Stem cell scandal reverberates in U.S.
S. Korea controversy leads to calls for more oversight

Bruce Lieberman
Union-Tribune

December 18, 2005

As a South Korean scientist defends against mounting accusations that he falsified evidence in a breakthrough stem cell study, researchers in California said the controversy has caused significant damage to a promising and fledgling field.

Doubts about Hwang Woo-suk's claims that he cloned human cells to create embryonic stem cells have made scientists wonder whether the prospect might remain elusive for years. Researchers and doctors hope to use this process to genetically tailor stem cells for patients suffering from such diseases as Parkinson's, diabetes and multiple sclerosis.

"It's a black eye on the whole world of science," Richard Murphy, president of the Salk Institute in La Jolla, said. "Exciting areas of research are always competitive . . . but healthy competition never justifies sloppy research, cutting corners or dishonest behavior."

In California, where voters approved $3 billion to jump-start stem cell research, the South Korean controversy has led to renewed calls for more oversight of publicly funded science.

Meanwhile, San Diego biologists say the scandal shows why the United States needs to lift federal funding restrictions on the use of human embryonic stem cells for research, which requires the destruction of embryos.

"We would have figured out very quickly that there was some problem here. . . . And the truth would have come out much sooner had we been in a position like we normally are – to be able to jump in and work with complete freedom," said John C. Reed, president of the Burnham Institute in La Jolla. "It's very important that we have laboratories throughout the country and around the world to . . . verify whether observations made by one group are reproducible by another."

In June, Hwang Woo-suk and a team of South Korean researchers announced in the journal Science that they had created 11 colonies of human embryonic stem cells. They supposedly did so by cloning cells from 11 patients.

The cloning procedure, called somatic cell nuclear transfer, was hailed as a huge technical success. It was the first time scientists reported having cloned human cells and then successfully grown them into separate lines of embryonic stem cells. The news catapulted Hwang to fame and brought international prominence to South Korean science.

This fall, however, revelations surfaced that some of Hwang's female lab workers had secretly donated their own eggs for the work. Scientists widely condemned the practice as unethical because it might have resulted from coercion.

A member of Hwang's research team, Roh Sung-il, accused him last week of faking nine of the 11 stem cell colonies by pressuring a lab worker to forge evidence. Yesterday, Roh said he planned to perform tests to determine whether all of the colonies were fabricated.

Hwang recently asked the editors of Science to withdraw the paper published in June. He has admitted to "fatal errors and loopholes in reporting the scientific accomplishment" but insists that his core results are valid.

In the United States, scientists and others connected to stem cell research said the misdeeds of one research group should not impugn an entire field.

"The withdrawal of the results by . . . the South Korean group is a serious setback," Zach W. Hall, president of the California Institute for Regenerative Medicine, said in a statement last week. The institute was established by Proposition 71 a year ago to review research applicants and disburse money.

"The good news is that many talented researchers will continue their work," Hall said. "I am confident that the field will recover and quickly move ahead."

To help prevent misconduct, some advocacy and watchdog groups are calling for stricter rules governing U.S. stem cell projects. The nonprofit Center for Genetics and Society in Oakland, for example, has criticized what it sees as a lack of oversight for California's stem cell institute.

"The scandal starkly demonstrates the need for strong and enforceable regulations," according to a statement on the group's Web site. "Voluntary guidelines such as those proposed for U.S. scientists are clearly inadequate."

In the United States, stem cell researchers say they follow guidelines set forth by the National Academies, an independent organization that advises the federal government on issues related to science, engineering and medicine. This year, the National Academies published a report titled "Guidelines for Human Embryonic Stem Cell Research."

"This document provides excellent guidelines for scientific experimentation within a framework of high ethical principles," said Murphy of the Salk Institute.

In California, efforts are under way to establish greater oversight of the stem cell institute.

State Sen. Deborah Ortiz, D-Sacramento, has called for more scrutiny of taxpayer-funded stem cell research in California. She sponsored a bill to protect women who donate eggs for research and require the state auditor to regularly review the institute's finances.

The measure overwhelmingly passed in the Legislature this fall but was vetoed by Gov. Arnold Schwarzenegger, who said it conflicted with a provision in Proposition 71 barring amendments until 2008.

Spokeswoman Hallye Jordan said Ortiz plans to introduce a bill in January that would resurrect elements aimed at protecting the rights of women who donate eggs. But the financial oversight issue remains unsettled.

"This whole unfortunate episode has pointed to the need for good governmental oversight of this important research," Jordan said last week. "We want to maintain the public's confidence in stem cell research, and the best way to do that is through accountability and openness."

Meanwhile, some scientists say additional oversight is unnecessary.

Dr. Evan Snyder, head of stem cell research at the Burnham Institute in La Jolla, said the embarrassing South Korea episode shows how science's built-in system of checks and balances can root out misconduct.

"This was an example of the scientific community doing what it does routinely, which is police itself," Snyder said.

For instance, Hwang's U.S. colleague on the disputed study, University of Pittsburgh biologist Gerald Schatten, helped bring the scandal to light when he ended his collaboration with Hwang a month ago. Schatten, who was senior co-author on the disputed paper in Science, still faces a separate investigation by his university.

"Dr. Schatten is not doing interviews until the University of Pittsburgh's Office of Research Integrity concludes its probe," Michelle Baum, a spokeswoman for the university, said Friday. "We expect that to be within a few weeks, but it's hard to predict."

Snyder and others said it's unlikely that a scientist in Hwang's position will ever recover from such a professional disaster, even though many details about the episode remain unclear.

"An event like this can ruin a scientist's career," said Reed, the head of Burnham. "This may be the end for him. A scientist is nothing without his or her reputation."

Snyder, who had hoped to begin working with Hwang's lab team as part of a new stem cell consortium involving South Korea, the United States and Great Britain, said those plans have been scuttled.

"I will not at all collaborate with them," Snyder said.

Biologists will probably have to go back to the drawing board if cloning is ever to become a tool for making new colonies of stem cells, scientists said.

"We'll all have to hunker down and get it to work and see if it's feasible," Snyder said. "In that respect, we probably are going to have to do a lot of heavy-duty, labor-intensive work again."

I'll gladly admit that I voted for the Stem Cell Research prop. It step up a board of advisors.
Now from what I've read in the news, what I feared may be coming true. It will amount to paying
a board a large some of money and not produce much tangible. The US leads health care for a
reason. That reason is because of our high cost of health care pays makes it profitable to search
for cures. Because of this, we have led the health care revolution. Stopping advancements like
this or by socializing health care, our leadership will wane quickly and someone else will
take the reigns and lead the world and we'll trail behind snapping up scraps.

What last great advancement has come from Canada?
Well, there was... Hmmm... What about... Hmmm... Well, I can't think of any.

Let's lead.

---

TEAM
LL

Stem cell lines confirmed fake; researcher quits

ASSOCIATED PRESS

December 23, 2005

SEOUL, South Korea – South Korean researcher Hwang Woo-suk resigned from his position as a professor today after his university said he had fabricated the results of at least nine of 11 stem cell lines that he claimed to have created.

"I sincerely apologize to the people for creating a shock and disappointment," Hwang told reporters as he was leaving his office at Seoul National University. "As a symbol of apology, I step down as professor of Seoul National University."

The statement by Seoul National University was the first confirmation of allegations casting his purported breakthroughs under suspicion.

In a May paper in the journal Science, Hwang claimed to have created 11 stem cell lines matched to patients in an achievement that raised hopes of creating tailored therapies for hard-to-treat diseases. But one of his former collaborators last week said nine of the 11 cell lines were faked, prompting reviews by the journal and an expert panel at Seoul National University.

In its first report on its progress, the panel said today it found that "the laboratory data for 11 stem cell lines that were reported in the 2005 paper were all data made using two stem cell lines in total."

The panel said DNA tests being performed would confirm if the two stem cell lines it had found were actually successfully cloned from a patient.

The panel said today that it found no records of two of the other stem cell lines Hwang claims to have created. Four others died from contamination, and another three were in the nurturing stage and hadn't yet become full stem cell lines.

Book sales bomb for 'South Korea's No. 1 scientist'

REUTERS

December 28, 2005

SEOUL, S. Korea – South Korean publishers rushed to put books on celebrated scientist Hwang Woo-suk on store shelves, only to find him embroiled in a scandal and their products becoming one of the biggest flops of the holiday season.

Hwang was once called the pride of South Korea for bringing the country to the forefront of stem cell and cloning research. Publishers aiming to cash in on his fame put out 16 books on him, 10 of which were children's books.

Most of the books made their way to store shelves in the past year. In past days, however, those same books were headed back to publishers because demand dried up when charges surfaced that Hwang's team fabricated data.

"We started taking children's books on Hwang off the shelves just before Christmas," said Kim Yea-won, a clerk at major book seller Kyobo. "Nobody wants them now."

Books for children are a popular gift for Christmas in South Korea, and one book timed for release with the holidays was "The Beautiful Life Path of Hwang Woo-suk." It was released on Dec. 20, just a few days after Seoul National University started to probe work produced by Hwang's team after two collaborators said a paper they published in May 2005 for the U.S. periodical Science was based on fabricated data.

The book for preteens was meant to be an inspiring tale of a humble national hero it called "South Korea's No. 1 scientist."

South Koreans reacted with shame and sorrow Friday when an investigation panel said data in the 2005 paper on tailored embryonic stem cells was intentionally fabricated and Hwang should shoulder a large portion of the blame.

Yesterday, the investigation panel at Seoul National University said it was conducting DNA testing on specimens that were part of a 2004 paper from Hwang's team on cloning the first human embryos for research. It said Monday that it expected results next week on DNA testing that should prove whether there is any truth to the claims Hwang's team produced tailored embryonic stem cells.

Remaining stem cell lines faked
Hwang's cloned dog also being reviewed

By Bo-Mi Lim
ASSOCIATED PRESS

December 30, 2005

SEOUL, South Korea – An already disgraced scientist lied about all of the stem cell lines he claimed were matched to different patients through cloning, investigating researchers said in a new jolt to the shattered reputation of Hwang Woo-suk.

Yesterday's announcement all but ends the fraud investigation into one of three major cloning breakthroughs claimed by the one-time scientific superstar and national hero. Probes of Hwang's two other groundbreaking experiments are still under way at Seoul National University where he worked before resigning in disgrace last week.

The latest news was one more disappointment to the scientific world, which had viewed Hwang's achievements as holding great promise for treating people with a variety of ailments, from spinal-cord injuries to Parkinson's disease.

In the experiment deemed fraudulent, Hwang, 53, had claimed in a paper published in May in the journal Science that he had created 11 colonies of human embryonic stem cells genetically matched to specific patients. The journal said it will retract the paper.

An investigative panel at the university reported last week that Hwang had faked the research on nine of the stem cell lines. Yesterday, it confirmed he also fabricated his research for the two remaining cell lines.

"The panel couldn't find stem cells that match patients' DNA regarding the 2005 paper and it believes that Hwang's team doesn't have scientific data to prove that (such stem cells) were made," said Roe Jung-hye, the university's dean of research affairs.

The university said that by next month it expected to wrap up all work on that case and have findings on two others: Hwang's first blockbuster claim in 2004 in the journal Science that he created the world's first cloned human embryo and extracted stem cells from it; and his research published in Nature in August claiming to have produced the first cloned dog.

Prosecutors said last week they are waiting for the university investigation before launching their probe. The scientific journals also await those findings.

Hwang first came under suspicion in November when he admitted, after more than a year of denial, that he had used eggs donated by lab workers, in violation of ethics guidelines. He also acknowledged that some of the eggs he used were bought, after first saying all the eggs were donated.

Yesterday, Hwang could not be reached for comment.

From here

Science News

Stem cell debacle will taint science

By Astara March Dec 30, 2005, 14:55 GMT

WASHINGTON, DC, United States (UPI) -- The discovery that South Korea`s prestigious researcher Hwang Woo-suk may have falsified results in the paper he published on stem cell research could have far-reaching impact on the field for a long time to come, health policy experts said this week.

The Korean debacle could even make it harder for the nascent technology to get funding in the future, they said.

At the center of the simmering controversy in an article published in the journal Science in May 2005.

Hwang, leader of the team that produced the world`s first cloned dog and credited with bringing South Korea into the biomedical world arena with patient-tailored stem cells, was accused by his colleagues of deliberately fabricating results in the research that described how the stem cells were produced.

'This whole scandal is incredible given the scope of collusion that has to be involved,' Glenn McGee, editor-in-chief of the American Journal of Bioethics, told United Press International McGee. 'Even if it`s a minor error or data was exaggerated to get the research to market, it`s still likely that this will turn out to be not just a bad apple, but a poisoned apple.'

An investigation into the allegations is being conducted by both Seoul National University and South Korea`s Board of Audit and Investigation, that said it suspected government agencies collaborated in the cover up.

Reports from a variety of sources have revealed that, although the first set of questions addressed to Hwang concerned whether the egg donors in his experiments were paid or not, current questions center on whether there were in fact any patient-tailored stem cells lines at all.

McGee said that he was appalled by the potential consequences of Hwang`s actions.

'The level of scientific fraud is unprecedented because it involves so many co-conspirators and a separate commercial dimension. It doesn`t just tarnish science, it`s going to expose science to the charge of crass commercialism.'

McGee said he thought Hwang`s mistakes would change the way peer-reviewers for scientific journals all over the world verify data, and badly damage future stem cell funding opportunities.

'The Korean investigators were able to work in this complicated field where there`s no federal money only because they could persuade venture capitalists that their investments were safe with them,' McGee explained. 'These events may be the undoing of a variety of government/corporate scientific partnerships and will make it even harder to raise already scarce funds for stem cell research,' he said.

'The people it will hurt the worst are the folks in the tiny, very vulnerable companies who are doing the actual start-up work in the field,' McGee predicted.

Roe Jung-hye, the chief of Seoul National University`s research office, said at a televised news conference that the university would use several techniques, including DNA fingerprinting, to determine whether the basic findings in the Science paper were true or not.

Meanwhile, Science announced that Hwang had asked the journal to retract his paper several weeks ago, when questions were raised about the egg donors. Editor-in-chief Donald Kennedy issued the following statement on December 29, explaining why the retraction process was taking so long.

'There is no question in our minds that the stem-cell paper published 19 May 2005 by the journal Science needs to be retracted, and we are proceeding swiftly but appropriately in that direction. As of this writing, however, editors at Science still have not received any official notification from Seoul National University regarding the interim findings just reported in the press, and so we have sent a message to the head of the investigation, Dr. Roe Jung-hye, seeking more information. Science also is continuing to try and gather all authors` signatures for the retraction agreement.'

McGee told UPI he felt a number of factors had created South Korea`s current problems.

'Unfortunately, when you have extreme funding mechanisms, insufficient oversight, excessive pressure, a crazy confederation of authors and institutions, and confusion about patents, nothing good can result,' McGee said. 'When you add a lab in Korea that isn`t subject to any of the laws most countries have for verifying data and a data interpreter who doesn`t speak Korean, it`s a recipe for disaster,' he said.

'There`s always a lot of this sausage making in frontier research and it`s always odious,' McGee added. 'I guess we know what they`ll teach from now on in Korean scientific ethics classes.'

Copyright 2005 by United Press International

---

"I'm trying to maintain a shred of dignity in this world." - Me

S. Korea researcher faked cloning data, report finds

NEW YORK TIMES NEWS SERVICE

January 10, 2006

Dr. Hwang Woo-suk, the South Korean researcher who claimed to have cloned human cells, fabricated evidence for all of that research, according to a report released today by a Seoul National University panel investigating his work.

The finding strips any possibility of legitimate achievement in human cell cloning from a researcher who had become an international celebrity and whose promise to make paralyzed people walk had been engraved on a South Korean postage stamp.

In his string of splashy papers, his one legitimate claim was to have cloned the dog he named Snuppy, the panel said.

"Dr. Hwang's team cannot avoid taking grave responsibility for fabricating its papers and concealing data," said Chung Myunghee, the head of the university's investigatory panel.

Last month the panel said there was no evidence to support Hwang's claim of June 2005 to have cloned cells from 11 patients with a new technique using very few human eggs.

But that still left the possibility that he had gotten the cloning technique to work to some degree, as he wrote in the report announcing his success in March 2004. The panel found that report was also fabricated.

The blow to the nation's scientific reputation may be cushioned because other South Korean institutions – notably the television program "PD Notebook" and a group of skeptical young scientists – took the lead in discovering the problems with Hwang's work and in forcing the university to investigate.

South Korean prosecutors have banned Hwang and nine other South Korean scientists from leaving the country and said they would investigate.

Stem cell cloning gets fresh start
UCSD, Burnham teams considering joint effort

By Terri Somers
Union-Tribune

January 11, 2006

California scientists are planning to jump into the field of cloning human embryonic stem cells now that a South Korean scientist who claimed to have mastered the technique has been exposed as a fake.

In San Diego, stem cell researchers at UCSD and the private Burnham Institute are discussing how together they could research the process that until recently was believed to have been mastered by a team at Seoul National University.

Scientists at the University of California San Francisco and Stanford University have also announced plans to get into the field. They plan to apply for funding from California's $3 billion stem cell initiative approved by voters in 2004. UCSD and Burnham may eventually do the same.

"My guess is that just about everyone who has a stem cell research center is going to jump into this," said Jeanne Loring, a stem cell researcher at the Burnham Institute in La Jolla.

All of the California research institutes stressed that in moving forward, they will follow the latest and strictest ethical guidelines to avoid the lapses uncovered in South Korea.

Researchers in that country claimed to have mastered a process for cloning embryonic stem cells, which theoretically would allow scientists to create patient-specific tissue that could be used to replace cells destroyed by diseases such as Parkinson's.

In 2004 and 2005, Dr. Hwang Woo-suk, a 53-year-old researcher at Seoul National University, published papers in the journal Science that claimed he had mastered the cloning technique.

Specifically, Hwang said he took DNA from skin cells of 11 patients and put them into the nucleus of eggs from women, creating embryonic stem cells of the patients.

In response, many other labs decided to direct their funding to other areas of embryonic stem cell research.

But Hwang's claims began to unravel in November when it was learned that he had used eggs secretly donated by women working in his lab, something most researchers consider a breach of ethics as the women could feel under pressure to do so.

An investigatory panel at Seoul National University said Monday that both of Hwang's papers were fabricated. The panel also said that Hwang used almost 2,000 eggs on his faulty research, rather than just hundreds he had reported using.

Now scientists aren't exactly sure what it will take to clone human embryonic stem cells, said Larry Goldstein, a stem cell researcher at UCSD.

"But we've been working with lots of different mammalian species for a long time – scientists have cloned mice cells and cow cells and the technique produced Dolly the (cloned) sheep – so most of us don't believe there's a magic ingredient," Goldstein said. "It's a matter of getting skillful people in the same place, a sufficient number of ovocytes and good quality donor cells to pull it off."

Between UCSD and Burnham, many of the pieces are in place for stem cell cloning research.

Burnham has an embryo bank with more than 800 fertilized eggs donated after they were left over at in vitro fertilization clinics. Burnham scientists have the ability to make, or grow, different lines of embryonic stem cells. And the institute has the equipment that would be needed, said Dr. Evan Snyder, who heads Burnham's stem cell program.

Neither Burnham or UCSD has anyone with experience with the process of transferring DNA into the nucleus of human cells.

Cloning human embryonic stem cells requires using many hard-to-acquire human eggs, which would make it "silly" to have two separate labs in La Jolla and not be communicating, he said.

"There's not enough research dollars to go around, so we might as well use what there is parsimoniously, and with intelligence, and not duplicate our efforts," Snyder said.

But the science won't proceed until all of the needed ethical constraints are in place, said Burnham's Loring.

"Imagine those 2,000 eggs (reportedly used by Hwang's lab) in the hands of someone honest and competent," Loring said. "We might have had a real breakthrough, but instead all of this is wasted. That's the greatest tragedy, and we don't want to repeat it."

It also won't be the only, or even the biggest, stem cell research program at the institute, she said.

"(Cell cloning) is important for certain situations, but it's not a panacea. And the projects done using it should be extremely and carefully chosen," she said.

Although California voters approved spending $3 billion of taxpayer money to fund stem cell research, the Burnham Institute and UCSD don't plan on waiting for those funds to be freed from legal challenges to start a possible collaboration, Snyder said.

"We're working on getting joint funding that would come sooner than Proposition 71," he said.

UCSF is also moving ahead with plans to conduct stem cell cloning research without taxpayer dollars, at least initially. The university is refurbishing a building that can be used for research that will be funded with $13 million of private money, university spokesman Jennifer O'Brien said. She said the university would likely seek Proposition 71 money later on to supplement its work.

From 1999 through 2001, scientists at UCSF tried to master the technique of cloning human embryonic stem cells. It was the only U.S. university pursuing the science.

The efforts were unsuccessful, so the labs never published results, O'Brien said.

Before Hwang's claims began to fall apart, Dr. Arnold Kriegstein, who runs the UCSF stem cell program, decided researchers should re-enter the field to try to improve upon the South Korean techniques or find others, O'Brien said.

Stanford intends to seek Proposition 71 funding to recruit scientists who will find ways to do nuclear transfer research, first in animal models and then with human cells, using the safest and most effective methods, said Dr. Irving Weissman, head of the stem cell program.

"In spite of this news from South Korea, I remain hopeful about the promise and potential of stem cell research," Weissman said.

Stem cell experts keep active while funds lag in limbo
Institute sidelined by court challenge

By Terri Somers
Union-Tribune

January 13, 2006

It will take at least 15 months for California's new stem cell institute to resolve court challenges and gain access to $3 billion that voters agreed to spend on the research, the institute's president said yesterday.

And that is if the institute wins the legal challenges, which question whether the program contains adequate controls over taxpayer funds.

The year-old California Institute for Regenerative Medicine is down to less than $4 million and expects to spend that by the end of June, without one cent going to research. It has already burned through $4.15 million, more than half the $8 million it has raised through a state loan and a philanthropic donation.

Faced with those realities, and the frustration of patient advocates who campaigned for the initiative in hopes of speeding the discovery of treatments for disease, the institute's leaders have devised a plan for staying afloat through 2006.

The plan involves raising more than $52 million in private donations, including a $2 million fund drive that started yesterday, said Zach Hall, the institute's president.

The goal is to put the entire infrastructure of the institute in place, so that when the funding becomes available it can be immediately dispersed among grant recipients and programs that would already have been vetted and approved, he said.

"We won't be spending the kind of money we would if we could (sell) bonds," Hall said yesterday. "But we are going to use this year to prepare as thoroughly as possible for when that bond money does become available."

Originally, the institute planned to hire a staff and simultaneously develop standards while slowly ramping up the grant-making process, beginning with small endowments for training programs and facilities.

Now, however, the institute is using its time in limbo to put its standards and strategic plans in place, get its computer systems installed and solicit applications for grant programs, he said.

"We want to hit the ground running once the money comes in," Hall said. "Rather than sending out a slow and gradual stream of funding, the plan now is to let a torrent of funding flow like waters set free from a sluice gate."

The image of a torrent worries Jesse Reynolds of the Center for Genetics and Society, a watchdog group that has been one of the toughest critics and most constant monitors of the institute. He wondered if there was enough good science to warrant such funding at this time.

But he was also somewhat comforted by the plan.

Originally, the institute's leaders talked about making their first grants last May, which Reynolds said was ludicrous. To hear them now talking about having their organizational infrastructure in place first sounds better, he said.

In November 2004, 59 percent of California voters approved Proposition 71, which allocates $300 million annually for the next decade toward stem cell research. The proposition is supposed to give preference to embryonic stem cell research, for which President Bush has severely limited federal funding.

Embryonic stem cell research is controversial because it involves the destruction of human embryos.

Last year, before the state could begin selling the bonds to fund the institute, consumer groups with ties to anti-abortion organizations filed lawsuits claiming Proposition 71 is unconstitutional.

The groups challenged the initiative on the ground that it lacks adequate government control over taxpayer dollars. The state has since been hamstrung, because it cannot sell bonds while there is a chance a court will find the proposition unconstitutional.

Meanwhile, patients advocates say the clock continues ticking for Californians with incurable degenerative afflictions such as Parkinson's and Lou Gehrig's disease.

"Obviously, I find the delays disturbing," said Diane Winokour, who has lost one son to Lou Gehrig's disease and had another diagnosed with it. "But what I find even more disturbing is that one small group of people, who represent a minority opinion and who lost at the polls, can reverse the action of all the rest of us who won at the polls by pursuing lawsuits nonstop."

Outside the courtroom, institute leaders have pushed forward. But they have been mindful that items previously high on their to-do list will have to wait.

For instance, the institute has hired a staff of 19 to date. It had expected to hire up to 50.

Institute Chairman Robert Klein has been trying to raise $50 million in philanthropic donations to make good on the grants and the institute's bills. The donation would be repaid if the institute prevails in the court challenges.

Yesterday, the institute started a separate fundraising effort for monetary gifts that would allow it to pay for nongrant scientific activity, Hall said.

For example, the institute plans to hold conferences, including one in May at which national gynecological and obstetric experts would be invited to discuss the medical risks of egg donation and how to reduce them.

Discerning stem cell hype and hope

By David A. Shaywitz, an endocrinologist at the Harvard Stem Cell Institute

January 13, 2006

The apparent fabrication of results by South Korean researcher Hwang Woo-suk already has prompted a serious re-evaluation of stem cell science, and the release this week of Seoul National University's final report on the affair is certain to add fuel to the fire.

Many detractors of stem cell research (and, privately, even some proponents) have begun to wonder whether this might mark the beginning of the end. More likely this controversy – and the ensuing scrutiny and self-reflection – will provide exactly what our discipline needs most: the opportunity to modulate the extravagant expectations for this research while we reaffirm our underlying commitment to it.

The rapid ascent of stem cell research into the spotlight reflects the collision of exciting science with uncharted ethics. President Bush's Aug. 9, 2001, prohibition on the use of public funds to create new human embryonic stem cell lines ignited interest in this field, even as it made it much more difficult for American scientists to conduct the research. The concern that important medical science was being deliberately thwarted by the federal government enraged many patient advocates and further ratcheted up the demand for results.

Meanwhile, stem cell research itself trudged ahead slowly, for all the usual reasons – as well as some unique ones. Scientific research is notoriously difficult, and progress typically incremental; human embryonic stem cells also happen to be intrinsically difficult to grow. Moreover, government restrictions severely hampered the ability of researchers to pursue the best science and discouraged many bright young investigators from entering the field.

As the demand for results far outstripped the ability of researchers to supply them, a seller's market emerged in which goods were overvalued and even low-quality merchandise was snatched up by eager buyers. This is the context in which Hwang's studies appeared.

While most in the field of stem cell research were shocked by the reports of fraud, the shock was only one of degree; it is common knowledge that the bar for publication in this field often has appeared remarkably low, with even well-respected research journals seeming to fall over one another for the privilege of publishing the next hot paper. The result of this frenzy has been an entire body of literature that is viewed with extreme skepticism by most serious stem cell investigators.

The good news is that underneath all this mess, stellar science really is happening. Stem cells have proved even more captivating than we could have imagined, and understanding the process by which a stem cell progressively differentiates into a specialized cell such as a neuron or a pancreas beta cell is perhaps the most compelling biology question for our generation.

But we're not going to figure out how they work overnight; it will take a very long time and require our best minds, as well as our collective effort (and, ideally, our collective dollars). Translating this knowledge into clinically meaningful applications is certain to take even longer and present still more challenges – yet it should be achievable. If the current controversy were to cause us to precipitously abandon this exciting area, it would be a catastrophic shame.

What we really need is to refine our expectations for this research. This doesn't mean we should scale back our ambitions or demand less of our researchers. Rather, we need to recognize just how arduous and painstaking good science usually is and remind ourselves that data do not become dogma when published, but only when independently validated.

Difficult or not, good research is the only responsible way to proceed. If the promise of stem cells is to be fulfilled, the pursuit will require a solid scientific foundation, one grounded in reliable, reproducible facts and not simply supported by hype and hope.

Group wants head of stem cell initiative to quit
Center says chairman has misled the public

By Terri Somers
STAFF WRITER

January 19, 2006

A public watchdog group called yesterday for the chairman of the board overseeing California's stem cell initiative to step down for allegedly misusing his position "in ways that have significantly undermined the (public's) trust and confidence."

The Center for Genetics and Society accused stem cell Chairman Robert Klein of misleading the public about the financial return and health benefits it would receive in return for its $3 billion investment in stem cell research.

In a scathing report analyzing the initiative's first year, the center said the oversight board has failed to adopt policies that would ensure Californians are guaranteed access to affordable therapies that might be developed with their tax dollars.

The center, which has been a constant critic of the initiative, said Klein's departure alone would not address the many problems with the implementation of the initiative. But the report said it would "open the door for the accountable and responsible leadership that is prerequisite for the needed changes."

The center gave the stem cell program an overall grade of C-minus for its first year. Klein got a D for leadership.

Klein was unavailable for comment yesterday, but a spokeswoman for the stem cell initiative was unfazed by the call for his resignation.

"They've been objecting to his being chair all along. (Klein's) not going to resign because of that," said Nicole Pagano, a spokeswoman for the California Institute for Regenerative Medicine. The institute was formed to administer up to $300 million annually in taxpayer-funded stem cell grants.

The nonprofit center has opposed the stem cell initiative known as Proposition 71 since its inception. Its report is essentially a rehash of criticism it has leveled at the stem cell initiative since it was first proposed for November 2004 ballot.

Topics of concern outlined in the report included conflict of interest issues, the lack of legislative oversight and failure to provide taxpayers a return on their investment and to provide adequate protection for women who donate eggs for stem cell research.

Additionally, the report refers to the stem cell cloning scandal now unfolding in South Korea, where a renowned scientist apparently faked data to support his claims that he could clone human embryos. Pressure to produce successful results from much-hyped stem cell research contributed to the fraud in South Korea, and could just as easily contribute to fraud in the United States, said Jesse Reynolds, an author of the report.

Pagano of the stem cell institute said California's effort should not be compared to South Korea's, where most of that government's money went to one lab and there was not enough objective oversight.

The center, Pagano said, should be reminded that 59 percent of voters approved the initiative.

"Despite the overwhelming support of the voters, they are up to the same old thing – criticism-based activism," she said of the center's report.

Marcy Darnovsky, the center's associate executive director, criticized the institute for attempting to rush grant money to scientists before it had all of its policies and standards in place. For example, the report lambastes the institute for its lack of policies protecting women who donate eggs for stem cell research.

However, the institute has been working to develop such a policy. It plans to hold a conference on the topic in May, which would involve national gynecological experts.

Watchdog suggests stem cell policies for state
Discoveries should benefit taxpayers, foundation says

By Terri Somers
Union-Tribune

January 23, 2006

A taxpayer watchdog group is expected to release a report today outlining how leaders of the state's $3 billion stem cell initiative could develop policies to make stem-cell-based therapies affordable and accessible to Californians.

Leaders of the initiative known as Proposition 71 "must put the interests of taxpayers and patients ahead of private biotech companies who have (a) financial stake in the outcome," the Foundation for Taxpayer and Consumer Rights said in its report.

For example, a portion of the money the state raises by licensing scientific discoveries made with Proposition 71 funds should be used to make new therapies available to people who can't afford them, the foundation report states.

Biotechnology or pharmaceutical companies that develop therapies using science that results from Proposition 71 should be required to sell those therapies to California at their lowest price, the report states.

It also recommends that the institute reserve the right to keep a Proposition 71-funded discovery from being patented if it is determined that it would do more good by remaining in the public domain.

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In addition, it suggests that the state create a pool of all patents resulting from Proposition 71 so that companies seeking to license those patents would have easy, one-stop shopping. The foundation suggests that the pool be controlled by an appointed, three-person board.

The release of the foundation's report coincides with a meeting today of the task force assigned to develop ownership rules of the scientific discoveries that result from Proposition 71-funded research. The scientific discoveries are commonly referred to as intellectual property, or IP.

Members of the task force include university administrators, scientists, venture capitalists and patients' advocates. All task force members also serve on the 29-member board overseeing implementation of Proposition 71.

In November 2004, voters approved Proposition 71, which allocates $300 million from taxpayers annually to stem cell research over the next decade.

Ed Penhoet, a former biotechnology executive who heads the task force and is vice chairman of the Proposition 71 oversight board, declined to comment on the foundation's report before the task force meeting.

The task force will present its recommendations to the entire oversight board.

Some of the foundation's recommendations are similar to ideas already being discussed by the task force. For example, the task force is interested in retaining "march in" rights to all Proposition 71-related discoveries. If a company licensed Proposition 71-funded IP and did nothing with it, the state would have the authority to come in and take back the intellectual property.

The foundation isn't the only organization offering input on intellectual property policy. The California Council for Science and Technology, a panel of scientists and executives from biotechnology and pharmaceutical companies, also has issued a report suggesting policies for handling IP.

Its report suggests that the stem cell initiative use the federal IP policy, known as the Bayh-Dole Act of 1980, as its model. The act allows a research institution or university to retain ownership of discoveries it makes during research funded by taxpayers.

Ownership gives the institution the right to patent a discovery and license it to others who are looking for new drugs or therapies.

John Simpson, author of the foundation's new report, said Bayh-Dole would charge taxpayers twice for therapies: once when their money is used for grants that fund research and again when they pay for high-priced drugs based on the research.

"Everyone agrees that Bayh-Dole is flawed, so why embrace it?" Simpson asked. "California has the opportunity to get it right and be a model for the nation, as other states consider funding stem cell research."

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me@rescam.org

Learning from stem cell stumbles

By Jesse Reynolds; director of the biotechnology accountability project at the Center for Genetics and Society, a public interest advocacy group that supports the public funding of embryonic stem cell research.

January 27, 2006

The leaders of California's ambitious stem cell research program should closely read the news of the last couple months. A scandal including fraud, lies and cover-ups has ended the careers of scientists in South Korea, including Hwang Woo-suk, one of the prominent stem cell scientists in the world.

Hwang's American collaborators are now under investigation at their own universities. One of them, Jose Cibelli, sat on the committee developing research standards for California's program. Although Cibelli “has voluntarily withdrawn from his activities,” he did so only last week – two months into the scandal.

It is now clear that Hwang's groundbreaking announcements of the last two years were almost entirely fabricated. What's more, he obtained thousands of eggs from women in a variety of unethical and illegal ways.

Many commentators initially downplayed the relevance of the scandal, framing it as a single rotten apple in a distant foreign barrel. But that's not the case.

The stem cell research atmospheres in South Korea and America – especially California – are quite similar. There's nothing that happened there that can't happen here.

First, the discourse in both countries is dominated by inflated hopes for the research – hopes that are created and stoked by scientists making irresponsible promises of imminent cures. Just as Hwang publicly promised a 10-year-old boy in a wheelchair that he would soon walk, a stem cell researcher in an ad for California's Proposition 71, which created our $3 billion program in 2004, said “When a 7-year-old girl comes up to me and she's scared, and she says, 'Will stem cells be an answer for me? Will they be a cure for me?' I'm absolutely confident in saying that, 'This will happen.' ”

Second, in both countries researchers and companies are in competitive races for prizes and patents. The Nobel Foundation does not issue a runner-up prize for second place.

There is no longer a distinction between scientists and entrepreneurs, as researchers mix scientific objectives with potentially hugely profitable enterprises. Hwang kept busy filing patent applications for his “discoveries.” And here, stem cell researcher David Baltimore sits on the governing board of California's program while he is a principal in a company dedicated to commercializing stem cell therapies. Haste and conflicts of interest inevitably lead some to cut scientific and ethical corners.

Third, the governments of South Korea and California are lavishly spending public money with far too little public oversight and control. Hwang's lab received tens of millions of dollars from the Korean government in recent years. Meanwhile, the South Korean president's science adviser had been given co-authorship on Hwang's publications and had even received money from his lab. When the president of California's stem cell research program was asked how to prevent such a scandal here, his answer was more science, not more oversight. He failed to note that Hwang's shortcomings were made public by investigative journalists, not scientists.

Finally, neither the public nor political leaders in either county has come to grip with what's at stake. The new human genetic technologies are giving scientists the power to change the nature of human life forever, and are being developed at breakneck speed.

Unfortunately, the leaders of the stem cell research program here in California are missing an opportunity to learn from the mistakes of others. For example, at the most recent meeting of the program's advisory committee to develop research standards, the members passed quickly over the unfolding stem cell and cloning research scandal.

Instead, they searched for loopholes in Proposition 71 that would allow them to pay women to provide eggs for research – a practice that would encourage economically vulnerable women to undergo risky procedures to pay the bills, and precisely one of Hwang's violations. This is the committee that included Cibelli, Hwang's American collaborator under investigation.

The Center for Genetics and Society has just issued a progress report on the first year of the program. After evaluating its performance in nine areas, we gave the program an overall grade of C-. The program's governing board is rife with conflicts of interest. Its leadership resisted calls for open meetings, and rejected a cooperative relationship with the Legislature.

This is particularly unfortunate because California could be in a position to adopt standards, policies and regulatory mechanisms that could serve as a model for the rest of the country – rather than the situation we're in now, in which California's stem cell research is best understood as a cautionary tale.

On issue after issue, the leadership of California's stem cell research program argue that strong polices standards might sound good, but they will slow the research. But the result is that the program has put moving rapidly over moving responsibly.

Stem cell research regulations mulled
Egg donors would be reimbursed, not paid

By Sandi Dolbee
Union-Tribune

February 1, 2006

LOS ANGELES – Women who donate eggs for state-funded embryonic stem cell research could be reimbursed for their expenses, including lost wages, under recommendations approved yesterday by a committee charged with setting medical and ethical standards for California's $3 billion stem cell research initiative.

The proposed regulations prohibit state-funded projects from paying donors for eggs, which complies with Proposition 71, the initiative approved by California voters in 2004 to jump start embryonic stem cell research through a decade of public funding.

“This is very complicated. It's going to be controversial,” acknowledged Bernard Lo, a medical ethicist at the University of California San Francisco and co-chair of the Scientific and Medical Accountability Standards Working Group, one of the advisory committees established by Proposition 71.

Lo, however, dismissed suggestions that reimbursing women for lost wages is a slippery slope toward creating a for-profit market that could coerce poor women into selling their eggs.

Zach Hall, president of the California Institute for Regenerative Medicine, the agency created to implement this initiative, said the guidelines drew that distinction. “Reimbursement is appropriate. Compensation is not,” Hall said.

The recommendations, covering topics ranging from informed consent of donors to the make-up of individual oversight committees, was hammered out Monday and yesterday in a Bel-Air hotel conference room by scientists, ethicists and patient advocates who make up the 19-member Scientific and Medical Accountability Standards Working Group.

The advisory group's 10-page draft guidelines now go to CIRM's governing board, which meets Feb. 10 at Stanford University. Seven months in the making, the proposed regulations were hailed by committee members as a model for other states wading into stem cell research.

Co-chair Sherry Lansing, the former chairwoman of Paramount Pictures, called the draft “the strongest regulatory package in the country.”

But some in the audience were not as gung-ho. “I think this compliance section is pathetically thin,” Susan Berke Fogel, founder of the Pro-Choice Alliance for Responsible Research, who wanted more specifics about enforcing the rules.

Perhaps the strongest section of the draft regulations involves informing potential donors about everything from the possible medical risks to how the stem cell lines might be used for undetermined future studies. Donors also will be told they will not receive financial benefits from any future commercial uses.

Even as members worked to ensure safeguards, the shadow of scandal hung over them.

Absent from this week's sessions was committee member Jose Cibelli, a researcher from Michigan State University who recently withdrew from participation pending the outcome of an academic review over a paper he co-authored with Dr. Hwang Woo-suk, the South Korean scientist who apparently faked studies about creating the first-ever stem cell lines from cloned human embryos.

“None of us should draw judgment on this until we know the facts and the investigation (of Cibelli's work) is complete,” said Lansing, noting that Cibelli himself requested the university look into his part in the apparently tainted study.

As for California, Lo admitted that there are no guarantees that similar wrongdoing could not happen here. “But we think this goes as far as you can go to protect against that without totally stifling research.”

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me@rescam.org

State's stem cell institute adopts 2 ethics policies

By Terri Somers
Union-Tribune

February 11, 2006

PALO ALTO – California's stem cell institute yesterday adopted two controversial but key policies that set ethical standards for research and establish a mechanism for taxpayers to recoup some of their $3 billion investment.

“I think you'll find that (both policies) go above and beyond national and state standards. . . . I believe we are setting a new standard that the rest of the country and the world can follow,” Zach Hall, president of the institute, told its governing committee at a meeting yesterday.

For example, the ethical standards require that women donating eggs for embryonic stem cell research be informed of possible health risks and of how their donations will be used.

The use of the eggs also must be reviewed and approved by two review boards. Also, the physician performing the egg extraction cannot be a principal investigator in the stem cell research.

Despite attempts to make both policies tougher than existing standards, as well as numerous public meetings to discuss both, opposition from the public and from state legislators remains.

The institute's governing committee has several months to change both policies and will hold further public hearings.

The policy regarding ownership and sale of state-funded discoveries, also known as intellectual property, creates the mechanisms by which cutting-edge science will be dispersed. It also dictates how taxpayers could be reimbursed for approving the stem cell initiative known as Proposition 71.

“The devil is in the details; that's why people's eyes glaze over when they hear the term intellectual property,” said John Simpson, a spokesman for the Foundation for Taxpayer and Consumer Rights. “This is really about who has access to cures. Ultimately, these rules could determine whether a person can afford cures or not.”

Overall, the policy adopted yesterday is similar to the federal Bayh-Dole Act of 1980. Under that law, scientists at research institutions nationwide get to keep money they make on discoveries using taxpayer dollars.

But the state policy differs from the federal in directing how a cut of the profits from taxpayer-funded research should be returned to California coffers.

Under the policy, stem cell grant recipients can keep $500,000 of their net revenue from licensing a discovery. After that, the recipient must give 25 percent of net revenue to the state.

The policy also requires broad sharing of institute-funded research. Even if a research institution patents a discovery, it must make that discovery available at no charge to other institute-funded researchers.

But Joydeep Goswami of Carlsbad-based Invitrogen said such broad sharing of discoveries is eliminating avenues for commercialization. Invitrogen is a major biotechnology tool company that sells to academic research institutions.

Stem cell policy - Ethical measures strengthen state efforts

UNION-TRIBUNE EDITORIAL

February 14, 2006

The California Institute for Regenerative Medicine, the agency set up under Proposition 71 to oversee a $3 billion stem cell research effort, has been roundly and rightly criticized for its less-than-open operations. That, combined with a lack of government oversight, has led to lawsuits which so far have prevented the agency from beginning its work toward finding cures for degenerative conditions such as Alzheimer's disease, spinal cord injuries, severe burns and Parkinson's disease.

But in a daylong meeting at Stanford University on Friday, the 28-member CIRM board went a long way toward helping to build public trust by adopting sound policies in two critical areas.

The first set of policies seeks to help determine how much a return on their huge investment California taxpayers can expect. Under these policies, stem cell grant recipients will be able to keep the first $500,000 earned from any licensed discoveries. After that, researchers must share 25 percent of net revenues with the state.

During the campaign for Proposition 71 in 2004, proponents promised that when and if taxpayer-funded research generated marketable products, the public would benefit. The oversight committee appeared to have been looking at a more flexible standard, but in the end it adopted the more clearly defined policy.

The second policy area concerns covering expenses for women who donate eggs for stem cell research. Scientists use eggs to grow stem cells, and most that can be used outside federal funding restrictions are obtained from those left over from in vitro fertilization efforts. It is the use of cells from human embryos a few days old that is at the center of controversy, with some critics claiming this research amounts to the taking of a life.

What oversight committee members were trying to avoid was providing any kind of financial incentive for women to donate eggs. The policies adopted would prohibit any form of payment, except for expenses incurred, including medical expenses if complications occur.

Since Proposition 71 prohibits legislative oversight for the first three years of the institute's existence, taxpayers must depend on the private oversight committee to do what is in the best interests of research and taxpayers. A lawsuit challenging the independence of the institute will be heard in Alameda County Superior Court later this month. The lawsuit effectively denies research funding for the institute until the case is settled, perhaps early next year.

In the meantime, the institute's oversight board must work to insure transparency and to make sure the rules under which the research is conducted are clear, fair and, most of all, morally and ethically sound.

STEMSELLs Science Hoax and Joke with media hype.

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May we All have a METAMORPHOSIS. REASON. GOoD JUDGEMENT and LOVE and ORDER!!!!!

Opening statements are made in trial over fate of state's stem cell initiative

By Terri Somers
Union-Tribune

February 28, 2006

HAYWARD – Arguments over whether California will spend $3 billion in taxpayer money for stem cell research began yesterday in a tiny San Francisco Bay Area courtroom crammed with lawyers, the media and about a dozen patients' advocates, some in wheelchairs.

During opening statements in the non-jury trial, a lawyer for critics of the plan said it is unconstitutional and doesn't represent the will of the people. Lawyers for the state accused the critics of using a “tortured interpretation of the constitution.”

The case involves two groups – the California Bioethics Council and People's Advocate – that filed separate lawsuits arguing that the stem cell initiative voters approved in 2004 is unlawful because state officials do not oversee the spending of taxpayer dollars.

An attorney for the bioethics council, David Llewellyn, said he would show Judge Bonnie Lewman Sabraw how those behind Proposition 71 over-hyped its potential and misled the voters to win approval in November 2004.

In defending the initiative, Deputy Attorney General Tamar Pachter said the plaintiffs weren't happy with the results at the ballot box and seek to use the court to change the outcome.

The lawsuits were filed last February, preventing the state from selling bonds to support the initiative until the courts have ruled.

The initiative and the stem cell institute it created have survived on a $3 million state loan and a $5 million donation from sound pioneer Ray Dolby and his wife. That funding will run out in June, without a dime having gone to researchers.

In November, the judge refused to toss out the lawsuits, but said the taxpayer groups had a high legal hurdle to prove the initiative was “clearly, positively and unmistakably unconstitutional.”

Robert Taylor, a lawyer for the People's Advocate, said yesterday he would meet that threshold, in part by making an example of the process used to decide who would get the initiative's first round of grants, which are for training new scientists in stem cell research. Although recipients were chosen last September, the state hasn't awarded the grants pending the litigation.

The state contends the decision for the disbursement of stem cell funding is the responsibility of a 29-member oversight board, whose members were appointed by elected state officials. But first, a working group of non-California scientists examines grant applications before recommending to the oversight board which applicants should receive the money.

Taylor said it's the working group who makes the decision on how taxpayer money is spent. And when some of the working group members could not make their meeting, alternates they had chosen replaced them. “This puts us even farther away from state control,” Taylor said.

Taylor told the court yesterday he would call no witnesses. Instead, he said, he would prove his case using campaign literature, initiative documents and excerpts of depositions taken from members of the oversight board.

Stem cell institute leader says state agencies in control
Constitutional questions at trial

By Terri Somers
Union-Tribune

March 1, 2006

HAYWARD – The constitutional argument at the heart of a legal challenge to California's stem cell institute took center stage here yesterday when a lawyer for the state questioned the institute's leader about whether state officials would have adequate control over stem cell spending.

Robert Klein, chairman of the committee overseeing the stem cell effort, testified about the numerous meetings he and other institute officials have had with state legislators, the state treasurer, the state controller and the governor.

Klein also testified that suggestions made at those meetings, as well as input from the public, helped direct policy of the institute, which plans to make $3 billion in taxpayer funds available for stem cell research in California.

“I'm thoroughly under the control of a spectrum of agencies of the government of the state of California,” Klein told Deputy Attorney General Tamar Pachter on the second day of a trial in state Superior Court.

Pachter is defending the institute and Proposition 71, the November 2004 voter initiative that created it, against lawsuits filed by the People's Advocate and the California Family Council on Bioethics, which describes itself as a stem cell watchdog organization.

Both lawsuits allege that Proposition 71 is unconstitutional because state officials are not controlling the $300 million the institute can spend annually over the next decade.

The lawsuits, filed a year ago, have been preventing the state from selling bonds to fund the institute.

In November, Judge Bonnie Lewman Sabraw refused to toss out the lawsuits, but said the taxpayer groups had a high legal hurdle to prove the initiative was “clearly, positively and unmistakably unconstitutional.”

There wasn't much testimony about constitutional issues during the trial's opening day Monday, when the lawyer for the bioethics council called Klein to the witness stand.

Instead, lawyer David Llewellyn spent much of his time focusing on conflict-of-issue policies for the institute's governing body and the working group that reviews grant applications before recommending whom the governing body should fund.

Pachter spent Monday morning questioning Klein about the involvement he and the institute have with state officials. Under her questioning, Klein said the working group serves only in an advisory capacity to the governing board.

After reviewing the working group's recommendations concerning who should get the institute's first round of training grants, the institute's governing body changed at least 20 percent of what the group had suggested, Klein said.

Yesterday, after Pachter was done questioning Klein, the plaintiffs' lawyers asked him about legislation introduced last year by Sen. Deborah Ortiz, D-Sacramento, that sought to give the Legislature more control over the initiative spending.

The governor vetoed that legislation because the initiative states that the elected officials cannot change Proposition 71 for the first three years, Klein said. However, the institute's governing body has since agreed to a legislative audit that Ortiz wanted, and drafted Proposition 71 policies to include transparency and accountability that she and other legislators wanted, he said.

Stem cell work steps forward in San Diego - Lab in secret location banks donated embryos

With stem cells, first-step success is not guaranteed