More MS news articles for Aug 2001

Brain Stem Cells Have Daughter Cells In Certain Order

http://unisci.com/stories/20013/0824015.htm

24-Aug-2001
[Contact: Chris Q. Doe]

During brain development, one group of stem cells divides to produce progeny cells that finish up in different layers of the brain and have different functions.

The stem cells, called neuroblasts, produce their "daughter" cells in a specific order, and cells that are born at a particular time are destined to become a specific type of cell.

Understanding how this is brought about will be important to help us understand brain development.

Although there are some differences, the same sort of process seems to operate across a wide range of species, from mammals to insects.

In this week's issue of Cell, Chris Doe and colleagues show that in Drosophila, the underlying basis for the specification is a "memory" in the daughter cells of the genes being expressed by the neuroblast at the time the daughter is born.

The "parent" neuroblast undergoes a very specific sequence of changes in expression of a group of key regulatory genes (transcription factors called Hunchback, Kruppel, Pdm and Castor) during the time that it produces the daughter cells.

The daughter cell remembers the regulatory factor that was present at the time of its birth, and this determines which layer of the brain it goes to and what type of cell it becomes. Thus, the changing cycle in the parental neuroblast allows it to produce a set of distinct daughter cells that go on to form different nerve cells in different parts of the brain.

(Reference: Cell Volume 106 Number 4 August 24, 2001) 


Stem-cell Line Availability Unclear 34 of 64 Too Immature for Research

http://www.nationalmssociety.org/articles.asp?SMContentIndex=0&SMContentSet=0

USA TODAY- August 29, 2001

Fewer than half of the stem-cell lines that the National Institutes of Health claims are available for publicly funded research appear ready or viable for use in any laboratory beyond where they were created.

A human embryonic stem-cell line is a colony of cells derived from a days-old embryo; many scientists believe the cells may be developed into treatments for diseases such as cancer and diabetes.

President Bush surprised the scientific community on Aug. 9 when he announced that 64 stem-cell lines would be made available to scientists. Most believed only 10 to 20 viable lines existed that fit the guidelines Bush outlined.

NIH on Monday released a list of the makers of the 64 cell lines, including laboratories in the USA, Europe, Israel and Australia. But an accounting of the lines has found that at least 34 of them are immature and currently unavailable to scientists for research. Some may not be stem cells at all or of insufficient quality to be useful for research, experts said.

Many scientists expressed surprise at some of the laboratories on NIH's list. Nineteen human embryonic stem-cell lines are from a laboratory at Goteborg University in Sweden and another five are from the Karolinska Institute in Stockholm. U.S. scientists were unaware that such a large number of lines had been created in Europe. NIH also listed nine cell lines by CyThera Inc., a little-known biotechnology company in San Diego.

Anders Lindahl of Goteborg University said Tuesday that only three of the 19 stem-cell lines at his lab are established and characterized as human embryonic stem cells. He expects 10 lines eventually to be available, he said, but none of the cells are intended for studies in humans.

At the Karolinska Institute in Stockholm, Lars Aehrlund-Richter said his laboratory has "five to 10 stem-cell lines, depending on how you define them."

He said only five of those were created before Bush's Aug. 9 address to the nation and that work on them was preliminary. Bush said he would not permit federal funding on embryonic stem cells created from embryos destroyed after that date.

"I cannot guarantee anything about these cells," Aehrlund-Richter said. "The success rate is far from 100%" for stem-cell lines to survive and prove useful.

Executives from CyThera also said Tuesday their cell lines are in preliminary stages of development and that it was premature to say when they might be available or how many would be viable.

NIH listed the University of California-San Francisco as having two stem-cell lines. Sue Shafer, assistant vice chancellor for research administration at UCSF, said two lines are being established, but only one is regarded as a viable line that might be ready to produce cells within a few months.

"The second line we are only beginning to characterize," Shafer said. "Until we know a little more about the second cell line, I hesitate to say anything about it."

Bush has stated that he relied on Health and Human Services Secretary Tommy Thompson and NIH for the information about the total number of lines.

Bioethicist Arthur Caplan of University of Pennsylvania predicted at the time of Bush's address that the stem-cell lines would be inadequate for scientists' needs. "The administration keeps saying that NIH checked for them on the number of available lines," Caplan said. "My question is, what did the NIH do? Did they just call people up and ask?"

NIH officials said they made inquiries at labs and that they also were contacted by labs that reported developing stem-cell lines. Lana Skirboll, who made the inquiries for the Bush administration, said there was no attempt to mislead researchers and that currently there is no agreed-upon definition of a stem-cell line.

* Skepticism in Congress, 11A

To see more of USAToday.com, or to subscribe, go to http://www.usatoday.com

© Copyright 2001 USA TODAY, a division of Gannett Co. Inc


Where the stem cells are

http://www.nationalmssociety.org/articles.asp?SMContentIndex=1&SMContentSet=0

Associated Press- August 28, 2001

Companies, universities and research laboratories with stem cell lines:

--

Goteborg University, Goteborg, Sweden, 19 stem cell lines. Goteborg is Sweden's largest institution of higher learning. The university's medical students and faculty engage in basic and applied research in such areas as cell and tissue surfaces, cardiovascular diseases, and endocrinology and metabolism.

--

Wisconsin Alumni Research Foundation, Madison, Wis., five lines. The foundation holds patents on the first embryonic human stem cells and the process that the University of Wisconsin's James Thompson used to derive them in 1998. The foundation has licensed a private company, Geron Corp. of Menlo Park, Calif., to use its stem cell lines, but also has said it wants to make the cells widely available to researchers. Earlier this month, the foundation sued Geron in an effort to limit its use of the commercial stem cell license.

--

BresaGen Inc., Athens, Ga., four lines. Founded in Adelaide, Australia, BresaGen announced in July that it had derived embryonic stem cell lines with a process different from that used by Thompson at Wisconsin. The company's work grew from Australian scientist Peter Rathjen's experiments on mice at Adelaide University.

--

CyThera Inc., San Diego, nine lines. CyThera is a privately held biotechnology company that was founded in early 2000 to develop cell replacement therapies for the treatment of human degenerative disease. The company's initial focus is on treatments for diabetes, though it is hoping to develop treatments for liver disease, Parkinson's disease, macular degeneration and stroke.

--

Karolinska Institute, Sweden, five lines. The Karolinska Institute, Sweden's only university for medicine, awards the Nobel Prize each year in physiology or medicine.

--

University of California, San Francisco, two lines. In July, the university suspended all embryonic stem cell research until it could move the work off campus. Roger A. Pedersen, who had been researching stem cells at the university with financing from Geron, then left to go to the University of Cambridge in Britain.

--

Reliance Life Sciences, Mumbai, India, seven lines. Reliance Life Sciences is a division of the Reliance Group, India's largest business conglomerate.

--

Technion-Israel Institute of Technology, Haifa, Israel, four lines. One team of researchers at Technion announced earlier this month that they had succeeded in growing the precursors of heart cells from embryonic stem cells. Another team claimed to have demonstrated that human embryonic stem cells can be used to produce insulin.

--

Monash University, Australia, six lines. Researchers at Monash have concentrated on cloning technology for the treatment of neurological diseases such as Alzheimer's and Parkinson's. They were among the first to grow human nerve cells in the laboratory and to successfully clone mouse stem cell lines.

--

National Center for Biological Sciences, Bangalore, India, three lines. The NCBS, a branch of the Tata Institute of Fundamental Research in Mumbai, specializes in research on the frontiers of biology, including genetics and cellular organization.

Copyright 2001 Associated Press


Diabetic teen debates merits of stem cell research on talk show

http://www.greenwichtime.com/news/greenwich/2001-08-25/article11.shtml

Saturday, August 25 2001

Her recent trip to New York City to appear on television was fun, Catherine Agonis said, but the subjects of the show - diabetes and embryonic stem cell research - are serious.

The 13-year-old Greenwich resident, who has had juvenile diabetes for the past eight years, will appear as a panelist on the Montel Williams Show to debate the untapped promise and moral quandaries of embryonic stem cell research. The episode will air at 2 p.m. Wednesday on UPN 9. The panel also included a Roman Catholic priest, a stem cell researcher and a congressman.

"It was great to be on TV, but, more importantly, it was a chance to talk about and give exposure to the issue," Agonis said.

Like many other diabetics, Agonis said she believes that without full-fledged government support for embryonic stem cell research, the road to a cure will be longer.

"When the money runs out, the research will just stop," she said. "They should go all the way."

The episode was taped Wednesday, with the Williams show putting up Agonis at the Hotel Beacon in Manhattan and paying all her expenses.

President Bush decided earlier this month to support only limited funding for research on stem cell lines that have been created already.

Williams, who was diagnosed with multiple sclerosis in 1999, has appeared on several other shows expressing his support for embryonic stem cell research and said he believes the research might help cure his disease.

Although largely untested, embryonic stem cells are believed by researchers to hold the potential for dramatic improvements in treating many diseases, including juvenile diabetes, which also is known as Type 1 diabetes, because of their ability to develop into many different types of cells and organs. But bioethicists and some religious leaders are wary because embryonic stem cells are obtained through the destruction of human embryos.

The Williams show also will feature a video of Agonis dealing with the disease.

Type 1 diabetes sufferers must take multiple insulin injections daily and test their blood sugar by pricking their fingers several times a day. As they try to balance insulin injections with what they eat, people with Type 1 diabetes must be constantly prepared for possible low blood sugar and high blood sugar reactions, which can be life threatening.

"I can't just go swimming or playing soccer because I might pass out," Agonis said.

Although she has her diabetes under control with insulin, the Greenwich High School freshman said she cannot participate in strenuous athletics and must be on guard against hypoglycemic episodes. When she was younger, she would often have to leave classes to have her blood sugar level tested by the school nurse, she said.

To help other diabetics, Agonis started Catherine's Hope Inc., a nonprofit foundation that provides moral and financial support to other diabetics. Since the group was founded last year, several fund-raisers, including a walk at Greenwich Point, a sale of Agonis' art and a bake sale, have raised more than $8,000 for diabetes sufferers and nonprofit foundations.

The Agonises are helping to organize the Mercedes-Benz of Greenwich Challenge Cup, a luncheon followed by a silent auction on Sept. 9, that will benefit the Juvenile Diabetes Enrichment Fund, a Connecticut organization that buys medicine and other supplies for diabetics.

"We're a small foundation, so we can't give a whole lot of money to people, but we do the best we can for everyone who needs us," Agonis said.

Agonis also suffers from two rare autoimmune disorders, Celiac Sprue, an intolerance to wheat products, and Autoimmune polyglandular syndrome 1, a disease that disrupts the interaction between organs. But diabetes is her most severe problem.

"I think (embryonic) stem cell research can potentially help with any and all autoimmune disorders," said Agonis' mother, Jill Agonis-Murphy.


Clinic to Supply Embryos to Harvard

http://www.latimes.com/news/nationworld/wire/sns-ap-harvard-stem-cells0824aug24.story

August 24, 2001
By Associated Press,

CAMBRIDGE, Mass. -- A fertility clinic will give embryos to Harvard in a deal that could make the university one of the world's top suppliers of embryonic stem cells.

Boston IVF, a Waltham-based organization of fertility clinics, said it has thousands of frozen embryos that could provide stem cells. The firm said it plans to begin contacting donor couples for permission to use their embryos so Harvard scientists can extract stem cells.

"It is our intention to make these cells available to anyone who would like them to do research," Douglas Melton, chairman of Harvard's cell and molecular biology department, told The Boston Globe for Friday's editions. "They are not being prepared with the intention of having any rights, commercial or otherwise."

The Howard Hughes Medical Institute will finance the arrangement between the school and the clinic. Melton is on the staff of the Maryland-based private foundation.

The institute will give Boston IVF $180,000 over two years to cover the cost of providing the embryos. The institute already provides general support for Melton's lab at Harvard, he said Friday, and the lab would receive no extra money specifically for extracting and preserving the stem cells.

Fertilized eggs, or embryos, are often left over from fertility treatments. Some scientists believe that stem cells can be coaxed to grow into any kind of cell, and might help cure diseases like diabetes, Alzheimer's and Parkinson's.

However extracting a batch of cells destroys the embryo, which opponents consider destroying a life.

Boston IVF serves about a thousand couples a year, and has helped conceive about 7,500 babies in five years. It stores all unused embryos in giant liquid nitrogen freezers.

Massachusetts law requires oversight by a scientific ethics board for donation of embryos. Harvard's institutional review board will monitor the deal with Boston IVF.

President Bush two weeks ago announced that federally funded researchers could use any of more than 60 embryonic cell lines that he said existed. Therefore, any scientist who drew cells from the Harvard supply would be ineligible to use taxpayer funds for research on the cells.

The American Association for the Advancement of Science said last week that there is doubt about the number and origins of those cell lines.

On the Net: http://www.bostonivf.com
 

Copyright 2001 Associated Press


Small Lab in Sweden Holds a Huge Trove of Stem Cells

http://www.nytimes.com/2001/08/29/health/genetics/29CELL.html

August 29, 2001
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."
 

Copyright 2001 The New York Times Company


Researchers Say Embryos in Labs Are Not Available

http://www.nytimes.com/2001/08/26/health/genetics/26EMBR.html

August 26, 2001
By GINA KOLATA

If scientists want to develop new supplies of embryonic stem cells, they may have to take the bold and controversial step of creating human embryos expressly for research, many leading fertility experts say.

Tens of thousands of embryos are frozen at fertility centers, and a widespread assumption in the debate over stem cell research has been that scientists can use them.

But in clinics around the country, embryologists and doctors tell the same story: almost every embryo is spoken for. The vast majority of couples use their frozen embryos, or plan to use them, in attempts at pregnancy. It may be that embryos will become available if there are concerted efforts to encourage couples to donate them. But so far, very few couples have agreed to do so.

An alternative, creating human embryos and nurturing them solely for experiments that will destroy them leaves even many supporters of the research deeply uneasy.

The harsh truth about the status of the frozen embryos "changes the debate," said Dr. Thomas Pool, scientific director of the Fertility Center of San Antonio. If the embryos already existed, were unwanted byproducts of in vitro fertilization, and were never going to be used to make babies, Dr. Pool said, people could ask, "Could I save them and do some good with them?" That was "a warm and fuzzy way for people to get around the question of making them," he added. "It's an easy way to not have to come back to the salient question: What are these things that we make in I.V.F. labs?"

This conundrum does not arise in the area where President Bush has proposed allowing federally financed research. He would permit work to go ahead on existing lines of stem cells Mr. Bush says there are 60 lines, while others say there may be as few as a dozen usable ones.

Rather, the issue comes up when scientists try to develop new stem cells, abroad or with private money. Some say this is necessary because the existing lines are insufficient and may not be safe for human use.

Most of these human cells were exposed to mouse cells while being coaxed to grow in the laboratory, to prevent them from developing prematurely. This has raised the question of whether mouse cells could transmit viruses to human patients.

There are no national data on the number of frozen embryos. But the Society for Assisted Reproductive Technology says that most of the approximately 400 American clinics that offer in vitro fertilization also freeze embryos. The frozen embryos are one to five days old and consist of one to 120 cells. They are less than three-thousandths of an inch in diameter.

Some clinics routinely ask patients if they want to donate embryos for research. Others the majority, fertility experts say do not ask.

One clinic that asks is the Institute for Reproductive Medicine and Science of St. Barnabas Medical Center in Livingston, N.J., one of the nation's largest fertility centers. Embryologists there have frozen 11,402 embryos since August 1995, from a total of 1,595 patients. Many used their embryos. One woman gave hers up for adoption, which was privately arranged. That left 6,284 in storage, from 1,006 patients. Of those patients, 191 signed or said they would sign a form directing that their embryos be discarded.

But only 22 patients signed or indicated a desire to sign a form allowing their embryos to be used for research, although Dr. John Garrisi, the chief embryologist there, said that he was certain many who no longer wanted their embryos would donate them for research if he asked them personally.

Patients at the Jones Institute for Reproductive Medicine of Eastern Virginia Medical School, another large center, are also asked to donate embryos for research. Embryologists there froze about 15,000 embryos in the last 15 years, two-thirds of which were used by the couples that owned them. About 200 embryos might be available for research according to forms signed by patients, said Dr. William Gibbons, a reproductive endocrinologist there. And that, he said, might not be enough to generate any stem cells.

Dr. Zev Rosenwaks, who heads a large fertility center at the Weill Medical College of Cornell University, said that his patients, too, almost always keep their embryos. But, Dr. Rosenwaks said, over "many many years," about 100 to 200 couples agreed to donate embryos for research. That could be enough for stem cell research, he said, although he is not doing such work.

Boston I.V.F., a group of fertility clinics based in Waltham, Mass., recently agreed to supply Harvard researchers with frozen embryos for stem cell research. Dr. Michael Alper, the group's medical director, estimated that the clinics had several thousand frozen embryos and that a small percentage of patients had indicated they no longer needed theirs. Two months ago, Boston I.V.F. began asking these patients to donate their embryos. "We've had several patients already who agreed," Dr. Alper said.

In San Antonio, Dr. Pool does not offer patients the option of donating embryos for research. He stores about 2,000 frozen embryos, he said, and almost no one discards them.

Dr. Richard Rawlins, laboratory director at the Rush Center for Advanced Reproductive Care in Chicago, said patients there were not asked about donating embryos. In Dr. Rawlins's 17 years at Rush, he said, only one couple broached the subject. Three couples in the last three years have asked to have their embryos discarded. He is storing embryos for about 250 couples, most of whom will use them, he said.

Even if scientists did want to use frozen embryos at fertility centers, there would be hurdles to overcome, Dr. Gibbons said. Each patient who has agreed to donate embryos must be contacted and agree to the particular stem cell project. Then scientists must buck the odds in getting the embryos to grow and isolating stem cells from them.

Those odds can be long.

Dr. Gibbons said that even if every one of the 200 embryos at the Jones Institute that might be available were used and were in the best possible condition, 50 or fewer would grow to the blastocyst stage. That is the stage, at about five or six days, when scientists can try to isolate stem cells. On average, only a small fraction of blastocysts yield stem cells.
 

Copyright 2001 The New York Times Company


U.S. Approves Labs With Stem Cells for Federal Use

http://www.nytimes.com/2001/08/27/health/genetics/27STEM.html

August 27, 2001
By NICHOLAS WADE
 
The National Institutes of Health will announce the names today of 10 organizations that possess human embryonic stem cells eligible for use by federally financed researchers.

The list has been keenly awaited by scientists since Aug. 9, when President Bush announced that the federal government would finance research on such cells which are created by destroying human embryos left over from fertility treatments but only with cell cultures established before that date.

Some biologists expressed considerable skepticism at the time that as many as 60 cell cultures had been established, as the administration said was the case, because only a handful had been described in the scientific literature.

According to a document made available to The New York Times, there are 10 universities and companies that derived cell cultures from 64 embryos before the cutoff date, and that have told the National Institutes of Health they will make the cells available to researchers.

The list includes four organizations in the United States and six in Sweden, Australia, India and Israel.

As to the quality of the embryonic cells, another issue that has worried many scientists, the agency says there is not yet any agreed-upon standard. But it said most of the cells were known to have the right set of proteins, or "markers," on their surfaces, and to be capable of developing into the three separate tissues of the early embryo.

Scientists hope that embryonic cells can be used to regenerate the tissues damaged in diabetes, Alzheimer's, Parkinson's, heart disease and other diseases.

Though the stem cell colonies were all derived from embryos left over from in vitro fertility treatments, opponents of abortion have condemned the research because it requires destruction of the embryos from which the cells are derived.

But despite President Bush's months of agonizing over these objections, his administration now appears eager to push ahead with the research as quickly as possible. The National Institutes of Health, the document says, will "ensure that the scientific community has an opportunity to fully and swiftly investigate the promise of human embryonic stem cell research."

The N.I.H. is part of the Department of Health and Human Services. Tommy G. Thompson, the department's secretary, has long been regarded as a supporter of this research.

The agency says it will make a registry of human embryonic cell lines available on its Web site as soon as possible. Until it does so, scientists will be uncertain whether the cells will be available in sufficient quality and without excessive restrictions.

Dr. Paul Berg of Stanford University, a leading biologist who was consulted by the administration, said that until the registry is posted, "it's hard to comment on where things stand." But, he added: "In my view if we have 60 lines that's an enormous opportunity. I think some of the fuss about whether the cells are suitable for therapeutic use is simply premature. I suspect it will take three to five years before anyone is ready to propose a clinical trial."

Dr. Michael Ross, chief executive of CyThera, a San Diego company that has derived cells from nine embryos in the hope of curing diabetes, said his scientists needed to study and understand the cells better before making them available to others.

The organizations that have derived the human embryonic stem cell lines, and the number of different embryos reported in each case, are: BresaGen, Athens, Ga. (4); CyThera, San Diego (9); the Karolinska Institute, Stockholm (5); the Monash Institute of Reproductive Biology, Melbourne, Australia (6); the National Center for Biological Sciences, Bangalore, India (3); Reliance Life Sciences, Bombay (7); the Technion-Israel Institute of Technology, Haifa (4); the University of California, San Francisco (2); Goteborg University of Goteborg, Sweden (19); the Wisconsin Alumni Research Foundation, or WARF, of Madison (5).

Researchers have expressed concern that the Geron Corporation of Menlo Park, Calif., which financed the first derivation of human embryonic stem cells at the University of Wisconsin, might control access to the cells or impose unacceptable conditions on their use. But Geron is only a licensee, though an important one, of the patent held by WARF, which has said it wants to make the cells widely available. The only restrictions are that the cells should not be made into viable embryos or used for human cloning.

Carl Gulbrandsen, the managing director of WARF, said yesterday that he was negotiating with the N.I.H. over the terms under which the foundation's cells would be made available to the agency's researchers, and that "both of us are pretty confident that this will get done soon and that scientists are going to be happy with it."

Some scientists fear that WARF's patent will give it a dominant position, but Mr. Ross of CyThera said his company's lines were derived by an independent method. Mr. Gulbrandsen said that any discussions between the foundation and other derivers over commercial applications needed not affect the distribution of cells to academic researchers. He said that he hoped to reach a research-friendly agreement with the N.I.H., and that if other derivers of the cells did the same, "they don't have to worry about our patents."

An administration official said yesterday that the impending publication of the embryonic cell registry "should put a lot of the skepticism to rest."

"Basically it's time to go to work and start doing some of the research," the official said.
 

Copyright 2001 The New York Times Company


The Job Nobody at the Fertility Clinic Wants

http://www.nytimes.com/2001/08/26/health/26SEMB.html

August 26, 2001
Gina Kolata
 
Fertility centers discard relatively few excess embryos. But when they do discard them, the destruction can be a solemn occasion.

"Discarding embryos is by far the least appreciated task that we do here," said Dr. John Garrisi, the chief embryologist at the Institute for Reproductive Medicine and Science of St. Barnabas Medical Center in Livingston, N.J. "Embryologists form a pretty good spectrum, from the deeply religious to the very practical, and no one wants to be assigned that job."

Most centers charge a yearly storge fee for frozen embryos that ranges from a few hundred dollars to more than a thousand. But many embryologists say they do not discard embryos if the patients do not pay even if years go by. And many staff members say they dread destroying embryos when patients request it.

Dr. Richard Rawlins, laboratory director at the Rush Centers for Advanced Reproductive Care in Chicago, said he destroyed the embryos himself because so many of his staff members found the task distasteful.

At Rush, the biological parents must be present and have to agree to each step of the process. The embryos are thawed as though they will be used, just in case the parents change their minds. "Even at the last moment, the patient may have second thoughts," Dr. Rawlins said.

At St. Barnabas, the parents do not have to attend the embryo thawing, but they do have to sign a consent form and have it notarized. Then the center waits months before actually thawing the embryos. And when the embryos are finally thawed, two embryologists are present and sign off at every step of the procedure, checking the records, which are kept in triplicate, to be sure that the correct embryos are discarded. Finally, they are put in a container with other medical waste.
 

Copyright 2001 The New York Times Company


Stem cell controversy swirls among those with chronic diseases

http://www.latimes.com/news/politics/sns-stemcells.story

August 29, 2001
By Charles Ornstein, Times Staff Writer

For 11-year-old Arianna Helfant, stem cell research is far more than an elusive topic being debated within the White House and the halls of Congress.

She sees it as a potential cure for her juvenile diabetes.

In contrast, Georgeanne Cifarelli believes stem cells offer a false promise for her husband and others who suffer from advanced Alzheimer's disease.

President Bush's recent decision to allow federal funding for limited research on stem cells has unleased a flood of emotions and questions among many of the 128 million patients with chronic diseases nationwide.

"Will this work for me?" they ask. "How soon will we see results?"

Stem cells taken from very young embryos offer great potential, researchers say, because they can be turned into different tissues.

That, in theory, will allow researchers to replace dopamine-secreting neurons in the brains of Parkinson's patients and insulin-producing pancreatic beta cells in diabetics.

As a juvenile diabetic, Arianna looks forward to when she doesn't have to test her blood six times a day or give herself three shots of insulin. Maybe stem cell research will allow her to eat ice cream with friends, attend overnight summer camp and fall asleep without worrying about her blood sugar level.

"I don't even remember what it's like to not test my blood sugar and take shots," said Arianna, who lives in Los Angeles and was diagnosed with diabetes at age 6. "Every day, I'm hoping for a cure. It's something that I'm always thinking about."

Cifarelli refers to Alzheimer's as the "devil's disease" because it has eluded researchers for so long. She isn't following the stem cell debate because she says it's of no use.

"The way we get through this every day is to say, "Forget about the past. The present is important.' And we don't speak about the future," said Cifarelli, who lives in the Los Angeles suburb of San Marino. "We just live in the present and take one day at a time. You don't have time to do anything else."

Her husband, Nicholas, was diagnosed as having the disease more than five years ago, and he has lost most of his faculties. Before the disease, he was an internist and chairman of the bioethics committee at San Gabriel Valley Medical Center. Two medicines briefly stopped the progression of his disease, but neither work anymore.

"I cannot ever imagine a day when they're going to find a cure for this, no matter what," Georgeanne Cifarelli said. "We need it right now. We need something right now."

It's no surprise that patients and caregivers respond differently to the promise of research. Audrey Goldman, who counsels patients with multiple sclerosis, said the reactions may be a function of how much the disease has progressed.

"People who are newly diagnosed see it as an opportunity to never become disabled," said Goldman, of the National Multiple Sclerosis Society in Southern California. "I'm not sure that people who are very disabled think of it as a cure. Because there's not a cure for MS, our greatest hope right now is arresting the disease or preventing it."

Harland Green, a retired Beverly Hills lawyer, doesn't assume that stem cells will reverse the 50-year course of multiple sclerosis in his wife, Melva. But the couple have closely followed the debate and fully support the research.

"By the time they do this research and it's perfected and it gets through all the channels, I don't see how it would be particularly beneficial for her," said Green, 71. "But I do think it would be beneficial for a lot of other people and for mankind in general.

"The world is bigger than the two of us."

For the present, though, Green spends much of his day caring for his wife -- dressing, feeding and bathing her. Even so, Melva Green reads and accompanies her husband to religious services and theatrical performances in her electric wheelchair.

"We try to live as normal lives as possible within the limitations of the physical condition," Harland Green said. "People with wheelchairs do not need to be hidden away."

Caregivers such as Green are often confronted with myriad tasks and have little time to track research developments, which are followed by patient groups such as the National Multiple Sclerosis Society and the Alzheimer's Association.

"For our families, they're struggling day to day," said Peter Braun, executive director of the Alzheimer's Association of Los Angeles. "Caring for their loved one is a marathon. They're looking for that silver bullet, but that silver bullet isn't there."

Davis Brown, a retired Navy aviator, sees himself in a fight against time. He was diagnosed with Parkinson's disease in 1997, and now has an intermittent tremor in his right arm, along with difficulty writing and a lack of energy.

"I can envision, from what I've seen with others, that there's going to be a progression in my disease unless there is some intervening force," Brown said. "Just dealing with day-to-day things is going to occupy me full time. ... That's double incentive for trying to do as much as I can now."

Brown, 66, leads a Parkinson's support group for 175 people in Sonoma County in Northern California. The group spent two hours at a recent meeting discussing stem cell research.

"It really seems to have the best hope right now, the most promise," Brown said. "To not pursue it as rapidly as possible ... is really doing a great injustice not only to us Parkinsonians, but also to fellow sufferers in all these other diseases."

Brown said he's realistic about his chances of being helped by stem cells, adding, "I understand the time lines of research."

Still, he said, "I'm going to fight it to the end and I want to get as much done as possible that can help me and those behind me."

Former Pasadena Mayor Kathryn Nack said she's interested in stem cell research more for her six children than for her husband, Donald, who has had Alzheimer's since at least 1991 and is now in a convalescent hospital.

"I can't look at them and they can't look at each other without thinking that it could happen to them," said Nack, 76, past president of the local Alzheimer's Association board.

"My hope would be that whether it's the stem cell research or something else, there will be research that can make a change in the dreadful outcome."

Copyright 2001 Los Angeles Times


What Only the Embryo Knows

http://www.nytimes.com/2001/08/27/opinion/27GOUL.html

August 27, 2001
By STEPHEN JAY GOULD

Thomas Henry Huxley designated three men as the finest intellects of 19th century natural history: his dear friend Charles Darwin; his most worthy opponent Georges Cuvier; and Karl Ernst von Baer, who discovered the mammalian egg cell in 1827 and wrote the founding treatise of modern embryology in 1828. Of these three, posterity has largely forgotten von Baer, who suffered a severe mental breakdown in the 1830's, but then recovered and moved to Russia (not uncommon for a German-speaking Estonian national), where he enjoyed a distinguished second university career, largely in anthropology and lasting well into the 1870's.

In 1828, von Baer enunciated the central principle of embryological development, later known as "von Baer's law" and now regarded as the correct interpretation of Ernst Haeckel's famous (and erroneous) claim that "ontogeny recapitulates phylogeny," or that the successive forms of embryology repeat the adult stages of a lineage's evolution with the gill slits of an early human embryo representing an ancestral fish and the later tail an ancestral reptile, for example.

By contrast, von Baer proposed a principle of progressive specification and differentiation: One can first tell that an embryo will become a vertebrate and not some sort of invertebrate, then a mammal and not another kind of vertebrate, then a carnivore and not a rodent or ruminant, then a dog and not a cat, and finally Buster the Beagle and not another breed.

Von Baer summarized his principle in an epigram: "The development of the organism is the history of growing individuality in every respect." In other words, successive narrowing and determination of parts as complexity coagulates. No turning back after the blueprint becomes finalized from a broad mass of initial potential. For an appropriate literary metaphor, think of Lot's wife or Omar Khayyam's lines: "The moving finger writes; and having writ, moves on."

Von Baer's law epitomizes the central issue, unfortunately rarely discussed and little understood, in our current debate over embryonic stem cells. The very structure of material reality imposes a principle of trade- offs in both nature and human affairs: One always gives something in order to gain. In particular, we usually pay for complexity by surrendering flexibility and von Baer's law encapsulates the embryological version of this structural generality.

In genetic terms that von Baer could not know, each cell of our body contains a full set of genes. But embryological differentiation into a specialized adult role as a brain cell, liver cell or heart cell, for example leads to a "freezing" or "turning off" of most of this potential apparatus, leaving active only those few components regulating the specialized adult form and function. The cells of the earliest, undifferentiated embryo (little more than a clump of identical units in appearance) maintain full capacity to develop in any direction; that is, all their genes remain potentially active and recruitable.

The irony of the trade-off, explicitly recognized by von Baer nearly 200 years ago, inheres in the evolved surrender of this embryonic flexibility as development proceeds toward our maximal complexity. Cut a planarian flatworm in two, and the tail end regenerates a head while the head end regrows a tail. For in this simplest of bilaterally symmetrical invertebrates, with minimal differentiation of internal organs, all cells retain the embryonic potential to build any part of the body. This capacity for regeneration the ability of cells at a wound site to "dedifferentiate," or return to a state of early embryonic flexibility becomes progressively lost in animals that evolve greater adult complexity by von Baer's universal process of "locking in," with increasing specialization of parts. We have, in short, traded regenerative capacity for the undeniable evolutionary advantages of maximal complexity.
 
For this reason, we must use embryonic stem cells if we wish to pursue a large body of enormously important, highly promising and deeply humane research in how specific tissues and organs grow from the broad potential of early cells derived from the fertilized ovum. Speaking personally, I do not grant the status of a human life to a clump of cells in a dish, produced by fertilization in vitro and explicitly destined for discard by the free decision of the man and woman who contributed the components. But I also have no desire to offend the sensibilities of those who disagree. Thus, if I could derive cells of similar flexibility in a different way, I would gladly do so, even at considerable extra time and expense. (By analogy, I did not mean to mock or flout our laws in using marijuana to stave off severe and continuous nausea during some particularly nasty and lengthy chemotherapy 20 years ago. But I tried all the available anti- emetics, and they just didn't work. I continue to regard my decision as fair, humane and, believe me, importantly sustaining and life-affirming.)

Unfortunately, von Baer's law, and nature's broader structural rules of trade-off between complexity and flexibility, give us no alternative to embryonic stem cells for now and the research is important and far more than merely theoretically lifesaving. (Moreover, if we hope to find ways to dedifferentiate adult cells and therefore learn to recover the requisite flexibility from cells derived without offense to anyone then we must experiment with embryonic cells in order to understand and control the mechanism of their broad potentiality).

As an old man, from his Russian periphery, von Baer made the famous and rueful remark that all new and truly important ideas must pass through three stages: first dismissed as nonsense, then rejected as against religion, and finally acknowledged as true, with the proviso from initial opponents that they knew it all along. Genetic technology has brought us through the first stage. Our current debate on stem cells resides in von Baer's second stage, with the religious views of a clear, if powerful, minority setting an unfortunate opposition to one of the most vital avenues of beneficial research in our time. The third stage will arrive, and we will marvel that we ever rejected a pathway toward knowledge so imbued with life-saving capacity. May this third stage come soon, as our understanding differentiates further into a true and humane grasp of the virtues of flexibility.

Stephen Jay Gould, a professor of zoology at Harvard, is the author of "Questioning the Millennium."
 

Copyright 2001 The New York Times Company


Religions Ponder the Stem Cell Issue

http://www.nytimes.com/2001/08/27/politics/27RELI.html?pagewanted=print

AUG 27, 2001
By GUSTAV NIEBUHR

President Bush announced his decision to back limited federal financing of embryo stem cell research, responses came quickly from Roman Catholic bishops, who criticized it, and some prominent religious conservatives, whose views were considerably more mixed.

But in the weeks since the president's announcement on Aug. 9, many major religious groups have yet to be heard from.

Take the Unitarian-Universalist Association, perhaps the country's most liberal religious body.

"We're getting quite a number of calls and e-mails, requests and wishes for us to take a position," said the association's president, the Rev. Bill Sinkford. The messages also reached the Rev. Meg Riley, director of the denomination's Washington office.

"I think they were concerned about who was monopolizing the debate and that our view, which is pro- science, pro-research, was not heard," Ms. Riley said.

One e-mail message came from Jim Rice, an Oklahoma City lawyer and a longtime Unitarian.

"I commented that other religious leaders had spoken out strongly," Mr. Rice, who favors the research, said. "I pointed out that we had not."

But among Unitarian-Universalists, power is vested at the grass roots, and official statements come from an annual assembly. The assembly was in June, before attention focused on whether human embryos should be used in scientific research, and did not take up the subject. Mr. Sinkford said he was certain the assembly would do so next year.

The Unitarian-Universalists are not alone in not having an official position. The Episcopal Church, the Evangelical Lutheran Church in America and the United Methodist Church do not have one either, yet. Even the Church of Jesus Christ of Latter-day Saints, whose only position so far has been that the issue warrants "cautious scrutiny," has not reacted to Mr. Bush's position.

Reform Jews, the Presbyterian Church (U.S.A.) and the United Church of Christ have taken nuanced positions generally favoring such research. It is not unusual for religious organizations to take months or even years to write statements on social issues.

Some groups, like Muslims, Hindus and Buddhists, are so decentralized that no one can really claim to speak for all members. Those who speak on social issues tend to do so as individuals or as representatives of specific organizations.

None of this means that people of the various denominations and faiths are uninterested in the ethics of stem cell research. In the last few weeks, it has become a topic of discussion among adult groups in some churches and synagogues, as well as in polls among American Muslims.

Within this landscape, Conservative Judaism is moving relatively quickly, and its Rabbinical Assembly expects to declare a position on Jewish law and stem cell research this year.

"It is something that rabbis want to know," said Rabbi Elliot N. Dorff, vice chairman of the Conservative movement's Committee on Jewish Law and Standards.

Shortly before Mr. Bush announced his decision, Rabbi Dorff, rector of the University of Judaism in Los Angeles, received a call from the committee's chairman, Rabbi Kassel Abelson, who asked him to send a paper on stem cell ethics to other committee members for study.

Rabbi Dorff, a member of a bioethics commission that met at the White House in 1999, had one on hand. In it, he concluded that Jewish law allowed support for stem cell research because it could serve a common good, combating disease.

After committee members send him their comments, the paper will be revised and adopted as the movement's standard on Dec. 19.

In June, a month before Conservative rabbis began their study, officials in the Episcopal Church created a task force to study the ethical, theological and legislative implications of "the new genetics."

But any formal statement must probably await the next General Convention, in 2003. Meanwhile, priests like the Rev. William Tully, rector of St. Bartholomew's Church in New York City, are trying to help Episcopalians think about the issue.

This month, Father Tully invited a professor of ethics and moral theology to speak to a gathering at his church on "thinking ethically." About 75 people attended to discuss how the Christian tradition could help them ponder such issues as stem cell research, he said.

Asked whether it mattered that the Episcopal Church had not yet come up with a statement, he said, "My view is that the days when people were hanging on the pronouncements of a denomination if they ever did are passing."

Muslims may lack a central governing body to offer an opinion on the ethics of stem cell research, but some prominent individuals, like Dr. Maher Hathout, a cardiologist who is spokesman for the Islamic Center of Southern California, have offered a Muslim perspective on the issue.

Muslims regard abortion as wrong, but they also hold that life does not begin until the fertilized egg attaches to the womb's wall, Dr. Hathout said. He added that this would not preclude research on stem cells from in vitro fertilization that would otherwise be discarded.

Still, Ibrahim Hooper, a spokesman for the Council on American- Islamic Relations, an Islamic advocacy organization, said he had not heard of any Islamic authority ruling on stem cell research from the perspective of religious law.

The week that Mr. Bush announced his decision, the Evangelical Lutheran Church of America held its biennial Churchwide Assembly. Perhaps one of the bigger surprises of the stem cell debate has been the absence of a direct response to Mr. Bush's stand from the denomination, of 5.1 million members.

But the Lutheran assembly had much internal business before it, including electing a presiding bishop, deciding whether to add a provision to an ecumenical agreement and debating whether it should undertake a study of how Lutherans should relate to gays and lesbians.

Asked whether any discussion had taken place in the denomination about the need for a statement on stem cell ethics, James M. Childs Jr., a professor of theology and ethics at Trinity Lutheran Seminary in Columbus, Ohio, said, "No concerted cry has come to my ears, at least."
 

Copyright 2001 The New York Times Company


Stem Cell Research Faces FDA Hurdle

With Mouse Cell Base, Tough Rules Apply

http://www.washingtonpost.com/wp-dyn/articles/A53580-2001Aug23.html

Friday, August 24, 2001; Page A01
By Justin Gillis and Ceci Connolly
Washington Post Staff Writers

Most or all of the human embryonic stem cell colonies approved for research funding under a new Bush administration policy have been mixed in the laboratory with mouse cells, which may create substantial hurdles for scientists trying to turn the colonies into treatments for Parkinson's disease, spinal-cord injuries and other ailments.

The cell colonies, or "lines," were created for early-stage research with no thought that they would become the only embryonic cells eligible for federal money. But that is the status President Bush conferred on them in his first prime-time address to the nation on Aug. 9.

The standard technique for creating human embryonic stem cell lines has been to extract cells from inside a microscopic embryo, then grow them atop embryonic mouse cells, known as "feeder" cells. The latter excrete some unknown nutritional or growth factor that helps the human cells stay healthy. Because they have been in close contact with mouse cells, the human cells pose a small but real risk of transferring potentially deadly animal viruses to people.

Because of that, under guidelines the Food and Drug Administration has been developing for several years, it would be difficult, though not impossible, to use the cells in human clinical tests.

Under the FDA rules, which are designed to prevent the accidental creation of a new plague, transplants of these embryonic cells into people would be treated as though they were "xenotransplants," or transplants of animal tissue. The guidelines impose stringent requirements on researchers and patients alike. They would likely rule out some groups of patients who might otherwise be eligible to participate in human stem cell tests -- notably, for instance, young diabetes patients whose disease can be treated in other ways.

The human embryonic stem cell lines reported in scientific literature were all grown in direct contact with mouse cells and might have picked up mouse viruses, which government officials acknowledged would bring them under the FDA policy.

Scientists are working on ways to grow human embryonic cell lines without using mouse cells, but any created after Bush's speech Aug. 9 would be ineligible for federal research money.

Patient groups and people who work with them expressed concern when told about the xenotransplant restrictions.

"This would be the exclamation point" on an already lengthy list of questions about the quantity and quality of the cell lines eligible for research funding under the Bush policy, said Kevin Ryder, a consultant to the American Cell Therapy Research Foundation, a New York foundation that supports research into many types of treatments using cells. "We would have a very difficult time getting those advanced into the clinical setting unless we get the FDA to make some exceptions down the road."

Most people on Capitol Hill are unaware of the issue, but as word of it began spreading late yesterday, some legislators expressed concern. "The president's going to have to make available lines of stem cells that will be available for the full measure of research anticipated," said Sen. John F. Kerry (D-Mass.) "If he doesn't, Congress will need to act to make that happen."

Jay Lefkowitz, a White House adviser who helped craft the Bush policy, said the administration was aware that the stem cell lines Bush approved for funding had been mixed with mouse cells and would come under the FDA's xenotransplant rules.

The White House concluded that the issue would not be a serious barrier at this stage, when scientists still need to do several years of fundamental laboratory work before human tests can begin, he said. By the time researchers are ready to begin those tests, he said, officials are confident that scientists will have found a way to grow stem cells without mouse cells, or will be able to work within the FDA's guidelines.

"President Bush has unlocked the door so that critical, basic research can be conducted in an area that is currently uncharted," Lefkowitz said. "To fulfill that mission, we believe the existing stem cell lines are more than adequate."

Opinion among scientists is mixed about how much of a problem the xenotransplant issue will be, but at the least, they say, it presents yet more practical difficulties in the execution of a policy already rife with them.

In the 15 days since Bush announced his policy, other lingering questions -- about how many cell lines exist, who owns them and how accessible they will be to academic scientists -- have gone largely unanswered by the National Institutes of Health and the Department of Health and Human Services. NIH administrators are negotiating with companies and labs to try to work out many of the details. Congressional hearings are scheduled in two weeks.

In an interview, a senior NIH administrator and an FDA regulator acknowledged that the xenotransplant issue could pose hurdles but said it was premature to speculate about how serious those might be.

"There is so little experience with these cells," said Lana Skirboll, director of science policy at the NIH. "There's a lot that needs to be done. I just think the scientific community is in a position that we have a lot more to learn."

FDA administrators who developed the xenotransplant policy declined to comment. But they pointed to written reports and meeting transcripts going back five years that make their position clear. The documents, posted on the Internet, leave little doubt that stem cells grown by current techniques would be covered. Although the guidelines are not final, officials said the agency has been following them.

Some laboratories that work with stem cells appear to be unaware of the policy; others are operating under the assumption that it will be a large hurdle in creating treatments from any of the existing cell lines. "It could be a real killer," said George Daley, a stem cell researcher at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

Executives of BresaGen Inc., the U.S. unit of an Australian stem cell company, met with the FDA last spring and learned then that their four lines of human embryonic stem cells, all grown atop a layer of mouse cells, would be treated as xenotransplant products. "We were a little bit shell-shocked," said Allan Robins, senior vice president and chief scientific officer. "I think a lot of companies will see it as a large burden."

This view is not universal, however, even among scientists who oppose the Bush plan.

Hugh Auchincloss Jr., a surgeon at Harvard Medical School and chairman of an FDA committee that reviewed the xenotransplant issue, noted that the FDA policy, while stringent, is not an absolute bar to research. Indeed, several hundred patients have already participated in various types of xenotransplant tests, including the transfer of fetal pig cells into patients' brains in an attempt to treat Parkinson's disease.

Moreover, Auchincloss said, with enough time and lab work, scientists might be able to alleviate FDA concerns. He noted that human tests of stem cell therapies are probably years away, largely because scientists know so little about the cells.

In his speech Aug. 9, Bush said 60 genetically distinct embryonic stem cell lines had been derived by laboratories around the world and approved federal funding for work only on those cell lines. To reduce incentives for further destruction of embryos, he ruled out funding for any cell lines created after his speech.

Because they can be used to grow almost any kind of human tissue, which could then be used to repair ailing body parts, the cells offer considerable, but unproven, hope for cures. The cell lines were created from early-stage human embryos slated for destruction at fertility clinics. Many anti-abortion activists, one of Bush's most important constituencies, oppose the research.

Several scientists have said publicly that they are working on ways to grow embryonic stem cells without mixing them with mouse cells. But no scientist has publicly claimed to have created an entirely new cell line by such a method before Aug. 9.

That has led most scientists familiar with the issue to conclude that all 60 lines were probably created using mouse feeder cells and will have to be treated as xenotransplant products.

"I don't think there's any one of the 60 lines that has not been derived using mouse embryonic feeders," said Daley, of the Whitehead Institute.

However, the possibility cannot be entirely ruled out until the location and details of all 60 cell lines have been disclosed.

The implications of treating most or all of the lines as xenotransplant products would be substantial.

The draft FDA guidelines make clear that labs researching stem cells will have to meet special burdens to win approval for any human test involving xenotransplantation. They will have to perform extensive research and documentation on their cells that go beyond normal FDA requirements, including elaborate study of potential animal viruses. At a minimum, this will introduce delay and extra expense.

Given the complexity of the FDA restrictions, Robins, the BresaGen scientist, predicted that few companies would plunge into human tests of stem cells grown together with mouse cells. He said those will be used for research for the next few years, but eventually companies will create new cell lines grown only on human feeder cells. They will do so either with private money or by overturning the Bush limitations on federal funding, Robins and other researchers predicted.

In fact, it appears the FDA restrictions have already set off a behind-the-scenes race among labs to create -- and patent -- alternative means of growing stem cells that don't depend on mouse feeders.

The only company that has publicly claimed success with a mouse-free technique is Geron Corp. of Menlo Park, Calif. "We have accomplished it," said David Greenwood, the company's chief financial officer. But he declined to say whether Geron had managed to create any new stem cell lines using the technique before Aug. 9.

Several researchers predicted that if stem cells began to show promise, the politics would change, and they would win permission to work on new cell lines with federal money.

"If the research looks great and we're ready to go to human trials, we will need more stem cells," said Jeffrey Rothstein, a neurologist at Johns Hopkins University in Baltimore who works in the field. "We'll turn to the president or Congress and get them to do the right thing."

Staff writer Rick Weiss contributed to this report.
 

© 2001 The Washington Post Company


Mouse-stem cell issue called irrelevant

http://www.upi.com/

Friday, 24 August 2001 19:07 (ET)
Reported by UPI Science Writer Scott Burnell.

WASHINGTON, Aug. 24 (UPI) -- The involvement of mouse cells in many lines of embryonic stem cells available for research won't affect the scientific value of the stem cells, officials in the U.S. Department of Health and Human Services said Friday, disputing published reports.

Many of the embryonic stem cells approved for research funding by the Bush administration are cultivated in the laboratory by placing them on top of colonies of mouse "feeder" cells, according to a National Institutes of Health report issued before Bush's Aug. 9 decision. The feeder cells excrete some form of growth factor or hormone that keeps the human cells healthy.

The mouse cells theoretically could transfer viruses or other harmful material to the stem cells, the Washington Post reported Friday. That could "create substantial hurdles" for scientists hoping the stem cells might lead to cures for Parkinson's disease and other ailments, the newspaper reported.

Also, inserting these embryonic cells into people would be considered "xenotransplants," transplants of animal tissue. Under Food and Drug Administration guidelines, it would be difficult, but not impossible, to use the cells in human clinical tests, The Post said.

Those people worried about FDA approval for stem cell therapies are getting far ahead of the game, said Don Ralbovsky, an NIH spokesman.

"We're going to be doing basic research, and (the stem cell lines) are perfectly useful for the research that needs to be done before we arrive at the point of clinical trials," Ralbovsky told United Press International. "There's a huge amount of basic research, a lot of things that have to be found out."

In Crawford, Texas, President George W. Bush reiterated his position that NIH's investigations into worldwide stem cell resources supported going ahead with funding for basic research.

"The NIH came into the Oval Office and they looked me right in the eye and they said, 'We think there are ample stem cell lines to determine whether or not this embryonic stem cell research will work or not,' " Bush said. "And I appreciated their candor and I appreciated their advice."

Bill Pierce, an HHS spokesman, said the Post article was far too hypothetical in nature to address what's going on with stem cells today. Some xenotransplants are in clinical trials today, so there's a precedent for the FDA to allow the stem cells to be used once they reach the same stage, perhaps in five or so years, Pierce told UPI.

"At that point, the hurdles, challenges or tests that have to be passed to get to the clinical trials stage may well have been overcome," Pierce said. "For example, you'll be able to discover the mouse feeder cells don't present any risk. We didn't see this as that big of an issue."

The ongoing discourse over stem cells, mouse feeder cells and the possible implications of their mingling is a normal part of scientific discovery, Pierce said.

Not all stem cells lines are affected by mouse cells, however. David Greenwood, senior vice president for Menlo Park, Calif.-based Geron Corp., which has worked on embryonic stem cell research since 1998, told UPI Friday the lines Geron owns have been raised without mouse feeder cells. Geron realized the complications feeder cells would raise, Greenwood said, and worked through the problem some time ago. The company isn't aware of other feeder-cell-free efforts in the embryonic stem cell community, he said.
 

Copyright 2001 by United Press International


The Adoption Option

Frozen embryo adoption offers hope to microscopic Americans.

http://www.shns.com/

August 27, 2001 8:25 a.m.
Mr. Murdock is a columnist with the Scripps Howard News Service.
Fullerton, Calif.

perm-pierced human ova have yet to yield baby chicks or puppies. If allowed to grow, such cells produce boys and girls. That's why the vocabulary surrounding stem-cell research, human cloning, and other fertility issues is so eerie. Discussions of "surplus embryos" that will be "discarded anyway" are cruelly dismissive of Microscopic-Americans who - if their potential body parts are not "harvested" - will become citizens sooner than Thanksgiving turns to Labor Day.

While this truth escapes so many people these days, it propels JoAnn Davidson, program director of the Snowflakes Embryo Adoption Program. From modest quarters in this Orange County community, she and two colleagues help couples adopt frozen embryos that often would be killed in the name of science or simply treated as so much medical waste. The path she has built to lead these souls on ice into loving families deserves reproduction from coast to coast.

"Our end objective is to work ourselves out of our jobs," says the 36-year-old Texas A & M graduate. "Every embryo would be adopted and no new 'extra' embryos would be created."

An estimated 188,000 embryos are suspended in liquid nitrogen canisters around America. Some fertility clinics help genetic parents donate their unused embryos to others who are trying to become pregnant. However, the process is usually anonymous with donors and recipients knowing little, if anything, about each other.

The Snowflakes program treats embryo adoptions just like open adoptions of children who scream and scamper. Those who relinquish their embryos can choose potential adoptive parents who have passed a rigorous "homestudy" process that Davidson calls "80 percent education and 20 percent screening." This includes counseling with social workers on parental responsibilities as well as background checks for credit problems or evidence of criminality or child abuse. Snowflakes even submits prospective parents' fingerprints for FBI clearance.

Genetic parents who work with Snowflakes, a project of Nightlight Christian Adoptions, tend to want their embryos to be raised in religious homes. However, Davidson says, "We wouldn't stand in the way," if a participating couple wished to donate to an atheist, single mother. "We don't define the criteria. It's up to the genetic parents. But the nature of our name narrows the kind of people who come to us."

Genetic donors and adoptive parents remain available to each other through the program (in case of medical emergencies). They also may stay in limited contact through Snowflakes' offices or can phone, e-mail or visit directly.

"They send us pictures of their kids, and we send them pictures of ours," says Lucinda Borden of the genetic parents whose embryos she adopted. She and her husband, John, now have 11-month-old boys named Mark and Luke after trying to get pregnant for six years. "It changed my life completely because I have twin sons," says the Fontana, California resident. "The other option for them, other than being adopted, was to be destroyed. Knowing that there are tens of thousands like them in freezers waiting for their fates to be decided breaks a mother's heart."

After they had twins through implantation and a subsequent child naturally, Atlanta's Susanne and Bob Gray offered for adoption 23 of the 27 embryos they and their doctor created.

"It's easy to attach a face to an embryo when you can see the faces of its brothers and sisters that came from the same cluster of embryos," Susanne Gray says. She adds that she and her husband "were actually shocked" when her doctor aspirated 33 eggs from her ovaries and fertilized all of them, thus producing more embryos than she ever would raise as children.

Davidson urges prospective parents to tell their doctors to create only as many embryos as they would bring home as newborns. Overly aggressive fertility techniques are largely responsible for the crowded purgatory in which so many frozen embryos languish.

Snowflakes is doing its part to ease this crowding. To date, it has matched 36 genetic families with 27 adopting couples. Of the 186 embryos the program has had thawed, 94 were viable for uterine implantation. Of these, eight babies have been born, and seven more are on the way.

JoAnn Davidson's office is festooned with snowflakes. Paper ones, that resemble doilies, cover her walls. Others - crafted from Styrofoam, wicker and pewter - dangle on strings from her suspended ceiling. They symbolize those she aims to help, each frozen, fragile and uniquely individual.


Stem Cells: Private Sector Can Do It Better

August 28, 2001
By Robert Oldham. Dr. Oldham is chairman of the South Carolina Biotechnology Association and CEO of Cancer Therapeutics, Inc.

President Bush's decision on federal funding of embryonic stem-cell research continues to arouse controversy. But much of the debate overlooks a very important question: Who can do the work better? The government or the private sector?

To answer that question, look at the race to decode the human genome, pitting a private company called Celera against the National Institutes of Health. That contest began when the government decided to fund selected laboratories to sequence genes. But the machines that do the sequencing were developed by the private sector, so they were available to anyone with the money to purchase them. That opportunity was eagerly seized by Craig Venter, president of Celera, working in conjunction with Perkin-Elmer, a company that makes gene-sequencing equipment.

The original projected NIH completion date was 2005. But Celera quickly raced ahead of the lumbering government project. The human genome sequence in a rough form was unveiled last year jointly by Celera and the NIH. Public relations aside, let there be no doubt: It was the private sector that was responsible for the rapid success of gene sequencing.

So did it make sense to spend billions in government money to achieve something that Dr. Venter's private company achieved faster and better? Many in the scientific community would say yes -- and for much the same reason they insist on federal funding of stem-cell research. Public-sector scientists believe they should pursue knowledge unfettered by grubby commerce. They fret that private companies would develop proprietary data and then deny society the fruits of their labors.

But does this distrust of capitalism make any sense? We don't depend on the government to develop life-saving medicines. Virtually all new drugs come from private pharmaceutical and biotechnology companies that spend billions on research because they know they can profit from it. The research dollars are provided through our capital markets.

That's how a free-market economy works. Valuable goods are delivered not because of the altruism of the producers but because they are risking their money in the hopes of profiting. If this principle works in every other sphere of our economy, why not in medicine too?

This is not to deny any role at all for government funding. Perhaps, instead of funding a massive research effort on the human genome, the government would have been better off letting Celera do the work and then purchasing the results for public use.

Another public-private race is now gearing up in the stem-cell field. A number of biotech companies, such as Advanced Cell Technology and Geron, are vying to play the role of Celera. Their chances of success have improved considerably because of the restrictions President Bush has imposed on federally funded research. Scientists working with government funds are forced to use only the 60 stem-cell lines already in existence, some of them not even located in the U.S.

The private sector labors under no such handicap. Private companies will be free to create more stem-cells lines from additional embryos that are going to be discarded by in vitro fertilization clinics. There is a tremendous entrepreneurial opportunity here -- stem-cell research may some day deliver cures for Parkinson's and other deadly diseases -- and there is no shortage of companies that will rise to the challenge. It is possible that, as the private sector races ahead, the Bush administration will find itself coming under growing pressure to allow more stem-cell lines to be used in federally funded research.

But whatever the government does, its money may be wasted. In stem cells, as in human genomes, the private sector will lead the way.