California's stem cell program: Legal triumphs, conflict challenges, hopes for cures

By: BRADLEY J. FIKES - Staff Writer | Saturday, January 5, 2008 8:04 PM PST ∞

Leanne Jones is trying to understand how stem cells turn into the hundreds of cell types found in the human body ---- and how to reverse the process.

John Simpson attends every meeting at the oversight committee governing California's $3 billion stem cell program, protesting against undue secrecy in dealing with taxpayers' money.

From their very different perspectives, the lives of Jones and Simpson are wrapped up with the state's groundbreaking attempt to turn a scientific curiosity into life-saving products for now-incurable diseases and injuries. Stem cells are the "ancestral" cells that differentiate into the various kinds of cells in the body.

Both can look forward to a busy 2008.

The program, long delayed by legal challenges, overcame its final hurdle in May. It awarded nearly $224 million for research and facilities in 2007.

This year, the program has an even more ambitious agenda. In the next few months, the oversight committee is scheduled to award $227 million for new laboratories.

The Burnham Institute, UC San Diego, the Salk Institute and the Scripps Research Institute have made a joint proposal to build a major stem cell research center in San Diego.

Such a new center would be very convenient for local scientists like Jones. An assistant professor of biology at the Salk Institute, Jones recently received a $2.7 million grant from the program to make a career move from studying fruit flies to mouse stem cells.

But with Simpson, with the Foundation for Taxpayer and Consumer Rights, says conflicts of interest among the oversight committee could divert public funds to other ends than what the program was intended ---- to further finding cures for patients.

The scientist
Eight years into studying the fruit fly Drosophila melanogaster, Jones is still in the early part of her career. The grant she received is intended to help promising young scientists enter the field of stem cell research.

Jones' task under the grant is to learn how genes and proteins can influence a specialized cell, such as a heart muscle cell or nerve cell, to turn back the clock to become a stem cell. This could provide an endless supply of stem cells that could be turned into replacement cells for damaged organs or tissues.

"Moving into another (research area) like this is not something that the National Institutes of Health would readily support, especially from a young investigator who doesn't have a really extensive track record," said Jones, 37. "For me, it has given me room to explore something that never would have happened otherwise."

The National Institutes of Health, with an annual budget of more than $28 billion, is the largest single funder of biomedical research in the country.

However, it and other federal institutions are sharply restricted by an executive order by President Bush as to the grants it can give governing research into human embryonic stem cells. Research with these cells, taken from days-old human embryos, is opposed by religious groups that consider embryos to be human individuals. Research with non-embryonic stem cells is unaffected.

In response to this restriction, supporters of human embryonic stem cell research enacted Proposition 71 in 2004, establishing the California Institute for Regenerative Medicine to fund the research. (Non-embryonic stem cell research is also funded.)

As part of the institute's mission, it is seeking to attract researchers like Jones.

On Dec. 12, the Independent Citizens Oversight Committee, which governs CIRM, awarded $54 million in grants to Jones and 21 other young researchers.

Jones said this grant gave her the freedom to explore stem cell research she otherwise wouldn't have had. She hopes to do more actual science instead of spending her time raising money to pay for her laboratory staff and experiments.

"Early on in your career, you have all these ideas, and you have to be very focused because your funds are so limited," Jones said. "Since I started my lab, I've had to spend a considerable amount of time writing grants to try to fund the lab once my initial funding from the Salk ran out. That meant that I could do very little in the way of "hands-on" experiments.

"This CIRM grant gives me enough of a base so that I don't have to write grants for a while, which means I can spend more time in the lab actually doing the experiments, rather than just talking or writing about them. ... This is going to be fun."

Jones said there's a good scientific reason for the grant: Research into fruit flies has a great deal in common with stem cell research. Fruit flies and humans develop from fertilized eggs into embryos and into adults by strikingly similar paths.

"A lot of the work I do in Drosophila has been shown to be directly applicable to what happens in other higher organisms like mice and humans," Jones said.

"But we couldn't do the experiments ourselves, so we had to pass it off to other labs," Jones said. "We tell them where to go, to ask better questions, to give them an outline of the experiments to do."

From now on, Jones said she plans to do those experiments herself. Working with mice is "just one step away from doing work with human cells," she said.

"It may actually allow me to get back into the lab," Jones said. "At least that's my hope."

The watchdog
Simpson, of the Foundation for Taxpayer and Consumer Rights, said his group agrees with the objectives of Prop. 71. The problem, he said, is that Prop. 71 set up the program in a way that guarantees conflicts of interest at its highest levels. Many of the same officials who vote on the grants have executive positions in institutions that get the grants.

Simpson is paid to monitor the stem cell program through a grant from the Nathan Cummings Foundation, which describes its purpose as furthering "democratic values and social justice, including fairness, diversity, and community."

The goal of his work, Simpson said, is to make sure that discoveries made with public funds go to benefit the public, at a price people can afford.

"We view our role in this particular process as that of constructive critics," Simpson said. The program's ultimate cost to taxpayers is $6 billion, he noted. Along with the $3 billion in principal that must be repaid to bond buyers, they get $3 billion in interest.

"Because such a high amount of money is at stake, the taxpayers are entitled to get the benefit of what they're paying for," Simpson said. "A fundamental principle of that is that any of the cures or discoveries that come out of this ought to be affordable and accessible to all Californians."

Simpson said the taxpayer foundation is doing more than just criticize and point out flaws.

"We've actively worked to remove impediments to stem cell research in general," Simpson said. "That is why we joined with the Public Patent Foundation and stem cell scientist Jeanne Loring, then of the Burnham Institute, now at Scripps, to challenge the validity of three stem cell patents held by the Wisconsin Alumni Research Foundation.

"So far the PTO (U.S. Patent and Trade Office) has ruled in our favor, rejecting all of WARF's patent claims."

But it is in the critic mode that Simpson is most visible. He makes his case meeting after meeting, urging committee officials to make full and prompt disclosures of conflicts and corrections of mistakes.

"Why can't you just simply say the facts in a simple, straightforward way and get it all out there?" Simpson asked at the Dec. 12 meeting. "It's best for everybody."

Committee members say they are doing their best to include the public, with publicly noticed meetings and agendas posted on the program's Web site at www.cirm.ca.gov. However, issues of confidentiality often arise, and they must be resolved before public statements can be made on some matters.

Simpson, however, says a lot is going on in private that shouldn't happen. In November, he filed a complaint against committee member John Reed with the California Fair Political Practices Commission. The complaint accused Reed of improperly lobbying to get a grant to the Burnham Institute.

Reed is president and chief executive of the La Jolla-based institute, and himself a noted researcher. While he did not vote on the grant, the complaint said he tried to influence the results behind the scenes, urging committee staff to recommend the grant.

On Dec. 10, the commission announced it would investigate the allegation. The next day, Reed, who has said he did not knowingly violate conflict of interest rules, said in a statement he would recuse himself "from all ICOC activities" while the matter is under investigation.

The program is now accepting grant applications from for-profit companies. Simpson said that's fine, as long as the public interest is taken into account.

"When companies start to line up at the public trough, you need to have even closer oversight than with research institutions," Simpson said. "But it's clear that you're not going to get meaningful cures unless the commercial sector is involved."

Contact staff writer Bradley J. Fikes at (760) 739-6641 or bfikes@nctimes.com.