What About WARF?

The announcement that Advanced Cell Technology has developed a new method for extracting embryonic stem cells has raised questions about its impact on WARF – the Wisconsin Alumni Research Foundation.

Reporter Jim Downing of The Sacramento Bee quoted Stanford law professor Hank Greely as saying:

"The mere fact … of having a new way to make embryonic stem cells weakens the WARF patents, which I think is a good thing."

Downing continued:

"Greely said that the main complaint with the Wisconsin patents is how the foundation has chosen to enforce them.

"'Stanford and UCSF have the seminal genetic engineering patent, and they … quite cleverly, had very lenient license terms for non-universities -- a relatively small cash amount and a small royalty,' Greely said. 'And the result was, the technology went everywhere and those two universities made a lot of money.'

"By contrast, he said, 'WARF is making enemies.'"

Downing reported that WARF did not respond to two requests for comment. However, the Wisconsin Technology Network did have a general reaction from WARF in a piece by Joe Vanden Plas.

"Andrew Cohn, a spokesman for WARF, said the new method of deriving stem cells should not hurt Wisconsin's standing as a leader in stem-cell research. He also said WiCell, the nation's first stem-cell bank and a subsidiary of WARF, would be interested in helping distribute stem cell lines derived from this method.

"He also said it's too early to tell how the new method would impact WARF's stem cell patents. 'We don't even know what they claim in their patents, but that's the last thing we're concerned about,' Cohn said. 'We need time to dissect and digest its full impact.'"

After the Lights Go Out at CIRM

What happens when the California stem cell party is over? That's one of the questions posed to the agency as it maps a strategy to give away $3 billion. The question is not insignificant. CIRM has only about eight more years left on its clock. The measure that created CIRM gave it a 10-year life, nearly 20 percent of which has expired.

Martin McGlynn, president of StemCells, Inc., of Palo Alto, gave this response:

"I would ask CIRM to clearly define success. Publish a road map to achieve those successes. I would offer two thoughts as to what you might deem success. I look to the notion of what happens when the party is over....:

"There would be Centers of Excellence in the state with a critical mass of world-class talent and a proven track record or diversity at each center in its chosen field of endeavor.

"You would have created a vibrant, sustainable for-profit sector that focuses on applied research and the translation of discoveries into use for the benefit of mankind. Those entities by then should be fundable by more traditional sources of funds.

"The cycle time for the work that needs to be done is twice what VCs wants to see, so get out of blocks quickly, leverage your dollars, and make sure you are the first money to accomplish your mission."

McGlynn was among a number of private sector folks who discussed strategic planning issues last month with CIRM. Their comments are summarized in a 40-page document now available on the Web. The summary adds considerable meat to the skimpy bones of their Power Point presentations.

Here are a few more excerpts.

Bruce Cohen, president and chief executive officer, Cellerant Therapeutics of San Carlos, Ca., on CIRM's goals:

"The taxpayer needs to see a return on this investment. You need to find a way for them to see company and job creation, which will come sooner than cures for some of the debilitating disease we are trying to address. So we need to encourage capital to come in to accelerate new businesses and let existing businesses get bigger.

"You also need to get therapies into the clinic so voters will see a potential change in their lives. You need to accelerate the process by which adult and embryonic stem cells therapies find their way to people. Even if it's an inconclusive Phase I trial, you'll be happy someone with state funding is trying to accelerate the process.

"It's those two things that will make people who voted for this appreciate what’s been done on their behalf."

Sumit K. Chanda, group leader,, Division of Cellular Genomics, Genomics Institute of the Novartis Research Foundation, on core facilities:

"We have started to get into a little bit of stem cell screening. These are the major challenges and possibilities that we have seen using high-throughput screens using stem cells:

"One of the possible solutions that I am proposing is a core facility for screening where everyone in California who is interested in running high-throughput stem cell screens can go. This would be parallel to the NIH roadmap project where they had the MLSCN [Molecular Libraries Screening Centers Network] centers located in different areas in the States.

"The only exception I would make to this is that the NIH had the centers run by academic groups. It is really the private sector that has been making advances in screening in the last 20 years or so, so it might make more sense to have the private sector spearhead a screening facility."

Chanda continued on the subject of cultural roadblocks.

"We have found that there are culture roadblocks between the academic and biotech sectors, even though we have pretty good relationships with various academic groups. We find that the collaborations are very fruitful, but most of our knowledge of what is going on from academic groups comes from publications, which usually do not give you enough information and often occur a couple of years later than the initial discovery."

Ann F. Hanham, managing director, Burrill & Company of San Francisco on "concerns:"

"How much more basic research is going to need to be done? Many of the companies that pitch to our firm are not ready for VC funding yet. They have not worked up their business metrics or their technology or their idea or how much time/resources they need to get to a final product.

"Patents are a huge issue for VCs. We need to protect our investment. If we are going to put capital in, we need to ensure protection of that asset. The University of Wisconsin patents have raised issues about whether we can invest in this field.

"We also need to see a commercialization strategy. Right now, stem cell science is much more on the research side than the development side of the R&D process.
"There are issues to be addressed around manufacturing and the scalability and reproducibility of manufacturing.

"There are questions to be answered such as: Can you pool stem cells? What is the right commercialization strategy? Wow do you become a company and earn back that money that was put in?"

Thomas B. Okarma, president and chief executive officer, Geron Corp. of Menlo Park, Ca.

"My message is going to be straight forward. Because of the depths of your pockets and lack of competition at the state and federal level, we have an opportunity to shape the way the field is developed.

"My take home message to you today is the 'D' word - development. My advice to you is to subordinate research to support development. Don't eliminate the research in R&D, but do the research as necessary to support the 'D.'"

CIRM Replies Re Public Disclosure by Grant Reviewers

Dale A. Carlson, the new chief communications officer for the California stem cell agency, is differing with an earlier item "CIRM, disclosure and conflicts" on the California Stem Cell Report.

Here are his comments verbatim:

"On Tuesday, August 22, you wrote: 'Putting the public universities aside, we suspect that nearly all California agencies require public disclosure of financial interests as opposed to 'secret' disclosure, which is what CIRM does with its reviewers. We base on that on several decades of experience watching California public agencies, but we could be wrong.'

"You are wrong. California public officials are indeed required to disclose their financial interests – only their financial interests – and to make those disclosures public, as specified by the Political Reform Act (PRA). CIRM staff and members of the ICOC are subject to and complying with those requirements.

"Members of CIRM’s working groups are not public officials. They are advisors, not decision-makers. The distinction is clear and well-defined by the PRA, by the Fair Political Practices Commission and by the courts. Like members of advisory bodies and committees at other state agencies, they are therefore not subject to the requirements of the Political Reform Act. Indeed, as a matter of law, advisors to state agencies – including CIRM – are not required to disclose any information about their personal, professional, or financial interests, to the agency or to the public.

"CIRM working group members are, however, subject to disclosure requirements adopted by the ICOC, pursuant to the mandate of Proposition 71.

"The ICOC requires CIRM advisors to disclose financial interests as well as personal and professional ties to grant applicants. We have a more complete picture of the potential conflicts of interests facing our advisors than the public has of any California official subject to the PRA.

"Our advisors’ disclosure statements are available to state auditors. If we find violations of our policies, the discovery will be reported to the legislature, along with corrective actions to ensure they are not repeated.

"Our conflict of interest policies, including our disclosure requirements for advisors, go beyond the requirements of the law, and beyond the practices of other state agencies, including the universities. If there are stronger policies in force, they’ve yet to be identified.

"The success of the CIRM research program and its ability to maintain the confidence of the people of California depends critically upon the agency’s ability to fund the highest quality research proposals, chosen without bias. We want to attract the best people we can find to help evaluate research proposals, and to ensure that the ICOC has sufficient information to make the best decisions possible.

"Our conflict of interest policies strike an appropriate balance, between the public’s confidence in the integrity of our decision-making and the public value of having the country’s best experts involved in the review of grant proposals."

Carlson raises a number of interesting issues, but he does not convince us that CIRM's disclosure rules for grant reviewers "go beyond the rules of other state agencies." Much more can and will be said concerning CIRM and disclosure, but CIRM and the California Stem Cell Report differ fundamentally on one central issue. We consider the grant reviewers de facto decision makers. Yes, legally they are advisors and make only "recommendations." But given the nature of such governmental agencies as CIRM, it is unlikely that reviewer recommendations will be overturned by the Oversight Committee in any significant number of cases. If only because the Oversight Committee will soon have no reviewers if it consistently rejects their recommendations.

We do believe that CIRM's disclosure rules go beyond the usual requirements elsewhere in the nation, as do a number of its other policies. Indeed, CIRM has become a benchmark for other states as well as other nations on stem cell policies.

Stem Cell Stocks Jump on ACT News

This is the kind of news that really captures the attention of those timid souls known as venture capitalists, who have shied away from stem cell enterprises.

On the day Advanced Cell Technology of Alameda, Ca., announced its new method of extracting stem cells from embryos, its stock more than quadrupled. Of course, it did not have far to go. The stock climbed from 42 cents to 1.83. Today the stock closed at $1.60.

The Wall Street Journal reported this afternoon that the ACT news also "pushed up shares of the four largest publicly-traded stem-cell researchers. StemCells advanced six cents, or 2.7%, to 2.31; Aastrom Biosciences added one cent to 1.20; Geron rose 31 cents, or 4.9%, to 6.67; and ViaCell jumped 19 cents, or 5%, to 4."

The 52-week low for ACT's stock price is 26 cents and its 52-week high is $2.95.

Earlier today, reporter David Hamilton wrote in the WSJ:

"Larger pharmaceutical and biotechnology companies have mostly steered clear of the field, in part because of the ethical controversy and the lack of federal research support. Advanced Cell Chief Executive William Caldwell, however, said he believes an embryo-safe method of deriving stem cells may help spark large-company interest in the area.

"'I think this is going to help address the problem and the issues they have' with stem-cell derivation, Mr. Caldwell said. Advanced Cell, which is currently raising new funds in a private offering to bolster its meager cash reserves, hopes to sign a development partnership with a larger company by the end of the year."

At mid-afternoon Thursday, the story on ACT in the WSJ did not make the paper's top 10 lists in either the most viewed or most e-mailed categories. But among Web readers of the New York Times, the story was the No. 5 most blogged and No. 6 most e-mailed. At the Los Angeles Times, it was the No. 8 most e-mailed stories but not in the top 10 of most viewed. At the Washington Post, it was the No. 12 most e-mailed story.

Rules for the $100 Million Stem Cell Giveaway

The river of money is beginning to flow, so it is time for some of you to dip your scoop in.

The California stem cell agency has posted detailed information on how to snag a chunk of more than $100 million for research involving embryonic stem cells. The deadlines are coming up quickly.

For those of you who do not work in the Golden State, you are mostly out of luck unless you can finesse the rules that limit the grants to academic and non-profit research institutions in California.

While this round does not include grants to businesses, it would behoove them to examine the current process, which is likely to set a pattern for future grants. CIRM said grants for businesses will not be awarded until intellectual property policies are developed (a hearing on that is scheduled for next Tuesday).

The agency is looking for innovation. One two-year, 30-grant program is called SEED, short for Scientific Excellence through Exploration and Development, and is funded at $24 million. The other program contains more cash -- $80 million over four years –for "comprehensive research grants." That 25-grant program will support "mature, ongoing studies" by scientists with a "record of accomplishment."

The deadline for letters of intent to apply for both programs is Sept. 15 with applications due Oct. 13 for SEED and Nov. 13 for the other grants. In addition to the usual scientific information, applicants are asked to provide a "public abstract" intended to explain the research to the lay public. A statement concerning how the research will benefit California is also required. The letters of intent for both SEED and comprehensive grants ask about sources of stem cells and the names of researchers, collaborators and subcontractors.

The application for comprehensive grants seeks "strong preliminary data." "Particular emphasis will be placed on impact and significance and quality of the research plan," the application says.

The lucky winners are expected to be determined at the CIRM Oversight Committee meetings either in February (SEED) or April (comprehensive grants).

Here are links on the grant program: CIRM press release, SEED letter of intent, SEED application information, comprehensive letter of intent, comprehensive application, discussion of the grant program by the Oversight Committee earlier this month (starts on page 149 of the transcript).

The Scientist Magazine: CIRM, Disclosure and Conflicts

The topic of conflicts of interests and stem cell research is surfacing again in the scientific media. The latest article can be found in The Scientist magazine.

Writer Andrew Holtz reported on the hooha out here in California – although hooha is probably too strong a word, given that the issue is nearly totally ignored by the mainstream media.

Holtz quoted Zach Hall, president of CIRM, as saying its disclosure rules for grant reviewers "go beyond the rules of other state agencies in California and in fact they go beyond the national standards." While we don't like to quibble with the good doctor, we are not sure he is really on target concerning California disclosure rules. Putting the public universities aside, we suspect that nearly all California agencies require public disclosure of financial interests as opposed to "secret" disclosure, which is what CIRM does with its reviewers. We base on that on several decades of experience watching California public agencies, but we could be wrong.

In the case of CIRM, it requires grant reviewers to disclose basically only to the agency itself.

The article quoted John M. Simpson of the Foundation for Taxpayer and Consumer Rights as calling for more disclosure because of the multimillion dollar impact of actions by the reviewers.

Holtz also interviewed some of the reviewers concerning their sentiments on public disclosure of their financial information.

"One reviewer, Rainer Storb, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, told The Scientist he isn't bothered by the idea of public disclosure of his financial statements. 'The burden is that you have to fill out these forms all the time. That's a bit of a nuisance. But I'm perfectly fine with things being made public,' Storb said.

"Other members of the Grants Review Working Group were either unavailable or said they didn't know enough about the debate to comment. Arlene Chiu,director of scientific activities at CIRM, said many reviewers she had spoken with oppose public disclosure.

"The Director of the Oregon Stem Cell Center, Markus Grompe, who said he was contacted about becoming a reviewer, said his financial ties are already public. 'If they bar you from being involved with biotech to be a reviewer, then that will scare off a majority actually; but if it's just about disclosing it, we disclose all the time,' Grompe said.

"Lisa A. Bero, from the Institute for Health Policy Studies at University of California San Francisco, who has studied conflict of interest issues in medical research, said people have difficulty judging their conflicts of interest. She said the specific CIRM disclosure rules improve upon policies that ask general questions about 'relevant' financial ties, but public
disclosure would still help detect cases where disclosure is less than complete."

For more on this subject, see "immune feelings" and "second tier."

FTCR: CIRM May be Moving Too Hastily

While the California stem cell agency is moving quickly forward with plans for its first research grants, a watchdog group continues to raise questions about whether the results will be affordable and available to Californians.

The Foundation for Taxpayer and Consumer Rights said today that it is "concerned that the pressure to show results from a program that was approved by voters in 2004 and stalled by legal challenges could lead to hastily made and poorly considered grants that waste public money."

The news release continued:

"FTCR also said that the stem cell institute must have policies in place that ensure any treatments and cures developed with taxpayer money are accessible and affordable for all Californians."

The trigger for the foundation's comments is posting of the timelines for application for the research grants. The foundation said that "the letters of intent to apply for CIRM SEED Grants and CIRM Comprehensive Grants will be due Sept. 15. Full applications are due Oct. 13 and Nov. 13 respectively. CIRM envisions awarding the SEED grants in March 2007. The Comprehensive Grants would be awarded in March or April."

Here is a link to the foundation's full statement.

IP Principles for Business Coming Up Next Week

Dividing up the stem cell spoils comes up again next Tuesday as the CIRM Task Force on Intellectual Property looks at "principles" for IP involving for-profit enterprises.

No details have been posted yet for the session, which will also consider comments from the Oversight Committee on IP for non-profits.

The actual meeting will take place at the San Francisco International Airport, but remote sites are available at UC Irvine, Los Angeles and Stanford. Here is a link to the full agenda.

More State Oversight of CIRM Not Likely

Events last week in Sacramento re-arranged the stem cell stage in California.

The California stem cell agency skated past the latest attempt to bring more stringent oversight to its unique, $6 billion effort to turn stem cells into cures. That means that critics of the agency are not likely to be successful at bringing CIRM under more state direction for the foreseeable future.

A hefty scandal is about all that would create a climate conducive to major changes at the agency. At the same time, the door has opened for a state politician or two to seize the stem cell issue.

The quiet demise of the stem cell oversight bill by state Sen. Deborah Ortiz, D-Sacramento, signalled the new arrangements. Ortiz is chair of the Senate Health Committee and a pioneer on California stem cell issues. But term limits are forcing her from office at the end of the year and have reduced her legislative clout.

Assemblywoman Judy Chu, D-Monterey Park, chair of the Assembly Appropriations Committee, Thursday dispatched Ortiz' measure (SB401) to legislative oblivion. No vote was taken as Chu ordered the bill held in committee. Chu indicated, among other reasons, that she did not want to move forward with another stem cell ballot measure, which Ortiz' bill would have been.

Ortiz had a different view. She said the bill would have improved the performance of the agency and ensured access to affordable cures.

"The measure was extensively debated and refined during two years of public informational and legislative committee hearings. It had bipartisan support in both houses of the Legislature, and was supported by public interest groups.

"The bill was steadfastly opposed by the CIRM and the ICOC, the two entities the bill would have opened to increased public scrutiny. This is nothing but an example of a special interest group killing legislation to avoid being held accountable to those it serves."

Normally state departments, of which CIRM is one, are subject to regulation by the state legislature, which approves their budgets and can change their scope or eliminate them entirely. CIRM is radically different. It is a creature of the ballot. Voters altered the state constitution and state law to create the agency. Changes in the agency can only be made by another ballot initiative or by approval of 70 percent both houses of the state legislature and the governor. And that legislative action can only happen three full years after adoption of Prop. 71, which would be in November 2007. The extraordinary, "super-super" vote requirement makes it virtually impossible to tinker with CIRM. It would only 13 state senators to block any changes affecting the agency.

Nonetheless, political hay can be made involving embryonic stem cell research – on all sides of the issue. Gov. Schwarzenegger, who is facing a re-election challenge, made that clear a few weeks ago when he ponied up $150 million to ease the financial strains at CIRM. The impending departure of Ortiz leaves a void in the legislature on stem cell issues. Just who may fill it is unclear. Assemblyman Dave Jones, D-Sacramento, has been mentioned as one possibility. Ortiz was a friendly critic of the agency, although some at the agency did not regard her in that fashion. An unfriendly legislative critic can create considerable mischief, even if he or she cannot effectively make changes legislatively.

If the concept of political hay mixing with stem cell research is troubling, consider the host of continuing public policy issues involving CIRM and the nature of the research, ranging from treatment of egg donors to conflicts of interest. The fact is that politics and stem cell research are inextricably linked. It behooves the agency to keep a close eye on the state Capitol.

California newspapers paid scant attention to the demise of Ortiz bill. Most, if they carried any article at all, relied on a brief from The Associated Press. Reporter Judy Lin of The Sacramento Bee had a somewhat longer piece.

On to the Deadly Vizcaino Plain

We are going to have one of those periodic pauses in postings on the California Stem Cell Report. This time because of air and land – as opposed to sea – travel. On Thursday Aug. 17, we will wing our way from Guaymas on the Mexican mainland to Loreto in Baja California in one of Aero Guerrero's finest tiny planes. (Guaymas is, by the way, where Charlie Chaplin married his first child bride. En route to the US by train from Mexico City with the prospective mother-in-law also in tow, he decided to do the honorable thing. They honeymooned in the port city for several days.)

From Loreto, we will leap into a 1986 VW Vanagon and forge north into the deadly heat of the Vizcaino Plain, average annual rainfall less than two inches a year. With luck, we will arrive in the Old Country (the U.S.) in a few days and resume postings as we re-enter the dirt life(life on land) for a short while.

CIRM Hires Senior Communications Executive

The California stem cell agency has found a communications director, a man with considerable business experience who has also wrestled in the public policy arena in the San Francisco Bay Area and elsewhere.

Dale Carlson officially begins work next Monday. As communications director, his responsibilities will include developing a "clear and consistent message about the new frontier of stem cell research in California" and promoting "a deeper and more sophisticated public awareness of stem cell research and therapy." His duties go beyond dealing with the ink-stained wretches of the fourth estate and include developing communications programs with the public, the patient advocacy community, the legislature and the scientific community.

Carlson was vice president for corporate affairs with the Pacific (stock) Exchange in San Francisco from 1987 to 2005. He dealt with the media, business, public and handled a wide range of responsibilities, including dealing with Web content. Carlson also served in a variety of volunteer positions with civic and nonprofit agencies in the Bay Area, including tours of duty as chair of the San Francisco library foundation and the Treasure Island Development Authority.

Carlson, who has a masters degree in health services administration from the University of Michigan, surfaced in February of this year as an "interim senior communications officer" at CIRM, working on a parttime, volunteer basis.

CIRM has had difficulties since its inception with its communications/PR programs, resorting to hiring Edelman PR for $378,000 for a 16-month contract that expires at the end of this month. One problem was the lack of a senior CIRM official with specific PR responsibilities, which Carlson's appointment seems to solve.

In the interests of full transparency, we must disclose that Carlson is a sailor, as are we. He describes himself as a "competitive" sailor. We are just your average sea dog.

The salary range for Carlson's position is from $130,000 to $195,000. We expect to have the specific figure soon.

Forbes on Private Stem Cell Giving

For more on private stem cell philanthropy and the California stem cell agency, see this Forbes piece. It popped up today after the Wall Street Journal carried its page one story. The timing has all the earmarks of a publication being a tad pressured to push its story into public view after a competitor got the jump on it. Of course, we could be wrong.

CIRM to Examine 'Outline' of $3 Billion Giveaway

The Strategic Planning Advisory Committee of the California stem cell agency has a meeting planned for Aug. 24 to discuss the outline of a plan to give away $3 billion.

Details of the outline are not yet available and may not be available by the time of the meeting, given the way the agency works. Nonetheless the San Francisco meeting is open to the public. See the agenda here but don't expect illumination.

Wrapping up the Private Giving to CIRM

One of the things that the Wall Street Journal is very good at is following the money. Reporter David Hamilton did just that this morning in a page one piece involving the California stem cell agency.

The article wrapped up the private giving and help that has come CIRM's way. It also quoted the critics on the propriety of CIRM's ties to private benefactors.

However, Hamilton did not cite an earlier WSJ piece about how even small financial favors can create a feeling of indebtedness that is not fully comprehended by the recipients of the largesse.

Most of the details of Hamilton's piece are familiar to our readers. But we should note that because of the prestige and wide national readership of the WSJ, his article is likely to have more impact than if it had appeared in a smaller, regional paper. Play prominence -- meaning the front page display -- also counts.

Hamilton's piece additionally looked at the impact of private funding outside of CIRM. He wrote:

"USC has a new building that could become the state's largest stem-cell research center on the drawing board. It also recently hired Martin Pera, a prominent researcher from Australia, to run its new stem-cell research program. That step is notable in part because the federal restrictions sparked fears that U.S. scientists would leave the country to pursue their work.

"UCSF is using private money to renovate an entire floor of a building so that its stem-cell researchers will be able to work in a central location. One team deriving new stem-cell lines currently works in a laboratory at Menlo Park, Calif.-based biotechnology company Geron Corp., while another labors at an off-site leased facility in San Francisco.

"The university also is proposing an entirely new research building at the cost of as much as $100 million. Much of that must be raised privately, although Arnold Kriegstein, director of the university's stem-cell program, hopes CIRM might also be able to kick in some funding. 'Fund-raising is one of the bottlenecks to getting moving as quickly as possible,' says Dr. Kriegstein."

Gritty, Gritty Details on CIRM's Planning Process

For those thirsting for more details on the latest in strategic planning by the California stem cell agency, here is an update on some of the material recently available online. The information included below is being added unannounced to the CIRM site in some sort of willy nilly fashion and can be easily overlooked by the casual browser. But if you are a casual browser of the CIRM Web site, you are probably are not interested in the following. Nonetheless, here it is.

The agency has nearly completed its interviews for the planning process. As of late last month, 59 persons were interviewed with a target of perhaps 70. The list ranges from Bruce Alberts, former president of the National Academy of Sciences, to Leonard Zon of the Harvard Medical School. Also included were a number of the agency's staunch critics.

Last month, the agency held a conference on "Industry and Stem Sells in California: Fostering Research and Development." The presenters came from a blue ribbon array of stem cell-connected companies ranging from Geron to Burrill. Here are links to their Power Point presentations.

Sumit K. Chanda, Ph.D., Group Leader, Division of Cellular Genomics, Genomics Institute of the Novartis Research Foundation

Bruce Cohen, President and CEO, Cellerant Therapeutics

Ann F. Hanham, Ph.D., Managing Director, Burrill & Company

Martin McGlynn, President and CEO, StemCells, Inc.

Thomas B. Okarma, Ph.D., M.D., President and CEO, Geron Corporation

Alan K. Smith, Ph.D., President and Chief Operating Officer, Cognate BioServices

Michael D. West, Ph.D., Chairman of the Board, President and Chief Scientific Officer , Advanced Cell Technology, Inc

E. Edward Baetge, Ph.D., Chief Scientific Officer, Novocell, Inc.

Another conference last month dealt with “The Scientific Challenge: From Basic Research to the Clinic.” The speakers and their Power Point presentations:

Stuart Orkin, M.D., Harvard Medical School, Chair, CIRM Scientific and Medical Research Funding Working Group, “Stem Cells: Looking Back and Ahead”

Jill Heemskerk, Ph.D., National Institute of Neurological Disorders and Stroke, “The SMA Project: A New Approach to Therapy Development at NIH”

Allen M. Spiegel, M.D., Albert Einstein College of Medicine, “Delivering on the Promise of Stem Cell Research: What Will it Take?”

Stephen A. Sherwin, M.D., Cell Genesys, Inc., “The Development of Novel Cellular Therapeutics: Some Lessons from the Private Sector”

Calling the Tune on ESC Research: Therapies or Tools?

As the California stem cell agency wrestles with how to give away $3 billion – otherwise known as strategic planning – along comes a related article in the nation's most prestigious newspaper, the New York Times.

In Monday's edition, reporter Nicholas Wade discussed the split between those who want to see development of stem cell therapies versus those who see embryonic stem cells as a research tool to study mechanisms of disease.

That discussion has rumbled through CIRM for most of its existence, with patient advocates making impassioned pleas for quick results, declaring the longer it takes the more people die – an argument Wade does not explore. Since patient advocates hold 10 seats on the 29-member CIRM panel that ultimately decides who gets the cash, their views are not to be sniffed at. The issue is also near the center of the strategic planning process, which is scheduled to end in December. (See "clashing interests" for a look at the splinter within CIRM.)

Wade wrote:

"Many (scientists) no longer see cell therapy as the first goal of the research, parting company with those whose near-term expectations for cell therapy remain high.

"Instead, these researchers envisage a longer-term program in which human embryonic cells would be a research tool to study the mechanisms of disease. From this, they say, many therapeutic benefits may emerge, like new drugs, which would probably be available at least as soon as any cell therapy treatment."

Wade said there is a "gap between scientists’ views and those of the public and of people for whom the overriding purpose of research with human embryonic stem cells is to generate cells that can restore damaged tissues."

Wade continued:

"Thomas M. Jessell, a neurobiologist at Columbia University Medical Center in New York, said that he hoped to see the research generate new drugs for neurodegenerative diseases within the next five years but that it could be a long time before rational cell-based therapies are effective.
"'Many of us feel that for the next few years the most rational way forward is not to try to push cell therapies,' Dr. Jessell said. Scientists have spent the last five years mostly in learning how to grow human embryonic stem cells in the laboratory and how to make them differentiate, meaning to turn into the body’s various types of mature cells.'"

Wade said:

"Researchers have not, however, abandoned cell therapy, in which cells themselves would be used to regenerate tissue. In Parkinson’s disease, for example, dopamine-producing cells from aborted fetuses, when injected into the brains of Parkinson’s patients, do have an effect, suggesting that a better source of cell could have therapeutic value. 'So it’s the perfect place to go in,' said Dr. Asa Abeliovich of Columbia University Medical Center. Dr. Abeliovich said that with Alzheimer’s disease, in contrast, 'We don’t know how or what to replace.'"

While scientists have preferences on the direction of stem cell research, no research is done without funding. Given the amount of money that CIRM can bring to bear on the subject (10 times the annual spending of the NIH on ESC research), the views of scientists oriented towards use of ESCs as research tools may not be the key factor in determining the main direction of new stem cell research in the United States.

Does Disclosure Mean Only the Second Tier Will Play?

A former president of the National Academy of Sciences has ridden to the support of the "trust us" disclosure and conflict-of-interest policies of the California stem cell agency.

Bruce Alberts, professor of biochemistry at UC San Francisco as well as president of the NAS from 1993 to 2005, said that scientists who make de facto decisions on requests for millions of dollars should not be required to disclose their financial holdings.

Writing in the San Jose Mercury News, he said CIRM has taken "strong measures" to avoid conflicts of interest. Alberts declared:

"Scientists view serving on (grant) review committees as a public service, and many of the best will decline to participate in institute reviews if their private financial information is to be made available for everyone in the world to see. California then runs the risk of wasting critical resources by not making the very best decisions on how to make these important investments for the public good."

Alberts does not address the issue of whether there is a significant conflict of interest problem involving medical researchers generally. But we all know of the continuing string of stories about researchers whose ethics are suspect. More recently, the Wall Street Journal wrote about just how favoritism creeps in and how researchers seem "immune" to feelings of conflicts of interest. The Journal said,

"Studies of psychiatric drugs by researchers with a financial conflict of interest -- receiving speaking fees, owning stock, or being employed by the manufacturer -- are nearly five times as likely to find benefits in taking the drugs as studies by researchers who don't receive money from the industry, according to a review of 162 studies published last year in the American Journal of Psychiatry."

We acknowledge that some scientists may beg off service on the CIRM grant review committees simply for privacy or philosophical reasons. But does that mean only the second tier will serve? Perhaps that is a question to be asked of the 29 persons who oversee the $3 billion California stem cell agency, all of whom must publicly disclose their financial information. One of those persons is the vice chancellor for medical affairs at UC San Francisco. He is also Alberts' boss.

Patient Advocates: More Collaboration Needed, Risky Ventures Okay

Patient advocates from throughout California say they would like the agency over the next 10 years to do everything from curing "many of the diseases that plague society" to improving collaboration and communication among scientists.

Their sentiments were voiced at a focus group called by CIRM last month as part of its strategic planning process. Their mostly anonymous comments can be read in a 17-page summary available on the CIRM web site.

The questions posed to the focus group ranged from how does CIRM measure success 10 years out to balancing high-risk research with the go-safe-but-slow approach.

In terms of 10-year goals, one sentiment jumped out, at least to us. That was the need for more collaboration, sharing and transparency. A variation of that feeling also surfaced during a segment involving public education.

Sometimes one is given the impression that collaboration and sharing go without saying in today's world of instantaneous communications. But apparently not, in the view of a number of patient advocates.

Some of the proposed 10-year measurements of success were more specific, such as this one:

"Success would be that stem cells or their derivatives would have cured many of the diseases that plague society."

Another patient advocate suggested a 10-year goal of one approved therapeutic intervention and three advanced clinical trials.

On the subject of risk, participants endorsed using portions of CIRM's $3 billion for riskier projects, although the proposed percentage varied.

CIRM President Zach Hall commented:

"At the time of the Human Genome Project, there were two proposed approaches to sequencing the genome. Someone who advocated the approach that ultimately wasn't chosen left the NIH to set up a competing project. That was Craig Ventner. The competitive pressure he exerted caused the NIH to change its strategy and accomplish things much faster. Some say they wouldn't have done that without competition from Craig Ventner. It's true the NIH study sections put a big priority on feasibility and likelihood of return. I don't know that we look to you for an answer but we do listen for whether it's more important to have tangible progress or are we willing to risk some of the money on a gamble that may fail."

Hall also indicated that a focus group will also address the question of public education.

Stem Cell Conferences: Eggs, Biocapital and Fair Cures

Get out your calendars, stem cell fans. Coming up are a three hefty conferences in the San Francisco Bay area on stem cell issues.

On Sept. 28, at the request of CIRM, the Institute of Medicine and the National Research Council will hold a conference near the San Francisco airport on the medical risks of egg donation. This is the conference that CIRM has talked about for months. A high-powered group from throughout the country is scheduled to speak.

On Sept. 28-29, "Ethical Worlds of Stem Cell Medicine" is the topic at UC Berkeley. "Academic Industry Alliances" and "Procurement and the Integrity of the Human Subject" are among the topics. The conference overview notes that today's stem cell medical environment has generated a "surfeit of promissory biocapital." The session is sponsored by the Science, Technology and Society Center at UC Berkeley.

On Oct. 14, "Toward Fair Cures: Integrating the Benefits of Diversity in California's Stem Cell Research Program" will be held at the Children's Hospital in Oakland. The conference is sponsored by the hospital, the Greenlining Coalition and the UC Berkeley Project on Stem Cells. CIRM President Zach Hall is scheduled to appear along with Evelynn Hammonds of Harvard. We do not have a Web site for this yet, but you can contact Joe Tayag of Greenlining at joseft@greenlining.org.

Finding Stem Cell Moolah on the Web

Connecticut has set an example for California to follow in raising funds for its embryonic stem cell research efforts – go directly to the people.

The East Coast effort is modest and not exactly ballyhooed. But nonetheless it is on the home page of its stem cell program. Right there with a big dollar sign, it commands: "Make a Donation."

Given the perceived widespread support for stem cell research in the Golden State, it would seem appropriate to make it easy for anybody to make a donation whenever the whim struck. Connecticut can only take checks and is looking into credit cards, but that is hardly an obstacle.

In California, it should be able to be done with a minimum of effort without waiting for the redesign of the CIRM website. At least one state agency, the Department of Motor Vehicles, already takes credit cards, so little would seem to be in the way.

Let the money roll in!