Conflicts of Interest: From Press Releases to Matching Funds

For those of you who may have forgotten -- at least 14 members of the 29-member Oversight Committee come from institutions that could benefit from the roughly $300 million in proposed grants from CIRM to build research facilities. The committee will decide which instititions receive the cash and under what terms. Members, however, are forbidden from voting on grant applications from their own institutions.

Those built-in conflicts of interests at the California Institute for Regenerative Medicine surfaced today during a discussion concerning the grants and the process of issuing press releases about CIRM-funded research.

Just what should CIRM require from medical schools and other institutions that receive grants for multimillion dollar laboratories? The law requires that applicants must secure matching funds from other sources that equal at least 20 percent of the award. But how that credit is calculated is yet to be determined. Applications will not be submitted for many months, and fundraising is already underway. So the issue of what expenditures made now or even earlier can be counted as matching funds is not an insignificant matter for the deans of the medical schools and others who are raising the cash.

Also up for debate was a provision that would favor grants to institutions that propose a higher matching percentage.

Given their responsibilities to the institutions they work for, some of the deans wanted to be sure their fundraising efforts and money for initial building plans would not be wasted. Some also noted that an early clarification of the issue would mean meaning speedier construction, a goal that CIRM advocates.

Brian Henderson, CIRM Oversight Committee member and dean of the USC School of Medicine, said favoring institutions offering higher matching funds could lead to a "ridiculous escalation" in which schools try to outbid each other. David Baltimore, CIRM Oversight Committee member and president of Caltech, noted that a bidding war disadvantages "poorer" institutions. He favored a straight percentage.

Also disturbing some directors of the agency were grant criteria that would consider the geographic location of applicants within California with an eye to assuring that facilities are available to researchers throughout the state.

Baltimore said the board is "too conflicted" to consider geography. But Henderson said, "Reasonable geographic distribution is a laudable goal." Gerald Levey, an Oversight Committee member and dean of the School of Medicine at UCLA, opposed the use of geography as did Oswald Steward, chair of the Reeve-Irvine Research Center at UC Irvine.

The press release issue can be crystalized in the following manner: Should recipients of $10 million grants, or for that matter any size, be required to "coordinate" with CIRM press releases on the results of the taxpayer-funded research.

Baltimore, who brought up the proposed requirement, said it "was an inappropriate transgression of the independence of (our) institutions." It was a sentiment heatedly defended by others at various institutions.

However, Jeff Sheehy, Oversight Committee member and deputy director for communications at the UCSF AIDS Research Instititute, said coordination on press releases was not an onerous requirement and would help protect CIRM. Ultimately he dropped his opposition to removing the language, declaring that the board was wasting time on the matter in extended debate.

Our point – for now -- about these discussions is not which position prevailed. What is important is that the directors of the $6 billion California stem cell agency are setting the terms of contracts that could benefit their institutions.

The directors are not in a good place. When a director votes, one can imagine him or her thinking: Whose interests do I serve? My employer's? The person who appointed me? The groups I am supposed to represent? CIRM's interests? Or the people of California?

Some of these issues are found in other segments of state government but rarely to the degree they are found on the Oversight Committee of the California stem cell agency. And it is all legal, courtesy of California voters, who created this situation in 2004 when they approved Prop. 71. Nonetheless, for those affected by CIRM and who follow its activities, understanding the conflicts and how they can affect multimillion dollar decisions is an imperative.

By the way, the matching fund issue comes up again at the Oversight Committee meeting in December. The geographic criteria was retained on a 15-10 vote. And grant recipients can ignore any coordination efforts on press releases. The offending press release language, which has been around for months, was removed, triggering another delay in official adoption of the regulations.

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Coming Up Tonight

Sometime in the next few hours we will post an item on today's meeting of the Oversight Committee of the California stem cell agency. It will look at the institutional but legal conflicts of interests that many of the members of the committee have.

Few Complaints Voiced on CIRM Strategic Plan

The California stem cell agency's proposed plan for spending $3 billion on stem cell research received its first real screening tonight, and the audience seemed nearly enamored with the effort.

A few minor questions were raised along with some remarks that could be construed as slightly critical, but generally the comments were along the lines of "extraordinary work product" and "outstanding document."

The screening of the plan occurred at a meeting of the CIRM Oversight Committee, a few miles from Hollywood at the Luxe Hotel on Sunset Boulevard. The proposal comes up for consideration again at another meeting of the committee on Wednesday.

CIRM President Zach Hall walked the audience – the 29-member Oversight Committee – through the document that he and his staff have been working on for about a year. He noted that is a "living plan" and subject to change by the committee, which is not expected to give it a final nod until December. Even then, he proposed that it be reviewed regularly and altered to meet changing needs and opportunities.

While the document contains specific figures, Hall said those are not "immutable" and were intended to be approximate. Final approval of grants is also in the hands of the board – not the CIRM staff.

Hall did highlight one aspect of the plan's special programs – collaborative research and disease teams that would cross multiple institutions and disciplines. They would be tightly focused and managed and encouraged to have a professional manager to push the project along. The plan envisioned $122 million for the disease team program and $60 million for the research team effort. (See page 87 of the plan.)

Oversight Committee member Claire Pomeroy, dean of the UC Davis School of Medicine, and others asked for insertion of language specifically discussing the funding of embryonic stem cell vs. adult stem cell research and human vs. nonhuman research.

Ted Love, another Oversight Committee member and president of Nuvelo, said safety should be an "extraordinary priority" of the plan. "Nothing creates a crisis like safety," he said, referring to public alarm that occurs when human experiments go awry.

Other board members emphasized the need for a top notch public education and communications effort. Committee member Joan Samuelson, president of the Parkinson's Action Network, said that the agency can "succeed only if they (the public) are with us." The plan suggests spending $4.5 million for "public outreach." (See page 105.)

John M. Simpson, stem cell project director for the Foundation of Taxpayer and Consumers Rights and often a critic of the agency, praised the plan's realism and outreach. But he reminded the board,

"At the end of the day the best scientific plan is meaningless unless there are guarantees for affordable access to cures and treatments."

While plaudits were handed out liberally during the evening meeting, the biggest round of applause came following testimony from another member of the public, Roman Reed, who is paralyzed as the result of a football accident.

He said he had told his young son that one day they would walk side by side.

And then Reed told the CIRM board,

"I believe that one day you will make my promise to my son come true."

Some Aussies Less Than Enthusiastic About CIRM Plan

While California stem cell directors heaped huzzahs on a proposed plan on how to spend billions on embryonic stem cell research, a different reaction came from half-a-world away.

BioEdge, a blog of the Australasian Bioethics Information website, carried a piece headlined "California Dreaming." It said, in part,

"Californian voters approved a $3 billion bond issue to finance the institute in 2004. With interest, the cost to the state will be about $6 billion. Now, it appears, that the Institute may have nothing to show for its efforts in cures or in royalties by the time it folds its tent and silently steals away. (The word royalties is not mentioned once in the entire (strategic plan)...."

Wisconsin Gives $1 Million to Thomson Firm, More Tidbits on WARF Patent Flap

The Cheeseheads have thrown down another stem cell gauntlet.

Here is the latest as reported by Kathleen Gallagher of the Milwuake Journal Sentinel:

"Stem cell pioneer James Thomson and two others have started a second company that aims to grow platelets and red blood cells from embryonic stem cells.
"The company, called Stem Cell Products Inc., believes it has a chance to be among the first in the world to bring an embryonic stem cell-related therapeutic to market."

Gallagher said that the state of Wisconsin has given $1 million in grants and loans to the firm, which was co-founded by University of Wisconsin-Madison researchers Igor Slukvin and Dong Chen and venture capital firm Tactics II Ventures.

Wisconsin-California relations also surfaced in a piece by Cathy Tran in The Scientist magazine. The article was a wrapup of the WARF patent flap. But it also had some interesting tidbits.

Tran wrote:

"(California stem cell scientist Jeanne) Loring said the first person to isolate human stem cells was Ariff Bongso at the National University of Singapore in 1994.

"That begs the question why, if the leap to cultivating human stem cells was an obvious one, it wasn't done sooner. Bongso told The Scientist that the scientific community seemed disinterested in the discovery, and so he did not pursue the research further.

"Loring said the first human embryonic stem cell line wasn't created until 1998 in part because the National Institutes of Health did not fund research on human embryos before 2001, which made it 'pretty close to impossible' for any U.S. academic lab to derive human embryonic stem cells. In addition, it was 'not easy to find an in vitro fertilization clinic that wanted to go to the trouble of providing embryos for this research.'

"Thomson, however, maintains that his discovery was far from obvious. 'In the early 1990s, when we started this work, it was not at all clear that the isolation of human embryonic stem cells was really possible, as other groups had tried and failed,' he told The Scientist in an email.

"One of the groups that tried and failed included researcher Michael West, CEO of Advanced Cell Technology and founder of Geron Corporation. 'From firsthand painful experience, [the techniques were] not obvious in the scientific community,' West told The Scientist. The challenge based on the discovery being obvious 'is easy in retrospect, but you really have to base it on real firsthand experiences of the people in those days.'"

CIRM Hires Finance Director

The California stem cell agency has hired University of California official Lorraine Hoffman as its chief finance and administrative officer, effective Nov. 1.

CIRM's press release, which is expected to be up on its site later today, said that Hoffman will be responsible for budgets, independent audits and human resources at the agency as well as assisting on facilities grants.

Hoffman is currently deputy to the senior vice president for business and finance for non-state capital development and facilities in the UC syste, office of the president.

CIRM to NIH: Forget You?

Optimistic Democrats and some stem cell scientists believe that this fall's elections are part of a trend that will trigger a veritable torrent of funding for embryonic stem cell research. But that amounts to little more than wishful thinking.

Certainly funding may increase somewhat if the political winds shift to a favorable direction, but there is no guarantee of that. Even with a president in 2009 who might support stem cell research, enormous federal budget deficits will continue to plague the country, and optional research is not likely to suddenly surmount that obstacle.

Moreover, California has embarked on a go-it-alone course that other states are emulating. California's position was reinforced in the draft of its strategic plan that will receive a full-blown hearing in Los Angeles on Tuesday and Wednesday. The actions by California and others are making the NIH – dare we say it – a tad irrelevant, at least in terms of embryonic stem cell research.

Writing in the blog of the American Journal of Bioethics,
James Fossett of the Rockefeller Institute’s Federalism Research Group noted that CIRM's plans include creation of "NIH-free zones." That will cost $250 million, compared to NIH funding currently of about $30 million annually for ESC research. Fossett wrote:

"While perhaps wasteful and inefficient in the short run, such expenditures ultimately mean that California can formulate its own policies around what goes on in those labs without having to care very much about what the feds do or don’t do. It also means that other states contemplating stem cell research programs funded with their own money are likely to look to Sacramento, rather than Washington, for guidance on how to manage conflict of interest, egg procurement, royalty income distribution, intellectual property and the other complex ethical and legal issues that surround this research."

He continued:

"The development of funding streams independent of Washington and dedicated research infrastructure free of federal funding restrictions means that if federal policy makers do decide to do something definitive on stem cell research, it may not have much effect on anything. Having spent the money on new facilities and done the political heavy lifting to get ethical and commercial agreements in place, states, companies and universities may well decide that they like things the way they’ve got them and they don’t need to pay attention to the feds."

Indirectly supporting Fossett's position was a Sept. 1 column in the Wall Street Journal by Sharon Begley. The piece focused on the impact of tight funding at NIH. The headline read: "A Smaller NIH Budget Means Fewer Scientists And 'Too-Safe' Studies."

Begley wrote that in 2004

"...Congress and the White House, calling for reduced budgets in the wake of tax cuts and a growing deficit, slammed on the brakes. Ever since then, NIH's budget has been flat or, adjusting for inflation, down. The chance that a scientist's work will be funded fell to 22% last year from 27% in 1995, and to less than 10% in some fields. Now the warnings are coming true: The plug is being pulled on promising research by scientists with solid track records.

"'When 27 percent of proposals were funded, it wasn't that hard to separate the top quarter, says molecular biologist Keith Yamamoto of the University of California, San Francisco. 'There was a natural cutoff,' he says. But at 10 percent 'the ability to distinguish a grant that deserves funding from one that does not vanishes. It becomes a crapshoot, with every grant in jeopardy.'"

The NIH and its enormous sway over research will not disappear any time soon. But it is an aging insitution, hobbled by its reliance on the good graces of the president and Congress, where a handful of truculent lawmakers can raise considerable mischief with its funding. CIRM does not share that weakness. Neither the California legislature or even the state's Terminator governor can fiddle with the agency's plans or restrict its budget.

An old cliché with considerable truth holds that pioneers are the ones with arrows in their backs. At the same time, pioneers snatch up the best land, the most favorable water rights and set the agenda for the latecomers. That favored position is where CIRM now finds itself.

CIRM to California: Lower Your Expectations

It was a message that could have been delivered by former Gov. Jerry Brown in his heyday.

Don't look for cures right around the corner. Science is hard and results are not guaranteed. Lower your expectations, as the former governor told Californians shortly after he was first elected. And it was a message that came through clearly in the California stem cell agency's draft of its strategic plan.

In the words of the Knight Science Journalism Tracker, the proposal "appears to be a rare case of prudence by public servants."

The plan was even heralded – sort of – in religious fundamentalist circles. A piece written by reporter Michael Foust in the Baptist Press said,

"In an announcement that some ethicists say should lead to a greater focus on adult stem cells, a much-celebrated California stem cell institute says any cures using embryonic stem cells likely are years away."

The strategic plan's theme of patience, at least as it was portrayed in the media, was somewhat different than the overheated rhetoric of the campaign for Prop. 71 two years ago.

A recent paper by Tamra Lysaght of the University of Sydney, published in the Australian journal Bioethical Inquiry, examined 99 news stories from the Prop. 71 campaign. Among her conclusions:

"Concerns regarding the hype surrounding the potential medical benefits of stem cell research and its implications for public expecations were notably absent from the public discouse prior to the passage of Prop. 71, though they were later noted by a number of scientific and institutional actors. The reasons for this phenomenom are unclear, but perhaps point to the reluctance on the part of the scientific and medical communities to openly question the value of this line of research or to critcize each other; fears about aligning with religious or other actors opposed to hESC research; or the influence of commercial, academic and media interests in framing and limiting crucial debate."

But even before the strategic plan emerged, CIRM officials talked of managing expectations and avoiding hype although the message was less than visible in the media.

The Center for Genetics and Society of Oakland, Ca., recently conducted a briefing on the politics of stem cell research for reporters and focused on the exaggeration question. Marcy Darnovsky, associate executive director of the center, said,

"Exaggeration is really one of the hallmarks of this issue. It’s pervasive on both sides of the debate, and each side’s hyperbole feeds the hyperbole of the other."

She continued:

"Just recently the Democratic Senate candidate from Missouri, who strongly supports the stem cell initiative (in that state), used the words "lifesaving," "cure," or "save [a life]" 22 times in a 732-word interview published by the Associated Press.

"Statements like these seriously degrade public understanding and distort political discourse. Perhaps more surprisingly, similar exaggerations have also become common in the world of science, in statements by scientists about stem cell research. It’s always been considered a matter of scientific integrity to refrain from making claims in the absence of clear evidence. But in the stem cell world, that principle is being regularly violated.

"One example: It’s common to hear that embryonic stem cell research will result in cures for Alzheimer’s disease, when in fact, unfortunately, the idea that stem cells have the potential to treat Alzheimer’s is far-fetched.

"Knowing this, Rick Weiss, the Washington Post’s science reporter, called a prominent stem cell and neurology researcher to ask why he and his colleagues weren’t correcting the misunderstanding. The scientist’s answer: 'To start with, people need a fairy tale... they need a story line that's relatively simple to understand.'"

CIRM has a difficult road. It must maintain the public's faith, which does require the delivery of easily understood messages with a vision of hope. But the controversy involving Advanced Cell Technology's report on stem cell extraction shows how nuances make a big difference. The $6 billion (including interest) that CIRM will cost taxpayers requires results. If something tangible and understandable is not forthcoming in a few years, it may erode public support for an endeavor that once gained 59 percent approval of the state's voters.

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Below you can find the verbatim statements made by Darnovsky and her colleague, Jesse Reynolds, at the Sept. 19 news briefing for editors and reporters. The statements are not currently available on the center's web site.

Text of Statements from CGS on Politics of Stem Cell Research

Here are the texts of remarks made by officials of the Center for Genetics and Society at a Sept. 19 briefing for reporters and editors on the politics of stem cell research. The statements are not currently available on the center's web site.

Remarks by Marcy Darnovsky , Associate Executive Director, Center for Genetics and Society


I’m going to talk first about several kinds of over-promising and distortion that are common in the stem cell debate. Then I’ll say a few words about some shifting political alignments and developments.

[Exaggerating cures]

Exaggeration is really one of the hallmarks of this issue. It’s pervasive on both sides of the debate, and each side’s hyperbole feeds the hyperbole of the other.

Opponents of embryonic stem cell research consistently overplay the current capabilities and the future potential of adult stem cells, and downplay what most scientists believe about the promise of embryonic stem cell research. Their major point is undeniable – that deriving stem cells from embryos necessarily destroys those embryos. But their objection is a minority position in the U.S., and one that’s being imposed on the majority.

The focus on embryos does another kind of disservice as well. The divide in our country over the moral status of human embryos, and over abortion rights, has overwhelmingly dominated the discussion of stem cell research, burying other important concerns. We need to look at this issue through a different lens.

Turning now to the situation among supporters of embryonic stem cell research: Far too many scientists, politicians, biotech entrepreneurs, and research advocates regularly exaggerate the likelihood and imminence of medical advances. The use of the word “cures” is routine – though as Jesse mentioned, the research is at an early stage, and right now there are no treatments or therapies based on embryonic stem cells, let alone cures.

Nonetheless, both the 2004 California ballot initiative and this year’s voter initiative in Missouri have the words “stem cell research and cures” in their titles, and the supporters of the Missouri initiative call themselves “The Missouri Coalition for Lifesaving Cures.”

And just recently the Democratic Senate candidate from Missouri, who strongly supports the stem cell initiative, used the words "lifesaving," "cure," or "save [a life]" 22 times in a 732-word interview published by the Associated Press.

Statements like these seriously degrade public understanding and distort political discourse. Perhaps more surprisingly, similar exaggerations have also become common in the world of science, in statements by scientists about stem cell research. It’s always been considered a matter of scientific integrity to refrain from making claims in the absence of clear evidence. But in the stem cell world, that principle is being regularly violated.

One example: It’s common to hear that embryonic stem cell research will result in cures for Alzheimer’s disease, when in fact, unfortunately, the idea that stem cells have the potential to treat Alzheimer’s is far-fetched.

Knowing this, Rick Weiss, the Washington Post’s science reporter, called a prominent stem cell and neurology researcher to ask why he and his colleagues weren’t correcting the misunderstanding. The scientist’s answer: "To start with, people need a fairy tale... they need a story line that's relatively simple to understand."

[Other distortions]

Other sorts of exaggerations and distortions are also rampant in the stem cell debate.

Opponents of embryonic stem cell research regularly blur the distinction between reproductive and research cloning. This can be seen as a logical extension of their position that an embryo is a full-fledged human being. But failing to acknowledge the difference between a cloned child and a cloned embryo certainly skews consideration of the issue.

Opponents of embryonic stem cell research often misrepresent concerns voiced by women’s health advocates and groups like the Center for Genetics and Society about issues such as procuring eggs for research. In Missouri, an anti-abortion rights group that opposes the initiative used our words to support their position, neglecting to mention that we support embryonic stem cell research

On the pro-embryonic stem cell research side, we’ve seen a clear pattern of overstating the economic benefits of allowing or funding research.

The coalition backing Missouri’s Amendment 2 is promoting a study that claims the initiative will "reduce state health care costs by billions." To the extent that it’s supported at all, this conclusion is based on savings that would be realized by curing a list of diseases that includes very unlikely candidates for stem cell research, such as stroke and Alzheimer's.

We saw similar hand-waving in the campaign for the California initiative – in fact, the economic studies were done by the same hired group.

[Why it matters]

Why do the exaggerations and over-promising matter?

First, they do real damage to public understanding, and to the possibility of a meaningful debate on a set of complicated issues.
Second, overblown claims can be very hurtful to those who suffer from debilitating diseases, cruelly raising hopes that are likely to be dashed.
Third, hype about stem cells has played a role in overheating the environment to the extent that we’re seeing fraud and embezzlement – as in the case of South Korean cloning researcher Hwang Woo Suk – and questionable claims like the announcement a few weeks ago by Advanced Cell Technology that seemed based more on their need to raise money through a stock spike than on any real advance.
And finally, hype is bad for science. It sets the stage for backlash or bad policy or both.


[Political alignments and developments]

I want to say just a few words about the political alignments on stem cell research. We’ve talked a fair amount on this call about the distortions caused by the political polarization on this issue. But in fact, there’s growing bipartisan support for stem cell research using embryos produced but not used for assisted reproduction. We’re seeing a growing realization that Americans can be religious and support embryonic stem cell research; that they can be liberal and support responsible regulation of stem cell and cloning research.

We’ve looked at opinion polling on this question. Stem cell research is even more subject to wording effects than many other issues. But our analysis of polls that provide balanced background statements shows clearly that

support for embryonic stem cell research has been growing,
significant uneasiness about the use of cloning techniques for stem cell research has persisted

Though some Democrats continue to use embryonic stem cell research as a wedge issue, the recent Congressional vote on extending federal funding showed that more and more conservatives are supporting it. There will eventually be a less restrictive federal funding policy, and it’s past time to shift the conversation to the question of how stem cell research will be conducted – what oversight and what rules of the road do we want to put in place.

This is particularly important when it comes to research cloning. An important piece of that story rests on the issue of women’s eggs for research. Here in California, the Center for Genetics and Society and several women’s health groups worked with a Democratic state senator on an eggs-for-research bill. It passed both the California Senate and House with near-unanimous votes, and is now sitting on the Governor’s desk awaiting his signature.

Let me wrap up with 3 points that we think are key:

First, the stem cell debate until now has focused so much on the status of embryos that some really important issues have been eclipsed
Second, the political polarization on embryonic stem cell research has created an atmosphere of hype, distortion, and as a result, public misunderstanding
Third, responsible oversight and enforceable regulation of stem cell research – the kind that are in place in many other countries with research efforts – are a high priority for the U.S. Putting a comprehensive policy in place will be a plus for everyone.

Remarks by Jesse Reynolds, Project Director- Biotechnology in the Public Interest, Center for Genetics and Society


These basics of science and policy can be complex, and key distinctions are easy to overlook. I’m sure you are familiar with much of this, but I want to try and get everyone on the same page.

The distinction between stem cells from adult body tissue and those from embryos has nearly monopolized the debate about stem cell research. But many people are not clear about a second distinction between two sources of embryonic stem cells. And its in describing these techniques where perhaps the most frequent mistakes in the coverage of stem cell research occur.

The first, which has been used to produce all currently existing embryonic stem cell lines, is to use embryos created but not used in fertility treatments.

The other is to use embryos created by the cloning process, called somatic cell nuclear transfer, to derive new stem cell lines with specific genetic compositions. This process of cloning for stem cells is sometimes called research cloning, therapeutic cloning, or just SCNT.

Cloning in stem cell research remains at an early, speculative stage. Although it has been receiving much attention, it is a tiny portion of stem cell research. Only a handful of labs in the world are working on such research cloning.

Research cloning brings up issues of concern beyond the moral status of the embryo.
First, is how to treat the women who may provide the eggs has been an issue of debate, particularly whether to pay them. Unlike “normal” stem cell research, many human eggs are needed for it. Egg extraction is a procedure with significant medical risk.
Second, treatments from cloning-based stem cell research are likely to be extremely expensive – and that they might therefore increase health inequities.
Third, the technique opens the door to unacceptable applications such as reproductive cloning.

Because “cloning” has a strong negative connotation, advocates and opponents for research cloning manipulate the language. The advocates just call it SCNT, imply that no embryo is created, and also imply that it is currently a critical part of stem cell research. The opponents will call it “human cloning,” in an effort to blur the distinction between cloning for stem cell research, and cloning for reproduction.

The distinction between research cloning and embryonic stem cell research in general is key to understanding and describing the scientific and political landscape. But this blurring between them has led to many outright inaccuracies in reporting. As an example, just last week, a columnist in a major Missouri newspaper wrote about a person whose cancer had been put into remission by a cloning-based stem cell treatment– when in fact stem cell lines have never been successfully derived from clonal embryos.

Moving on to policy, I’d like make a second key distinction – this one among what is allowed, what is regulated, and what is funded. I’ll start with federal policy.

There are no bans on stem cell research at the federal level, despite the rhetoric of some research advocates. Of course, laws that apply to medical research in general apply. Congress has supported a ban on research cloning, but the bill lacks votes to overcome a filibuster in the Senate.

There are also no regulations specific to stem cell research at the federal level. This is unlike other countries that have stem cell research programs, and despite widespread recognition among scientists that this work raises new oversight and regulatory concerns

The only national guidance is the area comes from the National Academies, a nongovernmental organization. It’s issued recommended guidelines for the conduct of stem cell research. These, for example, oppose paying women who provide eggs for research cloning. But these are not enforceable regulations, and some researchers have indicated that they will not necessarily follow them.

As you know, federal funding of human embryonic stem cell research has been restricted to the funding of work with lines created before August 2001. The recent bill that resulted in President Bush’s first veto, would have undone these restrictions. The passage and signing of this bill would have provided the opportunity to have discussions about federal oversight of this important research.

Moving on to the states: The lack of federal funding, and the accompanying lack of federal oversight, has resulted in an emerging patchwork of state laws and regulations. One state – South Dakota – bans the human embryonic stem cell research entirely. At least five other states ban research cloning. Research cloning is explicitly permitted in six states. Of course, when not cited in law, these practices are implicitly allowed.

Only two states are developing regulations for human embryonic stem cell research, California and Massachusetts. California will have two sets of regulations – one for state funded research, and another for any other source of funding.

Five states publicly fund stem cell research: California, Connecticut, New Jersey, Maryland, and Illinois. At $300 million per year for ten years, California’s program dwarfs the others. All these state funding programs except Maryland’s intend to fund research cloning.

Finally, I’d like to provide some details on Missouri, which is currently the site of the most prominent stem cell research debate. The Constitutional amendment before the voters would ensure that all stem cell research that’s legal at the federal level remains legal in the state. Because there are currently no laws specific to stem cell research in Missouri, the amendment would simply preserve the status quo.

It’s true that each year some conservative legislators introduce a ban on all cloning, including research cloning. But this ban is very unlikely to become law – it’s never even gotten out of committee in either house, and the governor has promised a veto. Moreover, research cloning is not even being done in Missouri. It is strange that the proponents of the proposed Amendment raised sixteen million dollars, as of the end of June, just to preserve the status quo. That is already more than has ever been spent on any race in the state.

The powerful emerging technologies of stem cell research are being developed largely without oversight. Some politicians talk of bans, and others advocate for protective constitutional amendments. But what’s missing is effective regulation to ensure that it is done right.

A Chockablock Stem Cell Agenda and Poetry

The folks at the California stem cell agency have been busy stuffing the agenda for next week's meetings of the Oversight Committee with weighty background papers on the topics up for debate.

The schedule is now chockablock with information, most of posted it on Wednesday, on everything from intellectual property to criteria for the first round of stem cell building grants.

We have been critical in the past of the lateness of postings of background material. This is a good step in the right direction. It helps the public and CIRM's special constituencies understand its activities and to respond in an intelligent, constructive and timely fashion.

If you need to rest your eyes from stem cell minutia, check out this ode to gin at the Internet Poetry Archive.

San Diego Stem Cell Researchers Enthused by CIRM Plan

Reporter Terri Somers of the San Diego Union Tribune has a more detailed story -- compared to her early report Wednesday -- on the CIRM draft plan in this morning's paper, including more reaction.

She wrote:

"San Diego-based stem cell scientists who will be applying for funding from the institute were enthusiastic after reading the proposal.

"'I think many of the five-year goals we are well on track for accomplishing, which probably means we'll be able to make the 10-year goals as well,' said Evan Snyder, a stem cell researcher at the Burnham Institute in La Jolla.

"'I also think there's a good appreciation (in the plan) for the fact that developing therapies depends on good fundamental knowledge of disease process and how cells work,' Snyder said.

"He and his Burnham Institute colleague Jeanne Loring said they were excited with a plan to provide about $182 million to interdisciplinary teams of scientists. Some of these teams will start out with a plan of addressing a specific disease.

In the early years, an important part of the institute's program will encourage scientist-initiated, curiosity-driven science relevant to the development of embryonic stem cell therapies. Limited federal funding for stem cell research makes the institute's funding of this what-if science imperative, the strategic plan states.

"Loring, one of many people interviewed by the committee drafting the plan, was enthusiastic to see that the funding included grants for scientists looking for many different ways to grow embryonic stem cell lines."

$3 Billion Not Enough?

Reporter Carl Hall of the San Francisco Chronicle wrote that the CIRM's draft strategic plan "suggests even $3 billion isn't enough to meet all the early expectations of stem cell research."

He said:

"The blueprint sets a strikingly modest tone for an effort ranked among the country's boldest research enterprises when state voters approved Prop. 71 in a hype-fueled 2004 election."

You can find his story here. The Sacramento Bee and Los Angeles Times do not appear to have written stories today on the plan.

The NY Times on CIRM's Proposed Spending Plan

Here is a link to the New York Times story by Nicholas Wade on the strategic plan proposed by the staff of the California stem cell agency.

An excerpt:

"Navigating between scientists who say that much basic research remains to be done and patients’ advocates who want the focus to be on new treatments, the institute says it will spend $823 million on basic stem cell research, $899 million on applied or preclinical research and $656 million on taking new treatments through clinical trials.

"A further $273 million is allocated for universities to construct “N.I.H-free” buildings, meaning laboratories in which none of the equipment has been bought with money from the National Institutes of Health. This is so researchers can be sure of not violating the rules that restrict federal money to research using government-approved stem cell lines."

CGS on the CIRM Plan

We queried the Center for Genetics and Society of Oakland, Ca., on their thoughts on CIRM's proposed strategic plan.

Here are the verbatim comments of Jesse Reynolds, project director, biotechnology accountability:

"First, the draft's assessment of the potential of embryonic stem cell
research is refreshingly honest. It cites as a ten year goal having a
single potential treatment at the proof of principle stage, and
describes the much-touted personalized stem cell lines as impractical.
This is in line with what most scientists will say, but is in sharp
contrast to the campaign language of Proposition 71. Voters would have
been better informed by this balanced assessment.

"Second, inadequate attention is given to the ethical, legal, and social
implications of CIRM's work. The human genome project set aside 3% of it
budget to this area. CIRM is overlooking a critical area by allocating
less than one percent to examining these implications.

"Finally, I am surprised at the small among of funds that is intended for
research into alternative sources of potent stem cells. If research in
this area leads to cell lines without destroying embryos or requiring
eggs, it would open up access to federal funds - worth hundreds of
millions of dollars. This seems to be a wise investment."

More Comment on CIRM's Strategic Plan

Patient advocate Don Reed has expanded a tad on his thoughts concerning CIRM's strategic plan.

Writing on his web site, stemcellbattles.com, he quoted a section that said,

“Given the time and expense of therapy development, it is unlikely that CIRM will be able to fully develop stem cell therapy for routine clinical use during the ten years of the plan.”

Then he remarked,

"I differ with that assessment with every fiber of my being."

Reed's comments can be found towards the end of the Oct. 4 item, which also has some interesting remarks on the recent round of stem cell meetings in California.

CIRM Posts Draft of Strategic Plan

The California stem cell agency's 194-page draft of its strategic plan has been posted on CIRM's web site, several hours after news stories with details of the report appeared. However, there is nothing on the CIRM's main web page at the time of this writing to indicate that this fundamentally important document is available to the public.

Interestingly, the cover has a quote from Roman Reed, son of patient advocate Don Reed, who expressed some reservations about the plan.

Roman is paralyzed with a spinal cord injury. It was he who came up with the motto of the agency: Turning stem cells into cures. That motto is on the cover of the plan.

A Quick Look At Who is Covering CIRM's Plan Today

As of the time of this posting, neither the San Francisco Chronicle (the hometown paper for the California stem cell agency), the Los Angeles Times (the state's largest paper), The Sacramento Bee nor the Orange County Register appear to have posted stories online concerning CIRM's strategic plan. The San Jose Mercury News and the San Diego Union Tribune both have stories online. The San Diego paper performed a nice public service, posting the executive summary online. As of this writing, the plan was not available on CIRM's web site. For links see items below.

Some Unhappy with CIRM's Strategic Plan

Reporter Steve Johnson of the San Jose Mercury News also moved quickly on the CIRM strategic plan, reporting in the lead of his story that the proposal dismayed some advocates of the sick and disabled.

Here are some excerpts:

"Zach Hall, the institute's president, said he and others who developed the plan were extremely careful about wording it so it set obtainable goals that didn't unrealistically raise the public's hopes.

"'One of the points really is to try to educate people about what a long process it is to get any `therapeutic' approved,' said Hall, who predicted it might take 15 years before the institute's research results in a medical product."

Johnson continued:

"But others found the plan's cautious approach disheartening.

"'I consider this report's estimate to err on the side of over-caution,' said Don Reed of Fremont, whose son was left a quadriplegic after he broke his neck in a college football game. "While it is right and proper for scientists to be careful,' said Reed, who attends many of the institute's meetings, "I take a more optimistic view. In 10 years, I expect my paralyzed son, Roman Reed, to be walking.'

"That sentiment was echoed by 60-year-old Bill Franklin of Los Altos, who has suffered from Parkinson's disease for 11 years.

"'There's no reason for things to take that long,' said Franklin, who worked to help pass Proposition 71, which created the stem-cell institute. 'People with PD and other diseases, they want things to happen faster.'"

Johnson also had comments from two CIRM Oversight Committee members:

"Jeff Sheehy, a member of the institute's board who suffers from AIDS and participated in the group that developed the plan, said no matter what progress companies make, it's vital for the institute to proceed cautiously and methodically.

"'There still is a lot of work that will need to be done to make these therapies widely available and safe,' he said. 'This is a daunting scientific challenge.'

"Joan Samuelson, a board member with Parkinson's disease, agreed that the institute needs to be thorough. 'But we also are in a rush,'' she added. 'That means every day we report to duty as if somebody is dying.'"

More Details on CIRM's Strategic Plan

Reporter Terri Somers of the San Diego Union Tribune moved quickly and was probably first on the Web with substantial details of the strategic plan drafted by CIRM staffers. It has been reviewed along the way by the Oversight Committee but final approval is not slated until December.

Here are excerpts from her story. The executive summary can be found on the newspaper's web site (see item below) and not on the CIRM web site at the time of this writing.

"The institute has already announced that it will be seeking applications for grants intended to “jump-start” human embryonic stem cell research in California. Under the plan, $135.3 million would be spent on the jump start initiative.
"An additional $148.5 million would be earmarked for annual innovation grants, and $75.3 million would fund work in the basic biology of stem cells.
"The plan also directs money toward science that is directed at a specific mission, such as the investigation of better methods of generating specific types of stem cell lines, such as those that can be used as models of diseases, or using stem cell to create copies of tissues and organs that can be used in the lab to test new therapies for various diseases.
"More than $60 million would be directed to scientists who are researching ways to create stem cells that would not create a toxic response from a patient's immune system if used in a therapy.
"About $451 million would be given to researchers in academia and biotech companies for early-stage clinical testing of promising therapies. and $108 million would be directed to academia and industry for core services such as accredited manufacturing facilities.
"The plan also calls for innovative funding techniques.
"For instance, about $122 million will be directed toward disease teams.
"These teams would include scientists who will work together over a number of years to develop a therapy. The work would have to follow a careful, detailed and plausible strategy with defined milestones for bringing the therapy to clinic.
"The plans calls for $60 million to be spent on interdisciplinary research teams working on a specific scientific goal.
"Recognizing that stem cell research will influence society in ways other than new therapies, the committee will sponsor empirical research and conference that take a more theoretical approach to dealing with moral issues. For that purpose, $25.5 million has been budgeted.
"The institute will also spend $2.3 million for outside experts to assess the economic impact of stem cell research in California, and $10 million for public outreach programs that include a web portal and educational workshops."

Executive Summary of CIRM Strategic Plan Draft

Here is a link to the executive summary of the draft strategic plan of the California stem cell agency. It is on the San Diego Union Tribune's web site and was not available on the CIRM web site at the time of this posting. See this location for the summary.

CIRM's Draft Plan Calls for $463 Million to Push Stem Cells into Clinics

The California stem cell agency today released the long awaited draft of its strategic plan and called for spending $463 million for research aimed at bridging the gap from basic stem cell discoveries to treatment in the clinic.

That was the single largest amount specifically delineated by the plan, according to the Foundation for Taxpayer and Consumers Rights, which posted a press release on the plan even before the plan was available on CIRM's own web site.

The foundation said $451 million was recommended for clinical trials, with costs shared with industry.

John M. Simpson, stem cell project director for the foundation, said:

"During the Proposition 71 campaign, proponents implied that miraculous cures were just around the corner. This plan acknowledges just how difficult the task ahead is and is a welcome change from the hype that has all too often been associated with stem cell research. Californians are entitled to an honest assessment of the prospects for research they are funding."

The draft will be discussed at the Oversight Committee meetings in Los Angeles later this month. Final approval is scheduled for December.

We will have more on this later today when the plan becomes publicly available.

(Editor's note: An earlier version of this said $423 million was recommended for bridging the gap between the lab and clinic.)

Feds Say 'Substantial Question' Exists on WARF Patents

The federal government will review Wisconsin's claims to patents on embryonic stem cells in a move that will probably take a few years to play out.

The agency agreed that "substantial questions" exist involving the patents.

Reporter Andrew Pollack of the New York Times wrote:

"Re-examinations brought about by a third party, as this one was, result in all the patent claims being canceled 12 percent of the time, said Brigid Quinn, a spokeswoman for the patent office. In another 59 percent of cases, smaller changes are made. Ms. Quinn said the patent office receives 400 to 500 requests for re-examinations each year and grants 90 percent of them.

"The Wisconsin Alumni Research Foundation, or WARF, a patent licensing organization affiliated with the university, provides academic researchers with free licenses and charges them $500 for cells. Companies are charged $75,000 to $400,000, depending on their size and the terms of the license. One company, the Geron Corporation, has exclusive commercial rights to heart, nerve and pancreatic cells derived from the embryonic stem cells."

Reporter Kathleen Gallagher of the Milwaukee Journal Sentinel quoted John M. Simpson of the Foundation of Taxpayer and Consumers Rights of Santa Monica, Ca., one of the two nonprofit groups challenging the patents, as saying his organization was not motivated by regional jealousy. Gallagher wrote:

"'If California had these patents with these claims, we'd be trying to challenge them,' said Simpson, who was born in Madison and whose mother worked in a research lab on the UW-Madison campus."

Here are links to other news stories and press releases: The AP(which appeared overseas), Terri Somers of the San Diego Union Tribune, Jim Downing of The Sacramento Bee, Bernadette Tansey of the San Francisco Chronicle, David Wahlberg of the Wisconsin State Journal, Rob Waters of Bloomberg, Foundation for Taxpayer and Consumer Rights press release.

Rules Approved for Millions in Lab Grants

After hearing statements that new lab space is running from $500 to $800 a square foot, a panel of the California stem cell agency Monday approved procedures to move quickly on laboratory grants to be awarded early next year.

The Facilities Working Group, in only its second meeting ever, approved criteria and bylaws that will go before the Oversight Committee for approval Oct. 11.

That will set the stage for a round of millions in grants for small-scale renovations of labs so that they can perform embryonic stem cell research.

Only a few changes were made in the selection process and criteria posted earlier on CIRM's web site. Added to the criteria were consideration of how soon a project can be operational and the record of the grant applicant in terms of staying on budget and completing projects on time. The exact language will be worked out and posted on the CIRM web site, probably on Wednesday.

The panel amended the bylaws to ensure that alternate members of the facilities group could vote on grants. The working group also indicated it would insert language to bar group members from discussing specific grant applications with the applicants once the proposals were submitted.

The group discussed a provision in the bylaws concerning the requirement of matching funds from applicants, giving preference to applicants with higher matching amounts. The issue involved whether applicants could get credit for money spent on the project prior to the grant. Just how that is all worked out will probably have to wait for the Oversight Committee meeting.

The agency is considering making as many as 15 grants, possibly up to $2 million per year. The current plan is to seek applications later this month with approval in March or April.

The agency can make about $300 million in facilities grants. Criteria for larger projects will be developed next year.

Read All About It! At Least Some Of It

The agenda for the Oct. 10 and 11 meetings of the Oversight Committee for the California stem cell agency is now available on CIRM's web site with the draft of the strategic plan expected on Wednesday.

As usual, the sessions are fully packed. Much of the background material is not yet available, but the agency seems to be doing a better job of posting the material earlier.

We make that comment after being obliquely chastized on Monday by one CIRM staffer for failing to note when the agency improves its performance. Point taken.

Scheduled to be posted on the CIRM web site on Wednesday is a rather hefty document – the draft of the strategic plan for the agency. We are told it is in the range of 90 to 100 pages, so plan on curling up in the front of the fire for a good read.

If you want to influence CIRM's spending plans, now is the time to weigh in. The plan comes up for discussion at the meetings next week. It is scheduled to be approved at the Oversight Committee in December.

Whittling Down the Researchers: The 'Unhappy' Result of Stem Cell Enthusiasm

The California stem cell agency faces a nearly overwhelming task in the wake of notices from about 350 scientists, saying they intend to apply for about $100 million in grants over the next few months.

The agency has already moved to whittle down the number of potential applicants by requiring the institutions involved to certify that the letters of intent were filed by principal investigators. One veteran stem cell scientist, who is not affected by the certification call, said the requirement has left "fair numbers of angry and anxious people."

The certification will elminate some, perhaps many applications from less senior scientists, despite CIRM's intention to encourage younger researchers.

The requirement for a letter of certification was not mentioned in the initial instructions for the letters of intent. The certification form that was posted on CIRM's web site was created on Sept. 19, four days after the deadline for the letters of intent.

In response to a series of questions from the California Stem Cell Report, Dale Carlson, chief communications officer for CIRM, said,

"The certification form was promulgated after the LOIs(letters of intent) came in, to clarify the qualifications necessary to apply for either grant (PI must be an independent investigator, full-time, on-site, etc.). It may eliminate some full applications from some who filed LOIs but aren't qualified for grants. It's common to require written confirmation of portions of a grant application. I haven't heard of any complaints."

However, it is clear that some folks are disappointed and feel as if the rules were changed in the middle of the game.

The scientist who discussed this issue with the California Stem Cell Report asked not to be named for a number of reasons. We understand that position. For us, it is enough to say that CIRM plays a vast role in the funding of research, and no prospective applicants are likely to want to appear to be grousing about its conduct. Anonymity of sources, however, always raises a flag. In this case, the individual we spoke with is well respected in the field and has had considerable experience with grant reviews, conducting them for the NIH.

Here is what we learned during our discussions, which dealt primarily with the SEED grants, which attracted 280 scientists. CIRM says the grants, which are scheduled to be voted on by the Oversight Committee in February, are aimed at bringing in "new ideas and new investigators."

Many of the scientists who filed letters of intent will be disappointed, we were told. Many aren't qualified under the terms of the certification. A good part of the problem is the classification of reseach scientists at many institutions as non-faculty. Instead they carry titles such as research professional or staff scientist. The letter of certification asks institutions to certify that an applicant holds a "faculty-level position," among other things.

The fundamental problem is the size of the potential applicant pool. The scientist compared it to an NIH experience in which the number of applications was far smaller but the number of reviewers much, much larger. Even if the number of CIRM grant applications is reduced by half, it is still too large for the 15 scientific grant reviewers.

We asked CIRM about the workload, assuming ultimately 200 applications with about two hours spent on each grant by each of CIRM's scientific reviewers. By law, as we understand it, each reviewer in the CIRM grants program must examine each application. That amounts to 400 hours or 10 "normal" work weeks for each scientist, who already has a full plate with his or her own work. Is that a reasonable estimate, we asked CIRM last Monday. If not what is? We have not yet had a response on that matter and others, such as whether it is fair to impose what appears to be a requirement that was not laid out in the original request for letters. We have indications that a response may be coming at some point. We will carry it when it arrives.

The scientist we talked to did not have a solution to the workload issue or how to fairly screen out some of those who filed letters of intent. But it is clear that fixing the number of reviewers in state law is a limiting factor, to put it mildly. It would be useful to be able to revise such minutia without going to a vote of the people, which is what is currently required for a change.

CIRM reviewers are all from out-of-state and cannot apply for CIRM grants. Although reviewers can learn from the reviewing process, our scientist said that it is a "great burden" to be a grant reviewer, either for CIRM or the NIH. Most do it out of an "irrational sense of altruism."

Let us know about what you think about this issue. Click on the word "comments" below to express your opinion. It can be done anonymously. Google, which hosts this blog, has set up anonymous comments in such a fashion that not even we can determine the names of those who use the "anonymous" feature.

Here is a link to the certification form and the application instructions.

Wisconsin Rachets Up Its Stem Cell Pitch

Like Arnold Schwarzenegger, Wisconsin Gov. Jim Doyle is in a re-election campaign. And like Arnold, Jim is courting the stem cell vote.

Last week Doyle announced that Wisconsin is not going to take the Golden State's $3 billion stem cell research program lying down.

He announced that Wisconsin Alumni Research Foundation (WARF) "will offer free, non-exclusive licenses to conduct embryonic stem cell research to companies that are sponsoring such research at Wisconsin non-profit and academic institutions," according to a story by reporter Kathleen Gallagher of the Milwaukee Journal Sentinel.

Reporter Anita Weier wrote in the Wisconsin State Journal:

"The agreement will give the state a significant competitive edge over California and other states that have been investing heavily in stem cell research. Doyle hopes to lure research companies to the state in order to capture 10 percent of the national stem cell market by 2015."

On the topic of challenges to WARF's patents by two nonprofit groups, Gallagher quoted Beth Donley, WARF's attorney, as saying,

"I find it fairly hypocritical that California says things like 'They need to get the dollar signs out of their eyes' because we license our technology to raise money to fund our research.

"We're just doing it the Midwestern way: We made an invention, and we're licensing this technology to fund the research, rather than like in California, where they borrow $3 billion, then hope to make an invention and repay the money."

Jerry Flanagan is a health care advocate with the Foundation for Taxpayer and Consumers Rights, one of the nonprofit groups challenging the WARF patents.

Reacting to Doyle's move, he said,

"The agreement between Gov. Doyle and WARF is an acknowledgment that the overly broad WARF patents stymie research and delay cures. It is absurd that WARF, or any organization, could own the rights to life itself. For the good of patients, these patents must be dissolved."

Two Days and Two Very Different Stem Cell Conversations

Biopolitics, biocapital and, yes, even biopiracy were all part of the rhetoric at a stem cell and ethics conference in San Francisco on Friday.

This one was offered up by UC Berkeley and UC San Francisco and was a tad different than the egg risk conference staged a day earlier by the Institute of Medicine and CIRM, also in the San Francisco area.

The expression "biopiracy" was never heard at the CIRM session. It would have shocked the room of physicians and scientists. Yet in many ways the concerns were the same both days. "Do no harm" was heard more than once at the CIRM conference, which explored some of the obligations of the medical and science commnity to egg donors.

"What do we owe each other," was a central theme of the UC conference, according to historian David Rothman of Columbia University, one of its final speakers.

He noted that it is a question that would not have been asked at the time of the creation of the National Institutes of Health.

Our read, albeit sketchy, on the group at UC San Francisco on Friday was that many in it were generally hostile concerning the stem cell efforts at CIRM and elsewhere around the world. More so than the usual critics who turn up at CIRM meetings. We were told that two scientists had refused to appear before the group when it was trying to arrange speakers.

Given that environment, and to his credit, Arnold Kriegstein, director of the stem cell program at UC San Francisco, appeared as the final speaker. He acknowledged that one concern of stem cell researchers is fraud. "We seem to be blessed with more of it more than the rest of science," he said.

Kriegstein said his researchers are trying to perform their work in an ethical way, which he said requires vigilance in a fast-moving area such as stem cell research.

A video recording of the session was made on Friday along with what appeared to be a transcript. Hopefully, those will be available on the Web site of the Science, Technoloogy and Society Center at UC Berkeley, which sponsored the conference.

Kleffman's Coverage on Egg Risk is First Out of the Cyberspace Gate

Online news reports on today's egg risk conference came early. Reporter Sandy Kleffman of the Contra Costa Times wrote a piece that is now available on the Web, many hours before it will appear tomorrow in the recycled-tree version of the publication.

Here is her lead:

"The women who donate eggs to California's $3 billion stem cell research program may take great pride in serving as medical pioneers, but they could also face psychological and health risks that have not been fully explored by scientists, experts said Thursday.

"Many of the nation's top scholars in fertility and women's health gathered in Burlingame for an all-day hearing to assess how much is known about the risks egg donors face.

"Their conclusion: Many questions remain."

Scientists Call for More Study of Egg Donation Effects

The dome did not blow off the Capitol, so to speak, at today's much-heralded conference on the medical risks of egg donation.

Probably nobody really expected an explosion anyway. But the meeting did force attention on a difficult and controversial issue – one that needs considerable tending not only for the sake of the women donors but for the general cause of embryonic stem cell research.

The occasion was the Institute of Medicine's "Public Workshop on Assessing the Medical Risks of Human Oocyte Donation for Stem Cell Research" – a title almost as heavy as the subject.

CIRM instigated the meeting, seeking more input for its efforts to craft solid standards for stem cell research. And CIRM was paying attention. Several staffers were there and at least one Oversight Committee member. CIRM President Zach Hall opened the session and was there for the entire day, taking copious notes during the end-of-the-session summary by Linda Giudice, chair of the session and chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Francisco.

The bottom line on the meeting: The process of extracting eggs has risks, but they are minimal, as understood by medical science at this point. But weaknesses exist in the current data, which primarily involve women who sought IVF because of fertility problems. More study needs to be done on "healthy" individuals who undergo the process solely for the purposes of donating eggs.

Giudice noted that despite 20 years of IVF in this country, not much is known on the health outcomes of those treated. "Varied" and "limited" are how she described the studies.

Giudice outlined some "challenges" facing scientists. They include differences in the way ovaries are stimulated to produce large amounts of eggs, finding alternate sources (possibly cadavers) and organization of the donation process.

While the meeting was devoted to medical issues, lying in the weeds were policy questions. Minimizing risk to donors can translate to changes in CIRM's research standards. And creating a database on the health of donors could be the focus of a CIRM grant.

The meeting was Webcast by the Institute of Medicine and presumably will be available online for viewing at your convenience at some point. CIRM had a court stenographer making a transcript which may be accessible online in a couple of weeks. And the California Stem Cell Report will have more on the session in the next few days.

Meanwhile, for those of you who were there or even those who were not, your comments or questions are invited. Just click on the word "comments" below. They can even be posted anonymously with your identity concealed even from the otherwise all-knowing California Stem Cell Report.

Multimillion Dollar Stem Cell Lab Building Program: The First Step

Building tens of millions of dollars in biomedical research facilities is the topic for next Monday's meeting of a working group of the California stem cell agency.

The Scientific and Medical Facilities Working Group will consider criteria for its initial grants which are likely to be approved early next year – upwards of $2 million per institution has been discussed at possibly 15 different locations. Funds would go for lab renovations and equipment.

Also on the agenda for the San Francisco meeting (no remote locations available) is a panel discussion on construction of biomedical research facilities. James Kovach, president of the Buck Institute on Aging; Rebekah Gladson, campus architect at UC Irvine, and Curtis Williams, vice president for capital construction, USC, are scheduled to take part.

The working group has 11 members. Six are patient advocates from the Oversight Committee. Four are real estate specialists, and the 11th is the chair of the Oversight Committee, Robert Klein, whose career has been in real estate development.

Egg Donation: 'People Think You Just Go In and Grab Some'

A day in the life of an egg donor:

"Somehow overcoming her fear of needles, (Julia) Thurman reported for a checkup midway through her regimen of ovary-stimulating shots. She felt fine, but her arms were tender from repeated blood draws -- four that week alone.

"A circle of red dots ringed her bellybutton, a calendar of shots past. Just below her bikini line was a greenish bruise.

"Four days later, the hormone surge was impossible to ignore. Thurman shuffled into the clinic, pale and slumping.

"'I don't feel very good today. My stomach hurts.' Her voice was flat. On the ride over, she thought she might throw up.

"'Is it your ovaries?' asked the doctor, Stephen Boyers, head of the division of reproductive endocrinology at UC Davis Medical Center.

"'It's my stomach.' She patted the spot.

"'That's your ovaries,'" Boyers replied.

"Thurman lay back for an ultrasound exam. Follicles showed on the computer screen as dark blobs like plums. 'These are ready,' the doctor pronounced."

That's an excerpt from an exceptional story by reporter Edie Lau of The Sacramento Bee on the experiences of one egg donor at the University of California at Davis. She followed a woman through the process, laying out the details in a vivid but restrained account. The name of the woman was changed in the article for privacy reasons.

Another excerpt:

"Thurman herself knew nothing at first of the arduous process called superovulation that drives the ovaries to produce up to dozens of eggs at one time. She did not know about the daily hormone shots in the stomach, how ovaries swell from the size of walnuts to the size of oranges or grapefruits, or of the 12-inch needle used to extract the eggs.

"Nor did she know about the hundreds of personal questions she'd have to answer during the screening, or the dozens of clinic visits required for invasive and uncomfortable tests and probes.

"More important, she did not know about the risks involved. Data about complications are scattered, inconsistent and incomplete, leaving even scientists without a full understanding of potential dangers.

"The lack of reliable information has spurred the state stem cell agency, the California Institute for Regenerative Medicine, to sponsor the first workshop on the subject. The meeting takes place Thursday in San Francisco."

The article was the result of cooperation between UC Davis and the woman involved. Lau wrote:

"Revealing a world usually hidden by medical confidentiality policies, the UC Davis Medical Center fertility clinic allowed The Bee to follow a donor through the process if she were not identified.

"Thurman agreed to share her experience so others could glimpse the complex procedure required to donate eggs. 'I think people think you just go in and grab some,' she said."

UC Davis and Thurman are to be commended for allowing Lau to pursue her story. Lau's perceptive reporting and restrained writing have added significantly to the discussion of women, eggs and stem cells.

Ortiz Legislation to Protect Egg Donors Signed Into Law

In a week when egg donations and stem cell ethics are the subject of some considerable attention, Gov. Schwarzenegger has signed the nation's first legislation aimed at protecting women who donate eggs for embryonic stem cell research.

The measure – SB1260 – was authored by Sen. Deborah Ortiz, who is one of the leading and early California advocates of stem cell research.

Marcy Darnovsky of the Center for Genetics and Society of Oakland, Ca., called the signing a "victory for women's health." She said,

"Similar provisions have been adopted as law in other countries and recommended as voluntary guidelines elsewhere in the United States, but the new California law is the first of its kind in the country."

Darnovsky continued:

"The passage of SB 1260 has taken on added importance because several biotechnology companies and research teams in California have begun experimenting with cloning techniques (known as somatic cell nuclear transfer or SCNT), which require large numbers of women’s eggs. An increasing number of scientists believe that if it is ever perfected, SCNT will be useful as an indirect research tool, not as the basis of medical treatments. But following revelations late last year of fabricated data and fraudulent claims of success by cloning researcher Woo Suk Hwang, what many have called a 'cloning race' has resumed.

"We hope that the Reproductive Health and Research bill is a step towards the consistent and comprehensive national regulation of stem cell research that the United States so urgently needs."

The bill signing comes two days before the CIRM conference on medical risks of egg donation and a UC Berkeley/UC San Francisco conference on stem cell ethics. (See separate items below.)

Ortiz' office summarized the measure, which deals with non-CIRM research, in a press release:

"SB 1260 ensures that women who are considering donating eggs for stem cell research are fully informed of the potential risks. The donors must provide written and oral consent before taking fertility or ovarian stimulation drugs and undergoing assisted oocyte production procedures. In accordance with the National Academy of Sciences, SB 1260 limits compensation to only allow reimbursement for direct expenses. This will ensure consistency between the procurement of eggs in California and other countries that have similar embryonic stem cell research programs and streamline international collaborations and the sharing of stem cell lines. It also ensures consistency with the limitations enacted in Proposition 71, the 2004 initiative that created the California Institute for Regenerative Medicine."

Ortiz said,

“Stem cell research holds great promise for chronic and life-threatening diseases that affect more than 100 million Americans. We all want biomedical research to move forward, but we must ensure that women who provide eggs for research are fully educated about potential reproductive health risks.”

Ortiz, a Sacramento Democrat, authored legislation in 2002 that made California the first state to authorize embryonic stem cell research. She is leaving the legislature this year because of a law that limits the number of terms an individual can hold office.

The Republican governor, who is in a campaign for re-election, buried the signing of the measure in a generic press release about a number of bills he signed related to women's health.

Here are links on the signing and the legislation: Ortiz press release, governor's press release, statement by Darnovsky, a text of the legislation and the last legislative analysis of the bill.

Coming Up

California legislation aimed at protecting women who donate eggs for stem cell research has been signed by the governor. We will have an item on it within the hour.

Live Webcast Set for CIRM Egg Donation Conference Thursday

For those of you who can't make the Institute of Medicine/CIRM daylong conference on the latest information on the medical risks of egg donation, you can catch all of it on a live Webcast.

The Thursday event is being held in San Francisco to "to assess and explore the nature and magnitude of risks, evaluating areas where more data are required, and assessing what is known about the potential for reducing risks through changes in procedures." Ethical and policy issues will not be a prime topic.

Advance registration is required for the conference, and the deadline is past, but you might be able to slip in. Here is the link to the registration site.

If not, the Webcast links will be active beginning at 7:30 a.m. PDT on Thursday. The institute advises that it is important to test your links in advance, which can be done at any time. See this site for details.

More Attention Needed to Public Needs in Stem Cell Research

More attention should be focused on the public obligations of embryonic stem cell research, says a UC Berkeley faculty member in an article in "Trends in Biotechnology."

David Winickoff, who is a discussant at a two-day stem cell and ethics conference later this week in the San Francisco Bay area, wrote:

"In the USA the selection of funding priorities, IP policies, a regime of egg donation in California, and other public initiatives will help set the national and international trajectory for hESC research. Considering the high stakes of these policies, more attention should focus on the public obligations of government-funded hESC research and its commitment to an equitable distribution of risks and benefits as policies are implemented. Taking a cue from the UK, centralized stem cell banking in California would bring general gains in efficiency and create a pragmatic opportunity to construct an ethical and legal architecture for long-term public return. This vision of stem cell banks as social infrastructure would provide useful flexibility in the face of a fast-evolving ethical frontier and help build trust between scientific institutions and society."

Winickoff, an assistant professor of bioethics and society, will appear on the panel on Friday at UC San Francisco on academy-industry alliances. Here is a link to the full schedule and other details.

Governor's Press Release on Azziz

Here is the link to the governor's press release on Ricardo Azziz.

LA Doc Named to CIRM Oversight Committee

The California stem cell agency has added a new member to its Oversight Committee – Ricardo Azziz, a physician who is chair of the Department of Obstetrics and Gynecology at Cedars-Sinai Medical Center in Los Angeles.

Gov. Arnold Schwazenegger appointed Azzis to the 29-member panel, replacing Keith Black, who resigned earlier this year.

Azziz is also a professor at the UCLA school of medicine and vice chair of the obstetrics department there. Previously he was with the University of Alabama.

Here is a link to the CIRM press release and the Cedars press release. Here is his bio page at Cedars. As far as we can tell, the governor's press office has not yet issued a release on Azziz.

Watchdog Group Praises CIRM IP Task Force

The California stem cell agency is sort of like the weather – as they say, everybody complains about it, or so it seems sometimes.

Now comes a note from one of the folks who has done some pretty consistent complaining, but also seems to be able to work with CIRM.

He is John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights of Santa Monica, Ca.. He said in a letter to Ed Penhoet, chair of the CIRM Intellectual Property Task Force:

"The IP Task Force, under your chairmanship and with the stellar staff support of Mary Maxon and Scott Tocher, has so far exemplified a perfect model of soliciting and considering input from all stakeholders."

The impetus for Simpson's remark was what he called a "disturbing suggestion from some biotech industry representatives that the Task Force's process was other than transparent, orderly and consistent."

He referred to a Sept. 15 letter.from the California Healthcare Institute concerning IP policies for businesses. Written by David Gollaher, president of the biomedical industry group, the letter said that the organization "remains concerned" particularly about the process through which the Oversight Committee and the Task Force have "addressed or failed to address substantial concerns" of the CHI.

Gollaher said he was "especially dismayed by the apparent disregard" of some CHI comments concerning access to CIRM-financed therapies by the uninsured and public agencies. He also expressed concern about the process involving "right to practice" language.

"We would have expected any decision-making process...to have included input from all interested stakeholders. This, unfortunately, was not the case. In the future, CHI urges the ICOC to ensure its processes are transparent, orderly and consistent."

Stem Cell Snippets: Sherry Lansing to Stanford Freebies

Here are some links to interesting news, information or press releases related to California stem cell issues.

Sherry Lansing – CIRM Oversight Committee member Sherry Lansing, once a bigtime Hollywood executive, discusses her what makes her tick now. "I loved my job, but at a certain point it became repetitive. The highs weren't as high, and the lows weren't as low. So I asked myself: What is it that really gives me pleasure? The answer is giving back."

CIRM Overseer Flap – More from the Foundation for Taxpayer and Consumers Rights which is dogging the California attorney general concerning what is says is the illegal appointment of John Hein to the panel that reviews the financial operations of the California stem cell agency.

Stem Cell Bank –Joe Vanden Plas of the Wisconsin Technology Network reports: "The Madison-based National Stem Cell Bank has announced it will receive human embryonic stem cells from the University of California-San Francisco, giving it 13 of the 21 stem cell lines available on the federal registry."

Medical Freebies – In case you missed this, here is a link to the Los Angeles Times, which wrote: "They are common fixtures in many medical practices: free pens, mugs, stationery, stethoscopes and doctors' bags, all emblazoned with the logo of a new drug or a pharmaceutical firm. And those catered lunches staffers flock to? It may be courtesy of a major drug supplier. No more — at least for all staff and students at Stanford University's medical school, hospitals and clinics. Under a policy announced Tuesday, even free sticky notes violate ethics rules."

Open Access: Suber Rebuts

Open access advocate Peter Suber has challenged statements by Duane Roth and the fears of the UC Berkeley researchers concerning the move towards open access at CIRM. You can find his full comments here.

Open Access: Time to Catch the Wave

The drive for open access at the California stem cell agency moved forward last week with a presentation by University of California officials to the agency's Intellectual Property Task Force.

Following the Thursday session, Ed Penhoet, chair of the Task Force, said the group had heard "strong sentiment" for open access as described by the UC officials. But he noted that UC itself has not implemented open access policies even after three years of discussion. One UC official said he expected they may be approved next spring. Penhoet said CIRM will continue to work on the issue.

Open access means faster dissemination of research, more use of the information by other scholars and a reduction in cost to readers, according to the open access advocates.

Ben Crow, chair of the UC Academic Senate's committee on libraries, likened the impact of the Web and the Internet to the invention of printing, indicating that it was a force impossible to resist.

Francisco Prieto, a CIRM Oversight Committee member, said that sharing of research and transparency is a "bedrock principle" at CIRM. He said that open access is becoming "the standard" and that "perhaps we should push it."

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights, said, "We're paying for it. We ought to be able to see it."

But Oversight Committee member Duane Roth said the marketplace seemed to be dealing with the issue of open access. He said he was "not sure CIRM should be doing something NIH isn't."

Because of the impact of open access, Roth also raised the specter of scientific journals changing from a subscription-based business model to the advertiser-based model that newspapers follow.

One faculty member from UC Berkeley noted that young researchers in his lab opposed open access policies because of the likelihood that they would limit their ability to have their research published in the top scientific journals. Publication in such journals is the key to securing good faculty positions, they said.

Coincidentally, a group of senior academic officials from around the country, including Barbara Horwitz, vice provost-academic personnel, at UC Davis, released a letter on Friday opposing federal open access legislation. Their letter contained a link to a Web site supporting the position of scientific journals.

Our comment: Fighting the Web is like trying to fight the tide. No information enterprise can resist it successfully. Newspapers, to their financial pain, have discovered that the hard way with significant loss of revenue. (However, their current sad state of economic affairs has more complex origins and was well underway prior to the widespread use of the Web.)

The choice before the scientific journals is whether to ride the wave of Web or to be smashed into the financial rocks trying to fight it. CIRM too really has no choice. It can only fiddle with the details.

As for the hiring practices at places like UC, changing realities will force some adjustments. Cheap sorting mechanisms such as counting the number of articles a scholar has published in a handful of journals are probably somewhat inappropriate any way. It is time to build a better model for finding good minds.

In addition to Crow, John Ober, director of policy, planning and outreach, Office of Scholarly Communication, University of California, and Lawrence Pitts, professor, Department of Neurological Surgery, UC San Francisco, and former chair of the UC Academic Senate appeared before IP Task Force.. The UC Berkeley faculty member that we mentioned got away before we could get his correct name. For more on open access and CIRM, see "fading print" and "call for open access."

Not Coming Up

We are holding off on our item on the open access discussions at CIRM despite our earlier promise to have something today. But here is the bottom line, IP Task Force Chairman Ed Penhoet said there was "strong support" for open access. More consideration of matter will come up in the future. The full item will be up by sometime tomorrow.

IP Policy for Business Moves on to Final Step

Call it the 25 percent conundrum. Or the payback puzzle.

That was one key issue facing the Intellectual Property Task Force of the California stem cell agency during its meeting Thursday on IP policy for grants to businesses.

Specifically, when do businesses have to come up with plans for access to CIRM-financed therapies, making them available to the uninsured and public agencies in California? (You folks out of state are out of luck.)

As originally proposed, businesses would have to come up with access plans when the agency's funding exceeded 25 percent of the invention. At that threshold, they would also have to provide therapies at the "federal Medicaid price" when the therapies were purchased with public funds.

The committee expressed concern about definitions of such terms as the Medicaid price and public funds, which are expected to be clarified in time for the Oct. 11 Oversight Committee meeting.

Task Force Chair Ed Penhoet introduced the topic of the 25 percent trigger by noting that some companies would find it onerous. Francisco Prieto of Sacramento, another Task Force member, said he "pulled the number out of my hat" when he originally suggested it.

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights, said a percentage might be the wrong approach. He suggested tieing access plans to when a CIRM grant was made -- a "decisive point." After discussion about concepts other than a flat percentage including the idea of an "enabling amount" from San Francisco attorney Ken Taymor of MBV Law LLP, Penhoet indicated the staff would work on a percentage figure that varied, depending on when it was made in the process of the development of the therapy. Generally, the percentage would be larger at an earlier stage and grow smaller as the development cycle matured. What ultimately will be proposed will have to wait until closer to the Oversight Committee meeting.

Todd Gillenwater, vice president for public policy for the California Healthcare Institute, a biomedical industry association, said he was reserving a position on the percentage, pending completion of informal survey of some of the group's members.

Also up for clarification prior to the October meeting is language requiring the sharing of biomedical materials. Members of the Task Force were concerned about creating a burden on companies but also wanted to ensure the free flow of research. A representative of Applied Biosystems of Foster City, Ca., said he would like a provision that would allow companies to make a profit on research tools.

Most of the rest of the draft IP policy remained relatively unchanged.

Speaking to audience of 15 to 20 persons, Penhoet noted the difficulty in devising a commercial IP policy even after months of work and detailed testimony from a number of businesses. He indicated that the Task Force had plowed much new ground. Penhoet said there was a dearth of organized material on the questions before CIRM, declaring that his deputy, Mary Maxon, who performed virtually all of the research, had become the "world authority" on the subject.

The Task Force did not have a quorum for the discussion, and no vote was taken. But Penhoet was given an affirmative response when he asked the other members whether he had their permission to take the IP draft to the Oversight Committee. The meeting took place in CIRM's San Francisco headquarters. Four members of the 12-member group participated through a conference call connection. No media were present with the exception of the California Stem Cell Report.

(Editor's note: A slightly earlier version of this item contained an error in the 7th paragraph. It incorrectly stated that the variable percentage would be smaller initially instead of larger.)