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 M. 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 http://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."
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Contact staff writer Bradley J. Fikes at (760) 739-6641 or [email protected].