company now faces its most intimidating challenge:
Great expectations.
Two years ago, Geron Corp. discovered what some called ``The Fountain
of Youth,'' a way to reset the genetic clock of aging cells. In January,
it isolated the most primitive human cells,which in theory could be
coaxed to grow into any part of the body. And, in a scientific coup last
month, it purchased the technologies used to clone Dolly the sheep.
Now, medical researchers talk excitedly of creating tailormade organs
for transplantation, artificially grown blood and ``patch
kits'' of cells to treat ailments from heart disease and Alzheimer's to
severe burns.
And investors talk of billion-dollar sales.
But without a product on the market, none even in human trials and a
workforce that only recently broke 100, industry analysts
say Geron will have to fight hard to make its dreams more than hype and
hope.
Chief executive officer Ronald Eastman said every employee at the
humble biotech company -- whose lobby is decorated by a
simple hourglass of sand -- has placed upon himself a tremendous
internal pressure ``to fully deliver on the promise of our
discoveries.''
Carl Gordon, an analyst with OrbiMed Advisors, an investment firm, said
``the world is holding its breath'' watching for
Geron's next move: ``Most companies in this stage nobody hears about,
nobody cares,'' he said. ``But Geron has this awesome
potential to change the way we . . . are born and age and die. And that
matters to everyone.''
At this precarious moment, Geron finds itself at the center of a
growing national debate on human embryo research, with some
legislators and religious leaders calling for new limits on the
experiments that are key to the company's stem cell program.
In addition, some analysts say Geron's greatest asset -- its broad,
ambitious vision -- may also be its greatest liability, that its
massive business plan overreaches its ability to deliver, especially as
the world's largest pharmaceutical companies have become
its competition.
And perhaps most critically, the company has seen heavy turnover in the
past 18 months or so, losing some of its chemists, its
top molecular biologists -- and even its founder.
Michael West -- Geron's aggressive visionary who colleagues compare to
computer software czar Bill Gates in his ability to
package ideas -- quit early last year and now heads up Geron's biggest
competitor, Advanced Cell Technology in Worcester,
Mass. With only 10 employees, it already is collaborating with some of
the world's top cloning scientists and amassing
impressive patents.
While it isn't unusual for founders to be ousted from their own
companies when it reaches a certain stage, it is less common in
biotechnology because ventures often take many years to bring a product
to market, said Mark Edwards, managing director of
Recombinant Capital, a consulting firm in San Francisco.
Some say West's departure may have come too soon. While his name
appears on few of the scientific publications that broke
Geron's developments, company leaders recognize the projects as his
brainchild. As one scientist described it, ``Mike was the
ideas person. Everyone else just carried them out.''
Michael West, son of a truck leaser from New Jersey, has always had an
eccentric streak, and his interest in aging seemed to
fit that part of his character.
In the late 1980s, the study of aging was on the fringe of respected
medical science, and only a handful of scientists devoted
their lives to the field. West, who had already obtained his Ph.D. and
was going for his M.D., sought out two of those legitimate
researchers while at at the University of Texas Southwestern Medical
Center.
There, West became an expert in telomeres, the tiny caps at the end of
DNA that shorten as cells age.
He soon quit school to work full time in an aging research lab at the
university and in 1991 quit the lab to start his own
company.
He named it Geron, Greek for ``old man,'' short for gerontology, the
study of aging.
For several months, he pitched his idea to more than 450 potential
investors across the country. Most of the time, West was
laughed out of conference rooms.
In 1992, West's passionate speeches finally caught the attention of
venture capitalists, who gave him $7.5 million. Alexander
Barkas, an influential partner at Kleiner Perkins Caufield & Byers,
based in Menlo Park named himself the company's
temporary CEO. West became Geron's chief science officer. And the
company moved west, setting up shop in Hayward.
Geron's secret to success, it seems, was financing several researchers
doing identical work, analysts say. This forced
competition allowed it to race ahead of its rivals time and time again.
In 1993, Ronald Eastman, who was a general manager for pharmaceutical
giant Lederle Laboratories, became the new CEO.
Eastman later recruited an old buddy, David Greenwood, to be chief
financial officer.
In those days, West's charisma was contagious, his fanciful talk of
immortalizing cells and organs inspiring to all those around
him.
``The building was full of enthusiasm,'' remembered Calvin Harley, a
Canadian who is now Geron's chief science officer and
was one if its first hires. ``It was like we were planning a big trip to
a new territory.''
The company went public in 1996 and, as is the case in many start-ups,
as Geron grew, West's role shrank.
He moved from science to business, coordinating collaborations with
other biotechnology ventures and large pharmaceutical
companies. Eventually, he settled into the role of vice president of new
technologies, an honorary title.
In time, it was clear West didn't fit in with the new corporate
leadership, employees say.
Eastman and Greenwood were golden boys, popular all-American graduates
groomed at Ivy League business schools. West
had little patience -- and knack -- for politics.
Eastman, whose boyish grin belies his graying hair and is fond of
wearing a polarfleece vest with Geron's logo stitched on it,
and Greenwood, a towering tri-athlete, made the company an intense but
fun atmosphere. Both now 47, they live less than a
mile from each other in Monte Sereno.
They made appearances at parties and sporty outings thrown by the
youthful Geron researchers and lab technicians. (The
average age of the company's employees is 35.) West rarely attended.
``It seemed like I always had too much to do to play,''
he said in a recent interview. ``I'm a bit more of a workaholic.'' He
was still well liked by the scientists but admits that their
relationships were more professional than social.
Under this trio's leadership, the company expanded steadily. Morale was
high, as Geron stock over the years resembled
mountains with new peaks each time an achievement was announced.
Geron reached its first milestone in August 1997, when scientists in
academic labs it funded discovered telomerase, the ``holy
grail'' of aging, extending the life of flasks of cells by resetting a
part of their DNA.
OrbiMed analyst Gordon said most biotech companies with Geron's
resources would have limited their research to telomerase,
focusing on its role in cancer development and inhibition. That may have
been more practical from a business standpoint, but
West and his colleagues had grander plans.
The company's hurricane-like growth only intensified. In December 1997,
Tom Okarma, a former Stanford University
professor, was named vice president for research and development. He was
recruited to jump start the company's stem cell
program, formerly West's domain.
With Okarma on board, it seemed clear that there was little
responsibility left for West. By February 1998, West said, he
knew he should leave.
``Being a gerontologist, I think about aging all the time and I
recognize our lives are short. I really wanted to make an impact
and I thought that I could get more done if I branched off and did my
own thing,'' West said. ``I made the decision and left
quickly.''
After West left, others started trickling out of the company. One
former employee said it was due mostly to Geron's trailblazing
that the field of aging had progressed so rapidly that there were now
many job options for experts.
Last November, a few months after West's departure, Geron announced
another stunning achievement -- isolating primordial
stem cells that, in theory, could be made to grow into any part of the
body such as skin, muscle and bone.
Geron's scientific leaders immediately recognized their technology and
the cloning techniques developed by Scotland's Roslin
Institute -- which had created Dolly -- were complementary.
They theorized that stem cells could be used to grow into new tissue,
and that the nuclear transfer could be used to move a
patients' own DNA to this tissue, preventing rejection. The telomerase
would ensure that the cells remained young despite
numerous lab manipulations, which tended to age them.
Early this year, Geron and Roslin Bio-Med, a spinoff of the Roslin
Institute, were married. Geron acquired the Scottish
company for 2.1 million shares of stock worth about $25.7 million. They
also promised to invest an additional $20 million in the
non-profit institute over the next six years.
In return, Geron won the rights to all the nuclear transfer patents and
a contract with the institute's famous cloning experts, Ian
Wilmut and John Clark. Under the agreement, Wilmut, the scientist
credited with creating Dolly, would spend around 75
percent of his time on Geron-related projects.
With this acquisition, Geron scientists believe they have all the
pieces to create hundreds of medical miracles. Whittling down
the huge range of possibilities quickly became one of their biggest
dilemmas.
Cancer? AIDS? Or stroke? Spinal cord injury? Or cuts?
In early June, leaders on both sides of the Atlantic met in Edinburgh
for an intense three days of scientific presentations and
debates.
One of the first things that emerged unanimously on their agenda:
cloned piglets.
The basic idea, to use the pigs as a source of organs to transplant in
humans, had been thrown around for decades. But in
every case, patients' immune systems repelled the transplanted material.
Geron was offering a new twist: delete the gene in the
pig that creates a sugar coating thought to be a major cause of
rejection.
Wilmut, who heads up the project, said they hope to produce such a pig
by the end of the year.
The rest of the agenda that emerged from the Geron-Roslin meeting was
even more ambitious. Geron even decided it would
move into livestock, cloning premium animals -- from derby horses to
meaty cows -- that would have taken generations to
breed.
Anne Anderson, president of Atlantis Investment Co., said she believes
the broad nature of Geron's business ambitions are
temporary and are important for fostering fertile and imaginative ideas.
But, she said, she expects them to ``prune down the
road.''
Meanwhile, analyst Gordon said investors are getting restless for the
company to bring a product into clinical trials. Geron's
most advanced program is in exploiting a cell's love of telomerase to
treat cancer.
In normal cells, telomere tips act like a burning fuse, shortening each
time the cell divides and ultimately triggering the cell's
death. In cancer cells, the enzyme telomerase prevents the tips from
shortening, causing the uncontrolled growth that leads to
tumors. Geron's goal is to inhibit the telomerase presence in tumors.
Its challengers are intimidating. Scientists at Bristol-Myers Squibb,
which currently dominates the cancer market, and other
pharmaceutical giants that are 200 to 500 times Geron's size have jumped
into telomerase research, building on Geron's
successes.
Geron's sudden success had another downside: close scrutiny. As more
and more people learned of its work, some began to
question the ethics behind it.
Geron faces challenges on two grounds. One is stem cell
experimentation. Anti-abortion and religious leaders have denounced
the practice because stem cells are harvested from human embryos, which
they say have rights because they could be grown
into a person. Another is the fear that Geron's advances in transferring
one being's nuclear material to another's may one day
help scientific renegades clone humans.
While human embryo research remains legal in most states so private
firms like Geron and West's ACT have been free to go
ahead with experiments, Congress has prohibited federal funding of such
activities.
Legislators are now reconsidering the philosophy behind that law.
About 30 patient groups -- for diabetes, Parkinson's disease, AIDS,
cystic fibrosis, stroke and cancer -- have formed a
coalition urging the government to give a green light to this research.
Without substantial federal funding, they feel the research
will make sluggish progress.
The National Bioethics Advisory Commission, formed by President
Clinton, announced on Monday that they would side with
the patient groups and recommended that federal funding be given to some
embryo research. Officials at the National Institutes
of Health hope the bioethics advisory decision will spur legislation
that would reverse the government ban.
But Sen. Charles Grassley, an Iowa Republican and chair of the U.S.
Senate Aging Committee, along with other political
leaders, the National Conference of Catholic Bishops as well as such
prominent people as former Surgeon General C. Everett
Koop have loudly fought these types of experiments.
Richard Doerflinger of the Catholic conference said Geron's experiments
``destroys one life for another. They take the embryos
apart at about a week old when they are perhaps a couple of hundred
cells,'' he said.
Okarma said Geron currently gets its human stem cells from embryos
discarded by fertility clinics -- and, despite reports to the
contrary, does not plan to clone human embryos for use in its
experiments. Geron's research remains controversial because it
involves destroying a living embryo. In another, less convenient method,
the cells are harvested from aborted fetuses.
As for the second ethical issue, the Roslin Institute's Wilmut said
fears over human cloning are misplaced, that there is a huge
difference between therapeutic cloning, where embryos are created for
their cells, versus reproductive cloning, where they are
grown into babies.
There must be ``public understanding for this technology so people are
not afraid of it. When you talk abut cloning, people
automatically think that you are copying people,'' Wilmut said. ``But
that was never and never will be a goal.''
Analysts predict many of these ethical debates will be settled in
Geron's favor in the next few years. Meanwhile, as Geron
moves from the freedom of childhood to the responsibility of
adolescence, it will have to quickly prove that it can live up to its
great expectations.
For the time being, Dr. Jerry Shay, a professor of cell biology at the
University of Texas Southwestern Medical Center, and the
other members of the the coterie of world aging experts who collaborate
with Geron or serve on its board of directors, are
betting on Geron: ``Soon, very soon, Geron will be up there with the
Amgens and Genentechs and some day it may even rival
the major pharmaceutical makers in the world.''
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