Commentary
Stem Cell Research in Minnesota
A bill moving through the Legislature threatens to disrupt progress on therapies that are already helping patients.
By Meri Firpo, Ph.D., and John Wagner, M.D.
Medical research that could help Minnesotans living with devastating diseases is being threatened by a bill working its way through the Minnesota Legislature. If passed, it would stifle innovation and criminalize research that could transform the way we treat disease.
On the surface, the bill (H.F. 998/S.F. 695), sponsored by Rep. Bob Dettmer, R-Forest Lake, and Sen. Michelle Fischbach, R-Paynesville, proposes banning reproductive cloning—that is, outlawing science that culminates in the creation of a human that is a replica of another. Banning human reproductive cloning is a move that every reputable biomedical scientist would wholeheartedly support. But proponents of the bill have admitted publicly at hearings in St. Paul that this legislation attempts not only to prevent human reproductive cloning but also to ban somatic cell nuclear transfer (SCNT), which has been referred to in the lay press as “therapeutic cloning,” and restrict embryonic stem cell research.
What is particularly concerning is that the proponents of the bill are acting without an accurate understanding of the science behind SCNT or the support of an informed public. SCNT is a laboratory technique that involves the transfer of a cell nucleus from a somatic cell into an enucleated egg (one from which the nucleus has been removed). The technique produces a formless group of cells that is smaller than the cross-section of a human hair. The bill’s supporters argue that SCNT could lead to the creation of a baby. This is not feasible because cells created through SCNT cannot survive for long in culture (they survive only long enough for extraction of their inner mass, from which a new cell line can be derived). Yet SCNT does have the potential to save lives, rejuvenate the biomedical industry in Minnesota, and change the practice of medicine as we know it.
Treating Disease
One of the areas most likely to benefit from SCNT for therapeutic purposes is tissue transplantation. We work at a university that is world-renowned for its success both in solid-organ and blood and marrow transplantation. We have been a leader in these areas since the 1960s. And while we have made great strides, there is more work to be done, particularly related to the problem of graft rejection. Today, all patients who undergo solid-organ and many who have cellular transplants such as islets are required to remain on lifelong immunosuppression to prevent rejection. Some reject their organ; and others suffer the toxic side effects of antirejection medicine resulting in life-threatening complications such as kidney and liver failure or opportunistic infections.
One strategy for obviating the need for lifelong immunosuppression is to transplant patients with cells or tissue that have been created through SCNT. Using SCNT, researchers would remove the genetic material from an unfertilized egg cell, then introduce the nucleus of a mature cell from the patient, such as a skin cell, into the enucleated egg cell. The resulting cells that would develop would acquire the surface antigens that are encoded in the patient’s genes, making it a perfect tissue match. Although it is being done elsewhere, SCNT is not currently being done at the University of Minnesota because of state funding restrictions; but it could be an important research tool in the future.
Being able to create tissue or cells for transplant would not only allow us to overcome the complications of immunosuppression but also make the transplant process less expensive and more accessible, as patients would not have to wait for organs to become available.
Those opposed to all uses of SCNT have made much of the possibility of using induced pluripotent stem (iPS) cells in research and for therapies. These stem cells are created by taking an adult cell, such as a skin cell, and introducing genes that reprogram it into an embryonic stem cell state. As with SCNT, this process results in a matched cell line for the patient. This technology holds promise, as it enables researchers to create pluripotent stem cells from adult stem cells. We are working with these cells at the university, trying to come up with a supply suitable for transplantation in people with type 1 diabetes, Hurler syndrome, Fanconi anemia, and other diseases. But we don’t yet know whether the tissues created in this way will be safe for transplant into human patients. If they are not, and if SCNT is criminalized, we will have no other option for making patient-specific cells.
In addition, using cells produced through SCNT is the only way to treat specific neurological disorders caused by defects in the mitochondria such as Leber’s hereditary optic neuropathy and myoclonic epilepsy with ragged red fibers. Adult cell reprogramming (iPS) is not an option because the process does not eliminate the diseased mitochondria.
Separating Fact from Fiction
Our legislators do not need to know every detail about SCNT. However, they do need to understand that it is not human cloning and that it is very important to research that is leading to new therapies. And before they set legislative limits, they need to be aware of a number of facts.
- The intent of research involving SCNT is to save lives and improve health. Beyond the ethics of replicating an individual, there is another reason why there is broad scientific consensus for not using SCNT for reproductive purposes. We know from animal cloning research, such as the work that resulted in the birth of Dolly the sheep, that severe birth defects and risks to the mother are common consequences of reproductive cloning. Supporters of the bill present a science fiction view of this technology as a scare tactic, and their view is based on a misunderstanding of the intent of medical research. Furthermore, there is considerable oversight in place at the federal and local levels that ensures that the research we do is ethically sound and appropriate.
- It would be premature and foolish to limit ourselves to the study of adult stem cells. Although there is substantial interest in figuring out how to make adult stem cells into useful therapies, today they are used to repair only one tissue—bone marrow.
- It is true that embryonic stem cells have not cured a single disease—and for good reason. The severe funding restrictions put in place under the Bush administration along with other local restrictions have severely limited research with embryonic stem cells. In the past six months, however, trials using embryonic stem cells elsewhere in the country have opened for spinal cord injuries, Stargardt disease (a progressive disease that leads to blindness in young people), and macular degeneration. It is unlikely that similar trials would ever be offered in this state if this kind of restrictive legislation passes.
- The pre-eminent leaders in stem cell science all recognize the importance of embryonic stem cell research, including that involving SCNT. Some of our state legislators, however, have argued that stem cell researchers have given up on the need for patient-specific embryonic stem cells derived by SCNT, citing remarks taken out of context from Professor Ian Wilmut, who cloned Dolly the sheep, and Professor Rudolf Jaenisch, who first used SCNT in studying immunodeficiency disease. The proponents of the bill never went to the primary sources—Wilmut and Jaenisch. We did. Although they are now involved in other areas of investigation, Wilmut and Jaenisch have never abandoned the need for SCNT for the reasons stated above.
- The ability to reprogram adult cells (iPS cells) does not eliminate the need for SCNT. Reprogramming requires genetic manipulations, which means resultant cell lines are years away from clinical testing. We know substantial hurdles need to be overcome before these cells can be used in any treatment, and we have shared that fact with Food and Drug Administration officials. Furthermore, it is yet to be proved that iPS cells have the full potential of embryonic stem cells. Interestingly, SCNT and the cell lines derived through that process are needed to help us understand how to make adult cells “embryonic-like.”
Limiting Research Limits Discovery
Lawmakers and the public need to understand there will be serious consequences for patients, medical researchers, and the state’s economy if this bill becomes law. Patients with incurable diseases will be cut off from future treatments developed anywhere—as it will become a crime even for patients who have had such treatments to return to Minnesota. (Language in the bill suggests a person cannot bring cells back into the state, and this could be interpreted to include cells that are in the body.) Minnesota will lose its standing as a leader in the biomedical field because companies will be limited in what they can produce. And some of the state’s most promising researchers will move to places with policies that are more welcoming.
From its inception, the University of Minnesota’s Stem Cell Institute has been interested in pursuing research on many types of stem cells—from adult stem cells, to embryonic stem cells, to the newest potential source—iPS cells. To cut off an area of related research now would be shortsighted. We should not let science and medicine be driven by a vocal minority. We must continue to be a state that welcomes scientific innovation and creativity. MM
Meri Firpo is assistant professor of medicine and a member of the Stem Cell Institute, and John Wagner is professor of pediatrics, director of the division of blood and marrow transplantation, and scientific director of clinical research of the Stem Cell Institute at the University of Minnesota.