In 1900, Major Walter Reed was given the responsibility of finding the cause of yellow fever and eliminating it. After many unsuccessful experiments, he decided to test an old but unproven theory that the disease was transmitted by mosquitos. Unfortunately, no animal was known to be susceptible to yellow fever at the time, so it was necessary to use human volunteers. In the painting, Dr. Lazear, who died a month later as a result of self-experimentation, is shown inoculating Dr. Carroll with an infected mosquito, The experiment proved conclusively that the mosquito was the carrier of yellow fever.
The title of this post is admittedly hyperbolic, but there is more than a kernel of truth to it. On Saturday, Glenn Reynolds linked to a lengthy Popular Science article that addressed the current clinical state of Stem Cell Therapies. Not surprisingly, in these very early days of therapeutic application of Stem Cell Technology, the results are spotty, there is a lot of room for it to be oversold to desperate patients, clinical research is minimal, and the long term benefits are uncertain:
Stem-Cell Tourism: Adventures at the Fringes of Experimental Medicine
It’s 2:30 in the afternoon in the Dominican Republic, and Karen Velline, a 66-year-old grandmother from Cold Spring, Minnesota, is lying on an operating table, swaddled in sterile surgical sheets. She’s just moments away from a procedure so experimental that no doctor will perform it on U.S. soil. Yet she calmly stares up at the ceiling, more excited than anxious. Despite the controversy surrounding it, Velline believes that this procedure—which she has paid Regenocyte Therapeutic, a stem-cell company in Bonita Springs, Florida, $64,000 in cash to perform—could save her from a debilitating lung condition. After months of anticipation and planning, she’s ready for things to get under way.
Cardiologist Hector Rosario nods to his team and begins inserting a clear, narrow tube into a vein in Velline’s leg, slowly threading it all the way up to the right side of her heart. “That’s the catheter,” whispers medical supervisor Leonel Liriano, who has agreed to let me watch the surgery. I can see the tube moving on an x-ray imaging screen, inching closer to its final destination, the branched pulmonary arteries that supply blood to her lungs. With the catheter in place, Rosario reaches for a syringe filled with a solution of Velline’s own stem cells: the $64,000 potion. He inserts it into the catheter and depresses the plunger. A subsequent injection of saline serves as a chaser, ensuring that the cells migrate all the way to the lung vessels.
If the technique works as advertised, the cells—hand-couriered on a plane from Israel, where they were mixed with platelet growth factor to make them multiply, and delivered minutes ago to the operating room—will grow into the delicate gas-exchange regions of the lungs. Over several months, they should regenerate failing tissues that have been ravaged by Velline’s hypersensitivity pneumonitis, a degenerative lung disease caused by an allergic reaction to dust and chemicals that has left her dependent on three liters of oxygen a day. Doctors at the Mayo Clinic in Minnesota told her that the only hope of reversing her condition was a lung transplant, a high-risk procedure with a drawn-out recovery period. “That was something I didn’t want to consider,” she says.
Karen Velline is desperate and has means. Current medical practice offers her nothing more than palliative treatments, ie she can be made more comfortable as she descends into chronic respiratory failure, becomes a pulmonary cripple, and dies prematurely. She is the kind of patient for whom Stem Cell technology cannot mature quickly enough. Perhaps if there were some hope that clinical applications of Stem Cell technology would become available in the near future in America, where she could become part of a well designed clinical trial, she would have some incentive to wait before undergoing an experimental treatment. By essentially volunteering to be an experimental subject in a less well controlled study, Ms. Velline is rolling the dice with her own life. Yet, were she inclined to take a more conservative approach, it is very likely she would be long gone before such treatments would become available for humans* in America. The FDA will see to it:
Every year, hundreds of desperately ill Americans like Velline are making similar decisions, sidestepping government regulations and heading overseas to access a smorgasbord of stem-cell therapies unavailable in the U.S. Many of these treatments—offered by companies like Regenocyte, Germany’s XCell-Center and China’s Beike Biotechnology—involve autologous adult stem cells, meaning stem cells harvested from your own blood or bone marrow. These are thought to be safer than stem cells drawn from other donors or harvested from embryos, because they incur fewer risks of rejection or tumor formation. Just how safe, though, no one knows precisely, which is why the U.S. Food and Drug Administration insists on stringent regulations.
The FDA thinks all stem-cell procedures should undergo clinical trials for safety and efficacy before companies begin selling them as therapies. Its formal review process, the agency maintains, is the only way to protect patients from treatments that are ineffective or downright dangerous.
But with multistage clinical trials lasting up to five years and costing as much as $100 million, a growing number of doctors and patients have started pursuing other options.
Cardiologist Zannos Grekos, Regenocyte’s founder, is at the forefront of this movement. His company is something of a renegade in the stem-cell world: an American firm that offers unsanctioned stem-cell treatments in the Dominican Republic to last-ditch heart and lung patients. Grekos argues that the FDA is unfairly limiting patients’ treatment options, ignoring overseas data and generally overstepping its boundaries. Autologous stem cells, he believes, should fall outside its jurisdiction, just as bone-marrow transplants and in vitro fertilization do.
Traditionally, the FDA is not in the business of telling doctors how to practice medicine. Its primary domain is medication, which, until recently, has not included tissues derived from your own body. Physicians have long been able to use patients’ own tissues in routine medical procedures—bypass surgeries, for example, or skin grafts—without government oversight. And patients have been receiving their own stem cells in the form of bone-marrow transplants for decades. These types of procedures fall into the “practice of medicine” category and thus have never required FDA approval. Free from those regulations, Grekos says, “orthopedic doctors will extract stem cells, mix them with a bone graft, and use them to heal fractures.”
Now that’s changing. In a controversial move in 2005, the FDA reclassified autologous stem cells that are manipulated by growth factors or other compounds as drugs. This criterion holds whether the cells are derived from a patient’s own body or from someone else’s. Many believe that the policy change gives the agency more authority than Congress ever intended it to have. Grekos’s theory is that pharmaceutical companies are pressuring the FDA to treat autologous stem cells as a drug in order to secure their own future profits. “The drug companies don’t want anything to pass unless they can make money off of it.” Although the FDA says any tissue that’s been manipulated and put back into the body is subject to regulatory oversight, Grekos argues that multiplying the cells and adding growth compound to them is in no way equivalent to turning them into medication. “There’s no genetic manipulation or splicing—you’re not altering the cells at all. All you’re doing is maturing them. The growth factors we use are naturally occurring in the body.”
Yet most scientists and clinicians back the current FDA system on the grounds that requiring investigators to perform double-blind, multistage trials is the only way to protect patients from ineffective or perilous stem-cell therapies.
There is much we do not know about the use of Stem Cells therapeutically. We will gain such knowledge and refine our knowledge only by using the technology. Unfortunately, in clinical medicine there is no short cut to the widespread use of a treatment in order to determine its risk benefit profile. It is a commonly understood among Physicians that were Aspirin or Penicillin to be discovered today, their side effects profiles would make it nearly impossible for them to pass muster by our risk averse FDA. Patients have been harmed and some have died from using Aspirin and Penicillin, yet the benefits have far outweighed the risks. Such a balance is rarely a factor with the FDA; a poor outcome with a drug, even one that has had tremendous benefits, once leveraged by the Tort Lawyers and the press, is a nightmare for the FDA. A treatment never approved silently kills and the FDA is spared criticism.
It may well be very premature to use Autologous Stem Cells in such a haphazard fashion as the clinic in the article, but there are groups elsewhere that are beginning to use ASC treatments on patients. We lag behind others, in part because of an attitude that does not accept the validity of non-American research results, and in part because our FDA jealously protects its bureaucratic prerogatives, all in the interest of what is best for us, of course.
For many years the charge was made, with some justification, that the Bush administration was retarding the advance of medical science by banning the use of Embryonic Stem Cells. This was considered a situation in which ideology was placed in the way of science. (The ethical and moral basis for eschewing the use of ESC is a separate issue.) Today it is a government bureaucracy, increasing its power as government bureaucracies are wont to do, in the thrall of an ideological position (the precautionary principle) that threatens to slow the pace of scientific advance in the field of Stem Cell therapeutics. Add in the disincentives for expensive new treatments in the Obamacare bill and this kind of research and treatment will be developed and used overseas long before the revolutionary promise of Stem Cell Therapy is available to the American people.
The FDA makes it extraordinarily difficult (ie, expensive and complicated) to bring new treatments to market. By treating autologous stem cells as if they were the equivalent of drugs, we are retarding progress at a time when the more people involved in the research the better it would be for all of us.
In 1900 Major Walter Reed led a team of Army Physicians in clinical research which proved that Yellow Fever was caused by a transmissible agent that was spread by mosquitoes. They achieved this knowledge at the risk of their own lives, by allowing themselves to be bitten by infected mosquitoes. Members of the team became quite ill with a disease for which there was no cure; several died.
Today we would not allow such research, in part because we now have a much better understanding of infectious disease. We do not purposely expose patients to dangerous illnesses in order to prove our theories. However, we have extended that most reasonable of approaches to now include refusing treatments of fatal illnesses because the treatment might be ineffective or dangerous.
Perhaps someday the epitaph of our reliance on Bureaucratic application of the Precautionary Principle will be a paraphrase of the Vietnam Era: we had to allow the patient to die in order to save her from treatment that might not have helped her.
*Our pets are already receiving the benefits of autologous stem cell treatment and will continue to do so well before we will; there is no Animal FDA to slow down the research and no insurance companies or government agencies which determine whether such treatment will be paid for.
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