As scientific advances bring cloning out of the realm of science fiction and into the domain of medical reality, concern is growing about what the possible implications will be. Tinkering with human DNA, many fear, amounts to playing God—and it could have disastrous consequences. Will experiments gone awry result in deformed human beings? Will people replicate themselves for egomaniacal reasons? Will the concept of human identity drastically change? "Life is a creation, not a commodity," President Bush argued last month in a speech before Congress, and as such, he emphasized, it should not be manufactured through cloning as though it were some kind of specialty good.
But many also argue that an important distinction needs to be recognized between "reproductive cloning," in which the goal is the creation of a full-fledged human being, and "therapeutic cloning," in which the goal is the creation of a several-day-old embryo from which undifferentiated stem cells can be harvested and potentially used to cure a variety of devastating diseases. Those who believe that human life begins with the very existence of an embryo cannot countenance a procedure that involves an embryo's creation and destruction, even at a very early stage. But those who believe that human life does not begin at least until an embryo's cells have begun to differentiate themselves into distinctly human tissues feel that prohibiting such research—which could save the lives of many people with cancer, diabetes, heart disease, Alzheimer's, Parkinson's, and other illnesses—would in itself be reprehensible and disrespectful of human life.
Federal funding for human-embryo research was outlawed in 1995, which limits the number of researchers who can pursue therapeutic cloning. Currently, a privately-funded company called Advanced Cell Technology (ACT) is the only group in the country openly pursuing the research. Curious about how this company was faring, and about the research that they do, Kyla Dunn, a science writer and former biotech researcher, last fall began studying their work. She interviewed ACT's executives and scientists, spent time in the laboratory observing technicians, and followed the case of Trevor Ross, a two-year-old boy with a rare and devastating genetic disease called X-linked adrenoleuko-dystrophy (ALD) whose parents had brought him to the company. In "Cloning Trevor," her June cover story for The Atlantic, Dunn describes ACT's genesis and development, and chronicles its efforts to help Trevor.
ACT's scientific work, Dunn observed, was by necessity painstakingly slow and very expensive. Keeping the company financially solvent was a constant challenge. Last November, ACT's directors anounced to the national media that the company had successfully created the world's first cloned human embryos, when in fact it had managed only to sustain a cloned embryo to the six-cell stage. Though ACT's claim was dismissed by most scientists as a premature publicity stunt, opponents of cloning seized upon ACT's announcement, urging that a ban should be enacted right away before any further ethically questionable progress could be made. Meanwhile, ACT's scientists doggedly continued their efforts to create cloned embryos using Trevor's skin cells, aware that their work might be deemed illegal at any time.
Although ACT has lofty goals and is staffed by talented scientists, Dunn suggests that it may be too much to hope that ACT, or any private company will be able to make significant headway in the field of therapeutic cloning:
The broad consensus in the scientific community is that therapeutic-cloning research merits significant exploration, and that real progress is likely only with government funding and support . As long as a federal-funding ban remains in place, the organizations most likely to move forward with therapeutic-cloning research will be companies like ACT—which, despite generally noble intentions, are bedeviled by the need to raise money, generate buzz, and please investors.
ACT and the many people who hope that they or their loved ones might one day benefit from therapeutic cloning know all too well, however, that the question of public vs. private funds may soon become moot. A proposal to ban cloning altogether has already been passed by the House. It is now before the Senate, and a vote may come as early as June.
I corresponded with Kyla Dunn by e-mail.
"Cloning Trevor" is available in the print edition of the June 2002 issue. It is also avaible for online purchase in our premium archive.
You make clear that there's an immense amount of ignorance and misunderstanding about the nature of therapeutic cloning. Many of those in a position to vote on the subject seem to have the mistaken notion that therapeutic cloning entails growing whole babies in the laboratory to be mined for spare parts. Is it your sense that those who do have a thorough and accurate understanding of what therapeutic cloning really means tend to support it?
Certainly among lawmakers confusion abounds—if not about the science of therapeutic cloning, then about the implications of outlawing it. I think Congressman Delahunt, of Massachusetts, put it well last July when he said, during the debate preceding the vote in the House of Representatives, "I do not believe that I know what I need to know before casting a vote of such profound consequence. I am not ready to decide the intricate and fundamental questions raised by this legislation on the basis of a single hearing held on a single afternoon at which the subcommittee heard only five minutes of testimony from only four witnesses, a hearing which many Members, myself included, were not even able to attend." Several of his colleagues voiced the same concern.
But misunderstanding of the procedure, to answer your question, is by no means the only reason for opposition. Many lawmakers, like many of their constituents, have deeply held beliefs about the sanctity of human life from the moment of conception. Senator Sam Brownback, of Kansas, a leading opponent of this technology, is one of them. He understands precisely what therapeutic cloning entails, yet characterizes legislation that would keep it legal as follows: "This will inevitably lead to the creation of cloned human embryo farms where embryos will be grown to specification and then harvested for body parts."
The senator's rhetoric, obviously, is inflammatory (and embryos, at five days of development, have no "bodies" to harvest "parts" from—although this is what his wording implies). The reason he gets away with it is that if you parse his sentence carefully, you'll see there's nothing technically wrong with it. Yes, cloned human embryos will be grown to specification in laboratories. Yes, stem cells will be harvested from them, destroying each embryo in the process. Yes, those cells will be used to create, in the lab, therapeutic tissues (which he's calling "body parts") for transplant into sick patients. His characterization is grammatically correct. It's the same reason President Bush can get away with characterizing this research as "growing human beings for spare body parts"; if you believe that a five-day-old embryo is a human being, there's nothing technically wrong with that statement.
To be clear: the embryos scientists intend to use for therapeutic cloning are approximately five days into their development in a lab dish. At this stage, a human embryo is a round, fluid-filled ball of about 150 undifferentiated cells. It is smaller than a grain of sand. It is smaller than the period at the end of this sentence. It would fit effortlessly on the point of a pin. Some people look at that embryo and see a "human being." Others look at that same embryo and see just a clump of cells.
It all boils down to a pair of maddeningly insoluble questions: "When does a human life begin?" and "At what point does that life deserve society's protection?" Each person will answer those questions differently depending on his or her personal religious and philosophical framework. One side of the debate has little hope of convincing, or converting, the other. And given such widespread disagreement, the real question becomes: Should Congress really attempt to impose the most restrictive view of human embryos upon federal law?
Just to add some perspective, similar embryos are created every day at fertility clinics—sometimes specifically for research—and discarded when they are in excess of clinical need. We do not, as a society, give early embryos in a lab dish the same protection we give living, breathing human beings. What's more, the future of an entire field of promising biomedical research hangs in the balance here—with real implications for the lives of patients who are suffering. There's not a person in this country who doesn't know someone affected by a condition that this research might someday help treat: heart disease, diabetes, Parkinson's disease, spinal-cord injury, cancer, kidney failure, liver failure... Those who are ethically opposed to human-embryo research may choose, for themselves and for their families, not to make use of any cures that arise. But to deny those cures to the rest of us, in my opinion, is simply unconscionable.
How did ACT and the Rosses respond when you first approached them to be subjects for this article?
The scientists at ACT realize that the better the public, and Congress, understands therapeutic cloning, the more likely this technology is to survive the current legislative onslaught. They were therefore willing to grant me a great deal of access, and a great deal of their time. Toward the beginning of the project, I was looking for a way to put a human face on this issue, and show how therapeutic-cloning research could impact the lives of real families. By chance, I had lunch with CEO Mike West just a day or two after the Ross family first contacted him. He put me in touch with them by phone, and invited me to sit in on their meeting the following week. The minute I met the Rosses, I knew I had found the story I wanted to tell.
The Rosses, for their part, were incredibly generous about letting me follow their efforts, at a time of great personal stress for them. They want people to understand why this technology offers so much hope to families like theirs—and what the consequences might be if it is shut down. Even though the fruits of therapeutic cloning might be too late for Trevor, they want to see this research move forward so that it might someday help other children who suffer from the same disease.
Having spent a significant amount of time at ACT and talked with its scientists and directors, what is your gut feeling about the company and its motives? Do Michael West (ACT's President and CEO), Bob Lanza (ACT's vice-president of medical and scientific development), and Jose Cibelli (ACT's vice-president of research) really believe they'll eventually make a profit? Are they in it mostly for the recognition? Are they—as they make themselves out to be—simply zealous scientists, eager to be able to help people with this new technology?
In some ways, ACT's scientists see this as their life's work. The potential of this research to cure disease and prevent suffering is so real to them they can taste it. And to be in a position to possibly help treat some of the most intractable diseases of our time is what drives them on, even in the face of strong opposition from Congress and the President.
There are secondary motivations, obviously. There's the intellectual and creative thrill of bringing a new technology to the world. Ego certainly plays a role—and I say that without any intent to malign that as a motivation. It's the dream of every scientist to make a pivotal contribution to the field, and to be recognized for that achievement. The rare moments of glory are what help make up for all the hard toil in the lab and the failures along the way.
It would be foolish to say that ACT's scientists don't hope for financial success. Everyone in biotech does. And more importantly, that's the only way that ACT can stay afloat long-term. This is a for-profit company we're talking about, with investors who expect a return on their investment, so to fault ACT for having commercial motives would be nonsensical. Keep in mind that Congress—by voting each year to withhold federal funding for human-embryo research—has forced this research into the private sector.
So, ACT's motivations are multifaceted. But most of them pale in comparison, I think, to the scientists' sense of obligation. Over the past few years, ACT's scientists have been offered jobs at bigger companies, with better salaries, as well as positions in academia. But they've chosen to be at ACT, because they believe that what they are doing is going to help people.
How might the state of cloning research be different today if federal funding for it had never been banned?
The importance of federal funding cannot be overstated. Federal funding attracts talented researchers at universities and research institutes across the country. With it comes ethical oversight and peer review, ensuring that experiments are well-designed, conducted by qualified scientists, and targeted at pressing questions in the field. As Elias Zerhouni, President Bush's nominee to be the new head of the National Institutes of Health, put it at his confirmation hearing in April: "Without federal funding it is hard for me to see how you develop a field of science in our country."
If federal funding for therapeutic cloning were available, the number of researchers working with human cells would be greater. As it currently stands, ACT is the only group in this country openly pursuing this research and, financially, they are running on fumes. With more resources available, someone might have successfully derived stem cells from a cloned human embryo by now. Also, more might be understood about the factors in an egg that "reprogram" an adult cell's DNA during cloning—information that could be used to improve the procedure's safety and efficacy.
It's not just therapeutic-cloning research that has been denied federal funding, of course—it's any form of research in which a human embryo is either created or destroyed. This has had a big impact on human-embryonic stem-cell research in general. A major challenge right now is to figure out how to coax undifferentiated stem cells into becoming useful tissue for transplant—like the hematopoietic (blood-forming) stem cells needed for Trevor Ross. And lack of federal funding has slowed these efforts. As Mike West told Trevor's mother, "It's a lot easier to cure this disease than to go to the moon, but there we had a very well-funded and well-organized effort to do so."
Fortunately, some relief is in sight: in April of 2002, the National Institutes of Health awarded its first grants in this area (President Bush approved limited federal financing, back in August of 2001, for work with a small number of human-embryonic stem-cell lines). The recent grants were designed to help four institutions get human embryonic stem cells into the hands of researchers. As of yet, however, no federal grants dedicated to medical research using these cells have been awarded.
How do you think events might have played out if ACT had not made its grand (but premature) announcement to the press about having supposedly created the world's first cloned human embryos?
You really never know. On the one hand, the Senate might have moved on to have an orderly, thoughtful debate about the merits of this technology. On the other hand, the Senate might have quietly outlawed all cloning research while the country, preoccupied by the war on terrorism, was looking the other way. What's more, ACT feared that an ill-timed announcement by the mavericks of the cloning world—those trying to produce a baby through cloning—could provoke a knee-jerk reaction from Congress.
So, ACT took a calculated risk. Its scientists knew that Senator Brownback and other political opponents of therapeutic cloning would react badly to the existence of cloned human embryos, but they were pretty convinced that the Senate's Democratic leadership could prevent hasty legislative action. And in the end, the announcement did bring light to the issue as well as heat. It got Congress and the public talking about the medical benefits of cloning technology—and perhaps this was for the best.
Does the extent to which ACT—a private biotech company—was able to manipulate the press when it made its dramatic, but in many ways inaccurate, claims concern you? Do you think the press will be more circumspect the next time a company like ACT launches a PR blitz? Or will most media outlets continue to jump at the big story and let questions be asked later?
I'm not sure "manipulate" is the right word. It's certainly true that ACT's inflated press release, and its teaming up with Scientific American and US News to produce cover stories, were designed to create an "event." But the announcement was accompanied by a peer-reviewed paper in the scientific literature—which made it more than suitable for science reporters to cover. What's more, any report of scientists creating cloned human embryos was sure to make headlines. The only previous report of this was in 1998, when South Korean researchers announced—without presenting proof—that they had created a four-cell cloned human embryo. ACT's was the first scientifically documented account of this kind of experiment, so the media had every reason to jump at the story.
The New York Times, incidentally, got it right. It ran the story on page A14, inside the National section, under the skeptical headline, "Company Says It Produced Embryo Clones." Over the next few days, the story quickly shifted to ACT and its motives, the current state of cloning research, and the political backlash that the announcement had unleashed.
In what ways (if at all) has your own background as a former biotech researcher influenced your views on cloning research and on the pros and cons of private versus federally supported science?
After working in biotech, I'm well aware that for research to be funded by a for-profit company, there has to a reasonable promise of return on investment. Many vitally important avenues of research—difficult, long-term projects with no near-term possibility of profit—won't get funded. That's the government's role: to support basic research. And it's crucial.
I think that's the underlying issue here that doesn't get enough attention: the importance of basic research. Basic research isn't about choosing what you're going to discover and then going out and discovering it. I think most of us, mistakenly, tend to view biomedical research as a long road trip to a known destination. The scientists are up front driving, while the rest of us sit in back and shout "Are we there yet?" at maddeningly frequent intervals. But that's precisely the wrong way to think about science. The most powerful accomplishments arise from the accidents—and from the detours.
The classic example, of course, is penicillin—an accidental discovery, made by a scientist who took a closer look when mold infected a culture plate of bacteria he was studying. And scientists studying obscure things known as retroviruses seemed to many people to be wasting their time until HIV came along.
My point here is that therapeutic cloning isn't important simply because of the applications we can currently envision—like tissue for transplant that won't be rejected by a patient's immune system. It's important because in the course of that research, other discoveries will be made that are completely unimaginable to us now. David Baltimore, a Nobel Laureate, puts it wonderfully in a recent documentary called "The Nobel: Visions of our Century."
He says, "I made what was a significant contribution to the cure of leukemia, but that's not what I was thinking about at all [when I set out]. I was thinking about how a virus changes the properties of cells. And it turned out that, just following my nose—which is really what science is so much about—we came across ... a target for the development of drugs. And the drugs are actually curing people." He goes on to add, "If we just follow our noses, we'll come up with things that are important for curing human disease. But we don't know how—we don't know that any given experiment's gonna do that or not gonna do that. So we have to just be free to do the kinds of things we think are important, and we believe in the end that everybody will benefit."
If therapeutic cloning is made illegal, a whole area of scientific inquiry will be lost. And this will be the first time in history that Congress has banned a promising biomedical laboratory technique—with many potential applications—outright. Imagine if Congress had outlawed recombinant DNA technology in the early 1970s. The entire biotech industry as we know it would not exist. Nor would treatments ranging from recombinant insulin for diabetics to gene therapy.
Did your views on cloning change at all in the course of researching and writing this article?
No, actually. I was in favor of therapeutic cloning at the outset and remained so throughout. In my opinion, Congress should not only ensure that this technology remains legal, but should provide federal funding for it. It is high time to remove the ban on federal funding for human-embryo research.
That ban has already hobbled medical research involving conditions ranging from infertility to birth defects to childhood cancer. To remove the ban would take a brave act by Congress, given the controversy surrounding this research, but it's clearly in the best interests of the country.
When you describe the process of inserting DNA into harvested eggs, you use a pseudonym to refer to the lab technician who performed the experiment. Is that because many researchers in this line of work are afraid that harm might come to them if it becomes known that they're doing cloning research?
I wouldn't put it that strongly. There is awareness, certainly, of the lunatic fringe of the abortion debate—and some concern that similar violence could spill over into this controversy. What goes on at ACT, however, bears no resemblance to abortion, and the discussion is sure to remain responsible and sensible. Still, work with embryos in the lab is controversial. Mike, Bob, and Jose are the public face of ACT, and they try to protect the technicians (who are often younger scientists, early in their careers) from intense public scrutiny. As a result, there are some talented researchers there who rarely get mentioned. I gave "Kate" a pseudonym not for safety reasons, but for privacy. She is not interested in seeking the spotlight, and it helped her relax around me to know that she would not be identified. She's simply interested in doing her work, doing it well, and moving the science forward.
Did you get a sense of whether the decision to try therapeutic cloning for Trevor was a wrenching one for the Rosses (in that they could have ended up finding themselves vilified or prosecuted)? Or were they simply eager to do whatever they could to help Trevor, regardless of the possible repercussions?
No, I don't think pursuing therapeutic cloning was a wrenching decision for them at all. The Rosses have been extraordinarily proactive in seeking out potential cures for their son's illness. When Trevor was diagnosed, they picked themselves up after about two weeks of intense grief and started asking the scientific community what new therapies might be coming down the pike. In the past year, in the hopes of advancing the pace of research, they have helped forge new research collaborations between ALD experts and scientists in fields like gene therapy, for instance. When they heard about therapeutic cloning from a scientist at a conference, they immediately started looking into who was doing it, and—just two weeks later—were sitting across the table from Mike West at ACT. This was one potential tool in the arsenal against their son's disease, and they did not hesitate to explore it.
What they are concerned about, however, is protecting their son's privacy—and understandably so. That's why they asked to be identified in this article only by pseudonyms. They certainly don't want Trevor to be teased on the playground, or bear the brunt of his playmates' parents' disapproval of therapeutic cloning. He might have fun telling his friends later in life that he's been "cloned" ... but his parents don't want to trumpet that for him on a national stage.
Do you know how Trevor is doing now?
On April 19, 2002, after ten days of "conditioning" with chemotherapy, Trevor received a transplant of umbilical-cord-blood stem cells from an unrelated donor. For children his age, there is a 20 percent chance of dying from this procedure. It's still too early to tell how successful the transplant will be, but Trevor seems to be progressing well. On May 10, he was released from the hospital (after spending a month in an isolation room, to protect him from infection), and allowed to return to a house that Ben and Adrienne have temporarily rented near the hospital.
Ben reports: "His appetite is coming back, and we are now 'outpatient' for the next three months. For the first month of that time, we have to go to the hospital seven days a week, about five hours per day. Plus, we have lots of meds and IV infusions we need to give him at home, and he still gets blood product infusions in the clinic as an outpatient."
Adrienne told me that "Trevor has an unbelievably great attitude." And Ben added, "He is a complete trooper. It's incredible what a two-year-old can withstand, and still remain in good spirits." Approximately one hundred days post-transplant, the Rosses say, their family will be able to breathe a sigh of relief.
What about the women who donate eggs for this research—are they well-compensated? Why do they do it?
ACT's research donors are paid $4,000—which falls into the middle of the range that fertility clinics typically pay young women who donate eggs to infertile couples undergoing in vitro fertilization. The donors undergo physical and psychological screening ahead of time, and they say they they donate their eggs in part out of a desire to contribute to disease research (interestingly enough, many of the research donors say they would not feel comfortable donating eggs to an infertile couple trying to have a baby).
The hope, incidentally, is that with further research the use of human eggs will become obsolete. Some of the opposition to this technology comes from those concerned about the potential health consequences to young women who, lured by the money, subject themselves to ovary-stimulating drugs and a minor surgical procedure in order to donate eggs. Each of these procedures carries a small amount of risk, although egg donation is now routine in the realm of infertility medicine.
These are the early days of this research, and it's not yet clear which alternatives to human eggs will turn out to be the most promising. Some groups, including ACT, are attempting to use animal eggs for the procedure. Others picture coaxing human embryonic stem cells, which can form any cell or tissue in the body, into forming eggs. And with further research, scientists may be able to move beyond the need for eggs entirely. Scientists are currently trying to understand how an egg reprograms an adult cell's DNA during cloning, so that the factors involved might someday be manufactured in large quantities, taken off the laboratory shelf, and used to transform a patient's skin cell directly into useful tissue. The entire process could then be done without ever requiring an egg or generating an embryo.
Have there been any notable scientific or political developments with respect to cloning since this article went to press?
Yes, there have been a number of significant political developments, with the Senate expected to vote soon on this issue.
On April 10, just after we went to press, President Bush gave a speech at the White House in which he reiterated his firm opposition to cloning research of any kind. He urged the Senate to pass a bill, put forward by Senator Brownback, that bans all forms of human cloning—whether for reproduction or medical research. This bill is similar to the legislation already passed by the House last July.
On April 30, however, Senators from opposite ends of the political spectrum joined forces to introduce a new bill—one that would keep therapeutic cloning legal, while banning any attempt to produce a human infant through cloning. Democrats Dianne Feinstein, of California, and Edward Kennedy, of Massachusetts, were joined by moderate Republican Arlen Specter, of Pennsylvania, in supporting it. Conservative Republican Orrin Hatch, of Utah, also threw his support behind the bill. "I come to this issue with a strong pro-life, pro-family record," he said. "But I do believe that a critical part of being pro-life is to support measures that help the living."
Hatch explained, "At the core of my support for regenerative medicine research is my belief that human life requires and begins in a mother's nurturing womb," and "not in a petri dish." It was the same reasoning he used last summer, when he helped convince many Republicans to support the effort to obtain federal funding for human-embryonic stem-cell research. "I have to tell you," he added, when explaining his support for therapeutic cloning, "when I finally got all the facts that I feel are essential to make a decision, it wasn't even a tough decision. It wasn't even close." At the beginning of May, another conservative anti-abortion senator, Republican Strom Thurmond, of South Carolina, endorsed the bill as well.
In your view, how likely is it that cloning research will soon be banned altogether in the United States? What would the consequences be?
There is widespread agreement among both scientists and politicians that reproductive cloning, whose aim is to produce a child, should be banned for the time being—if for no other reason than that the technique is not yet safe enough to be applied to humans without potentially disastrous consequences for both mother and infant. The fate of therapeutic cloning in the Senate, however, is really too close to call.
Remember that creating human embryos specifically for research has always been a political sticking point. In 1994, a panel assembled by the National Institutes of Health recommended broad federal funding for human-embryo research—including experiments of potentially "outstanding scientific and therapeutic value" for which embryos must be specifically created. For President Clinton, however, funding the creation of embryos for research was going too far. He blocked that provision of the panel's recommendations. And for the Gingrich-era Congress that took up the matter in early 1995, funding any work with human embryos was going too far. Within a year, Congress had passed a sweeping ban on using taxpayer dollars for any experiment in which a human embryo is either created or destroyed.
As for the consequences, there's something important to keep in mind. Those who say that human-embryonic stem-cell research will be rendered useless without cloning are oversimplifying. Scientists can envision other ways of getting around the problem of immune rejection—although therapeutic cloning is among the most promising. But given the urgent needs of patients, scientists feel that all promising avenues of research should be pursued aggressively, since it's entirely unclear which approach, if any, is going to pan out. What's more, there are other important research applications of cloning technology that have nothing to do with generating tissue for transplant. If the technology is outlawed, all of those other applications are outlawed with it.
In the end, therapeutic cloning, if successful, will add tools to the physicians' toolbox. It will not, most likely, be the approach used in every case. It may well be a last resort. But fighting disease is hard enough without denying physicians options and alternatives.
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