082901Small Lab in Sweden Holds a Huge Trove of Stem Cells
By DONALD G. McNEIL Jr.
GOTEBORG, Sweden, Aug. 28 - The Lab That Shot to the Top of the
Charts, turning out to have more embryonic stem cells than anyone
else, is actually a warm little closet in Building 9A of Sahlgrenska
University Hospital here.
Inside a room that is roughly 10 feet long and 7 feet wide, Ulf Dahl
spends up to two days each week hunched over a microscope with his
remarkably steady fingertips and the tiny glass knives he makes over
a hot flame. Slicing up each sample crosswise, like a Sicilian
pizza, into clumps of a mere 30 or so cells, he picks out and keeps
the squares that do not seem to be metamorphosing into anything
particular.
These clumps of human cells - not yet shifting toward life as a
liver or a spinal column, nor degenerating into a tumor - are a sort
of family tree, one made more precious by President Bush's Aug. 9
announcement that only lines already created will be eligible for
federal research funds.
On Monday, the National Institutes of Health announced that there
were 64 such lines in the world. Of those, the agency said, 24 are
in Sweden - 19 here at the University of Goteberg's hospital.
In fact, nearly all the cells are in the refrigerator-sized
incubator that divides the tiny room, ``except for the ones we
freeze,'' Professor Henrik Semb said. ``You can't work on all of
them at once. It's too much.''
The university's scientists are cautious about the statement by the
American government that they have 19 cell lines. They say they have
3 established ones, 4 that are being studied and described, and 12
that are still in early stages.
``Those 12 perhaps ought to be called potential cell lines,'' said
Professor Lars Hamberger, a group leader. ``If we get 3 good lines
out of them we'll be satisfied.''
All, however, are surviving, and all met President Bush's criteria.
They came from embryos made by in- vitro fertilization clinics in
Goteborg and Upsala, said Dr. Hamberger, who in 1982 performed the
first successful in-vitro fertilization in Scandinavia.
Some were from embryos frozen for the five-year legal limit; some
were donated ``fresh'' by parents who did not like the idea of
freezing any embryos for future use. The donors all signed consent
forms allowing the blastocysts - a five-day stage when one cell has
become a couple of hundred - to be used for stem cell research.
Also, at the moment, though Professor Dahl looks sheepishly at the
floor as he admits it, they are all named Ulf: ``Ulf's Human
Blastocyst No. 1'' for example.
``We'll change that soon,'' he says hastily. ``Actually, we must,
because some of them are female. But we use only numbers in the
computer, not names.''
The program here is quite new. It was begun only last fall, with
little fanfare. Approval from hospital and university ethics
committees came late last year. Some government funds are involved.
The cell lines, by coincidence, all easily met President Bush's Aug.
9 deadline - the team wanted the summer off, so they finished by
June.
The goal, said Dr. Anders Lindahl, the chairman of the team's
corporate entity, was to establish many cell lines for their own
clinical work.
``It just happened that President Bush making this decision made us
suddenly very interesting,'' he said.
The Bush decision presumably means that the Goteberg cell lines will
be in great demand by federally financed researchers in the United
States. The Goteborg team put out a statement saying its cells
``cannot be purchased, but will be accessible in the future to
collaborating researchers in the U.S., Europe and other countries
where a mutual collaboration agreement can be made.''
sv29,2if,,v29 Dr. Lindahl could not say exactly what would be in
those agreements. ``It's too early to say we have any criteria
yet,'' he said.
The project has six joint chiefs leading a total of 30 scientists,
and they represent the whole spectrum in what might be the plot of
``I Am Joe's Stem Cell'' - the life of any cell manipulated for
medical purposes:
some like Professor Hamberger harvest cells, some like Professors
Semb and Dahl keep them alive,
some like Dr. Lindahl use them in patients.
Human embryonic stem cells are not yet ready for use in clinics, of
course, but Dr. Lindahl has done pioneering work on injecting humans
with adult stem cells that produce cartilage. Professor Semb's bad
knee even made him one of Dr. Lindahl's patients.
The other six cell lines in Sweden are at the Karolinska Institute
in Stockholm, according to the National Institutes of Health.
The Goteborg team does not, by any means, plan to stop at 19.
``We won't be satisfied until we have 100-plus,'' Professor
Hamberger said. ``We have a lot of things we want to do with them.''
Many of the world's cell lines, including the Goteborg ones, are
grown on mouse cell mediums, beds of ``feeder cells'' that secrete a
signal that prevents embryonic cells from maturing. They can be used
for research but probably can never be implanted in humans for fear
of mouse diseases or mouse genes, Dr. Semb said.
``The goal is to get cells to grow on mediums from no animal
sources,'' Dr. Semb said. Since mouse embryonic cells already can,
he said, it is theoretically possible.
More lines will be needed, Dr. Hamberger said, because cell lines
may not have always been grown in complete sterility.
To ever consider using any line on patients, ``you have to know
there's no hepatitis, no H.I.V.,'' Dr. Hamberger said. ``I mean, you
have to really be sure.''
Also, more cell lines means more assurance that there will not be
flaws in the number or shape of chromosomes. And more lines means
more alternatives if tissues or organs made by one line are rejected
by a human recipient.
The team soon plans to begin collecting more fertilized embryos from
clinics in two other cities in Sweden, Dr. Hamberger said. Right
now, it has about a 10 percent success rate
- 1 out of 10 blastocysts yields stem cells that can be coaxed into
reproducing themselves. He hopes to raise that to 15 percent. The
rest die for unknown reasons, but Dr. Hamberger said it may be an
indication that recent research suggesting that a surprisingly large
percentage of embryos in real life are not viable is correct.
Sweden's political climate is benign for the team's work, Dr.
Lindahl said.
In-vitro fertilization came here early, and there has been public
debate over stem cell research without much loud objection from
opponents of abortion, as has been the case in the United States.
Human cloning has been banned by government advisory ethics panels,
and consideration of ``therapeutic cloning,'' in which an embryo
would be created from a patient's cells to make life- saving tissue,
has been put off for now because it is not seen as useful. But in
general, ethics committees favor stem cell research.
The government raises no political objections, Dr. Lindahl said, but
its budget for basic science was drastically cut during Sweden's
economic difficulties in the 1990's. Besides government financing,
the team gets money from foreign donors like the American Juvenile
Diabetes Research Foundation, and it has created an off-campus
corporation, the Stem Cell Research Center, to raise venture capital
by licensing the potential uses of the cells.
The team has not really tackled legal issues yet. Its cell-culture
techniques, Professor Semb said, are essentially the same as those
developed at the University of Wisconsin, which are under an
American patent. The American rights to develop them into liver,
muscle, nerve, pancreas, blood and bone were sold to the Geron
Corporation of Menlo Park, Calif.
Professor Semb noted there were many other tissue types and said it
would be impossible for one entity to control all of the research.
``They can have all the patents they want, but they are not going to
be able to generate all these cell types,'' Professor Semb said.
``This patent business is a jungle.''
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