Pity the scientists of St. Louis.
For the past four years, they have been defending themselves against social-conservative groups who want to ban a promising new scientific procedure called somatic-cell nuclear transfer, a method of creating embryonic stem cells through genetic cloning. Researchers harbor great hopes that these cells, which can transform themselves into any tissue type, will one day yield treatments for a host of now-incurable diseases, from Parkinson's to diabetes.
But because SCNT involves creating embryos and destroying them days later, it has become a target of the powerful Missouri pro-life lobby and thereby linked (unfairly, researchers say) to the politically radioactive issue of abortion. What's more, because some worry that a cloned human embryo created through SCNT could develop into a crying, burping baby if it were placed in a woman's womb, the procedure has also been linked to the equally toxic issue of "live-birth human cloning" (just as unfairly, the scientists say--nobody wants to clone babies, nor do most think it's even possible).
As their state representatives consider making Missouri the seventh state to outlaw SCNT--joining Arkansas, Iowa, Indiana, Michigan and North and South Dakota-- local researchers say the atmosphere in which they conduct their quest for cures is turning downright chilly.
Faculty and students at the Washington University School of Medicine, the local research institution with the strongest national reputation, report that their efforts to attract top scientists have been complicated by this issue. And last year one of Wash U.'s most celebrated scientists, John W. McDonald, was lured away from St. Louis by the Kennedy Krieger Institute, an affiliate of the Johns clone wars by Matt Shaw Hopkins School of Medicine in Baltimore.
McDonald, whose laid-back manner and surfer-blond hair give the impression of a man who'd be equally at home in a research lab and a beach-volleyball game, achieved world renown as Superman's doctor: Using techniques he developed, he was able to restore some mobility to the late actor Christopher Reeve, who was paralyzed in a 1995 horseback-riding accident. McDonald has advocated for research into new treatments based on embryonic stem cells for spinal injuries, and it was widely speculated that the stem-cell issue had something to do with his departure from Washington University.
"It played a role in my decision," says McDonald. "It was not the sole reason." He does believe that that uncertainty about the status of SCNT has discouraged St. Louis scientists from pursuing certain types of research, which has in turn stunted the growth of science here. "Washington University was one of the strongest places in the nation. They're not anymore," he says, adding that the worst effects "won't be fully realized for a decade."
A proposed ban on stem-cell research sends the message that the state is anti-science, and talented researchers may very well move to states that are more supportive of scientific work. Others may steer clear of promising research because of the political controversy.
And years later, when research conducted in states that have embraced all types of research involving embryonic stem cells begins to produce lifesaving cures, it may be too late for St. Louis to get into the game. McDonald says the St. Louis scientific community was too slow to recognize the threat that it faced from social-conservative groups and too slow to take control of the debate.
"The fault is with us, the scientists," he insists. "All of us as individuals need to take a little of the blame."
Now take a moment to pity the social conservatives. After more than four years of building a political coalition, this was supposed to have been the year that they finally passed an anti-cloning law. Instead, it may have been the year that the scientists actually took control of the debate, holding the line with the help of a new ally: the Missouri business community.
State Sen. Matt Bartle, the Republican from Lee's Summit who has been behind most of the attempts to ban SCNT, went into the 2005 legislative session full of hope. His message that creating cloned embryos for research purposes crossed a clear ethical line was finding an audience; he had secured 18 co-sponsors for his bill, a winning number in the 34-member Missouri Senate.
The year before, he'd been frustrated when a couple of pro-life colleagues changed their minds about his proposal at the last minute, stalling his bill in committee. But this year Bartle's bill made it out of committee and onto the Senate floor, where he had lined up the support he needed. According to Rose Windmiller, director of state relations and local governmental affairs for Washington University, things looked bad.
"He should have been able to pass it out" of the Senate, she says.
Instead, Bartle watched his coalition fall apart on the Senate floor, with even some of his co-sponsors turning around to verbally attack the proposal. His Republican colleagues wouldn't allow the bill to come to a vote, and he ultimately withdrew it.
Meanwhile, proposed anti-cloning legis- lation in the Missouri House of Representa- tives didn't get a hearing, either. And Matt Blunt, the Republican governor newly elected on a pro-business platform, said he would likely veto any bill that banned SCNT.
What happened?
According to Bartle, it was a matter of "social conservatives' losing the battle to the business interests.
"I had a lot of people abandon the cause behind closed doors," he adds. "Business stepped in and began to pressure the Legislature."
A compromise law that bans the cloning of babies but explicitly allows SCNT would have settled the dispute to the satisfaction of the science and business communities, patient-advocacy groups and at least some Republican legislators. Such laws have been passed in California and New Jersey. But Bartle's backers weren't biting.
Larry Weber, executive director of the Missouri Catholic Conference--which, along with Campaign Life Missouri, has lobbied on this issue for years--says a compromise was unacceptable because it wouldn't stop the creation and destruction of embryos for research.
"It's not even half a loaf," Weber says. "It's like getting the heel off one end of the bread."
Bartle doesn't see a middle ground either. "Whenever you hear Republicans talking about compromise, they're talking about the pro-life community capitulating," he notes. He believes that if an anti-cloning bill passes without a ban on SCNT, the issue won't stand a chance of coming up again--which shows how important it is for him to keep the idea of "human cloning" front and center.
Bartle believes that he won't be able to pass a law next year, either--but neither does he think a compromise law permitting SCNT will pass. He thinks the issue won't be decided until the next election cycle, when politicians will be forced to grab one side of this political hot potato. Until now, he says, many lawmakers "haven't taken a position or have been very ambiguous. It's allowed them freedom of movement."
Meanwhile, groups on both sides continue to wage an intense public-relations battle. The scientists and their allies are pitching cures and downplaying anything that makes SCNT sound like a "life" issue. Bartle and his supporters are raising the possibility that innocent embryos will be destroyed, and scary human clones created, right here in Missouri.
Who's telling the truth?
The trouble is, when it comes to stem cells, the truth is buried under a mountain of daunting--and often inconsistent--vocabulary. It's possible to listen to people on both sides of the debate and not even realize that they're talking about the same thing.
To understand the substance of what they're saying, you need to understand the science behind the semantics, which means understanding a little bit about what embryonic stem cells are and where they come from.
Very quickly:
Embryonic stem cells are typically harvested from a 5-day-old embryo called a blastocyst. Viewed under a microscope, a blastocyst looks like a ring of cells with more cells clumped in the middle. Those cells in the middle are the embryonic stem cells, which are special because they can transform themselves into any tissue type.
Although a blastocyst doesn't yet possess a single physical feature that looks recognizably human, each cell within it does contain a full set of 46 chromosomes of DNA, the genetic blueprint for the baby it could become if it were to find its way into a woman's womb. In a normal embryo, half of those chromosomes came from its mother in the form of an egg, half from its father in the form of a sperm.
So what's somatic-cell nuclear transfer, also known as SCNT?
SCNT is a way of creating a blastocyst without having to combine a sperm and egg. It has been used for years in animal research, and it was recently shown by a South Korean scientist to be possible in human beings. In this procedure, scientists take a donated human egg and suck the DNA-filled nucleus from its center, leaving it pretty much an empty vessel. They then take a body cell (also called a somatic cell) from anywhere on a patient, remove its nucleus, and put that into the empty egg--hence the phrase "somatic-cell nuclear transfer."
They give the whole thing a small electric shock, and the cell begins dividing. Within a few days, it's turned into a ring of cells with a clump of embryonic stem cells in the middle. Sound familiar? It should--it's the spitting image of a "normal" blastocyst. The difference is that this blastocyst has received all of its genetic information (a full 46 chromosomes) from a single person, the patient, rather than receiving half from a mother and half from a father. It is technically a "clone" of the patient, which is why SCNT was originally given another name: therapeutic cloning.
When it comes to picking names for scientific procedures, scientists can be their own worst enemies. Therapeutic cloning, with its science- fiction overtones, was a term that would come back to haunt the research community, even after they jettisoned it in favor of the equally accurate (but completely benign-sounding) somatic-cell nuclear transfer.
Bartle first heard of therapeutic cloning about four years ago, after South Korean researchers announced that they were working to clone a human being. A colleague at Bartle's Kansas City law firm sent a one- sentence e-mail: "Is this illegal in Missouri?"
Bartle did some research and discovered that the answer was no.
He did some more research and soon became one of Missouri's most knowledgeable and outspoken opponents of the procedure.
While a member of the Missouri House of Representatives, he attached language to a crime bill that would have banned all types of cloning. It didn't pass, but, when he was elected to the Senate in 2002, he began making his case again, and, with support from pro-life groups and St. Louis' conservative Archbishop Raymond Burke, finding more allies among legislators.
He has since introduced anti-cloning bills every year.
Primarily Bartle argues that creating a cloned blastocyst and destroying it for its stem cells is wrong in itself. He believes that an embryo at the 100- to 200-cell blastocyst stage is an innocent human being and should not be killed. In his view, a human life is present from the embryo's earliest stages because even the tiniest embryo could develop into a baby under the correct circumstances. Cloning blastocysts is "cloning human beings," plain and simple--and destroying those human beings is morally wrong.
It's worth noting that this argument bears a striking resemblance to one used against in vitro fertilization. In that procedure, doctors fertilize several of a woman's eggs outside her body, creating multiple blastocysts, and some of those blastocysts-- which, by Bartle's definition, count as human beings, are destroyed.
This incidental destruction of blastocysts is one of the reasons the Roman Catholic Church opposes in vitro fertilization. (Other reasons are that it creates babies in a manner that's "dissociated from the sexual act" and it usually requires the father to masturbate, which is a sin.) Nevertheless, most Americans, including plenty of pro-lifers and religious organizations, don't have a problem with IVF. At least no one is picketing IVF clinics. So why is a blastocyst created through SCNT deserving of more protection than a blastocyst created through IVF?
"The primary focus of IVF is to create a August 2005 stlmag.com 77 human life," explains Bartle. "With cloning, the purpose is to create a human life for the purpose of destroying it. I see a distinction."
He also argues that allowing scientists to clone blastocysts will create a slippery slope, tempting scientists to put a cloned blastocyst into a woman's womb and turn it into a baby.
There are a couple of problems here, one of them rather technical: Many scientists believe that, as a result of genetic instabilities in cloned human embryos, a blastocyst created through SCNT cannot be turned into a baby. Still, it's hard to imagine that this problem could not ultimately be surmounted. So let's say Bartle is correct in assuming a cloned baby could be created. Why ban both therapeutic and reproductive cloning to stop this from happening? He says we just have to trust him on this one: "If society decides to go down this path, we are going to have live-birth human clones."
Bartle would rather see research confined to adult stem cells--which most scientists believe have less potential for treating disease--because they pose no moral dilemma and have a proven track record.
Dr. Steven L. Teitelbaum, a professor of pathology and immunology at Washington University School of Medicine and a proponent of SCNT, says this kind of reasoning betrays a deep ignorance of how science actually works. He notes that adult stem cells have years of research behind them, whereas human embryonic stem cells are just beginning to be studied.
"Science is knocking on 20 doors and finding nothing behind 19 of them--but you never know which door has gold behind it."
Teitelbaum is familiar with the promise of adult stem cells. In the early 1980s, he was part of a medical team that was the first to use them to cure a rare disease of childhood.
The patient, a baby girl, had osteopetrosis-- a disease in which the patient's bone tissue does not stop growing. At that time, patients with osteopetrosis invariably died in the first year of life; eventually the skull grew inward, crushing the brain.
"We thought if we gave these kids healthy bone-marrow cells, which are stem cells, we would be able to cure them," Teitelbaum says.
They were lucky, finding a perfect genetic match in the baby girl's brother, and a bone- marrow transplant did cure the girl, who recently graduated from college.
"The trouble is, we can only cure 10 percent because we have to find that genetic match," Teitelbaum says. With stem cells created through SCNT--which would be "clones" of a patient's own cells--he might be able to create bone-marrow cells that are a perfect genetic match for each sick child.
"This is not an insignificant motivation for me," he says. "I had this wonderful thing happen, yet I can't adapt it to most of the kids that I'm consulted about.
"The opposition carves this debate into terms of adult stem cells versus embryonic stem cells, and this is not a debate between adult stem cells and embryonic stem cells. It's a debate between society and disease, and we should be moving forward using whatever technology we have.
"Forty Nobel laureates have signed on to this technology; there are no serious scientists on the other side," he says.
This isn't to say that there aren't respectable scientists who oppose SCNT for other reasons, he adds. Take Dr. Richard A. Chole, head of the Department of Otolaryngology- Head and Neck Surgery at the Washington University School of Medicine and one of the few opponents of SCNT on campus. Chole agrees that the procedure offers some hope of curing disease. But he agrees with Bartle that creating an embryo for research purposes raises unique moral concerns that trump this medical possibility. "The idea of actually producing a human being to harvest the tissue is Orwellian," he says. "We all want to cure disease--but we need to take the high road."
Chole and Teitelbaum quibble about terminology (is a cloned blastocyst truly an embryo?), but they agree that the real dilemma facing policymakers is essentially this: whether a cloned blastocyst, a 5-day- old embryo created through SCNT, is worth more than the possibility of cures.
Chole says yes; Teitelbaum says no.
"At the end of the day, this is not a scientific issue," Teitelbaum says. "The science is clear. This is an ethical issue, and there are good people on the other side."
There may be good people on both sides of the ethical debate, but the people on one side appear to greatly outnumber those on the other. According to a recent poll, Missouri residents favor moving forward with SCNT by more than a 2-to-1 margin--at least, they favor it once they understand the science. "At the end of the day, this is not a scientific issue. The science is clear. This is an ethical issue, and there are good people on the other side."
Making sure that Missourians--including legislators--understand the science has become a big part of Donn Rubin's job.
Rubin is executive director of the Missouri Coalition for Plant and Life Sciences, a group created four years ago to make sure the region's life-sciences companies prosper. A University City native who graduated from the Wharton School of Business at the University of Pennsylvania and the University of Michigan School of Law, Rubin has a resume strikingly similar to his opponent's.
Bartle studied economics at the University of Missouri-Columbia and law at Northwestern University before spending several years with the prestigious Bryan Cave law firm in Kansas City. He went on to become a partner at Berkowitz Stanton Brandt Williams & Shaw.
Rubin began his career at the flagship St. Louis office of Bryan Cave. After five years toiling in the law library, he left for Albania, using his law and finance background to help with the transition from a closed to a free-market economy. Turning St. Louis into a life-sciences leader should have been a cinch by comparison. But Rubin encountered familiar obstacles.
"In both cases, progress can be held hostage by ideologues with narrow and obsolete views," he notes, "whether it's Communism or a narrow anti-science attitude."
In January, Rubin took a second job chairing a brand-new coalition: the Missouri Coalition for Lifesaving Cures. An advocacy group formed specifically to protect the legal status of SCNT, the coalition has garnered the support of patient, civic, business and, yes, religious groups.
"Opponents of this research work very hard to frame this issue as 'business versus religion,'" Rubin says. "This is a distortion of the issue. Religion isn't on one side of this. Medical researchers are pursuing the noble endeavor of curing disease and suffering. They're not doing it for profit."
In February, the coalition commissioned the Republican pollster Fred Steeper to present both sides of the stem-cell issue to Missourians and assess their attitudes toward SCNT. Respondents said they favored moving forward with the procedure, 66 to 30 percent. So why has this issue been deadlocked?
Chole, the Washington University physician who opposes SCNT, says the results may be misleading. "If I formed the questions, I'd get a different result." But even then, he concedes, "I don't know if a majority would be on my side. They probably would not."
Rubin says the results are solid; people support SCNT when they understand the science. It's just that Bartle has misled people about what's at stake, particularly by allowing people to think that scientists want to clone babies. "There's no question that he has adopted, very purposefully, language that will confuse legislators and the people," Rubin says. When people hear the word "embryo," for example, they often picture something that looks like a fetus-- not a ring of cells: "People who aren't really following this think we're talking about abortion, or fetuses. The fact of the matter is, you're talking about a microscopic speck of cells in a petri dish. Our opponents do not rely on their own narrow moral argument because they know it does not resonate with people. They need to bolster that with lots of contrived scientific-sounding arguments, none of which holds water."
Rubin says people also may not realize what's at stake for the local economy. Since 2001, he has been working to establish St. Louis as the heart of the BioBelt, a trademarked name for a multistate life-sciences district. He first got involved in the stem-cell fight after legislation to support the local bioscience industry kept dying in the Missouri Senate. According to Bartle, lawmakers "were afraid to bring up the legislation for fear that I would attach the cloning language to it." So would he have? "You bet."
Rubin and his coalition partners quickly realized that the proposed stem-cell ban could have far greater effect than a few blocked life- sciences bills. If it actually passed, it would threaten their entire enterprise.
The BioBelt was built on the strength of research conducted at local academic institutions such as Washington University (which alone brings in about $400 million in National Institutes of Health research grants each year), Saint Louis University, Southern Illinois University-Edwardsville and the University of Missouri, as well as on the resources of the many commercial and not- for-profit life-sciences groups in the region, such as the agricultural giant Monsanto and, farther west, the Stowers Institute for Medical Research in Kansas City.
"That's a lot to build on," says Rubin. "It makes us the envy of most wannabe regions trying to make themselves centers of life sciences."
Historically, despite the world-class research being carried out in St. Louis, the city lacked the infrastructure to transform much of that research into viable businesses. If a researcher wanted to turn a medical discovery she'd made into a thriving busi- ness, there was a good chance she'd eventually have to look outside the area for adequate funding and commercial lab space. Usually she'd look to California or Massachusetts.
"We didn't want to be a farm team for the coasts," says Rubin.
The Coalition for Plant and Life Sciences was created to build a physical infrastructure and "public-policy environment" where companies could thrive. So far, it's working, says Rubin. Right now there are about 400 plant- and life- sciences enterprises in St. Louis, employing around 25,000 people. That's still a tiny fraction of the total number of private jobs, but it's a sector worth building. The average life- sciences worker makes $70,000 per year, more than double the average salary in the region. According to Dick Fleming, president and CEO of the Regional Chamber and Growth Association, which is a key sponsor of the coalition, "If you create a lot of $70,000 jobs, it creates more $30,000 and $40,000 jobs."
Rubin sums up the issue: "St. Louis is well- positioned, because of our intellectual capital, to be among the best life-sciences regions in the country, but we're stuck in the mud right now. The threat of a ban has kept us from moving forward. An actual ban would push us backward very quickly."
For his part, Bartle thinks that the idea of turning St. Louis into a national life-sciences powerhouse "is a little quixotic. Every major city in the U.S. thinks it's going to be the life-sciences mecca. California is where all this stuff is going anyway--they're handing out $3 billion" in bond money for research involving embryonic stem cells.
And even if SCNT is not a pipe dream, he says, a ban won't hurt St. Louis' chances of achieving life-sciences superstardom:
"It's just silliness. Look at Switzerland-- it's the home of Europe's pharmaceutical industry, and Switzerland has banned SCNT--or Germany; I wish we had a life- sciences economy like Germany." (Germany has also banned SCNT.)
Closer to home, Bartle notes that Michigan banned SCNT in 1998, and that state's life-sciences economy hasn't tanked. A spokesman for the Michigan Economic Development Corp. confirms that the sky there has not fallen; the state's life-sciences industry is doing better than ever before. However, a recent article in the Saginaw News mentions that one of the university's top stem-cell researchers, Michael Clarke, recently left for Stanford University. And human SCNT is only beginning to make the transition from theory to practice. Now that the procedure has been shown by South Korean scientists to be practical in human beings rather than just theoretically possible, the ban may begin to have more of an effect on companies' plans.
Rubin notes that in a survey his group conducted of 14 life-sciences companies, 10 said they would be less likely to remain in Missouri if a ban were to pass. Recently the Stowers Institute was unable to attract two Harvard researchers to Kansas City because of this issue, he says; the institute has been sending millions of local research dollars to Cambridge so that these scientists can conduct their research there instead.
Nevertheless, Rubin says, "It's hard to quantify the decline that medical research infrastructure witnesses, particularly over- night. If a ban in Missouri were to pass, you wouldn't wake up the next morning and see the world change. You'd see a slow decline in Missouri's ability to attract the best and brightest researchers."
Rubin says Bartle's claim that Missouri doesn't have much of a chance of becoming a life-sciences leader "ignores reality," noting that during the past four years St. Louis has attracted nearly $500 million in venture capital dedicated to the bioscience industry. Still, Rubin doesn't think the economic argument alone will carry the day. He believes his group can only win by advancing its own ethical argument against Bartle's.
"Every person in Missouri has a personal story, someone in their family or a close friend who suffers from a disease that could be cured by this research if it's allowed to go forward."
He adds that Bartle's bill would have made it illegal for Missouri patients and physicians to use treatments derived from SCNT, treatments that could ease the suffering caused by everything from Parkinson's to Lou Gehrig's disease, heart attacks to strokes.
"If cures are found in other states with this technology, wealthy Missourians might travel, but the average Missouri citizen would be condemned to second-class medical care," "I had a lot of people abandon the cause behind closed doors. Business stepped in and began to pressure the Legislature." he says. "The access to cures and treatments is something that touches everyone."
So where does all of this leave St. Louis? No one can say with certainty what the effect of a ban on SCNT would be. But one thing is sure: If our representatives don't make this tough political decision soon, the decision will effectively be made for them. Without a law that specifically allows SCNT, scientists will begin to avoid St. Louis just as surely as if a ban were already in place. And if cures are found through the procedure, they will be found elsewhere.
Missouri's lawmakers already have all the information they need to make up their minds. The fundamental ethical question that SCNT poses is not going to change, no matter how many cures are stacked up on the table. If it is wrong to destroy cloned blastocysts for potential cures, it is wrong to destroy them for any number of actual cures.
Dr. William Danforth, chairman of the board of directors of the Donald Danforth Plant Science Center and of the Coalition for Plant and Life Sciences, says the question they need to ask themselves is this: If they do pass a ban, will they be willing to sustain it if cures are actually developed? Will they be able to tell a woman whose son was paralyzed in a car accident that he will never be able to walk again because he can't have a treatment created with the use of SCNT? Or inform a constituent with Parkinson's that he must simply stand by as he gradually loses control of his body? Danforth says this is difficult to imagine.
"It would be very hard for the Legislature to tell people they could not avail themselves of cures," he says. He thinks a law banning SCNT would ultimately be reversed, but by then it would be too late to spare St. Louis the consequences of not participating in the research: "The cures would come late to Missouri. By then we would have already dismantled our clinical care."
St. Louisans take justifiable pride in being at the center not only of the country but also of medical research and clinical care. We need to decide whether a ban is worth risking our preeminence. Danforth put it this way in his Senate testimony: "If we become a backwater, it is our own fault. We are not one now."
