Westward Whoa!

After conventional treatments offered no relief, stem cell therapy helped Ruth Pavelko's heart problems.
Daniel Kramer

Amid the Christmas rush at the Mall of the Mainland in Texas City, Ruth Pavelko's back scrunched into a prickly knot. The 49-year-old mom stumbled through the Foley's parking lot to her Pontiac, her lungs feeling as if they were filled with Jell-O. Three blocks down the street, Pavelko lurched to a stop and heaved up mucus. She clawed herself out along the side of her idling car and collapsed.

"I didn't know what was wrong with me," she says timidly, fiddling with her short, clear nails. "I just thought it would go away."

Pavelko spent Christmas in 1999 next to the red and green LED lights of an oxygen machine, recovering from a massive heart attack. A surgeon chopped and pricked, slicing through her ribs with an electric saw and conducting a bypass operation on two of her arteries.

Most people Pavelko's age can get by for at least 15 years on a double bypass; she made it six months. She was at home watching television when the clogged arteries turned her heart into a pressure cooker. A surgeon installed stents -- mesh tubes like Chinese finger cuffs -- to keep the passages open, but they stopped up again four months later, nearly killing her.

Doctors gave Pavelko less than two years to live, and for good reason: Her goopy blood, strawlike arteries and high blood pressure made beating coronary heart disease nearly impossible. A fourth heart attack on a sidewalk late last year left her desperate. She got zapped with radiation, received another stent and even pondered a heart transplant. Nothing worked.

"It seemed hopeless," she says.

Her situation was so hopeless, in fact, that she qualified in January for an experimental treatment developed by Dr. Yong J. Geng, a hotshot researcher at the Texas Medical Center. In one of the first attempts to use his technique in a human, Geng's doctors sucked bone marrow from Pavelko's hip with a giant syringe and parsed out 30,000 stem cells. They injected the cells through a catheter, straight into her arteries, in hopes that the cells would reconstruct them.

Pavelko waited three months without noticing any signs of improvement. About a month ago, she decided on a whim to clean the dishes and washed them all, by herself and without resting, for the first time in six years. A week later, she made her bed faster, did more laundry and started climbing stairs at will. "Just before you got here, I went up and got my shoes," she tells a visitor, sitting at her dining table and breathing normally. "I'm feeling a lot better."

By many accounts, Geng's stem cell treatment is one of the biggest medical breakthroughs of the decade. Expanding on the work with better cells from frozen and cloned embryos, Geng and other researchers eventually could unlock cures for everything from heart disease to hair loss. But it's just as likely that this cutting-edge research will be shut down and shipped off.

A growing cadre of activists in Texas is convinced that scientists shouldn't save lives by killing babies, and they're aiming this month to back up their beliefs with law.

Think of modern medicine without donated organs, without blood banks and without chemotherapy -- tools scientists helped develop over the past 30 years at the Texas Medical Center in Houston. A new generation of Texas researchers expects that, in years to come, those advances could look almost as quaint as castor oil peddled by the country doctor, all thanks to stem cells.

Doctors at the M.D. Anderson Cancer Center use the cells to treat leukemia. Baylor College of Medicine professor Peggy Goodell studies stem cells with an eye toward someday manufacturing human blood, thereby eliminating the need for donors. And colleague Thomas Zwaka hopes his research eventually will allow scientists to use the cells in place of animals and human subjects in the study of diseases and drugs.

Even so, support for embryonic stem cell research in Houston and across most of the country is extremely conditional. Citing moral concerns, President George W. Bush four years ago approved federal funding for the work on the condition that it be limited to cells already extracted. The move left less than two dozen highly imperfect cell lines available for federally funded research.

But the restrictions haven't yet done much to slow down researchers such as Geng, who gained plenty of experience jumping through government hoops after graduating near the top of his high school class in China. His reward for good grades was to travel to the mountainous countryside for "conditioning" at a Maoist labor camp, where he farmed rice and pigs and nearly froze under a thin blanket.

"It was just like the life you lived 2,000 years ago," says the balding, 48-year-old cardiologist, who is sitting at his desk next to a plant growing in a beaker. "No different."  

Studying almost every night, Geng escaped the camp four years later for medical school. But he didn't shake the government. Communist officials discovered that he was dating -- a banned activity for students -- and sent him to do his medical residency in a remote mining camp.

Geng later married his contraband sweetheart and went on to a career of international renown. He studied stem cells in France and coronary disease in Sweden under Goran K. Hansson, who serves on the Nobel Prize Committee (and likes to visit Geng at his house in Pearland). In the United States, he bounced from teaching at Harvard to research at a heart institute in Pittsburgh. He's currently directing the Center for Cardiovascular Biology and Atherosclerosis Research in Houston, where he has studied the effects of stem cells in heart tissue using, appropriately enough, pigs. "I know how they behave," he says.

After receiving Geng's stem cell treatments, some patients have responded more dramatically than the pigs or even Pavelko: They've gone jogging on the beach and have had sex for the first time in years. No wonder scientists during a recent visit to Geng's lab were overheard referring to him as "the Master of the Universe."

Scientists close to Geng aren't the only ones thinking big. Stem cells are widely valued for their unique ability to create and repair tissue. Adult human stem cells, discovered in bone marrow roughly 30 years ago, sometimes don't serve this function as well as the more recently discovered embryonic stem cells, which scientists are now harnessing in hopes of rebuilding ailing human bodies -- an emerging medical discipline known as regenerative medicine.

If they wanted to, peer-reviewed medical journals could almost go sci-fi with headlines about recent breakthroughs: Stanford researchers create insulin-secreting cells, possible cure for diabetes. Japanese scientists inject dopamine-producing neurons into monkeys, reverse effects of Parkinson's. Rat with broken spine walks again. Researchers think stem cells will reverse blindness, end baldness, cure cancer.

William Brinkley, dean of the Graduate School of Biomedical Sciences at Baylor College of Medicine, takes the hype seriously. "We are going to be able to potentially replace most of the organs and tissues of the body," he says. "It is going to be, potentially, one of the greatest medical breakthroughs in the history of the universe, but it's also certainly the greatest of the 21st century. I think it will dwarf others."

As the field matures, Houston's Med Center could be especially well positioned to attract more top scientists. Its 13 hospitals and 11 educational institutions form the largest medical center in the world. It's a good place for anyone who needs patients or money for clinical trials. The center already employs more people than any other single entity in the city, generating $12 billion a year in economic impact. Boosters say stem cell research could continue that growth, fueling Houston's diversification from petrochemicals into the vaunted knowledge industries.

"We will be able to attract not only attractive companies but brilliant minds," says Representative Senfronia Thompson, a Democrat from north Houston. "And we will be able to help find critical cures for people who are suffering from forms of cancer, diabetes, organ diseases -- who need transplants."

Thompson and Democrat Elliott Naishtat of Austin authored separate bills this session to provide more than $1 billion in state funding for Texas stem cell research, but neither bill went to a vote by last week's voting deadline.

A more modest proposal passed the House last Thursday as a rider that Houston Republican Beverly Woolley attached to an education bill. It provides $41 million for an "adult stem cell research center" at the Texas Medical Center, with $63 million for a similar facility in Dallas.

Woolley says the bill's wording also would allow embryonic cell research at the new centers.

The scientists "work day and night trying to help people," Woolley says, "and we really need to do this."

California already has wagered heavily on the same ideas. Its voters last year approved Proposition 71, which created the California Institute for Regenerative Medicine and authorized a whopping $3 billion in state bonds for the research. Proposals in nine other states this year would together nearly match California's wad of cash.

Bush's cold shoulder has allowed California to woo Houston's stem cell experts. Geng has been offered positions in Los Angeles, San Diego and San Francisco. His lab recently lost two job candidates to labs in California, where they said they could find more funding. "Baylor, UT, M.D. Anderson, should be working together to establish this research," he says, "but without the money, we can do nothing."  

That concerns U.S. Senator Kay Bailey Hutchison, a likely contender for governor in 2006, who is among a handful of Republicans to indicate that they might support stem cell funding. But taking a strong stand on even moderate proposals could be political suicide.

Woolley's rider still must pass the Senate, escape an appropriations committee's ax and somehow slide past Governor Rick Perry, who has said he'll oppose any legislation that funds the destruction of a human embryo. Perry knows what he's doing. The conservative right is the home team in Texas, and its players in suburbia are swinging for the bleachers.

On a Little League field in the modest suburb of Red Oak, south of Dallas, the Mustangs send their slightly pudgy right fielder to the plate. Riley Boswell ignores the other team's fourth-grade taunts. He gets a walk, steals second and takes third off a grounder -- all with a $5,000 computer jostling in his pocket.

The inning ends and he jogs into the chain-link dugout, against the flow of his teammates taking the field. "Riley, you all right?" a coach asks. The ten-year-old silently unzips a black medical kit, pricks his arm twice with a needle and watches it pool with blood. He might need to adjust the computer -- an insulin pump -- but the other team's batter is already swinging. The coach says, "Riley, you've got to move."

Riley knows that juvenile diabetes is a constant pain in the ass, the back, the arm and everywhere else he has to prick himself. That could change, of course, now that doctors are working on a cure for the disease using embryonic stem cells.

His mom, Amy Boswell, knows such a cure could extend her son's life and make both of theirs easier. But that doesn't matter to her. "If they found a cure from embryonic stem cells," says the former nurse, "Riley would never be cured. We just wouldn't do it.

"I feel like human life begins at conception," explains Boswell, 33. "And every human life is precious and unique and should be respected, should be protected, should be dignified, basically."

Despite its black-and-white simplicity, or because of it, Boswell's view is gaining increasing support. Texas Right to Life, a group lobbying hard against embryonic stem cell research, has more than tripled its membership in the past ten years.

The group last year helped push through two pro-life-oriented state bills: The Prenatal Protection Act recognizes a state crime against two people if a pregnant woman is attacked, and the Woman's Right to Know Act requires that women receive an informational pamphlet 24 hours before having an abortion. Thanks to ousters of incumbents last year in the wake of Republican-led redistricting, "We have a more pro-life legislature than we've ever had in 130 years," says Stacey Emick, Texas Right to Life's legislative director. "So this is a big time for us."

Of course, states such as Texas can't simply outlaw abortion -- that would violate the Roe v. Wade Supreme Court decision -- so pro-life groups focus on related hot-button topics. The Terri Schiavo "natural death" case is one example. Embryonic stem cell research is another. "Our mission is to protect innocent human life from fertilization until natural death," Emick says, "so embryos that are…subjects of experimental research and would die because of that fall under our purview of protecting human life."

Emick and Boswell oppose embryonic stem cell research in both of its forms.

The traditional form involves extracting stem cells from a fertilized egg -- usually only a few days old -- which can be obtained, for example, from an in-vitro fertilization clinic with the consent of the parents. There are an estimated 400,000 such embryos in frozen storage, many of which never will be implanted in the womb of the original mother and will be destroyed if they are not used for research.

The newer form, therapeutic cloning, involves the same methods used to clone Dolly the sheep, but cut off at a much earlier stage. In a process known as somatic cell nuclear transfer, scientists take a nucleus from almost any cell in the human body, implant it into a human egg, grow the resulting cloned embryo for a few days in a petri dish and harvest its cells.

Texas Right to Life conducted a poll in 2002 that found that 69 percent of respondents in Texas opposed medical research using therapeutic cloning. Some national polls, however, show mild overall support for the practice. Even so, five states have banned it.

Last session, Texas nearly joined them when Representative Phil King, a Weatherford Republican, proposed an anti-cloning bill. Although the original bill never went up for a vote -- a fact his allies attribute to the flight of the Democrats to New Mexico -- King attached the proposal late at night to a funding measure for higher education. It came within ten votes of passing. Both sides say it failed only because legislators hesitated to vote for something they didn't understand.  

Stem cell debate this session kicked off with an overflowing, 13-hour hearing before the House State Affairs Committee. King showed up with his laptop and beamed onto the wall a drawing of petri dishes filled with identical googling babies. "I think this is really a crossroads time for Texas," he said. "I think the public wants a cloning ban."

However, King's own anti-cloning bill failed to reach the House floor. An identical bill, pushed by GOP Senator Ken Armbrister of Victoria, is still pending. (Three other Senate bills would protect therapeutic cloning.)

One King comrade at the recent hearing was Amy Boswell, who carted her son Riley up to the podium and testified in favor of the ban, eliciting audible gasps from diabetics in the audience. Boswell is no stranger to martyrdom.

She joined an e-mail group composed of moms of diabetics and was flamed so viciously for her sentiments that she dropped out. But the Catholic mother of six also is capable of defending her Christlike stance without invoking God -- a trait typical of the state's evolving pro-life movement. Texas Right to Life is "nonreligious, nonsectarian and nonpolitical," Emick says. True, the group's office is plastered with crosses, but they're only "decoration for whatever employees use the office space."

Getting down to the corporeal nitty-gritty of why embryonic stem cell research is wrong, most opponents present a simple, even graceful secular argument: All that any petri dish embryo needs to grow into an adult is time and nourishment. Boswell's analogy: "I have the potential to be an old lady," she says, "but you put me out in the desert with no food and no water and the poor conditions, I'm going to die…That doesn't make me any less human."

Prompted by his mother, Riley summarizes the problem this way: "You have to kill babies."

Ultimately, the research is all the more atrocious, opponents say, because it isn't even necessary. Boswell is convinced that embryonic stem cells will never cure diabetes. A handout distributed by Texas Right to Life points out a variety of problems with the cells, such as their tendency to form strange tumors consisting of clumps of teeth, eyes and hair. "Some scientists think that stem cells extracted from cloned human embryos will be useful for the treatment of human diseases," it says. These "claims are unfounded."

Physically speaking, the foundation for Geng's science is a petri dish filled with gel and proteins -- nourishment for a smattering of embryonic cells. In his expansive laboratory on the ninth floor of the Texas Heart Institute, Geng plucks one of these dishes from a refrigerator and places it beneath a microscope.

The view, a few years ago, admittedly might have been a Frankenstein mix of skin, bone and intestine cells -- almost anything the cells wanted to form. But Geng has refined the mixture of proteins to direct the cells' growth. "These are heart muscle cells," he says, "derived from the stem cells."

A nearby computer shows a strangely recognizable video of the cells' movements. Every second or so, they throb in unison. "The mature cardio cells are spontaneously beating; they have a pulse," Geng says. "It's like you grow a heart, in vitro, in a petri dish. A small, tiny heart."

Eventually, Geng wants to know whether embryonic stem cells can be grown into full-sized hearts for patients who need transplants. But in the near term, he's investigating how well the cells repair existing hearts. The investigation mirrors the ones he's conducting with adult stem cells in human patients such as Pavelko. "What we want to do is find out how we can use embryonic stem cells and adult stem cells," he says, "and which ones can do better."

The work is time-consuming and expensive.

After the cells in the petri dish mature and multiply, Geng's lab techs remove them, concentrate them in a vial and insert them into a flow cytometer. The photocopier-like machine costs about as much as Geng's home. It attaches the cells to antibodies, activating fluorescent marker genes, which identify different cell types. They might glow green for vascular cells, for example, or red for muscle cells. Another machine across the street at M.D. Anderson, priced competitively with a house in River Oaks, uses the colored markers to separate out each cell type.  

Like preparing a mixed drink, scientists next assemble a fortifying cocktail of the different types of cells. Recipients are diseased mice, dogs or pigs, which have been given severe atherosclerosis and other heart problems. Their ailing hearts are injected with a catheter through the coronary artery to transmit the cells. Taking root and differentiating into veins and tissue, the cells hopefully will make the needed repairs.

Several months later, Geng's scientists kill the animals and remove their hearts to examine the results. Adult stem cells so far have done a better job patching things up than embryonic cells. Despite Geng's ability to control the embryonic cells in the early stages, they often revolt once injected into the mice and form cancerlike tumors. Geng's opponents, it seems for the moment, are correct.

But Geng thinks he can overcome this hurdle. Research on embryonic cells is incredibly young -- they were only discovered in 1998 -- while adult stem cells have been studied for decades. Given more time, he says, he will be able to develop "molecular manipulation pathways" to guide the cells' development. "Using these techniques," he says, "we can selectively change these cells into heart muscle cells or vascular cells -- so-called tissue-specific development."

To Geng's credit, some of the shortcomings in his embryonic stem cell work are due less to science than to a lack of political support. Geng's embryonic cells come by necessity from one of the lines preapproved by President Bush, but those cells don't differentiate into heart cells as well as newer, unfunded lines of cells. All of the Bush-approved cells are also contaminated with mouse viruses and thus can't be used in clinical trials in humans.

"We need better stem cells," Geng says. "I hope that the Texas government can provide us with some funding for this."

Geng suspects that adult stem cells ultimately will face firmer limitations. So far, they've just been made to differentiate into only a small range of cell and tissue types, which means that researchers who want to grow a kidney from scratch or cure diabetes, for instance, might not be able to use them. And though adult stem cells work in patients such as Pavelko, they don't work in all patients, especially older ones, who lack enough stem cells in their bone marrow to harvest for treatments.

It's precisely this supply problem, in fact, that scientists believe could be solved with therapeutic cloning. An embryo cloned from a patient could yield plenty of new stem cells, which could form new, genetically identical tissue. The tissue could be implanted in the patient's body without being rejected by his immune system. "I believe this is one direction we could go in this century," Geng says. "I would say therapeutic cloning really will eventually prolong our lives."

Other scientists agree. "The more short-term applications might be from adult, but the long-term and the very long term may even be all embryonic," says Goodell, the Baylor researcher. "And that's why, even though I really love my adult stem cells, I'm starting to work on them too. I think they really are going to have a lot of potential."

Of course, such news isn't likely to mollify some opponents. In fact, publicity stemming from Goodell's research four years ago prompted a flurry of hate mail, even though her work at the time focused on adult cells.

The situation has been worse in Geng's building. Dr. Emerson Perin, Geng's collaborator on the adult stem cells project, has received death threats and reports of a strange man walking through the lab, claiming to be a doctor. There wasn't much he could do about it, Perin says, except change the locks.

Public relations has never been a priority for most Texas stem cell scientists. They may hope the public eventually will focus on other reproductive issues, such as the marital status of Eva Longoria, or they may just be reluctant to speak outside their professional niches. Geng, confronted with the pro-life arguments against his work, pauses and says, "Okay. I'm not a reproductive or cell biologist."

Unwilling to take a firm stand on the moral issues, Dr. James Willerson, Geng's boss and president of the UT Health Science Center, has instead focused legislative efforts on funding the adult stem cell center; other scientists privately criticize that proposal as inadequate for supporting embryonic research. Willerson declined to comment on why he chose to focus on adult cell lines.

Meanwhile, the vacuum left by scientists is being filled by professional bioethicists offering rebuttals to the pro-life arguments. One of the most prominent opinion makers is Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, who supports therapeutic cloning.  

He notes that scientists repeatedly have been foiled in their attempts to nurture cloned primate embryos into full-blown fetuses, which means giving birth to a cloned human is probably similarly impossible. "Oddly, a cloned embryo may be less ethically controversial once the facts are understood," he says, "because it has the least potential to turn into an adult human being."

Caplan also supports research using conventional embryos. He responds to the pro-life "time and nourishment" argument with the idea that a young embryo, as a mere bundle of cells, has more in common with an iPod download than with a baby. "You wouldn't see a little baby in there; you would see a little program in there," he says. And statistically speaking, 60 to 70 percent of embryos self-abort before maturing, he adds, so there's nothing magic about conception.

Even so, Emick of Texas Right to Life isn't swayed. "That's a natural death," she says. "This death that would happen with the embryo would be induced by the scientist. So there is a clear difference there."

Of course, the embryo can't "die" if it isn't alive. On this point, Geng offers his wisdom as a cardiologist: There is no life until there are heartbeats. "After the heart is beating," the embryos "have circulation and life is going, because of their blood flow; they move."

You might call this the modern version of "the quickening."

The modern version of life, post-quickening, post-death threats, post-79th Legislature, would have Geng taking the quickest plane to California. After all, six years ago he barely passed up a job in Los Angeles for his position in Houston. He interviewed here during a temperate December; he visited the lab in L.A. during a torrential shower and an earthquake. But now a job in California might be more stable.

Of course, Geng's lab is large and shiny and Geng's house is large and affordable. But his daughter graduates from Rice next year, and losing those other perks isn't something a better salary couldn't fix.

Geng sums up his plans on a recent afternoon, sitting inside the blank walls of his office, which is unencumbered by anything personal that couldn't be packed up in five minutes. "If they did not allow us to do work with embryonic stem cells, at this moment, I would not think about moving to other states," he says.

"Unless there was a good job offer," he adds, laughing and slapping his desk. "Double my salary. I want to do that."

His chuckles die down. As a seeming afterthought, he adds: "I'm just joking."

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