CQ WEEKLY – IN FOCUS
Feb. 4, 2013 –
Stem Cell Backers Heartened, Wary
By John Reichard, CQ Staff
Things are looking up for the boosters of human embryonic stem cell research.
The cells possess the almost miraculous power to change into virtually every kind of tissue and cell found in the human body. If scientists can figure out how to use that morphing power to replace damaged or diseased tissue, they may be able to cure diseases afflicting tens of millions of Americans.
WORK IN PROGRESS: Stem cell research, such as that taking place at the University of Connecticut's Stem Cell Institute, has grown since Obama's executive order in 2009 allowing the use of more embryos. (SPENCER PLATT/GETTY IMAGES)
An executive order signed by PresidentBarack Obama almost four years ago appears to be accelerating progress by those researchers, who have used the cells to develop powerful new research tools to study disease. In some instances, researchers have used them to develop specialized cells now being tested in a handful of clinical trials.
Scientists studying stem cells were buoyed when they saw a major legal challenge to their work fall by the wayside early this year. The Supreme Court on Jan. 7 declined to take up Sherley v. Sebelius, a case challenging the legality of federal support. An exuberant Rep.Diana DeGette, a Colorado Democrat, issued a statement that day vowing to work “tirelessly” to pass legislation codifying guidelines written by the National Institutes of Health to comply with Obama’s order.
“I am very pleased,” NIH Director Francis Collins blogged the same day. Patients and their families looking forward to new therapies “should be reassured that NIH will continue supporting this promising research.”
Even if the supporters of embryonic stem cell research are breathing easier, doubts continue to dog the field. Money isn’t growing, and competition for scarce resources from other areas of research is intensifying. Moreover, the field remains controversial and the underpinning of current policy is nothing more than an executive order that might be easily overturned — raising the stakes for boosters on Capitol Hill such as DeGette.
Abortion foes say the executive order promotes the destruction of human embryos and therefore is immoral. The 2012 platform adopted at the Republican National Convention called for banning public and private research on human embryonic stem cells. And opponents and supporters of the research say it’s likely that Mitt Romney would have rescinded the order had he been elected president.
But uncertainty about the field’s future isn’t purely a matter of politics. Scientists themselves are increasingly drawn to research involving cells that aren’t derived from human embryos; these alternative cells have also shown exciting medical promise.
Studies of these cells have become a magnet for NIH research dollars. Their use also helps researchers avoid the troublesome ethical questions surrounding embryonic cells.
Human embryonic stem cell research has long had its supporters in Congress, and perhaps no lawmaker stirred up hopes for medical breakthroughs from this field more than the late Arlen Specter of Pennsylvania.
As a way to pry more medical research funding out of his colleagues, the Democrat continually lectured NIH officials during appropriations hearings about the importance of predicting, as specifically as possible, when stem cell breakthroughs would materialize. At a May 19, 2006, hearing, Specter called for a million-person march on Washington by patients and their families affected by serious diseases. He said they should demand increased spending and legislation to promote research.
Click here to view graphic: Research Rising
(MICHAEL STANALAND/CQ ROLL CALL)
“This is a battle that has to be waged by the 110 million Americans that are suffering from these illnesses in the United States,” he said.
Owing to strong bipartisan support, legislation lifting a restrictive 2001 human embryonic stem cell policy instituted by President George W. Bush was passed by Congress and sent to his desk for his signature in 2006. But Bush vetoed the bill, and its House supporters couldn’t muster enough votes to override.
On March 9, 2009, Obama issued an executive order requiring NIH to write guidelines opening up more human embryonic stem cell lines for federally funded research. For the cell lines to qualify for federally funded studies, the guidelines, issued in July 2009, require documentation that the lines were developed from embryos donated under circumstances that meet certain ethical standards.
For example, the lines must have been taken from embryos left over from in vitro fertilization procedures. They must have been supplied under informed consent procedures, with donors declaring that the embryos were created not for research but for reproductive use and they were no longer going to use them for that purpose. Donors could not have been paid to provide the embryos.
NIH officials say that since then many more human embryonic stem cells have become available for study. While they say progress is occurring at a breakneck pace, they also find themselves having to tamp down expectations that stem cell treatments will emerge quickly.
“One can even put it in the context of putting a man on the moon,” says Paul A. Sieving, director of the National Eye Institute at NIH. “How long did that take — a decade or so?”
But Sieving says much less is known about the basic science involved in tweaking stem cells to become safe and effective therapies than was known in 1960 about the science of getting a man on the moon. “This is true, fundamental discovery,” he says. “You can work as hard as you want, but things do take time.”
Even so, Sieving emphasizes that there is much publicly and privately financed research to develop the medical potential of human embryonic stem cells, both to treat a medical condition called macular degeneration that leads to blindness and to address human disease in general. “The whole research world is just on a super-fast track on this one,” he says.
Story Landis, director of the NIH National Institute of Neurological Disorders and Stroke, also expresses excitement about recent activity concerning embryonic stem cells and their potential, despite the unknowns.
“The thing about human embryonic stem cells that’s totally cool is they will divide in culture forever,” she says. “You can take those cells and turn them into many, many, many different kinds of cells that are present in the human body. They’re called ‘pluripotent’ — ‘giving rise to all or virtually all.’”
Bush opened the way for the first federally supported studies of the cells. But he was worried that the increased money would lead scientists to destroy new embryos. So his policy limited grants to studies of embryos that had been discarded by in vitro fertilization clinics before Aug. 9, 2001 — the day he announced the policy. That led to funding for just 21 human embryonic stem cell lines.
Instead of focusing on the timing of when the embryos are donated, Obama’s executive order addressed whether the circumstances of donation “met really good standards” to ensure that the donation was for reproductive and not research use, Landis says.
The original 21 “were good lines but didn’t have much diversity” in terms of including embryos from racial minorities, for example, Landis says. Now there are 200 lines available, 55 of which were under study in March 2012, the last time NIH examined grants to develop such a tally.
Basic research has followed in which scientists learned developmental signals controlling differentiation of the blank cells into many specialized types of cells in the human body, Landis says.
“Human embryonic stem cells have really been useful in helping us understand how development of human tissues and organs takes place,” she says.
As a result, scientists can now grow big batches of human heart, liver, neuronal, retinal and other cells. They can then use them to test the safety and efficacy of many experimental drugs quickly without having to put them into actual human beings. That’s “just a huge advantage” that speeds screening of compounds and accelerates the pace of drug development, Landis says.
Forty-one of the 200 lines are from embryos with genetic mutations that are linked to various diseases. Women undergoing in vitro fertilization chose not to implant them because the mutations were linked to conditions such as cystic fibrosis and spinal muscular atrophy.
But those mutations make it easier to screen drugs to treat the diseases they cause. “Let’s say you think compound B would be good for treating spinal muscular atrophy,” Landis says. “You could grow a vat full of motor neurons containing the mutation for the disease and see if the compound prevents those cells from dying.”
Three clinical trials have begun testing the direct therapeutic use of specialized cells developed from human embryonic stem cells, she says. The first trial approved to go forward by the Food and Drug Administration was conducted by Geron, a biotech firm based in Menlo Park, Calif. Geron used the cells to treat five patients for spinal cord injuries.
“Despite the fact that it was going extremely well, Geron closed it down for financial reasons,” Landis says.
The company estimated it would take a decade or longer to get marketing approval to treat spinal cord injuries. It chose to focus instead on developing cancer drugs that it thought would yield a profit more quickly.
Two other trials are under way that were launched by Advanced Cell Technology Inc., based in Santa Monica, Calif. Retinal cells developed from human embryonic stem cells have been transplanted into patients with two eye diseases that lead to severe vision loss: Stargardt’s macular dystrophy and the dry form of age-related macular degeneration.
ACT became the first company to get a study published on clinical use of a treatment derived from human embryonic stem cells, Sieving says. The British medical journal The Lancet published data in February 2012 saying the company’s cells attached in the eye without evidence of safety problems or of being rejected by the immune systems of the two patients involved.
“The two patients both say they are seeing better,” Sieving says. “Whether that’s reality or not is a close call,” he adds. “So far, tumors have not grown,” he says. “That is a very positive outcome.”
Landis says there were concerns that some of the embryonic stem cells would not differentiate into the specialized cells needed for treatment and would continue to divide.
“[The concern was], ‘Oh my God, you’ll get horrible tumors.’ There’s no evidence of that, either in the spinal cord safety trials, where they have had five patients, or in these eye trials,” Landis says. “And that’s huge. And you can actually look in the eye and see that the cells are exactly where you injected them and they’re behaving in a really appropriate fashion.”
Even so, the amount of grant money NIH has awarded for human embryonic stem cell research has remained flat at roughly $120 million a year for several years and is expected to remain at that level for fiscal 2013.
But it’s a different story for another type of cell.
A growing share of NIH research dollars is going for “induced pluripotent stem cells.” Kyoto University researcher Shinya Yamanaka discovered that cells could be taken from adults and, by inserting four genes, could be turned into something that looks like a human embryonic stem cell. “It’s amazing,” says Landis.
The technique entails no destruction of human embryos. What’s more, because the cells would be taken from the patient’s own body, immune system rejection wouldn’t be a problem. “People have embraced this technology,” while NIH funding for human embryonic stem cells has remained flat, Landis says. NIH was not immediately able to provide specific funding totals for studies involving induced pluripotent stem cell lines.
Opening door: Obama signs the order March 9, 2009, leading to an increase in stem cell research. ( CHRIS KLEPONIS/AFP/GETTY IMAGES)
Abortion foes and many Republicans have strongly supported federal research into these kinds of cells. Their enthusiasm, along with strong scientific interest, could make even tougher an already uphill battle for DeGette to gain congressional approval of her legislation to codify Obama’s executive order.
“One of the big questions is, should we all just use induced pluripotent stem cells now?” Landis says. But that’s not the view of the scientific administrators at NIH, who say researchers should be free to use federal money to do research into both types of cells.
It’s going to take years to figure out, for example, whether a tweaked adult cell will replace tissue as well as a human embryonic stem cell, Landis says. “There are so many, many different kinds of cells in the body, and it may be that induced pluripotent stem cells won’t make some of those cells.”
The work on embryonic cells also aided progress on induced cells. Yamanaka “might have gotten there anyway, but it would have taken him a lot longer,” Landis says.
Leaving multiple avenues of stem cell research open would allow scientists rather than politicians to determine how federal stem cell research dollars are allocated.
“If the scientific community believes that we’d be better off using one or the other, they’ll vote with their grant applications,” she says. “It will be a choice that the scientists, not that politicians, make.”