A Search for the Cure: How University scientists are defining the field of stem cell research

Jed Moch/Daily
Buy this photo

By Stephanie Steinberg, Daily News Editor
Published September 26, 2010

It’s 5 a.m. and Eva Feldman is heading to her office to devour a hearty breakfast of scientific articles. Over the next two hours she’ll sample a bit of cell biology, molecular biology and, her favorite, neurodegenerative diseases.

Jed Moch/Daily

By 8 a.m. Sean Morrison and Max Wicha arrive, and all three begin the tedious task of responding to the hundreds of e-mails they’ve received through the night. As the morning proceeds they visit their respective laboratories, which house not only their life’s work but also “their people,” without whom there would be no work at all.

The three, all top scientists at the University, make up some of the principle players in the most innovative research in the world. Trying to solve more than simple scientific questions, they are on a mission to cure the most torturous and fatal diseases that strike mankind.

Wicha runs the University’s Comprehensive Cancer Center. Morrison directs the University’s Center for Stem Cell Biology Research as well as the International Society for Stem Cell Research. When they’re not on campus they can most always be found in Washington, D.C., Europe or Asia, presenting their research at conferences or meeting with international colleagues — Morrison traveled 135,000 miles least year alone.

But Feldman’s day, it seems, can be a bit more hectic.

On Tuesday she can be found in the Neurology Clinic. Wednesday she’s in the Motor Neuron Disease-ALS Clinic treating patients. Other afternoons she’s directing the A. Alfred Taubman Medical Research Institute.

For Morrison, Wicha and Feldman, time is their enemy. While they’re barely afforded enough of it to breath, the real challenge is working against the clock to develop treatments that may ease the pain and save the lives of millions of people.

The answer, they believe, lies in stem cells — microscopic units present in all multi-cellular species that can regenerate and morph into different cells, tissues and organs. While scientists believe stem cells have the potential to treat dozens of diseases and conditions like Alzheimer’s, diabetes and spinal cord injuries, no one yet knows their full potential.

And as researchers try to find out, the clock keeps ticking.

“It takes years of your life to answer a scientific question,” Morrison says. “So if I’m going to spend years of my life trying to answer a question, I really want people to care what the answer is.”

Feldman doesn’t mind the life commitment that eats up her days, hours and seconds.

“I don’t really have a ‘job,’ " she said. “I have a passion. And if you want to call it a job, it’s the best job in the world.”

Close to a cure

In a laboratory on the fifth floor of the Biomedical Science Research Building, 30 students, Ph.D.s and lifelong researchers work ferociously to find a treatment for a ruthless disease — one that creeps through the body, weakening tissues so that victims are, quite literally, unable to move a muscle. Even the seemingly most invincible athletes don’t stand a chance.

Meet amyotrophic lateral sclerosis — more commonly known as ALS — or Lou Gerhig’s disease, named after the legendary New York Yankees baseball player who suddenly came down with the disease at the height of his career.

ALS damages nerve cells and motor neurons in the spinal cord that control muscle movement. The disease tends to strike people in their 30s and 40s, and once a patient is diagnosed it may take only three to five years for the disease to take over the body and kill its host. It’s a painful process — as most victims lose the ability to walk, talk and even breath.

Feldman, who has seen thousands of ALS patients die from the currently untreatable disease, is on a medical mission to find a cure.

“I would say on a near-weekly basis one of my patients will pass away from this disease,” she said. “I am very impassioned about understanding ways and means to develop new treatments.”

The 30,000 people in the United States diagnosed with ALS have reason to remain hopeful, however, because Feldman claims she’s not too far from a potential cure.

In January, Feldman started the first human clinical trial approved by the U.S. Food and Drug Administration to apply stem cells to treat ALS. Five ALS patients have since volunteered to receive injections of neural stem cells into their spinal cords. Researchers at the University of Michigan study and approve the cells before shipping them to Atlanta where the patients undergo the stem cell transplants at Emory University.

The majority of the work occurs in Feldman’s lab in the Biomedical Science Research Building, where bottles of solutions, petri dishes and test tubes clutter shelves and rows of DNA-filled refrigerators line the hallways.

“I’ve got more refrigerators than I have shoes,” Feldman joked while strutting down a corridor lined with white refrigerators.

The trial is still in its first phase and can only move onto phase two when researchers prove the injections cause no harm to the patients. Once safety is established, Feldman and her team will enter the next phase, where they will watch to see if the stem cells actually benefit patients by slowing the progression of the disease. If successful, Feldman can recruit more patients for phase three, which, she said, must confirm both safety and efficacy.

The goal is to enter 18 patients in the trial, which is receiving stem cells and funding from Neuralstem Inc., a biotech company in Rockville, Md. In an interview in July, Feldman said she was not allowed to comment about the five current patients in the trial. However, she spoke with optimism as she relayed her progress, noting she anticipates no trouble finding the remaining volunteers.

“I think the one really amazing thing about this patient population is how willing they are to step forward and really do something that is brand new, that is clearly experimental — it has never been done before — and they realize that it may not necessarily help them, but it will potentially help other patients with the disease in the future,” she said.

Feldman believes it may be 14 months until they complete phase one of the trial, and it’s uncertain how long phases two and three may last. And after researching ALS for the last 20 years, Feldman wants to get it right.

How they got here

It wasn't long ago, however, that researchers like Feldman couldn't touch stem cells without fear of landing in jail.

Before the passage of the Michigan Stem Cell Amendment — a ballot initiative referred to as Proposal 2 — in November 2008, fertility clinics were forced to throw away unwanted embryos. The 53-47 voter approval gave women in the state the opportunity to donate their unwanted embryos to research. The proposal also permitted the creation of new embryonic stem cell lines to study diseases and allowed University researchers to transfer their work to the state of Michigan.

Before the proposal passed, Feldman worked three months out of the year in a lab at the University of California at San Diego. Feldman said she made “great strides” in California, where she laid the groundwork for her current ALS clinical trial.

“But it was difficult managing a laboratory nearly 3,000 miles away,” she said. “It slowed progress and added unnecessary costs.”

Besides Election Day, March 9, 2009 stands out as an equally important day for most University researchers. On that Monday, the University announced the opening of the A. Alfred Taubman Medical Research Institute Consortium for Stem Cell Therapies — a $2 million center housed in the BSRB where University researchers can develop new stem cell lines. Earlier that morning, President Barack Obama issued an executive order that would lift restrictions on embryonic stem cell research. His announcement overturned former President George Bush’s executive orders that limited stem cell research and funding.

“This is a great day for America, and a great day for science, and a great day for the University of Michigan,” Morrison said in an interview with The Michigan Daily at the time.

Today, Feldman calls Obama’s decision “a huge triumph for anyone interested in medical science.”

“It means we can obtain funding for research that will eventually lead to easing the suffering of millions of people afflicted with currently untreatable diseases,” she said.

Before the Michigan Stem Cell Amendment passed, University researchers were only allowed to use human embryonic stem cell lines that had been derived outside of Michigan. Morrison said the regulation posed major problems for research because groups of people like African Americans, Native Americans and indigenous populations from North and South America were underrepresented in these lines.

“The existing embryonic stem cell lines that had been derived in other states don’t come close to mirroring the diversity that’s present in our society,” Morrison said.

More than a year and a half old, the consortium is one of a few centers in the nation where researchers can derive new human embryonic stem cell lines. Since Proposal 2 passed, donated embryos have been slowly trickling through the door.

According to Gary Smith, co-director of the Consortium for Stem Cell Therapies and an associate professor in the Department of Obstetrics and Gynecology, the consortium has received approximately 20 donated embryos from four couples.

The controversy isn’t over

Though voters approved the 2008 ballot initiative, the fight to impose stem cell research restrictions in Michigan and across the country continues.

In August, U.S. District Court Judge Royce Lamberth issued a ruling that blocked federal funding for human embryonic stem cell research. Lamberth decided that Obama’s March 2009 statement violated the Dickey-Wicker Amendment — a federal law that prohibits the government from funding research that creates or destroys embryos.

The U.S. Justice Department is currently appealing the decision that Morrison called a “nuclear bomb” for human embryonic stem cell research.

“It’s a far more extreme position than we’ve ever encountered before,” Morrison said. “If that injunction remains in place for a significant period of time, it will destroy the field because there will be no federal support.”

Wicha also said the injunction is “a big blow” for stem cell research in the United States. If the ruling isn’t overturned, he said, scientists will take their work outside the country.

Last year, the National Institutes of Health gave $6.8 million in stimulus funds to 13 stem cell research projects at the University. But at least five NIH grants for projects related to the treatment of human diseases will be suspended this year if the injunction remains in place, according to Morrison, who testified before the U.S. Senate this month about how to change federal law to prevent the judge from blocking funding.

As researchers await a final decision, the U.S. Court of Appeals ruled yesterday that the government can continue funding human embryonic research while the appeal is pending.

Meanwhile, the Michigan state Senate passed a bill in April that amends the stem cell research guidelines spelled out by Proposal 2. The bill, currently being reviewed by a state House of Representatives committee, proposes new documentation requirements that mandate researchers to write reports about each donated embryo — tracking information about when it was received, what research was performed and the outcome of any experiments.

Ed Goldman, an associate professor in the Department of Obstetrics and Gynecology and an opponent of the legislation, said this type of report is dangerous for researchers because it requires them to list their names and addresses.

“Giving information about the researcher allows some person with a gun and a grudge to come to the lab and start shooting,” he said.

Any violation of the law would be a felony, punishable up to five years in prison. There would also be a $5,000 fine for failure to submit a report or obtain written consent from an embryo donor.

Goldman, who has analyzed the stem cell legislation and has written recommendations to Congress, said these additions create a “chilling effect” that will deter researchers from studying stem cells.

“Why would someone want to do this research with a possible felony charge hanging over their heads if there was a bookkeeping error?” he said.

According to Goldman, no state that permits stem cell research requires the amount of documentation proposed in the bills, nor do any states impose significant monetary fines for violations.

If passed, the amendments may intimidate researchers and force them to again move their work to one of the other 45 states that allow stem cell research, Goldman explained. He added that this would only worsen Michigan’s “brain drain” and destroy the opportunity for economic gains.

The 2008 Michigan Stem Cell Economics Study, sponsored by the non-partisan public policy institute The Michigan Prospect, found stem cell research could add nearly 4,000 new jobs in the state. University Regent Olivia Maynard (D–Goodrich) is president of The Michigan Prospect.

The study also reported that stem cell research has the potential to treat more than 770,000 Michigan residents who suffer from diseases like diabetes, ALS, Parkinson’s and Alzheimer’s. For patients who often take time off from work, stem cell therapies have the potential to cut down sick days and increase employee productivity. According to the study, if annual employee absences decreased 2 percent, the state would generate $19.2 million each year. Over 30 years, this would total $576 million.

Despite the potential economic and medical benefits, the original opponents of Proposal 2 and new embryonic stem cell challengers continue to fight for greater research restrictions.

“Unfortunately, even though the voters voted to protect embryonic stem cell research in the state constitution, there are repeated and ongoing attempts to try to block this in the legislature,” Morrison said.

Right to Life of Michigan, a non-profit organization against embryonic stem cell research, supports the proposed amendments to the law. Ed Rivet, Right to Life of Michigan legislative director, said there needs to be more public reporting because the voters who approved Proposal 2 have “a right to know” information like how many embryos are being donated.

“That’s just transparency and a little sun shining research, as you might say,” Rivet said. “You hear a lot about sun shining government. Well, there shouldn’t be a problem with sun shining publically-funded research.”

The World Stem Cell Summit

On Monday, University researchers will join more than 1,200 scientists, lawmakers, industry leaders and patients — hailing from 30 countries — at the Renaissance Center in Detroit for the 2010 World Stem Cell Summit. Over the course of three days, the sixth annual summit will feature more than 150 speakers and 50 hours of presentations designed to “unify the stem cell community” and “advance the field in a robust way,” according to World Stem Cell Summit founder and co-chair Bernard Siegel.

“We want to make sure that we can move this from the lab bench to the bedside quickly to impact human health and well being, and the meeting makes that happen,” Siegel said.

The summit is sponsored by the Genetics Policy Institute and co-hosted by the Michigan Economic Development Corporation and the University Research Corridor — a research collaboration between the University of Michigan, Michigan State University and Wayne State University. Scheduled speakers include Democratic Gov. Jennifer Granholm and U.S. Sen. Carl Levin (D–Mich).

The University will have a large presence at the event. About a dozen University researchers — including Feldman, Wicha and Morrison — are scheduled to give presentations. Feldman will lead a panel on current and future clinical trials for stem cell therapies, Wicha will give a talk about cancer stem cells and Morrison will discuss the new insights his lab has gained into the mechanisms that regulate stem cells and the links between stem cells and disease.

Last year the summit was held in Baltimore in conjunction with John Hopkins University and the University of Maryland. Previous summits partnered with the University of Wisconsin and Harvard University. When looking at potential locations to hold this year’s conference, Siegel said organizers based their decision on three criteria. The first: is important research occurring in the state?

“Clearly, Michigan is a leader in the field of stem cells,” he said. “You have first class researchers, not only at the University of Michigan, but also at Michigan State and Wayne State University.”

Check.

Second, organizers evaluated residents’ support for research.

“We were very impressed that the voters of Michigan passed Proposal 2 basically to protect embryonic stem cell research in the state Constitution,” Siegel said.

Check.

Lastly, organizers looked for philanthropic support for medical research within the state. Taubman, who will receive a National Advocacy Award at the summit, helped Michigan meet this condition, Siegel said.

Check.

Overall, Siegel said organizers chose Michigan because it is a “state that supports the field.”

In just a short time period, human embryonic research has made considerable legal and medical strides in Michigan and across the country. But even though medical breakthroughs and events like the World Stem Cell Summit give researchers hope for the future of the field, political roadblocks always have the potential to halt progress.

As Feldman points out, it’s the sick and dying against the healthy and powerful.

“I wish one day they would come into my clinic and ask my ALS patients, who are suffering terribly, whether they wanted to be denied the one, bright ray of hope for a treatment for this awful disease,” Feldman said. “It is just unconscionable what they are attempting to do in the name of politics.”