Time for Tougher Disclosure on Working Groups

The Sacramento Bee and San Jose Mercury News have editorialized in favor of more stringent conflict of interest standards for members of CIRM working groups, an important element in SB401.

CIRM has so far resisted such requirements, but the newspapers say more disclosure is needed of the economic interests of scientists and others who make influential recommendations on multimillion dollars.

The Bee said,

"That would do much to ensure the integrity of the Institute for Regenerative Medicine and put it on a less contentious path."

The Merc said,

"Disclosing financial conflicts at all levels of grant review is necessary to maintain the integrity of the research and the use of public dollars."

California Stem Cell Research Regulation: CIRM is Not the Only Player

So what is a woman to do? Donate her eggs to Brand X research and lose her wages or donate her eggs to CIRM research and recoup her wages?

That is one of the subjects likely to be addressed, at least in one form or another, by the other California stem cell committee. It will meet next Thursday to consider ethical standards for embryonic stem cell research that is not financed by CIRM.

This group is an advisory panel to the state Department of Health Services and has held only one meeting so far. During its initial session Feb. 24 (See "research"), it seemed in agreement on creating guidelines consistent with CIRM regulations.

The voter-approved measure that created CIRM made it constitutionally independent of the state Department of Health Services and the advisory committee.

The agenda for the committee, chaired by Henry Greely, a law professor at Stanford, is a tad shy of details. But one item to be discussed is SB1260 by Sen. Deborah Ortiz, D-Sacramento. Among other things, that measure would extend the life of the advisory panel, but it is basically aimed at protecting women who provide eggs for stem cell research.

Ortiz' bill would additionally ban reimbursement of lost wages for egg donors, which CIRM permits. (See "wages of eggs."). That is where the double standard for egg donations comes in. No reimbursement for run-of-the-mill egg donors while donors to CIRM research can recover any lost salaries. One might imagine there will be few donors of eggs for research outside of CIRM.

SB1260 would also bar women from selling their eggs for the purposes of medical research, but does not speak to the question of women selling their eggs for other purposes. The bill has passed the Senate and seems headed for legislative approval. The governor has already indicated that he favors protecting women egg donors just as long as it doesn't interfere with CIRM.

The advisory committee might also want to examine the latest critique of the CIRM research regulations by the Center for Genetics and Society. The group sent a detailed later to CIRM on its rules, which are going through the formal adoption process, recommending a number of changes, including one dealing with a loophole involving payment for eggs.

One section of CIRM's rules, accord to the center, creates a "fiction and an illusory distinction between eggs provided for fertility and eggs provided for research."

The center said,

"Common practice in fertility treatment is to pay women per cycle, not per egg, and in fact, paying women per egg would create perverse incentives as happened in South Korea for women to be given higher doses of hormones than necessary. Suppose a woman provides one cycle of eggs from which 10 eggs are retrieved. This new regulation says that if a woman undergoes one cycle and provides 10 eggs, the clinic can pay her for 8 and then pretend that she gave 2 for free! This is nothing but a sham to create compensation for eggs for research, which is against the law."

The center proposed language that reads:

"A woman providing oocytes for donation for another person’s reproductive efforts may not donate any of these eggs to research unless she has received no valuable consideration for her donation of oocytes for either research or reproduction."

The group also had more comments on CIRM's rules for informed consent arrangements, assurances of medical care for egg donors and activities not eligible for CIRM funding.

Can CIRM Help Reduce Health Care Costs?

Suggestions that the California stem cell agency create a patent pool received renewed support recently in an article that said the state has a "unique opportunity to create a climate that will not only be hospitable to innovation but also simultaneously deliver affordable medicine."

Merrill Goozner, director of the Integrity in Science Project at the Center for Science in the Public Interest, pitched his patent pool idea again in an article on PloS Medicine. The piece is titled "Innovation in Biomedicine: Can Stem Cell Research Lead the Way to Affordability?"(See the "over the top" item below for quite a different view.)

Goozner wrote that the maze of medical patents has played a significant role in increasing costs because of the "exclusive rights/high prices model" of conventional markets. He said:

"CIRM and other stem cell funders can become catalysts for cutting through this patent thicket. They can require that all grant recipients agree to donate the exclusive license to any insights, materials, and technologies that they patent to a common patent pool supervised by a new, nonprofit organization set up for that purpose. A patent pool serves as a one-stop shop where investigators can obtain no-cost or low-cost licenses for subsequent research. Patent pools have been successfully used in other high-technology industries such as consumer electronics and software to facilitate the development of new technologies that either require common standards or rest on a common base of basic research. Several patent law firms and close observers of medical research have suggested that patent pools can work in biomedicine."

Goozner also suggested that a prize could be used as a stimulus.

"A government body such as CIRM could establish a major prize for companies and institutions that collaborate to produce a successful stem cell therapy. The prize would have to be large enough to justify the substantial investment required to carry out the final stages of research. It would also have to be large enough to share with the upstream patent holders whose basic and applied research became part of the pool that led to the new therapy. One could imagine prizes in the billions of dollars based on considerations such as the prevalence and public health impact of the disease, the difficulty in developing its cure, and the capital investment required to achieve results. A prize system has been proposed at the federal level."

Goozner continued,

"By combining a patent pool, an open-source model of IP development, and a shared prize system for developing stem cell therapies, the California state stem cell program can point the way to a new medical innovation system for the 21st century. This model could be used by all advanced industrial economies grappling with how to pay for the rising cost of the new medical technologies sought by their ill and aging populations."

Goozner pushed his patent pool concept at a hearing last fall conducted by State Sen. Deborah Ortiz, D-Sacramento. The Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., has advanced it during IP hearings by CIRM.

CGS: Democrats Over The Top on Stem Cell Research

Democrats should beware of the seductive lure of stem cell research. So says Richard Hayes, executive director of the Center for Genetics and Society in Oakland, Ca.

Hayes, who describes himself as a lifelong liberal Democrat, says he is worried about the feverish efforts by Democrats to seize stem cell research as a potent vote-getting wedge issue. Why?

Writing on Tompaine.com, Hayes says,

"I’m worried because in their over-the-top enthusiasm for stem cell and cloning research, Democrats are ignoring the many ways in which it could, if irresponsibly promoted and inadequately regulated, have consequences at odds with core Democratic values. The short-term political advantage that fervent support for stem cell research now gives Democrats could backfire when the problematic aspects of this research come to light."

Hayes says "there is no question that stem cell research should go forward."

But he says some avid supporters ignore important issues, including the question of affordability.

"If stem cell-based therapies are ever successfully developed, how affordable will these be? After passage of California's $3 billion stem cell initiative last November, its leaders acknowledged that the 'individualized' stem cell therapies highlighted throughout the campaign could cost in the neighborhood of $100,000 per patient. Who would be able to afford such treatments? Individualized medicine for the wealthy is the antithesis of the affordable, comprehensive health care that Democrats have historically and correctly made a top domestic policy goal."

Hayes also says,

"Americans want stem cell research to succeed. Democrats are in a position to take the lead on this research, but with leadership comes responsibility. We need policies that allow stem cell research to proceed at a robust but reasonable pace, while imposing tough regulations to ensure that the fruits of this research are affordable by all, that they do not endanger the well-being of women who provide eggs for research, and that they are not used for socially and ethically unacceptable purposes."

Stem Cell Advocacy Conference at Stanford

Politics and embryonic stem cell research will be topic No. 1 at a conference next week at Stanford University featuring a Nobel laureate and the governor of Wisconsin, the state with the lock on the key stem cell research patents.

The Genetics Policy Institute in Florida, headed by Bernard Siegel, is sponsoring the June 10-11 event, which is called, “Stem Cell Policy & Advocacy Summit: Empowering the Pro-Cures Coalition.”

Scheduled speakers include Paul Berg, the Nobel laureate, Wisconsin Gov. Jim Doyle, California stem cell Chairman Robert Klein, Michael West of Advanced Cell Technology of Alameda, Ca., and Larry Goldstein of UC San Diego, among others.

You can find more information about the conference by clicking here.

"Dualing" Execs at CIRM: Touchy Issues Between Klein and Hall

On the surface, the problem seemed ridiculously simple.

But at its heart lay matters of trust between two strong executives in a new, $3 billion organization hobbled by an inflexible structure virtually impossible to change.

The flap surfaced at the May 19 meeting of CIRM's Governance Subcommittee. The nominal topic was internal policy at the California stem cell agency – normally a soporific subject. But all were alert when the focus fell on who decides which staff members will have offices with windows and who approves travel – Robert Klein, chair of the CIRM Oversight Committee, or Zach Hall, president of CIRM?

The details, however, are less important than what they reveal about CIRM, the Oversight Committee, its two top executives and their relationship.

The transcript of the session exposes an organizational rawness that rarely is seen in public from any business or government agency. Most of the members of the Oversight Committee have undoubtedly encountered comparable situations from time to time in their careers as managers and executives. But dealing with it was troubling for some.

"If there's just not a level of trust with the president and the office of the chair...it causes me great concern and heartache," said David Serrano-Sewell, a member of the Oversight Committee and a patient advocate. He added that "a million people are coming after us" and that the agency did not need internal dissension.

Another member of the Oversight Committee, Claire Pomeroy, dean of the UC Davis Medical School, was among others concerned about the relationship between Klein and Hall. "If we have a situation where our chair does not trust the president will make appropriate decisions about the travel budget and office space, then that's a larger issue," she said.

Normally such a management split could be resolved relatively easily or avoided entirely by an organization's board of directors – the Oversight Committee, in the case of CIRM. But the voter-approved law that created the stem cell agency spells out in statutory language the specific duties of the president and chair of the agency and creates something of a dual executive situation. Many of Klein's and Hall's responsibilities are locked into state law that cannot be touched by the legislature for two years or so, and then changed only by a super-majority vote of both houses and the signature of the governor.

Adding to the complexity is the 29-member Oversight Committee, a quasi-legislative body attempting to act as an executive committee. The group does reasonably well as a deliberative body, but sometimes it resembles nothing more than an elephant trying to dance as it wrestles with its executive chores. In this case, months ago it approved organizational details that created more overlap in the dual executive situation. That might not have been a problem if Hall or Klein were a weaker leader or manager. But both are strong, capable executives, albeit with different personalities and styles.

The issues reflect "tensions and challenges" rumbling through CIRM for the past year, according to Oversight Committee member Philip Pizzo, dean of the Stanford University School of Medicine. Those tensions surfaced when Hall presented the Governance Subcommittee with a draft of CIRM's mostly routine internal policies. He said that he and Klein were in agreement except for two issues – who controls office assignments and travel, particularly out-of-state travel.

The two men have discussed the matters since September, when Hall was named permanent CIRM president, but he said they have been unable to resolve their differences. Hall asked for a decision by the subcommittee.

He said he was held accountable for the activities of all CIRM employees, including those assigned to the "office of the chair."

"I need to be sure that both whatever is done are things that I can defend as a responsible manager and administrator of the institute and also that policies are applied consistently across the institute so that we're one organization and not two....I feel very strongly about it," Hall said.

Later he said in reference to such matters as assignment of offices,

"All these little status things sound small, but in actual fact they weigh heavily often in terms of people's morale and the sense that there's a set of rules and that they're applied fairly to all people."

For Klein as well, it was a matter of responsibility. He said,

"First of all, the chairman is responsible as an individual to the board and to the public. and if the chairman isn't responsible, there shouldn't be the chairman."

He also said,

"I don't want responsibility without the ability to perform. And what's important here is that the office of the chair is responsible to the board for many functions. And if we're going to micromanage the ability to perform those functions, the office of the chair, whether I fill it or you get somebody else to fill it, will not be able to perform."

As the discussion intensified, Klein responded to one question by saying:

"I'm limited out...I'm really at the edge where if I'm going to be able to perform, having another level of approvals is just so redundant, that I question the organization and the burdens being put on me and whether they're reasonable."

Ultimately the subcommittee approved a motion that said expenses for travel exceeding those budgeted for the office of the chair must be approved by the president. Hall and Klein were directed to work out a "peaceable solution" on a system for office assignments, with the assistance of Tina Nova, CEO of Genoptix, Inc., and also a member of the Oversight Committee. "If there is disagreement," the motion said, "it is the president's final approval authority that stands."

The split could surface again on Friday when the internal policies of CIRM come before the Oversight Committee in a public session. The matter may arise as well behind closed doors as a personnel issue.

The fundamental problem, however, is not going to go away easily, as more than one Oversight Committee remarked.

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For a look at how Klein views the specifics on the travel issue, see the item below that includes comments from Hall and others. Klein's office is budgeted $30,000 for travel for the current fiscal year, up from $20,000 earlier. The office of the president is budgeted $6,000 for travel, up from $5,000. Another $5,000 is also budgeted for travel by the agency's science and administration offices. For the first six months of the next fiscal year, $37,000 is budgeted for all CIRM travel.

You can find the full transcript of the subcommittee hearing here. The discussion begins on page 54. A cautionary note: It is easily to misunderstand emotions and emphasis in raw transcripts that are missing voice inflection and other nuances. Read with care.

CIRM Travel Comments

Here are comments from Robert Klein, chairman of the California stem cell agency, and Zach Hall, president of CIRM, concerning out-of-state travel and related comments from two Oversight Committee members.

Hall introduced the topic of travel at the May 19 Governance Subcommittee meeting by saying,"

My understanding is that all out-of-state travel and out-of-the-country travel requires my approval. And I think the reason for that is in the end I'm held responsible if we have abuse or misuse. This is the kind of thing that is apt to, I think, make the headlines, and I also think that this is an area in which we need consistent policies across the institute. And so although my intent is not to micromanage here, but simply to be sure that in the final analysis, since I'll be held responsible, I want to be sure that I am able to approve those."

Later Klein said:

"What's important here, if I have to go to Washington, D.C., on a drop of a hat because Frist moves the Castle/Degette bill in the Senate without notice -- which is, in fact, the anticipated strategy – I need staff that may have to pack on a weekend to get there. And I will be rearranging my life as well as my business as well as all of our CIRM functions, and having another level of encumbrance, we still have to get to ... to get the state director of finance's approval, and we have budgeted in our budget out-of-state travel for staff that we have support in situations like that. So fulfilling my function just on a real-time operational basis is challenging at best. and as long as we're within the budget here, I need to be able to do that to perform my functions that are critical to the mission."

Philip Pizzo, dean of the Stanford University School of Medicine, responded shortly thereafter with a quick follow from Claire Pomeroy, dean of the UC Davis School of Medicine.

Pizzo:

"In fairness, I think all of us can resonate to the boundaries surrounding this. If I needed to, you know, get approval to travel to Washington because of (a) key issue, I would object to that as well because I think I need to make certain decisions about that."

Pomeroy:

"I have to get approval every time I travel."

Pizzo:

"Well, that's why I left the NIH actually, to be honest with you."

Pomeroy:

"You work for a private organization, and CIRM is not a private organization."

Staff Turnover at CIRM

Two "veteran" staffers of the California stem cell agency are leaving the agency. We place "veteran" in quotes because both have been in place for only a little more than year, but that does make them relatively long term employees in an organization that still has not reached its second birthday.

One of them is Walter Barnes, chief administrative officer, and the other is Nicole Pagano, who has served as the spokeswoman for CIRM.

Barnes initially was on loan from the state controller's office to CIRM as it struggled in January 2005 to set up procedures and to learn the ropes of being a state agency. Barnes plans to leave CIRM in mid-September.

CIRM President Zach Hall described Barnes as "invaluable and superb."

"He's been an incredible link to the state government. He's advised us all in the ways, arcane ways, of being a state agency in government, and so we are going to miss him," Hall said.

Hall's comments came at the May 19 meeting of the Governance Subcommittee when news of Barnes departure slipped out.

Barnes said,

"This is a major, major jewel in my crown as I get ready to retire. I can't think of any way I would have preferred to spend my last years."

Pagano's departure also slipped out. Stem cell chairman Robert Klein said Pagano has done a "fabulous job."

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Right and a once a newspaper editor, told the subcommittee,

"She's been a wonderful press person to work with. I'm a former journalist, and you often don't run across talented and capable professionals in that side of things. She's been outstanding, and we're going to miss her."

No replacements have been announced.

Klein Caught in Stem Cell Blow-back

California stem cell chairman Robert Klein was hoist on his own political petard during an ironic moment involving legislation to tighten oversight of the California stem cell agency.
The subject was SB401, which would be placed on the ballot for approval by voters.

Klein, an attorney and one of the main authors of Prop. 71, objected strongly to the proposal during the last meeting of the Oversight Committee. Among other things, he told the CIRM overseers:

"This is legislation that creates an initiative. So if this is passed, you can't even, if there's an error in it, you couldn't even change it with (normal) legislation. You have to go back to the voters with an initiative. So it's not just what's being attempted, but the form of what's being attempted. Is an initiative to the voters necessary? That's a question. And is an initiative to the voters premature?"

Klein is exactly right – at least about the nature of SB401. He used the same technique (Prop. 71) to create the stem cell agency and froze out nearly all normal government oversight of CIRM. Klein sees the absence of what he perceives as political interference as an asset for the agency. That is why the folks that see defects in Prop. 71 – and there are many – have to resort to ballot measures to get the attention of CIRM. It happened last year at this time with SCA13, and it is happening again with SB401.

Just call it stem cell blow-back.

(For more on the views of the Oversight Committee concerning SB401, see the transcript of the April 27 meeting. The subject comes up again this Friday at the next meeting of the group.)

Ortiz' CIRM Bill Delayed Until August

Action on sweeping legislation to tighten oversight of the California stem cell agency has been put off until late this summer.

The measure, SB401 by Sen. Deborah Ortiz, D-Sacramento, was amended at her request to eliminate a provision to place it on the fall ballot. That removed the most imperative reason for quick action on the bill. (See "critical elements." )

Her office said the proposal will not be heard in the Assembly Appropriations Committee until August when the committee takes up other Senate-passed bills. CIRM's Oversight Commmittee is scheduled to discuss its position on the measure at a meeting Friday.

Another stem cell measure by Ortiz, who is the most influential state legislator on stem cell matters, cleared the Senate floor this week and moved to the Assembly.

That bill, SB1260, is aimed at protecting women who donate eggs for stem cell research. It would not affect research financed by the stem cell agency, which has approved separate standards.

This is Ortiz' last term as a state senator and chair of the Senate Health Committee. She is running in next week's primary election for the Democratic nomination for California secretary of state.

See this link for the latest Senate analysis of SB1260. See this link for the CIRM analysis.

BioCentury: NIH Looking Korean Stem Cell Lines

BioCentury, which offers business intelligence for the biotech industry, has come up with an item concerning the use of Korean stem cell lines in the United States. It is not clear whether any California institutions are affected.

Here is the headline and lead paragragh:

"NIH halts use of Korean stem cell line

"An NIH spokesperson said the institute has received 'credible information' that a South Korean hospital has replaced a federally approved human embryonic stem cell line with an unapproved cell line. NIH's John Burklow told BioCentury that the institute has launched an investigation, and NIH intramural and extramural researchers will be notified that they should halt all research involving the Miz-hES1 stem cell line from the MizMedi Women's Hospital in Seoul. NIH estimates that three of its intramural scientists and a "handful" of extramural grantees have received Miz-hES1 cells and will have to halt ongoing projects."

Uncertainty and the Ostensible Stem Cell Swag

How can California share the wealth from inventions created by California businesses that receive funding from the state's stem cell agency?

Ed Penhoet, a multimillionaire businessman and vice chair of CIRM, will offer some thoughts on the subject next Friday at a meeting of the agency's Oversight Committee.

Penhoet is chair of CIRM's Task Force on Intellectual Property, which has held two hearings in the past few months on the matter of splitting up the ostensible booty. Businesses, industry organizations, economic developers and nonprofit groups have testified. At least one more hearing is scheduled. Given the complex and difficult nature of the subject, that may not be enough.

Penhoet's role so far seems primarily as a facilitator. If he has specific approaches he favors strongly, they are not readily apparent, based on an examination of the transcripts. The closest he has come to staking out a position may be a comment in the April 27 meeting. He said that there should be a return to the state if the technology is successful. He also said it should be capped, which helps deal with businesses' uncertainty about the size of their ultimate payouts.

Uncertainty is one of the themes underlying the entire IP issue. No certainty exists, for example, that any CIRM-funded inventions will generate significant amounts of cash, despite grandiose assumptions by some. As Duane Roth, one of the newer members of the Oversight Committee and CEO of Alliance Pharmaceutical Corp., said, "100 percent of nothing is nothing."

At the April 27 meeting, Roth laid out a framework for any IP policy:

"What I think you're trying to do with intellectual property for start-up companies is create an environment where you can leverage financing and try to get people to invest in an idea, a dream. and they aren't going to do that unless they think, if they go through all this work and expense and risk, that there in the end is return. That's the first thing IP needs to do.

"The second is you want that IP to lead to products that actually get to people. and from our standpoint, you start these things, and that's what it's all about, getting products to patients. Taking good science and develop products and get them to the people that need them.

"The third consideration, and an important one, is royalty. If there is a contribution to the intellectual property that eventually leads to a product, which is a rare occasion, then there should be a sharing of the profits that are derived from that."

Roth's view was one of many expressed during the IP hearings. John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., advocated state ownership of patents on CIRM-funded inventions by businesses, 25 percent royalties, low cost access to the therapies, patent pools and designation of the state attorney general as the enforcer of IP agreements. Simpson prepared a position paper for CIRM which said,

"Already some biotech executives have said the industry will decline CIRM money if the companies must share the rewards of Proposition 71 stem cell research grants with California taxpayers who put up $6 billion to finance the research. Too many biotech companies act like committed socialists when it comes to taxpayers and the government bearing the risk of drug development. But they are greedy capitalists when it's time to parcel out the profits."

"Ignore the bluff and blustering threats of picking up the Petri dishes and going home if they don't get their way. Any attempt to grab 'free money' without equitable public benefit requirements for biotech won't work. First-class companies understand that with the acceptance of taxpayer dollars comes the responsibility of public benefit. And with $3 billion on the table, there will be plenty of top-flight firms and researchers ready to play by fair rules like those outlined here to search for cures.

Julie Meier Wright, CEO of the San Diego Regional Economic Development Corp., said 25 percent was unrealistic, suggesting other figures that were as low as one percent.

"Three billion dollars in California sounds like a lot of money, but it will be spread over ten years and over a broad array of investments for many worthwhile endeavors. so even if CIRM makes what for it would be a significant investment in a for-profit company developing new therapies, this investment will likely be a small percentage of the total investment required to bring these therapies to commercial success," she said.

"So if you assumed a $10 million investment, and I don't know what your threshold for investment is going to be, but a $10 million investment in a young company that ultimately requires $500 million before commercial success, CIRM's investment is 2 percent. So my question is how does a 2-percent investment warrant onerous royalties or IP requirements?"

She continued,

"The framework that you've developed for not-for-profit institutions was the 25-percent royalty payment would truly be a disincentive on the private side to attracting private capital. and I think most private investors would tell you that they don't expect more than 1- or 2-percent royalties on therapeutics and maybe 5 percent or so on medical devices. so you could have the unintended consequence of discouraging private sector investment with some things that would be very good, and it could prevent CIRM from really being a catalyst for the best ideas and the best science at a really critical time in the life cycle of a for-profit company."

She and others focused on indirect but unquantified benefits to California, such as enhancement of the biotech industry, which in turn will generate business and income taxes and lead to related economic growth. Again, projections filled with uncertainty.

Representing the biomedical industry was John Gollaher, president of the California Health Care Institute, who emphasized what business can bring to stem cell therapies.

"CIRM should discount any claim that stem cell science can benefit patient groups without aggressive participation of commercial companies. The fact is that we live in a market-based, market driven economy, and the theory that most commercial companies operate on is the theory of capitalism And the best distribution of goods and services happens through the active participation of the market and of commercial enterprise. and, again, any of us who spent significant time in academic institutions or within government institutions, I think, have a low level of confidence in the ability of those organizations to quickly move technology through the widest possible allocations for the greatest public benefit.

"Finally, CIRM should discount attempts to regulate commercial transactions in ways that discourage participation of the best companies and entrepreneurs. I think the concern that we've heard more than once is that the more strenuous conditions, royalties, caveats that are attached to technology transfer relationships, the more reluctant commercial participants are to capitalize on those relationships and those technologies. So I think from CHI's point of view, guiding principles for CIRM with respect to commercial IP policy should be, first, maximum acceleration of the best science. And whether that science as technology exists in a commercial company or in an academic institution, CIRM should be rigorous and thoughtful in making investments behind the best science. CIRM has collected an astonishingly good set of expert scientific reviewers, and the ability of CIRM to make intelligent judgments with respect to where the best science is and where funding opportunities lie, I think, is superb and should be applauded."

Joydeep Goswami, vice president, stem cell and regenerative medicine, Invitrogen Corp., Carlsbad, Ca., discussed motivations for companies to seek financial assistance from agencies such as CIRM. He said CIRM grants might back research that a company could not currently fund or research that "doesn't make economic sense to fund immediately."

In the case of his publicly traded company, Goswami said,

"There are some very serious conditions of the kinds of risk profile of investments we make and the research we conduct. So having public funds or government funds sometimes allows us to take on risk profiles and projects that the market would not, frankly, like us to take...but it could have rewards for the research community and others."

Allan Robins, vice president and chief technical officer of Novocell, an embryonic stem cell company in Irvine, Ca., spoke about his company's experience with the Juvenile Diabetes Research Foundation, an organization whose research funding program was viewed favorably by several of the IP Task Force members. Robins said the foundation's contracts are individually negotiated, which he recommended that CIRM emulate. He also said the foundation's contract with his firm did not require royalties. Rather it asked for repayment of three times of the total, depending on product sales. Robins also objected to Simpson's 25 percent royalty figure as too high.

Here are links to the full transcript of the April 27 hearing and the Power Point presentations by Simpson, Gollaher, Robins, Wright and Goswami. See "swag" and "greed" for discussion of the earlier meeting this spring. Closely related to the IP discussions is the strategic planning process now underway at CIRM. You can find more on that by clicking here.

WARF: Onerous and Outrageous

The friendly folks at WARF were thrashed thoroughly at last month's meeting of the California stem cell agency group looking into who gets the money from stem cell inventions.

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., led off the April 27 session of CIRM's Intellectual Property Tax Force with a statement of some vigor. "Really outrageous" is how he described the WARF stem cell patents.

We have presented Simpson's position before so we will offer up the thoughts of others at the April 27 meeting, but first a comment from Ed Penhoet, chair of the IP Task Force. His statement came late in the meeting after he listened to much of what you will read below.

Penhoet said,

"There is a thread in these conversations: Patents are extremely important...except the ones they don't like.... You can't have it both ways. So hopefully the field as a whole can reach some sensible accommodation to WARF for the pioneering work that they did do, but at the same time not stop the entire field from going forward. It's a hard problem actually."

Penhoet also said that WARF has been invited to make a presentation before the IP Task Force.

Penhoet's comments, however, do little to minimize the deep seated antipathy to WARF's position as reflected in the comments below. One might imagine that WARF might be concerned that potential customers are so distressed.

Joydeep Goswami, vice president, stem cells and regenerative medicine, Invitrogen Corp., Carlsbad, Ca., was asked whether the WARF patents are "a significant obstacle to private investment."

His reply:

"I think they are....I know a lot of you know about the WARF policy for not-for-profit research tends to be somewhat, well, somewhat generous, although many scientists that we have spoken to are quite taken aback at some of the restrictions that are put on academic institutions in terms of collaborating with companies such as us.

"For private institutions, I think it is a big disincentive because what WARF does is it looks at the size of the institution or the company that wants to license this product and wants to charge an upfront payment, which is very steep in any licensing terms, and then, of course, royalties obligations which are twofold. one, a direct royalty obligation which depends on products directly produced using stem cells, human embryonic or primate embryonic stem cells, but they also have a reach-through royalty clause where they say anything you've invented remotely by using human embryonic stem cells will now have a royalty obligation back to WARF. So, for instance, even if you had a treatment that was somehow brought to the market that has touched an embryonic stem cell in the United States, you will have to pay a royalty back to WARF. I think this is particularly onerous....

"Let's say we make a discovery of a tool using at some point a human embryonic stem cell. They want a royalty back on that particular product. and not only do they want a royalty back on sales of that product to the embryonic stem cell market, but any market that we touch, they want a royalty back on that particular tool. So it is quite onerous."

Francisco Prieto, a member of the task force, then asked, "Even markets outside the United States?"

Goswami:

"Yes. In general they would. See, the other part is...if you look at companies in the United States versus outside...which is actually even more interesting. Let's say there's a company in India....For anything they do with respect to human embryonic stem cell research, they owe no royalties to WARF. They do not have an obligation to WARF in any manner, way, shape, or form, and they can develop exactly the same therapies companies in the United States are trying to develop without any kind of restrictions or obligation to WARF. So from that point of view, setting up a company to do stem cell therapy in the United states, I think, is a major disincentive, and people are not realizing this business issue....The issue is not whether the patent is legitimate or not, but there are serious business implications of the patent in making cures available to the public here."

Later, Allan Robins, vice presidennt and chief technology officer for Novocell Corp. of Irvine, Ca., said,

"I thought Francisco (Prieto) brought up a very good point. and, Joydeep, I just wanted to add a little bit to your answer.....If a company in the field or the United Kingdom or Singapore develops a product or human embryonic stem cells and that product is different from the human embryonic stem cell, that product can be imported into the U.S.A. and sold here, and that would not infringe the (WARF patent) line. and so you really are putting companies that operate in the U.S. at a disadvantage."

Goswami:

"That's a great point."

Prieto:

"That was sort of what I was starting to glean from this that as they currently operate, that these patents are a disincentive to the research in the United States."

Goswami:

"It is enormous. And the patents only, as Allan rightly points out, are to the composition of matter of the primate embryonic stem cell and the method of derivation. So absolutely."

Later Goswami said:

"The (WARF) licensing model is...is huge upfront payments for a field that is, you know, pardon the pun, but embryonic. Just from a business point of view, it makes very little sense. and that's why maybe CIRM could help in enabling that particular patent because it will be used by almost everybody that is engaged in this form of research in the state of California."

We should note that the WARF issue was only part of the IP discussions. The full text of the session can be found by clicking here.

Looking at Legislation to Aid Biotech Biz

"Investors' disinterest" in California biotechnology came up for examination in a recent piece in the Vacaville Reporter, the daily newspaper for the community that lies between San Francisco and Sacramento.

The article by business writer Amanda Janis focused on the "realities of the manufacturing side of biotech." It was of interest to Vacaville readers because of the area's efforts to land biotech manufacturing facilities. But the piece also has interest to California as a whole.

Janis wrote:

"Industry leader Genentech chose to build its new $250 million facility in Oregon, where corporate income tax structures are more favorable. Then there was the start-up firm that passed on Vacaville in order to capitalize on biotech tax breaks offered in Washington. And most recently Chiron parent Novartis announced it would build a $400 million vaccine plant in the United States, but not in California."

She touched on state legislation aimed at helping the biotech business.

"Proposed bills include changing the corporate income tax structure with a four-year phase-in of single sales apportionment tax (an issue Genentech calls its primary legislative concern); sales and use tax exemption on manufacturing equipment; extension of research and development tax credits; and the allowance for companies to sell their net operating losses to other companies, which would gain a tax credit.

"The latter proposal, which has found success in states like New Jersey, has some of the greatest potential impact because of the loss-operating nature of the biotech industry, according to Matt Gardner, president of trade organization BayBio.

"'It takes 15 years for us to get a product,' he noted.

"Another proposed bill in California would help level the playing field, he said, because it would allow for designated "shovel-ready" land, or land that has been pre-zoned, with environmental impact reviews completed."

Legislation to help out the biotech industry has received little notice. But it is likely to become increasingly important to the industry as the CIRM investments ramp up.

WARF to CIRM: Don't Mess With Us

The Wisconsin Alumni Research Foundation has served notice that it is going to slug it out with the California stem cell agency on the matter of stem cell patents.

Referring to comments in California concerning WARF's position on the Wisconsin patents, Andrew Cohn, government and public relations manager for the organization, said, "These folks are absolutely going off the deep end. If it wasn't for WiCell and for the University of Wisconsin, they wouldn't have anything to spend the $3 billion on in the first place."

Cohn was quoted in a piece by Joe Vanden Plas on the Wisconsin Technology Network. Vanden Plas said the patent dispute between California and Wisconsin "promises to be an intense fight." Cohn's pugnacious language certainly seemed to confirm that. His rhetoric was definitely more aggressive than comments made by WARF General Counsel Elizabeth Donley earlier this year.

The Wisconsin article noted that WARF this month was awarded $1 million in a case against Xenon Pharmaceuticals. Cohn said, "WARF has proven over and over again that it will enforce its patents and its contracts. This company [Xenon] made a very, very bad tactical decision by trying to get out of, or trying to ignore the contract they made with us. They are now paying for it dearly."

The starting point for Vanden Plas' article was a statement by the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., that said a recent U.S. Supreme Court decision means that WARF has less power to assert "dubious patent claims to control all human embryonic stem cells in the United States."

Stem Cell Snippets: Swells, Scholars and Door Knockers

Here are links to recent, interesting news stories, press releases or information connected to California stem cell issues.

CIRM Gala – Aldrich Tan writing on sanfranciscosentinel.com – Possibly the only coverage of the event, includes many photos with the headline "Swells turn out in force to support CIRM fundraising event."

CIRM Scholars – San Francisco Business Times -- "Demand for fellowships funded by the California Institute for Regenerative Medicine's training grants are far outstripping available spaces, according to Bay Area institutions awarded funding."

Q&A with Alan Lewis, new CEO of Novocell, of Irvine, Ca. – Written by Terri Somers in the San Diego Union-Tribune – Lewis, who is fond of "photographing old door knockers," says, "We expect to be the only company to provide a cell therapy for all insulin-requiring diabetics -- approximately 6.5 million patients in the U.S. alone. We also expect to generate an unlimited source of insulin-producing cells that we can encapsulate to deliver under the skin to this group of patients and hopefully change their lives by reducing dramatically their need for insulin shots as well as the many diagnostic procedures they face each day."

The Chronicle Calls for SB401 Compromise

The San Francisco Chronicle is telling the California stem cell agency and the state legislature's most influential stem cell advocate to settle their differences and move on with stem cell research efforts.

In an editorial, the Chronicle said that it would be better to avoid a ballot measure on the stem cell agency, which would be required by legislation – SB401 – authored by Sen. Deborah Ortiz, D-Sacramento, chair of the Senate Health Committee.

The Chronicle said,

"Ortiz has helped open a dialogue with the CIRM that will prove immensely useful to the public as their money is spent over the next decade. In her bill, she has prodded CIRM to adopt intellectual-property standards that would require for-profit companies using Prop. 71-funded research to return some revenue to the state, and the agency has agreed. She has also asked the board to take publicly available financial conflict-of-interest statements for the scientists who will review grant applications -- and it's still resisting."

The Chronicle continued,

"Far better would be for Ortiz and CIRM to work out their differences -- which, from where we sit, don't look too daunting -- outside of legislation. Ortiz is reasonable and flexible -- last week she agreed not to push SB401 for the November ballot. In recent months, CIRM has made an exemplary effort in trying to balance the concerns of industry, taxpayers and scientists as it proposed high governing standards. Ortiz's move allows not just her, but also a host of other interests, a tremendous opportunity to engage CIRM as it firms up a set of guidelines that take into account what's best for everyone in California.

"The key will be to lock in these regulations so that promises of transparency and checks against conflicts of interest are not dependent on the whims of whoever happens to be in charge of the stem-cell program at any given moment."

There is a bit of a rub in the "lock-in" requirement proposed by the Chronicle. The only way to do that is with a ballot measure. Indeed Proposition 71 is perhaps the best example of locking in matters bettered suited for regulation or legislation. If CIRM were not "locked in" the state constitution, it could have avoided some of the problems that have beleaguered it. Others, however, may well have arisen.

Regulations enacted by CIRM can be changed by CIRM. But Ortiz last year was satisfied with other regulations approved by the stem cell agency. And she may well be satisfied with them again.

Legislation, Budget and More on Oversight Committee Table June 2

CIRM's Oversight Committee is scheduled next week to take up sweeping legislation that would make major changes in the operations of the California stem cell agency.

Also on the table at the June 2 meeting in La Jolla are conflict of interest regulations for CIRM working groups, one of the issues involved in the legislation, SB401 by state Sen. Deborah Ortiz, D-Sacramento. Last week Ortiz said she would modify her bill substantially to mollify critics, including removing a provision that would have placed it on the November ballot.

She has indicated that she is not wedded necessarily to a legislative or electoral answer to her concerns. It may well be that the Oversight Committee may find some common ground at its meeting.

Also on the agenda are a report on the efforts to define an intellectual property policy in connection with grants to businesses, the strategic plan, regulations on human stem cell research and the agency's 2006-2007 budget.

Some of the background documents are available on CIRM's Web site, largely ones that have been previously posted for subcommittee meetings. The report from the legislative subcommittee is not yet available nor is the the 2006-2007 budget or additional information on the the conflict of interest regulations.

San Diego Paper Had It First

A national story earlier this month involving the resumption of the human embryo cloning at UC San Francisco is a good example of how the media works – or doesn't work.

The case in point was a piece in the Wall Street Journal that said UC San Francisco was going to restart its program. The story was a follow on a story in the San Francisco Chronicle, which is obviously read by Journal reporters.

What neither story pointed out was that it was a bit of old news. Reporter Terri Somers of the San Diego Union-Tribune actually had it on Jan. 11, but the San Diego paper is not one that is regularly examined by reporters and editors of national publications or for that matter the San Francisco Chronicle. Her story said,

"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."

She focused primarily on research efforts in San Diego, which is a hot bed of stem cell research, mentioning the San Francisco effort deep in her story.

The episode is a good illustration of the tunnel vision of national news gathering organizations -- not just the WSJ -- which rarely detect what is happening outside of what they perceive as the major news centers.

The California Stem Cell Report carried an item in January on Somers' story but also failed to note specifically the UC San Francisco effort. We thank patent attorney Lawrence Ebert for pointing out Somers' work to us.

Devising a Plan for a Multi-Billion Dollar Project: The CIRM Approach

If you are interested in how the California stem cell agency plans to give away $3 billion, check out the agency's Web page on its strategic planning activities.

It is a useful step in the process with information ranging from meeting schedules to biographies of some of the important players.

One of the more interesting items is a summary of a meeting earlier this month by the Strategic Planning Advisory Committee. It itemizes ideas that were broached at the session, ranging from cord blood research to the harvesting of tissue from cadavers. The ideas are just that; the agency cautions that none are endorsed at this stage by CIRM. Nonetheless they provide some idea of what is being seriously discussed.

The document also indicates some concern about CIRM's outreach to researchers. For example, it said,

"CIRM needs to find more aggressive ways to engage and inform scientists about stem cell funding opportunities than sending out grant requests through the CIRM web site or the standard Request for Application (RFA) process. A newsletter might be a one way to accomplish this; to keep the 'buzz' alive and to distribute information."

The Internet postings on strategic planning are a good start on the buzz. One of the notices announces a daylong conference at Caltech on Thursday. The topic is "Funding Structures to Advance Stem Cell Research and Therapy."

Here are the speakers and topics: Michael Rudnicki, M.D., Ph.D., University of Ottawa, Canada, the Canadian stem cell network; Michael Amos, Ph.D., National Institute of Science and Technology, The Advanced Technology Program: Innovative Technology Solutions Through Industry-led Public-Private Partnerships; Ethan Signer, Ph.D., High Q Foundation, Managing the Search for Huntington Disease Therapy; Richard Insel, M.D., Juvenile Diabetes Research Foundation,Research Strategy and Funding Programs of the Juvenile Diabetes Research Foundation, and Jonathan Shestack, Cure Autism Now Foundation, who is also a member of the CIRM Oversight Committee, no topic announced.

The calendar also shows that the Strategic Planning Advisory Committee will meet in San Francisco next Monday at noon. Included will be a report on the Caltech session as well as discussion of funding mechanisms for the private sector and whether new ESC lines should be a focus for early funding.

Another strategic planning meeting involving the CIRM Oversight Committee will come the evening of June 1 in La Jolla. The panel is scheduled to act on a proposed mission statement and objectives.

It is not too early to think about a daylong meeting on July 13 in San Francisco on the topic of "The Scientific Challenge: From Basic Science to the Clinic." Confirmed speakers are: Stuart Orkin, M.D., Harvard Medical School; Joan Samuelson, Esq., Parkinson’s Action Network and a member of the CIRM Oversight Committee, and Allen M. Spiegel, M.D., Albert Einstein College of Medicine.

CIRM also provides an email address for those who want to comment on the plan or make suggestions: scientificstratplan@cirm.ca.gov.

Stem Cell Snippets: Liberal Folly, WARF and SB401

Here are links to some recent, interesting news stories, press releases or other items connected to California stem cell issues.

Problematic payoff on stem cell research – Daniel Callahan in Bioethics Forum -- "The California stem cell initiative had a super-rich real estate tycoon leading the charge, lots of money from the biotechnology industry, the support of celebrities, and that best of American mixes, the possibility of saving millions of lives while making millions of dollars.... We may or may not ever see a payoff from stem cell research, but that’s where the action is, and with the blessing of liberals. This is not a proud moment for us."

WARF not helped by U.S. Supreme Court – Press release from Foundation for Taxpayer and Consumer Rights -- "A ruling by the U.S. Supreme Court this week involving online auction giant eBay means an affiliate of the University of Wisconsin has less power to assert its dubious patent claims to control all human embryonic stem cells in the United States."

San Diego Union-Tribune endorses SB401 – Editorial written prior to Ortiz' proposed changes in the bill -- "Increased accountability and openness from the institute and its oversight board are needed....Instead of fighting the Legislature and those concerned about openness and accountability, the institute's leaders should continue to work closely with lawmakers and reach agreement on what needs to be done. That would be a better outcome than legislation that may, in some places, be too restrictive."

CIRM Meeting Documents Posted in Timely Fashion

The California Stem Cell Report has repeatedly noted that the California stem cell agency regularly falls short of its oft-repeated goal of adhering to the highest standards of openness and transparency.

The chief example is the extreme delay in posting on the Web background material for meetings. Even members of the Oversight Committee have complained about not receiving the material in a timely fashion. The laggardly posting shows in their meetings when it is clear that some members of the committee have not read the material. Of course, they just may not be doing their homework.

This week, a notable and praiseworthy exception occurred concerning the background material. The documents for the Governance Subcommittee meeting Friday were posted about a week ago. That allows the public, interested parties and Oversight Committee members ample time to review the documents. The timely postings also permit individuals to make decisions on whether they want to testify on a particular point.

Among the items on the agenda is a report on contracts, including the $400,000 agreement with PricewaterhouseCoopers to work on the strategic plan, and compensation for CIRM employees. Another item involves discussion and changes in CIRM's gift policies, which may trigger a discussion of the $1 million gala fundraiser next Monday for CIRM.

The meeting can be heard at multiple locations throughout the state, including Stanford University, La Jolla, Carlsbad, Sacramento, San Francisco and Irvine. Persons attending can also comment from those locations. For details, see the agenda.

Ortiz Drops Critical Elements from CIRM Oversight Bill

Major changes will be made in legislation to tighten oversight of the California stem cell agency, including the elimination of provisions that could have required royalties as high as 50 percent on inventions financed with state funds.

The moves may well be an initial step in a compromise on the sweeping legislation by California State Sen. Deborah Ortiz, D-Sacramento, who is the leading legislative voice on stem cell issues. Her decision to strip significant provisions from SB401 makes it clear that CIRM needs to address the other issues in the legislation. Ortiz has made it known for some time that she is not wedded to a ballot measure or legislation to ensure accountability and openness.

Her office indicated late Wednesday that the measure will be amended before it comes up again in the Assembly Appropriations Committee, which is its last stop before it goes to the Assembly floor. The committee Wednesday delayed action on the bill until late next week.

According to Hallye Jordan, director of communications for Ortiz, the senator told the committee that she intends to address critics' concerns that "the bill’s intellectual property provisions are inflexible and will discourage industry participation in stem cell research and that she is carrying the bill for political purposes."

Here is most of Jordan's statement on Ortiz' appearance Wednesday:

"She told committee members that she intends to amend the bill's IP provisions so that they mirror the regulations that the Independent Citizen’s Oversight Committee and the California Institute for Regenerative Medicine (ICOC/CIRM) have already adopted and which are currently under review by the Office of Administrative Law, per the Administrative Procedure Act. In doing so, she noted she is giving up the ability to get a higher share of royalties and better prices that might have been achieved under the original provision of SB401.

"She also said she will amend the bill to make it clear that it will not go on the ballot until after the November 2006 election.

"These amendments are expected to go a long way in addressing critics’ concerns, leaving, perhaps, only the argument that opponents don’t want to have stem cell research back on the ballot. Senator Ortiz and other legislators believe voters have a right to determine whether SB401 will provide public accountability and the appropriate protection of the state’s $3 billion-$7 billion taxpayer-funded investment into stem cell research.

"SB401 is important to ensure that the CIRM, ICOC and working group members are subject to public accountability, and hold meetings in public, make their records public and disclose of their financial interests as required of all public officials.

"SB401 includes exceptions so that the working group members may conduct scientific peer review and protect proprietary or scientific prepublication information when appropriate. The Senator and other SB 401supporters believe the ICOC/CIRM proposed regulations allowing the ICOC president to waive the conflict of interest provisions in 'exceptional' circumstances, do not provide clear, defined criteria as to what constitutes 'exceptional' circumstances. They also are concerned with ICOC/CIRM provisions that exempt from open meeting discussions and public record disclosures 'critical mission' matters, which also are vague and overly broad.

"Senator Ortiz also pointed out that there is no guarantee that the ICOC/CIRM regulations that have been submitted to the Office of Administrative Law will remain intact after the public comment period.

"SB401 is supported by Californians Aware and California Common Cause," Jordan concluded.

The Appropriations Committee staff analysis, prepared by Scott Bain, said the bill's requirement that the Department of Justice review CIRM intellectual property agreements would likely cost around $150,000 annually. The department currently does not have IP expertise. Cost of the state auditing function in the bill was estimated at least than $20,000. Cost of placing the measure on the ballot would be $330,000. Legislation that has a price tag of $150,000 or more is being held for consideration next week as lawmakers wrestle with state budget matters.

Listed in the staff analysis as opposing the bill were CIRM, the Juvenile Diabetes Research Foundation and the Coalition for Advancement for Medical Research. Both groups contend the bill "will have the effect of unnecessarily impeding the research program," according to the analysis.

Under the topic of "concerns," the analysis said,

"The California Healthcare Institute (CHI) expresses concern that this bill applies licensing and other conditions to CIRM grants and loans that are in the best interest of the state, but these provisions may discourage industry participation. The California Institute of Technology, Stanford University, the University of California and the University of Southern California write that they believe CIRM's intellectual property policy should be given a chance to work and be tested before either codifying in statute or making significant changes."

On Tuesday, CIRM's legislative subcommittee met for "consideration" of SB401 and a number of other stem cell-related bills. We have queried CIRM about what action was taken at the meeting, but are still awaiting a definitive response.

Coming Up

Later today we expect to carry the results of today's California legislative hearing on SB401 by California State Sen. Deborah Ortiz. The measure would tighten oversight of CIRM and ensure a return on the state's $6 billion stem cell investment.

Stem Cell Snippets: Eggs, Cloning, David Baltimore

Here are links to some recent, interesting news stories or other items related to California stem cell issues.

Hwang and Prop. 71 – Patent attorney Lawrence Ebert in Ezine.com -- "Eggs will be needed to carry out embryonic stem cell research, and the potential for abuse, and disregard of that abuse, in obtaining eggs is a major, foreseeable, problem. Because the abuse in Korea occurred in the face of strong laws, the assertion that CIRM has adopted strong standards as to egg donation is not the final answer to this issue. Pressure on researchers to obtain significant results can lead to fraud. The Hwang matter involved independent frauds by at least two researchers, and does not fit neatly into the 'one bad apple' box."

Orange County stem cell lines – Writer Gary Robbins in the Orange County Register -- UC Irvine and West Coast Fertility Clinics are teaming up in a $100,000 annual effort "to create at least five new lines of human embryonic stem cells, becoming one of the few groups in the country to try to produce fresh lines for the study of everything from spinal cord injuries to Parkinson's disease."

David Baltimore and stem cell climate – Writer David Epstein in Insidehighered.com – A look at the Washington, D.C., environment for federal stem cell research. CIRM Oversight Committee member Baltimore quoted on the need for a change.

Human embryo cloning – Emily Singer in Technology Review – Overview of human embryo cloning including look at California. "Scientists who had planned to collaborate with Hwang had spent months thinking seriously about what they could do with cloned stem cells, from creating new tools to shed light on the diseases they had studied for decades to investigating new treatments. The excitement those possibilities aroused, along with new influxes of cash from state and private sources, made many unwilling to wait on the sidelines any longer. (Evan) Snyder, a (California) pediatric neurologist and neonatologist who wants to develop new treatments for his patients, is now considering starting his own cloning program."

CGS Criticizes CIRM Fundraising

The Center for Genetics and Society of Oakland, Ca., is pointing out some of the difficulties involved with the unusual – for state government agencies – funding methods of the California stem cell agency.

In its latest newsletter, the center says,

"With the CIRM's ability to issue bonds still hampered by legal challenge, it has turned to novel methods of funding. It has not requested support from the state, a move that would likely open the door to legislative oversight. Instead, CIRM has turned to private sources for donations and below-market rate loans, an approach that increases the likelihood of undue private influence on the agency, and reinforces the perception that CIRM acts more like a private firm than a state body. After months of hints and speculation, CIRM board chair Robert Klein announced that five private foundations will loan $14 million to the cash-strapped agency via risky loans at below-market interest rates. Although it is not surprising that the lenders who agreed to this arrangement are people who have shown past support for biomedical research, the nature of their support reveals a likely interest in how the CIRM will later allocate its $3 billion in grants.

"For example, the foundation established by the founder of the biotechnology firm Amgen, William Bowes, loaned CIRM $2 million. A recent report by a venture capital firm described Amgen as a "stem cell company." Another $2 million came from the foundation created by John Doerr, a prominent venture capitalist who has investments in numerous biotechnology corporations. And Eli Broad, who previously donated $25 million to the University of Southern California for a stem cell research center, also loaned $2 million to the CIRM. It would not be surprising if he was especially eager to see CIRM research funds going to USC."

Big Week Ahead for Legislative Move to Tighten Stem Cell Oversight

Efforts to tighten oversight of the California stem cell agency and ensure that the state benefits from its $6 billion investment come up Wednesday in a key state legislative committee.

If SB401 clears the Assembly Appropriations Committee it goes to the Assembly floor. Then its only other normal legislative stop is the floor of the Senate.

The day before the committee session, CIRM is scheduled to discuss the measure by Sen. Deborah Ortiz, D-Sacramento, during its own committee hearing. Presumably that session is aimed at drumming up opposition to the proposal, which the Oversight Committee has already opposed as premature.

The public is not likely to see most of the important action taking place on the bill. Opponents and supporters will be meeting privately with lawmakers to explain their position. Email and letter-writing campaigns undoubtedly are already underway. Both sides will be asking key opinion leaders and behind-the-scenes operators to contact legislators on behalf of their positions.

Part of the backdrop to the maneuvering is Ortiz' campaign for the Democratic nomination for California secretary of state. She is in a tight contest with many undecided voters. Favorable action and publicity on the bill could help her campaign. The campaign will also color the positions of other lawmakers, who may find themselves making decisions on the electoral impact of the measure – not on its merits.

Here are links to the latest version of the bill and the analysis. Here is a link to more on the bill from the California Stem Cell Report.

Stem Cell Snippets

Here are links to recent, interesting stories, press releases or other items on California stem cell issues.

Dolby gives $16 Million more to stem cell research – Paul Elias of The Associated Press – "Sound pioneer Ray Dolby and his wife gave $16 million to the University of California, San Francisco to start a stem cell center that will perform research without federal funds." Dolby has the institute renamed to replace stem cell with "regeneration;" Dolby says "stem cell" gives bad vibes.


Tougher rules needed for CIRM nonprofit IP -- Press release from Foundation for Taxpayer and Consumer Rights -- "Proposed regulations governing the ownership of discoveries resulting from Proposition 71-funded stem cell research must be strengthened to allow the California Attorney General to intervene if the drugs or cures are unreasonably priced."

Overview of current CIRM controversies – Writer Michelle Chen on the NewStandard website. "Groups that support stem-cell research are warning that the state's massive research-funding plan is not immune to narrow interest groups that could undermine the potential public-health benefits."

Comment on Los Angeles Times editiorial – Patent attorney Lawrence Ebert takes Times to task for simplistic thinking. "To be helpful to Proposition 71, the Los Angeles Times needs to get a fuller grasp of 'where' CIRM currently is and 'what issues' it needs to resolve, especially in the intellectual property area."

Video of Prop. 71 ad – Posted by one of the persons in the ad, who says, "This is a 30-second TV commercial I was featured in with my brother for California's Proposition 71 in 2004 about stem cells' potential to treat cerebral palsy."

Mary Poppins' Latest Position on CIRM Gala

On May 2, we reported that we had queried CIRM on the question of whether it would accept donations at the $1 million gala fundraiser from executives of biotech firms. The agency has responded and says it will accept funds from those executives. And it will not disclose their employer affiliation, although it is not clear whether that information is being gathered. We presume not, but perhaps we are wrong.

The agency has said it will disclose only the names of the donors, a position which pays mere lip service to the principle of disclosure. We are retracting our earlier assertion that Mary Poppins would approve of CIRM's feeble nod in the direction of good and open government. See "gala disclosure" for more on this.

ACT Reports its Cloning Efforts

Advanced Cell Technology today issued a press release on its plans to attempt to clone human embryos and identified members of its Institutional Review Board.

The firm said:"The IRB is chaired by Judith A. Frazier, RN, M.Ed. Ms. Frazier is the Manager of the Metabolic Research Unit at the Jean Mayer Human Nutrition Research Center on Aging (HNRCA) at Tufts University. The Metabolic Research Unit recruits approximately 3,000 adult subjects every year for population, longitudinal, metabolic and free-living nutrition studies. She is also a Vice-Chair of the Tufts-University-New England Medical Center Institutional Review Board. Renee Landers, J.D., serves as Vice-Chair. Ms. Landers is an Associate Professor of Law at the Suffolk University Law School where she focused on Health Law and Administrative Law. The IRB recently held several meetings and has approved the Company’s SCNT program.

"The IRB carefully reviewed the Company’s plan to solicit volunteer donors of embryos and oocytes for the SCNT program. In accordance with California and Massachusetts law and the guidelines set out by the National Academy of Sciences, such volunteer donors will receive no compensation other than the reimbursement of certain permitted expenses and will be required to acknowledge and execute a detailed donor consent form. The Company recognizes that the progress of this program is dependent upon identifying volunteer donors and hopes that the public will recognize the promise of this research for millions of patients and respond accordingly."

Chron First on Embryo Cloning Story

The San Francisco Chronicle was the first to report on the UC San Francisco efforts on cloning of human embryos, a story that the Wall Street Journal carried today.

Reporter Carl Hall wrote a piece on Saturday that said:

"UCSF's project is the only one of its kind on the West Coast, although this type of work also is being pursued by researchers in San Diego and is expected to be a key priority of the California Proposition 71 program.

"The first stage of the work at UCSF is being backed by private donations, and the experimental protocol has passed all the necessary ethical approvals. The research team is led by Renee Reijo Pera, a UCSF associate professor of obstetrics, gynecology and reproductive sciences. She also is co-director of the UCSF Human Embryonic Stem Cell Center."

Hall's piece also contains greater detail on the San Francisco work than reported by the Journal.

Gala Disclosure Mere Lip Service

Years ago, government in California and the United States did not have the laws that now tell us who is giving millions of dollars to lawmakers and political candidates. We did not know what lobbyists were spending and what corporations were backing them.

Today's disclosure laws recognize that the public has a right to know who is attempting to influence the public's business. This month CIRM, which is engaged in $6 billion worth of public business, is also involved in a $1 million fundraiser, probably the first such effort involving a state government agency. CIRM has pledged to disclose the names of donors to the gala, but little else.

The public will not know whether, for example, the Jane Smith who coughs up $10,000 for CIRM is a top executive of Geron, the San Francisco Bay area stem cell firm. Nor will we know whether the John Smith who ponies up $5,000 is a venture capitalist with a $2 million investment in Advanced Cell Technology, of Alameda, Ca.

The names are not real. But neither is the disclosure promised by CIRM. It is better than nothing and to be commended. But it amounts to little more than lip service to the principle of disclosure. We realize that most donors to charities are not normally identified and that there are issues of privacy. But the overriding obligation is to the public – not the donors.

With considerable work, nonprofit watchdog groups such as the Center for Genetics and Society and the Foundation for Taxpayer and Consumer Rights will be able to dig up the economic connections of at least some of the donors. The result will be unpleasant publicity for CIRM. Better that the agency identify donors up front than appear to be concealing information about individuals or enterprises whose economic interests could be affected by CIRM.

While we are on the subject of disclosure, some at the stem cell agency have raised questions about the financial links of the two watchdog groups. Their logic is that if CIRM is compelled to disclose such information, so too should the two groups. However, CIRM is a government agency – not a business or a nonprofit. Nonetheless, nonprofits do enjoy special legal treatment. A good case can be made that they too should disclose the details of their financial backing. We would also argue that news outlets and many of their employees should do the same, a position that almost raised major hackles when we advanced it to a former employer.

For a disclosure from the California Stem Cell Report, see this item.

WSJ Reports on Embryo Cloning in California

The Wall Street Journal reported today that UC San Francisco and Advanced Cell Technology of Alameda, Ca., are resuming a "controversial medical endeavor"-- the effort to clone human embryos.

While the news may not seem surprising to those who have followed California's stem cell efforts, the article may trigger unforeseen and possibly negative public reactions, given the Journal's reach.

Reporters Antonio Regalado and David P. Hamilton wrote:

"Officials at the University of California, San Francisco said Friday that they would immediately resume a cloning program, with the goal of creating new stem-cell lines that can be used to model genetic diseases.

"Separately, executives with Advanced Cell Technology Inc., of Alameda, Calif., said they plan to announce their cloning plans soon. Advanced Cell's vice president of research, Robert Lanza, said the company is recruiting female egg donors and is interested in creating tailored transplant treatments."

The article also said:

"Cloning programs are moving forward thanks to state laws put in place to protect and regulate the research. In California, voters also approved a ballot measure designed to provide as much as $3 billion in stem-cell funding over 10 years.

"UCSF began its cloning effort in 1999, but the program ran into trouble in 2001 after UCSF lost its top stem-cell researcher, Roger Pedersen, who took a job in the United Kingdom, citing a hostile atmosphere in the U.S. Advanced Cell's cloning effort was last active in 2003, Dr. Lanza said, and stopped because of political pressures and because the company lost its source of human eggs."

Filling the Ethics Void

"A lot of scientists don't really see ethics as part of their job." -- Mildred Cho, bioethicist at Stanford University.

We found the quote from her on the blog of the editors of The American Journal of Biotethics.

Cho's comment is interesting in more ways than one. First, she is at Stanford, where some very advanced stem cell research is underway. Second, it seems at odds with the apparent position of some who seem to think that scientists know best, and outsiders should not meddle in research. The comment also speaks to a whole range of CIRM policy issues.

But let's focus on CIRM's position that the scientists making recommendations on grant applications should not make public disclosures of their economic interests. If what Cho says is correct, it seems imperative that public disclosure should be required.

Members of the Oversight Committee have remarked that many of their initial policies are works in progress and could well be changed as circumstances warrant. It is time for a re-examination of the disclosure policy, particularly in the wake of legislation that would require more openness and transparency at CIRM.

California Stem Cell News Links

Here are links to some interesting, recent stories or press releases involving California stem cell issues.

Legislation to tighten oversight of CIRM — stem cell advocate Don C. Reed wrote an opinion piece in the Oakland Tribune. "The bill attempts to override the will of the California voters, micro-managing and changing the new program before it has a chance to get started. It contains unfunded expenses and threatens the program's success," he says. In The Sacramento Bee, three patient advocates said the measure is "untimely and uncalled for."

WARF patents – Emily Singer wrote in the Technology Review. "CIRM is facing a troubling prospect: a set of broad patents covering embryonic stem cells could substantially inhibit industry from investing and partnering in the research."

New Novocell exec – company press release on the hiring of Alan Lewis, formerly of Signal Pharmaceuticals, as CEO of Novocell of Irvine, Ca.

California Newspapers Opine on CIRM and Trial Decision

Three major California newspapers have weighed in with editorials in the wake of the court decision upholding the legality of the California stem cell agency. The Los Angeles Times threw more support to CIRM while The Sacramento Bee remained more critical. Also writing was the San Jose Mercury News.

The Times called on the legislature to reject a measure to tighten controls over the California stem cell agency, although the Times says CIRM needs to do more on its conflict-of-interest regulations.

Here are some excerpts:

"It may have taken more protest and rancor than it should have to get the governing committee to make its dealings transparent, ensure that any future treatments are accessible to the state's poor and provide the public with a fair share of profits made from medical discoveries. But in recent months, the agency has addressed these concerns. It also has adopted top-notch standards for research ethics and the protection of potential egg donors.

"That's why another effort to rein in the stem cell agency's work, in the Legislature, should be rejected as well. Senate Bill 401 would put on the ballot a measure to set up various rigid and picayune regulations on the institute. The agency's board already has adopted key elements of these proposed regulations. But by carving the rules into stone now, the measure would take away any flexibility the board might need as this fledgling research unfolds.

"The bill's author, state Sen. Deborah Ortiz (D-Sacramento) has been one of those forces pushing the agency in the right direction, but her measure is at best premature. The stem cell committee could still stand to make some improvements, of course; for instance, it resists making financial conflict-of-interest statements public for the scientists who will review grant applications. But the agency is on the right track. It should be given the chance to work out its rules and begin its important research before the Legislature starts micromanaging every aspect of its work."

The Bee, which has had the most active voice among California newspapers on CIRM, said:

"While we could quibble with a few of Sabraw's conclusions, they will get a full review from a state appeals court if plaintiffs take their concerns to the next level. Regardless, it is far from certain that the stem cell institute, despite the paranoid nature of Proposition 71, is incapable of operating like a normal state agency. Partly because of public pressure, the institute has opened up the deliberations of some of its advisory groups and established intellectual property policies that try to satisfy competing needs.

"Has it settled all outstanding issues? Not by a long shot. For reasons unclear, the institute continues to shield its advisers - prestigious scientists from out-of-state universities who will be making recommendations on multimillion-dollar grants - from disclosing their outside income. Some of that income comes from industries that hope to profit from stem cell research.

"Imagine the outcry if Caltrans set up an advisory group to advise it on building bridges, yet the public was unable to find out if bridge contractors were serving on the panel.

'Stem cell research could be a bridge to the future, and because of this potential, the institute's oversight board should require its advisers to publicly disclose their outside income. Anything less will leave lingering doubts about this freshly certified public agency."

The San Jose Mercury News said:

"The state has already awarded $14 million in grants with money raised from private investors. That may seem like peanuts next to the $300 million that the state will issue annually over the next 10 years. But it will permit California to hire more than 150 scientists to conduct stem cell research. That amount already equals 50 percent of the grants for stem cell research nationwide by the National Institutes of Health.

"Californians must learn to be patient with the progress of stem cell research. The majority of medical breakthroughs have occurred incrementally. The accumulated work of many hands over many years creates an environment in which someone can make an historic advancement."

A Look at a Key CIRM Planning Document

From "educated ignorance" to "transformative thinking," the California stem cell agency has it all in a report aimed at "charting new directions" in its quest to finance $3 billion in stem cell research.

The 98-page document is one of the fundamental references used in CIRM's strategic planning process. It came out of a two-day international stem cell conference last fall that cost CIRM $128,489.

The report is primarily scientific but is worth reading even if you miss some of the scientific nuances. It points to possible CIRM funding directions that top scientists think would be worth pursuing. Some of scientists voiced opinions that CIRM highlighted. They even turned a phrase or two. Here are some excerpts from the report, which can be found on the CIRM Web site.

"With cell replacement therapy, we are 'at the stage of educated ignorance. We know what we don't know.' – Paul Berg(Nobel laureate from Stanford University)."

"The field of stem cell research 'needs more transformative thinking....Think of Eric Lander and the genome project....California is in a position to do something transformative.' – George Daley(head of Harvard University's stem cell effort and who also now serves on the advisory committee for CIRM strategic plan)."

"'If your goal is to advance medical knowledge, you have to push just as hard as you can at the edge … and that includes making chimeras. Pushing at the edge is what CIRM should be about.' – Irving Weissman(of Stanford University, Stem Cells Inc. and Cellerant)."

"'You can't separate basic research from therapy. '"— Nissim Benvenisty( of the Hebrew University of Jerusalem)."

"Bench-to-bedside is a two-way street." – Arlene Chiu(director of scientific activities at CIRM)."

"If preclinical studies represent a bridge between the bench and bedside, then it is important to remember that the bridge runs in both directions. Although clinical trials often fail on the first try, new knowledge from both successful and unsuccessful trials can be brought back to the laboratory and used to design experiments that re-examine and extend basic premises. This process will lead to refined hypotheses and improved protocols for subsequent preclinical and clinical testing. In this way, basic, preclinical, and clinical research form a partnership that facilitates the development of well-designed, successful clinical trials and, ultimately, efficacious treatments for patients."

"The session revealed that stem cell research will benefit greatly from the development of critical tools, reagents and techniques. Few individual laboratories or institutions however are able to bear the financial burden of creating these tools alone. One recurrent suggestion is that CIRM could create central facilities or cores where new technology and tools for stem cell research would be developed and/or made available to researchers in California."

"Although stem cells are frequently associated with cell replacement therapies, the first practical uses of stem cells may be in applications such as drug discovery, toxicity testing and the development of diagnostics. Session 6 entitled Stem Cells as Tools for Disease Research and Therapy focused on research in which ESCs serve as novel tools for the molecular dissection of genetic-based diseases and for discovering new therapies, rather than for cellular transplantation. It is these tools which may offer the most significant near term rewards from stem cell research."

Egg Donor Protection Advances in State Senate

As expected, legislation to protect women who donate eggs for stem cell research in California has advanced to the Senate Appropriations Committee.

The bill, SB1260, by State Sen. Deborah Ortiz, D-Sacramento, easily cleared the Senate Health Committee on a 9-0 vote last month, which she chairs. The measure does not affect the rules adopted earlier this year by the California stem cell agency, which only affect research funded by CIRM.

The staff of the Health Committee prepared a detailed analysis of the measure, including comparisons to the CIRM rules and listed no opposition to the legislation.