Reality check for stem cell optimism
The meeting was almost over when Roman Reed steered his wheelchair to the microphone.
On the table before him sat a 149-page book of budget charts and timetables, the first concrete outline of what California’s voter-approved stem cell institute plans to accomplish in its 10-year lifespan.
“I want to thank you from the bottom of my heart,” Reed said to the institute’s staff and 29-member oversight board in October. “I promised my son that one day I would be able to walk, stand next to him and go hold my wife’s hand. And seeing this road map to cures, I know that this will come true.”
The room at Los Angeles’ Luxe Hotel thundered with applause for the Fremont resident, who broke his neck while playing college football in 1994.
Despite the enthusiasm of Reed and his audience, the book offered no promise of a cure for his paralysis.
Two years after California voters authorized $3 billion in bonds to fund stem cell research, the institute created to oversee the enterprise has just begun what experts see as a long and slow scientific journey. Even with the $150-million state loan approved recently to kick-start work stalled by legal challenges, there are no breakthroughs in sight. Gone are the allusions to healing such afflictions as spinal cord injuries and Parkinson’s and Alzheimer’s diseases that dominated the 2004 campaign for Proposition 71. In fact, scientists say, there is no guarantee of cures -- certainly not any time soon -- from the measure that was optimistically titled the California Stem Cell Research and Cures Act.
Set for final approval at UC Irvine this week, the draft plan is clear: “It is unlikely that [the California Institute of Regenerative Medicine] will be able to fully develop stem cell therapy for routine clinical use during the 10 years of the plan.”
Instead, the top goal is to establish, in principle, that a therapy developed from human embryonic stem cells can “restore function for at least one disease.”
That would be only the first step toward persuading pharmaceutical or biotech companies to fund expanded clinical trials, a process that takes years and millions of dollars. Fewer than 20% of potential therapies that enter trials make it to market.
In addition, the institute hopes to have treatments for two to four more diseases in development within the decade.
“We picked a goal that we thought was realistic, that, with some luck, would be achieved,” institute President Zach Hall said. “The field will go on beyond 10 years. We want to have a whole pipeline of things that are in movement.”
Jesse Reynolds of the Oakland-based Center for Genetics and Society, a watchdog group that supports stem cell research but advocates better public accountability, called the goals “refreshingly honest.”
“The Prop. 71 campaign went beyond the line of responsible political rhetoric,” he said. “If there are therapies, they’re decades out.”
One TV ad, for instance, showed an unidentified young mother beside a child strapped in a wheelchair and breathing through a tube.
“I will vote ‘yes’ on Prop. 71, definitely,” the woman said. “I believe that it’s something that can cure spinal cord injuries.”
State Senate Health Committee Chairwoman Deborah Ortiz (D-Sacramento), another research backer, was philosophical about the campaign’s optimism.
“A campaign requires a message to be driven home,” she said. “You can’t raise those hopes and then say, ‘Oh by the way, it may take us 10 or 15 years.’ That’s just the nature of campaigns.”
California’s attempt to cure diseases by referendum is unique. But touting dramatic cures in exchange for research dollars has become “the American way” of doing medical research, said Robert Blendon, professor of health policy and management at the Harvard School of Public Health.
The Nixon-era “war on cancer” suggested that a country that could put a man on the moon -- in less than a decade -- could surely find a cure within the same time frame. Now, Blendon said, “You can’t just talk about investing in research without the equivalent of the trip to the moon.”
Such campaigns appeal to an American public that expresses great faith in science but shows little understanding of the plodding nature of most scientific research. Blendon doesn’t see downplaying the time frame as dishonest as long as the research truly holds potential.
Proposition 71 came about in response to President Bush’s August 2001 mandate restricting federal funding to only a handful of human embryonic stem cell lines, prompted by moral concerns about destruction of embryos during such research. When the measure passed in November 2004, jubilant supporters had predicted that $350 million a year from bond sales would start flowing to scientists by May 2005.
The first reality check came in the form of lawsuits by taxpayer and antiabortion groups.
A loan from the state
Today, the bonds remain tied up in litigation, though stem cell institute officials are confident that an appellate court will uphold a favorable ruling from a Superior Court judge. To tide over the institute, Gov. Arnold Schwarzenegger in July promised a $150-million state loan. A state finance committee formally approved the loan Nov. 20, and the institute is gearing up to award its first research grants in January.
Even if researchers hit the ground running, the field is young and progress is likely to be slow. Scientists at the University of Wisconsin derived the first human embryonic stem cells just eight years ago, using donated embryos left over from in vitro fertilization clinics.
Dana Cody, executive director of Life Legal Defense Foundation, which represents two of the groups that sued, said the plan’s modest ambitions are a sign that the initiative’s promise was overblown.
“I just don’t understand the fascination with embryonic stem cell research other than that it’s something supported by Hollywood,” said Cody, whose organization supports research using adult stem cells. “Even proponents say it’s going to be years before any breakthroughs are made, if at all.”
Those who support the research -- especially those whose lives could depend on it -- see the institute’s plan through a lens of hope.
The science “is coming along fast, in my opinion,” said John Ames, whose son David was diagnosed with amyotrophic lateral sclerosis, or Lou Gehrig’s disease, four years ago. “I’m not trying to contradict the position of the strategic plan, but we have hope. We’re going to win.”
The life expectancy of someone diagnosed with the devastatingly progressive neuromuscular disease is three to five years.
“The thing that drives these individuals and their families is hope,” said Christopher Thomas Scott, executive director of the Stanford Program on Stem Cells in Society. “Without that hope, it’s very difficult to get yourself going.”
Joan Samuelson prefers to call it determination. The Napa Valley attorney founded the Parkinson’s Action Network 18 years ago, two years after being diagnosed with early onset Parkinson’s disease. She now sits on the institute’s oversight board.
“I care deeply about how urgently we pursue the mission of Prop. 71,” she said. “I wake up every day with a disorder that gets worse with the passage of time.”
To Samuelson, the campaign was about potential. The institute’s plan is about day-to-day implementation. They may sound different, she said, but they are steps toward the same goal.
“I read the realism, if you will, as a statement of the fact that this isn’t going to be easy,” she said. “Nothing great is easy.”
Cells’ unique ability
What makes embryonic stem cells unique -- and so full of potential -- is their ability to become any type of cell in the body.
Some researchers envision someday transplanting such cells into patients whose own cells have been damaged by injury or disease, with the hope that the transplanted cells develop into new spinal cord or pancreas cells. But scientists don’t yet understand the cues that trigger an undifferentiated embryonic stem cell to become, say, an insulin-secreting pancreas cell.
The plan more accurately reflects what most scientists studying human embryonic stem cells are actually doing, at least in this early stage of the research: not so much curing a disease as studying it.
Scientists, for instance, can introduce the gene for Lou Gehrig’s or Parkinson’s into a human embryonic stem cell and unravel some of the mysteries of how such diseases develop. They can use such cells to quickly test thousands of drugs.
“What’s happening even now is that human embryonic stem cells and their derivatives are being used for models for developing therapies,” said Dr. Arnold Kriegstein, who runs the stem cell research program at UC San Francisco. “It allows us for the first time in a petri dish to have a human disease, not an animal disease. It brings us so much closer to coming up with a therapy that really will work.”
Who knows? advocates say. Treatments -- even cures -- sometimes crop up unexpectedly.
Jeff Sheehy, who represents HIV and AIDS patients on the institute’s citizen oversight board, tells the story of his friend Jeff Getty, who died in October of complications from AIDS. In 1995, Getty volunteered for a controversial bone marrow transplant from a baboon.
The transplant didn’t take, but Getty, who had been near death, experienced a then-amazing remission that lasted more than 10 years. It turned out that the drugs used to prepare him for the transplant anticipated the antiretroviral cocktail that, a year later, would turn AIDS from a death sentence to an often manageable, chronic disease.
Similarly, Sheehy asked, if scientists fail to successfully transplant embryonic stem cells but along the way discover drugs or other treatments that work, wouldn’t the research be considered a success?
“My thing is just not to get obsessed with what was presented in the campaign,” Sheehy said. “Science is a very complex business. It’s full of failure. It’s full of opportunity. And failure often equals opportunity.”