Life on Wheels (78 page)

In the fall election of 2004, the voters of the state of California approved $80 billion dollars to be raised with a bond issue for stem cell research in the state. The following May, San Francisco was approved as the city to be host to the California Institute for Regenerative Medicine. The bond issue continues to be challenged in the courts. Meanwhile, the University of California has established the Human Embryonic Stem Cell Research Center (www.escells.ucsf.edu)

The primary ethical concern is around the question of whether an embryonic cell is equivalent to a human life. These cells are the product of an egg and a sperm creating a viable embryo, capable—in the right conditions—of growing into a person able to survive outside the womb. A significant number of people—principally based on religious beliefs—object to what they consider the destruction of life. Or worse, they view it as a form of enslavement, producing life in order to destroy it in the name of research. The potential benefits, in their view, do not override the essential ethical wrongness of using these cells for medical research.

A large number of human embryos are being generated—and stored— in fertility clinics, a product of new technologies that allow a woman’s eggs to be removed from the ovaries, inseminated outside of the womb, and then placed into the womb to be carried to term. Necessarily, in the process, an excess number of embryos are generated to increase the odds that one will survive implantation into the uterus. From the many couples for whom this process succeeds, a considerable number of remaining embryos are destined for destruction. Supporters of embryonic stem cell research feel that it is, in fact, unethical to dispose of viable embryos that could be used to achieve potentially historic gains in medical therapies for such a wide range of human conditions.

At this writing, the 2008 presidential campaign is under way. Should a Democrat gain the office, we will likely see the release of federal funds for embryonic stem cell research. As long as this issue has the rhetorical power it does, we will see it swing back and forth depending on who holds majorities in the White House and the Congress.

In the hope of circumventing these complex ethical questions, there are efforts at hand to genetically produce cells with the same features as embryonic cells. If these efforts succeed, actual viable embryos will no longer be necessary for the therapy.

One solution to take the ethical controversy out of stem cell research is the development of somatic cell nuclear transfer (SCNT). SCNT uses a patient’s own cells and an unfertilized human egg to make embryonic stem cells that match the patient’s genetic makeup. The SCNT process does not use or harm an embryo or fetus. It is sometimes referred to as “therapeutic cloning” because it matches the DNA of the donor. This differs, however, from “reproductive cloning,” in which the goal is to bring to life another being with the same DNA. SCNT is a process only for producing stem cells capable of differentiating into tissues that can be transplanted as a therapy without risking rejection. Some people object to SCNT, feeling that using a woman’s egg toes the same ethical boundary as using an embryo.

In November of 2007, the journal
Nature
reported two dramatic advances that were widely reported in the international media and considered major steps forward that could potentially defuse the entire ethical debate over stem cell research. Shinya Yamanaka of the University of Kyoto in Japan and his team had “reprogrammed” human skin cells into essentially believing they were embryonic stem cells. They called them “induced pluripotent” cells. A team at the Oregon Health Sciences University had also succeeded in cloning the embryos of a monkey, the first time that this had been achieved successfully with a primate. However, neither of these research studies had been put to the full scientific test of whether they produce truly pluripotent stem cells that will supplant the need for the use of human embryos.

Researchers are experimenting with many kind of cells, from both human donors and animals. Cells are studied for the various features we have seen—a capacity to stimulate growth, to resist or suppress inhibitors, to multiply and go to the right place, and so on. The variety of possible sources for cells is huge.

In a study by Dr. Geoffrey Raisman, at the National Institute for Medical Research in London, cells were taken from inside the nose. These olfactory ensheathing cells succeeded in stimulating the recovery of a small SCI in rats. These cells are of interest because they are easy to collect and are continuously produced in the body, providing a generous supply. They are also the only type of cell in the CNS capable of regenerating themselves. There is also hope that they can act as a chaperone, helping newly generated axons to cross that difficult boundary between the peripheral and central nervous systems. This is the point where axonal growth often stops and is one reason why growth has not reliably led to functional improvement.

In Tijuana, Mexico, a group of neurosurgeons is working with embryonic cells from the blue shark. Although they report improvements in the 16 human subjects with whom they have worked, they have not documented their research in a detailed fashion, making American researchers uncomfortable. Rather than conducting a carefully documented research study, the team at the Mexican clinic is interested in offering what they believe is a useful cure and are able to do so without the constraints placed on physicians in the United States by the Food and Drug Administration (FDA). Anyone considering participating in such undocumented research should go to every possible extreme to understand the work and its risks before considering an unregulated procedure.

Another controversial treatment for SCI is called omentum transposition. The omentum is a band of tissue in the abdomen of mammals that seals off abdominal injuries. A surgical procedure partially detaches the omentum, reconnecting it at the injury site. Removing it seems not to have a negative effect on the abdomen. The theory is that the omentum—which is rich in blood vessels—may supply the damaged nerve cells with vital oxygen and, possibly, may secrete chemicals that stimulate nerve growth.

Initial animal trials seem to show some functional improvement if the operation is completed within three hours of injury. Little or no improvement is shown when the procedure is done six to eight hours after injury. Scarring at the cord, as well as abdominal complications, have been observed as a result of omental transplant. Clinical trials for people who have had a chronic SCI had been scheduled and were then canceled. This research has not been scientifically documented, so there is considerable skepticism regarding its value.

Although the search goes on for an ultimate solution to regenerating the spinal cord, there have already been early accomplishments that help reduce the extent of damage to the cord at the time of injury. Methylprednisolone is a steroid that has been found to reduce the inflammatory process that occurs after injury.

A milestone in practical treatment occurred in May 1990. The results of the National Acute Spinal Cord Injury Study showed that methylprednisolone was found to reduce the extent of spinal cord trauma when given within eight hours of injury. Improvements of up to 20% have been measured, compared to people who were given no drug. The use of methylprednisolone with spinal cord trauma is now standard in emergency centers and in the toolkits of ambulance and EMT personnel throughout the United States.

The effect of methylprednisolone is significant, according to Wise Young:

Methylprednisolone is an anti-inflammatory agent in common use for other purposes, such as a treatment for flare-ups of multiple sclerosis, lupus, severe asthma, and other conditions. The use of methylprednisolone has been the first time that treatment of any kind has been found to have an effect on the spinal cord.

Methylprednisolone might also play a role in regeneration. Future spinal cord treatment might itself be inflammatory, so the tissue would need protection. Dr. Kleitman of the Miami Project points out:

The Multicenter Animal Spinal Cord Injury Study (MASCIS) was funded by the United States government’s National Institutes of Health. MASCIS is following up on the initial work with methylprednisolone and other pharmaceuticals. These drugs have shown potential. The task now is to determine dosage, extent of follow-up therapy, and so on. This is a huge job, requiring thousands of experiments, well beyond the capacity of any one laboratory. Linda Noble, PhD, was a member of the MASCIS team. She says that the project is a very important development:

Such research is very slow and for good reason. According to Dr. Noble, the issue is reproducibility. What is done in one lab must be capable of duplication in another to prove consistent results. The only way to do this, and to find out the specific behavior of a drug or a therapy, is to closely control the conditions. She says:

Established at a time when spinal cord research was uncoordinated and marginally supported, MASCIS represents an important step in making the research more efficient and a newfound cooperation among laboratories and scientists, making it possible for answers to be found that an individual lab could never have pursued on its own. This project is an important evolutionary step in the history of the research effort.

One of the greatest results of the MASCIS project was the development of the MASCIS Impactor, a device that accurately reproduces specific SCI in rodents. For research to be reproducible across various laboratories, there had to be a reliable and consistent means of creating the exact basis for the injury in laboratory rodents.

Another method being explored to limit secondary damage at the time of injury is to lower the body temperature by two or three degrees, intentionally inducing hypothermia. This reduces the release of free radicals and glutamates, which destroy healthy cells not affected by the trauma. This treatment is counter to common sense, which would dictate that the body needs optimal circulation in order to respond to injury and recover. However, in the case of spinal cord trauma, it appears that interrupting the destructive process of secondary damage is of greater value. W. Dalton Dietrich, PhD, scientific director of the Miami Project, says:

Large-scale controlled studies have not yet been performed on this question.

The first effort to have an effect on the chronically injured spinal cord—well after the trauma—involved a drug called 4-aminopyridine or 4-AP, sometimes referred to as fampridine. Animal studies have shown that some nerve axons that survive a spinal cord trauma nonetheless fail to conduct an impulse past the injury site because of damaged myelin, the insulation of our spinal nerves. 4-AP appears to improve the function of demyelinated nerves. It does not actually restore myelin but, instead, helps existing axons with otherwise complete connections to relay impulses.

Dr. Andrew Blight of the University of North Carolina discovered the effects of 4-AP on the spinal cord. It was initially used as a treatment for multiple sclerosis and in the laboratory to study neurons and axons. The loss of myelin surrounding nerve axons allows potassium to intrude, among other effects, interfering with the passage of nerve impulses. 4-AP is a “potassium channel blocker,” which limits potassium from interfering with conduction in demyelinated nerves, allowing these otherwise healthy axons to pass on an impulse. Since the greater portion of SCIs are incomplete—and presumably there are myelin-deprived but undamaged axons present—this could be a hopeful therapy for some people with CNS disorders.

Clinical trials performed in Canada in 1995 showed improvements in both motor and sensory functions following injections of 4-AP. Some of the subjects were more than a year post-injury. The degree of improvement varied. A man in Canada was able to consummate his marriage as a result of 4-AP treatment, yet other trial participants showed no reaction whatsoever. According to Dr. Blight: