Cloning, Stem Cells, and Medicine's Future

Thomas B. Okarma

Issue: Embryonic-stem-cell and cloning research. The U.S. political climate is proving inhospitable to biomedical research that could benefit millions, and other nations are jumping in to fill the void.

Technology Review: Human embryonic stem cells, primitive cells with the ability to form every type of tissue, could lead to effective treatments or even cures for ailments such as heart failure, Parkinson’s disease, diabetes, and spinal-cord injury. But creating the cells requires destroying human embryos, a hugely controversial issue. How do you address that?

Tom Okarma: These cells are derived from embryos created using in vitro fertilization that are donated under informed consent by couples who no longer need them to achieve pregnancy. For the couple, their choice is threefold: have the extra embryos stored frozen, forever; have them destroyed; or donate them for research. Our whole justification for trying to develop this field isn’t that we don’t have regard for the sensitive issues of creation of life. It’s because in that unused embryo is the most incredible cell ever discovered, a cell that solves the technical, commercial, economic, and medical problems that have prevented cell therapy from making it in the past 20 years. The fact that one embryo produces untold billions of cells for thousands of patients’ therapies is enormous ethical leverage. A master cell bank of embryonic stem cells can make enough dopamine-producing neurons for 10 million Parkinson’s patients. That is beyond our wildest dreams, even three years ago!

TR: One argument you hear quite a lot is that experiments by academic researchers have shown that stem cells from adult tissues, such as bone marrow cells, can be transformed into all these cell types, too. So why use embryonic stem cells?
Okarma: Well, first of all, no one has actually shown that. That is a misinterpretation of the data. With this kind of research, you’re asking a cell that is naturally programmed, let’s say, to make blood-to use the most commonly cited adult stem cell-and you’re trying to turn it into a liver cell or a heart cell or a brain cell. These cells are not programmed to do that. So even if you are able to belt those cells over the head to make a half a percent of them morph into heart muscle cells or neurons, those cells are not making that transition in a scalable way. So you’ll never be able to address the market with that kind of process. You’re back to an individualized, case-by-case therapy, back to the old bone marrow transplant model.

Okarma: I’m not making the case that the Bush decision has stifled the research or prevented us from making progress, but it is shortsighted. For example, as far as we’re aware, all of the lines in the world were derived by the initial patented process from the University of Wisconsin-Madison that involves culturing the early embryo on mouse feeder cells. The FDA [U.S. Food and Drug Administration] appropriately classifies all of these lines as xenogeneic-as if they came from a mouse-simply because they were cultured on mouse cells. We don’t quibble with that classification. It’s a problem, though, because when you try to put those cells into humans, the bar is higher. There’s a theoretical possibility that mouse viruses could have jumped from the mouse cell into the human cell. So both the FDA and the research world want to produce cells in a slightly different way that would not ever utilize mouse feeder cells. And we are in the process of doing that. There’s no question we will be successful in doing that. But once we are, because of the Bush decision, the National Institutes of Health cannot use those lines, because they were derived after the Bush decree. This is, to our mind, anti-intellectual. One branch of the government is saying no; another branch of the government-the FDA-is saying, make these lines safer.

TR: In February, the U.S. House of Representatives passed legislation that would ban all research into human nuclear transfer-the technology behind human cloning. But some scientists believe nuclear transfer offers a way to make stem cells that would be a perfect tissue match to the patient who needs them. How would this affect efforts to create therapies using embryonic stem cells?
Okarma: The efficiency of making a stem cell line from an embryo made by nuclear transfer is vanishingly small, and you’re going back to the case-by-case, individualized-therapy story again, with enormous costs. The whole idea is to make this therapy internationally available, broadly. Nuclear-transfer procedures just are never going to get us there.

There are, however, reasons why we are opposed to the current congressional mood of criminalizing and banning all nuclear-transfer research. Everybody’s on the same page about not cloning people. There are many reasons not to do that. But there are valid reasons why we should be doing nuclear-transfer research. We know the sequence of the whole genome and are now in a position to start doing very intelligently the kind of genomic research that will lead to understanding how it is that my family history for disease X-let’s say breast cancer-gets manifested. How do the genes that cause people in my family to have a high likelihood of developing breast cancer work in my cells?

There is no platform, biologically, to work that out, except embryonic stem cells. So you would do nuclear transfer with my cells, which carry all those genes, and you’d make a stem cell line from me. Now you can make breast cells and study how my inherited predisposition for breast cancer is actually working to produce disease. It’s the perfect platform to take the next step in genomic research, to make it real for patients. This is absolutely bona fide, important, potentially breakthrough research for people with these genetic diseases. Not just cancer: Tay-Sachs disease, sickle cell anemia, on and on and on. It’s the most viable way to unravel how genetic disease is manifested in tissue that will lead directly to treatments. Now our House of Representatives, in their wisdom, want to criminalize that research.

TR: How would such a ban affect stem cell research?
Okarma: It would be a huge chill. Now, is that going to result in 50,000 scientists leaving the country? Probably not. But what is happening is that other countries-Australia, Canada, Scandinavia, the U.K., Singapore, China-where the governments and academic institutions see an opportunity to leapfrog the United States, are pouring a lot of money into stem cell research, including nuclear transfer. It’s not that they’re ahead of us today. But it’s very clear from my personal travels that they recognize how harmful our political debate is, and how potentially meaningful-even for the developing world-this therapy is, because it’s scalable. It’s not going to be prohibited from reaching the masses because it’s sophisticated, Western medicine. And that’s crucial to understanding why the developing world wants this technology, and why governments and academic institutions are pushing it. So what’s happening is that Asia sends their brightest young folks over to the NIH for a half-dozen years of training, and normally those folks stay in this country. Now they’re going back home, if they’re in the field of embryonic stem cells, cell therapy, or nuclear transfer, because they’re going back to an environment where they can practice what they’ve learned.

Web extra: Okarma on anti-cloning ideology