Stem cell harvest
A view of the controversy from the eye of the storm
Tom Okarma started out life at a dairy farm in New Jersey, but once
he reached the Stanford farm, he didn't stray far.
After earning a degree in biology from Dartmouth College, he earned
all of his postgraduate degrees at Stanford -- MD in 1972, PhD in
pharmacology in 1974 and a certificate from the Stanford executive program in 1997. He was also an assistant
professor in the Department of Medicine from 1980 to 1985. Then he left
the university to work in the private sector developing biological therapies.
Now he runs Geron Corp., which is at the center of the stem cell controversy.
It's one of just a handful of U.S. companies creating new stem cell
lines from embryos and developing therapies from them. As a private company,
Geron is unaffected by federal regulations on stem cell research involving
embryos -- at least for now.
The company has developed eight cell types from its embryonic stem
cell lines so far: neurons, cardiac muscle cells, glial cells that insulate
nerves, pancreatic islet cells that produce insulin, liver cells that
can be used for drug toxicity testing, and cells that form blood, bone
or cartilage. The company also holds patents on the telomerase gene, which
allows cells to grow indefinitely, and on the nuclear transfer cloning
process, which created Dolly the sheep.
Stanford Medicine's Mitzi Baker interviewed Okarma in his Menlo
Park office.
Your company is at the frontier of embryonic stem cell research.
So tell us, just what can these cells really do?
Okarma: We've had our lines growing in culture for years. They've
undergone hundreds and hundreds of cell population doublings without any
significant changes in their genome expression pattern or in their phenotype.
What we have done is learn how to selectively drive these cells down very
specific differentiation lineages to turn them into specific cell types
that would be useful for therapy. For the six cell lines we are studying
in animal models of human diseases, three of these differentiated cell
types are engrafting and repairing the damage caused by the disease or
the injury.
What do you predict will be the first use of embryonic stemcell-based
treatments?
Okarma: Our most advanced program is the glial cell, which is the cell
destroyed in chronic diseases like multiple sclerosis and damaged in acute
spinal cord injury. In an animal model of spinal cord injury, these glial
cells show the potential of this platform: to go beyond the reach of pharmaceuticals
and fundamentally change the root cause of the disease or the injury by
restoring the function of the cells that were lost. This will be our first
clinical test of the platform.
When do you think approval will come for this use?
Okarma: We plan to file an IND [FDA Investigational New Drug application]
to begin clinical testing of these cells at the end of 2005. It will be
several years after that, if the trials are successful, before the therapy
will be approved.
You have said that adult stem cells hold less commercial promise
than embryonic stem cells. Is the profit motive the real force behind
embryonic stem cell research?
Okarma: I'm not arguing here for huge profit margins, rather for
low cost of goods. What this means is that this is a technology that can
be commercialized broadly and therefore can be made widely available at
a cost the system can bear. In the cases of Parkinson's, diabetes,
heart failure and arthritis, we are talking about permanent cures with
a single infusion of cells made from embryonic stem cells into the dysfunctional
organ. That is an enormous paradigm shift.
How has the current political environment affected stem cell
research?
Okarma: Whether it's federal funding policy that restricts money
for new cell lines or whether it's threatening legislation on nuclear
transfer from Congress, they have the same impact, which is to deny the
world's most sophisticated biomedical research community --
U.S. NIH-funded investigators -- from contributing to and advancing
this field.
Has this affected your company directly?
Okarma: To give a concrete example, new human embryonic stem cell lines
that we have made have never been exposed to either an animal cell or
an animal protein, so they are far more appropriate for human experimentation
than all of the lines currently in existence. And yet we can not send
any of these lines to a single NIH investigator in this country because
the cells were derived after the August '01 White House decree that
no lines made after that date would be eligible for federal funding. That
makes no sense. Why should the very best lines be kept in the drawer of
industry and not distributed broadly to the academics who are crying for
more?
What are the implications for the United States?
Okarma: I don't fear the so-called brain drain -- you know,
our best and brightest going to Canada and Asia and the U.K. I think it's
more likely that we will just become a second-rate innovator in this field
because the money and the human expertise just won't be here. This
means citizens in other countries could benefit from these therapies first.
Did you expect the controversy over embryonic stem cell research?
Okarma: We're not surprised by the concern about the embryonic
derivation of these cells. It's appropriate to be concerned and
thoughtful about this advance and to debate its pros and cons openly.
But the point simply is that society adapts when it recognizes what value
to itself – whether social, economic or medical – a breakthrough
really has. Since we knew we were getting into a controversial area, we
formed a five-member ethics advisory board just before the cells were
first derived. We wanted an environment in which we could openly discuss
the issues of this technology among a variety of religious traditions.
It gave us all a great deal of confidence that what we are doing is right,
both scientifically and ethically.
How do you explain the research's value to someone opposed
to destroying embryos?
Okarma: All the work that we have done over the last five years –
deriving eight different cell types, putting six of them into animal models
– was done with two embryonic stem cell lines, which are still in
use today, each made from one embryo. For me and for those of us in the
field who are knowledgeable about these cells, the ethical debate has
a clear answer. A 3-day-old frozen embryo is not a thinking, feeling person.
We may be able to impact many thousands of patients with cells made from
a single embryo that would have been otherwise destroyed because it was
rejected for achieving pregnancy – for us there is no moral dilemma
here.
Any final words?
Okarma: We need more lines and more trained researchers in this field.
We need a change in the constrained U.S. funding policy, and we need it
urgently. The work is being slowed significantly by what I think is a
regressive and ideologically based national policy that is slowing down
the progress on what what we think could be the most significant medical
breakthrough of the 21st century.
On a personal note
Tom Okarma's favorites:
- Book -- The Sorrows of Empire: Militarism, Secrecy, and the
End of the Republic by Chalmers Johnson. Not Okarma's all-time
favorite but "a very important book that sheds light on the current
crisis in the Middle East as an extension of a U.S. global militaristic
policy that dates back to the Spanish-American War."
- Hobbies -- Scuba diving, water- and snow-skiing, fishing; most
anything outdoors.
- Place -- Fallen Leaf Lake in California's Sierra Nevada.
"It's a pristine lake that comes out of the Crystal Range
and drains into Lake Tahoe."
- Movies -- Most recently interested by "Osama," A
story portraying life during Afghanistan's Taliban occupation
as experienced by a 12-year-old girl.
Comments? Contact Stanford Medicine at
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