The Cells=Drugs Argument Has Suffered A Significant Blow

The Regenexx blog site has a fascinating article on tow approaches to reducing transplantation rejection. Osiris Corporation has tried to market a stem product that is a kind of one-size-fits-all stem cell approach for regenerative medicine. This takes mesenchymal stem cells from the bone marrow of young patients and concentrated them in a vial for use. Unfortunately, once these stem cells differentiate into other cell types, they are rejected by the patient’s immune system. While using mesenchymal stem cells from a different person can provide regeneration under particular circumstances, the transplants that use a patient’s own stem cells are always the best from the perspective of the immune system.

A study from Northwestern showed that kidney transplant patients who were also given transplants of bone marrow from the kidney donor did not require any immunosuppressive drugs to prevent the immune system from rejecting their new kidney. This shows that instead of stem cells in a vial (a one-size-fits-all approach to regenerative medicine), an individualized approach seems to be far superior. However, the stem cells = drugs dictum of the FDA argues for the stem cells in a vial approach. Unfortunately, in a Phase III clinical trial, Osiris’ Prochymal product spectacularly failed to provide relief to patients suffering from “Graft versus Host Disease (GVHD). Therefore the stem cells in a vial approach failed, but the individualized worked. This shows that the stem cells = drugs ideology is not one that is tied to reality.

To read Regenexx’s fascinating blog post, go here.

Forbes blogs About the FDA v. Regenexx Stem Cell Lawsuit That May Shape Our Medical Future

Gergana Koleva blogs about public health for Forbes. She has written an excellent piece on the FDA’s lawsuit against Regenexx in their quest to regulate (read shunt down) a procedure that uses a patient’s own stem cells to treat ailing joints. In this lawsuit, the FDA justified their action by stating that cells are chemicals, just like drugs, and therefore, the have the right to regulate them. Ms. Koleva rightly notes that this lawsuit will change the face of medicine and medical innovation in this country. Read her blog article here.

According to the FDA your body is a drug and we get to regulate it

The Food and Drug Agency (FDA) serves a very necessary purpose. If you remember history at all, you will recall the Massengill Corporation and their elixir of sulfanilamide that was spiked with diethylene glycol that killed over one hundred people, most of whom were children. Were it not for the herculean efforts of FDA field agents who collected the containers of sulfanilamide elixir, far more people would have died. Also, were it not for an error made in the labeling of the elixir, FDA fields agents would have had no authority to confiscate the poisonous containers. This tragedy led to resolutions in the US House and Senate in November of 1937 to ask Secretary of Agriculture Henry A. Wallace to report on the Elixir Sulfanilamide deaths. Wallace’s report, the content of which became widely publicized, was submitted to the Secretary of the Senate, Edwin A. Halsey, on Thanksgiving morning, November 25, 1937,

Wallace’s report revealed the extent of known elixir-related casualties in the United States, and the chronology of events that led to them. It cataloged the elixir recipe, the lack of testing before marketing, the wide distribution of elixir shipments, the evasive words of Massengill’s first recall telegrams, and the FDA’s yeoman efforts to confiscate the poisonous medicine—often in the face of considerable obstruction. This led to the passage of the 1938 Food, Drug and Cosmetic Act, which empowered the FDA to determine if patented drugs were safe for consumption before they were marketed.   The 1938 Food, Drug, and Cosmetic Act also shored up many of the shortcomings of the Pure Food and Drug Act of 1906.  For example, the old law did not provide for the government regulation of cosmetics, since all language relevant to such regulation was dropped from the proposed law in 1900.  Secondly, the 1906 law did not adequately cover the regulation of patented medicines, since the definition of dangerous drugs was outdated, given the pharmaceutical innovations of the early 20th century.  Third, language concerning the definition of food adulteration was vague and ambiguous; and the law also provided no control over false advertising.

However, the FDA has presently become too highly enamored of itself and has tried to grab power simply for the sake of power.  For example, in November, 2011 the FDA rejected attempts by Genentech to gain approval for its anti-cancer drug Avastin (bevacizumab) for breast cancer.  Avastin had already bee approved for colorectal, lung, brain and kidney cancers.  With respect to breast cancer, Avastin was first approved on the basis of progression-free survival, or PFS, the time women live without their disease spreading or worsening.  In 2009 Genentech applied to upgrade the approval status of Avastin to full approval.  They had some new studies that showed PFS improvements, but they were less statistically robust than the initial trials.  The FDA withdrew Avastin’s breast cancer approval last year—leading to Genentech’s unprecedented appeal and a two-day trial in June, 2011.  In her decision denying that appeal, FDA Commissioner Margaret Hamburg conceded that there are groups of “super responders” who experience dramatic improvements when treated with Avastin.  However, she then made the extraordinary claim that such patients don’t count because “it is not possible to determine if there is some subset of patients within the population as a whole that may have had a meaningful benefit.” Dr. Hamburg also conceded that Avastin may produce better results when used with different chemotherapies, but that those prospects haven’t been sufficiently tested.  The denial is about FDA reasserting its political culture of delay and control, rigging the re-review against Avastin and emphasizing safety risks.  Mind you, the risks of Avastin are real.  However they are also well-understood and manageable, especially during end-stage oncology where there are no good options.  The FDA’s real goal was to send a warning to the rest of the drug industry about who is in charge of drug development.

If you need further evidence of the FDA’s political power grab, take a look at the Regenexx-C treatment.  This protocol uses bone marrow mesenchymal stem cells (BM-MSCs) that have aspirated from the top of the pelvis and cultured for about 6 weeks, and are precisely applied to the areas of need in joints, bones, tendons and ligaments.  Because the BM-MSCs are cultured and then reintroduced into the patient’s body, the FDA claims that they are a drug and should be subjected to the FDA’s political culture of delay and control (read about 12 years of bureaucratic nonsense and millions of dollars).  Regenexx replied that our body is ours to regulate, and the question should end there.  However, according to the FDA, in court documents has now said that since it regulates chemical drugs, and since all living things produce chemicals, then all living things fall under FDA jurisdiction.  No you read that right, these people actually believe that.  There is a very good summary of the legal issues here.

This nut-ball statement by FDA came in recent court filings in response to a judge’s order slapped on the agency in the Regenexx case.   The judge pointed out that Congress only authorized FDA to consider chemicals which had “chemical action” as a drug.  The judge also asked the obvious question: “How do you get from chemicals=drugs to cells=drugs?  She gave the FDA 30 days to respond and denied their motions.

The FDA’s response is a remarkable example of political hubris, and every American should find this troubling.  According to the FDA’s own internal expert: “When living cells interact with their environment to mediate repair of and/or regenerate damaged tissue, they do so by chemical action.”

So here’s the FDA’s “logic:  1) Congress said that chemicals are drugs; 2) Cells produce chemicals and are made of chemicals; 3) Therefore, cell are drugs.

To which all God’s people said, “huh?”  If you are confused, join the party.  We know what drugs are.  They are compounds that interact with bodily processes to achieve a particular physiological outcome.  That outcome could be bringing some physiological read outs back within normal ranges (blood pressure medicines, heart medicines, diuretics, etc.), relieving pain, killing invading microorganisms, and so on.  However, cells taken from your body and expanded and re-introduced you body are not drugs, unless they are derivatized so that they not longer resemble their original state.  Increasing the numbers of those cells does not make them a drug.  All the legal hand-waving in the world does not change that.  The FDA’s argument is radical at best and asinine at worse.

The real danger in all this is that the FDA is completely serious about their views.  Look at the note from the FDA here.  Fat-based stem cells are a drug according to the FDA.  It doesn’t matter that they came from your body and were only isolated, expanded and reintroduced into your body.  The FDA wants to regulate it even though they do not regulate in vitro fertilization.  Certainly human eggs and “minimally manipulated” when they are fertilized, but the FDA does not regulate them.  Why not?  Nether should they regulate fat-based stem cells.

In order to balance this, I should add that there are non-drug things that the FDA regulates and should regulate.  For example medical software that delivers medical imagery and radiation dosage information are regulated.  If these devices were not properly regulated, we might have another Therac-25 incident.  Therac-25 was a radiation therapy machine and it was involved in at least six accidents between 1985 and 1987 that consisted of patients receiving massive overdoses of radiation (approximately 100 times the intended dose).  Also autotransfusion of blood is regulated by the FDA even though one’s own blood is used.  In this case the blood is pre-donated before a those procedures that cause large blood loss (aneurysm, total joint replacements and spinal surgeries).  Blood is collected by a device commonly known as the Cell Saver.  Since the blood is collected by a specialized device and then reintroduced during surgery, it makes sense to regulate autotransfusion.  Likewise, normal hormones that are given for menopause are regulated by the FDA and they should be.  However, regulation of your own cells is ridiculous and FDA should know better.  The agency is still working within a regulatory mindset that is appropriate to the 1960s.  It’s time to upgrade the FDA and stop this vast encroachment of government over own bodies.


Geron Corporation has made a cell line called GRNOPC1 from embryonic stem cells. GRNOPC1 is an “oligodendrocyte precursor cell” or OPC line. Before you blow a gasket at the sight of such a long-winded description, just remember that nerves are like wires and wires need insulation.  OPCs are the cells that make the insulation.  During spinal cord injury, the insulation dies off and it causes nerves to malfunction.

In collaboration with Hans Keirstead at UC Irvine, Geron developed a protocol for the administration of GRNOPC1 cells to animals with acute spinal cord injuries. His protocol showed that the OPCs were safe (no tumors were seen, even after one year) and somewhat effective. Some scientists were skeptical, since the mice had somewhat less severe spinal cord injuries.  Nevertheless, Geron was granted an Investigational New Drug Application from the FDA to conduct a Phase I trial with their OPC cell line.

They apparently, however, have bit a bit of a snag. Here is a press release from Geron Corporation.

Geron Corporation today announced that its IND (Investigational New Drug application) for GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the FDA pending the agency’s review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial.

Since filing the IND, Geron has been undertaking studies to enable dose escalation of its spinal cord injury product, and has been investigating application of the product to other neurodegenerative diseases. The company has also been performing additional product characterization and conducting further animal studies. Data from this work has been submitted to the FDA. Geron will work closely with the FDA to facilitate their review of the new data and to release the clinical hold. No patients have yet been treated in this study.

From the sound of it, this hold is merely an administrative procedure that the FDA routinely undergoes when presented with new data.  However, if the new data is completely consonant with previous findings, why would there be a hold? We simply do not know at this time.  It is entirely possible that nothing is amiss, and this is merely FDA policy.  However, it is also possible that Geron’s new product does not behave exactly as they thought.

The development of the first cholesterol-lowering drug (lovastatin) experienced a slow-down when a related product being developed in Japan caused cancer in dogs. Roy Vagelos, president of Merck at the time, contacted the FDA and suspended all clinical trials. Further testing by Merck showed that this was an anomaly, and extensive clinical use has vindicated this finding. Maybe this is a similar situation for Geron’s OPC line?  Only time will tell.

My response to Obama’s Executive Order

This executive order violates the Dickey-Wicker amendment, which states that “none of the funds made available in the Act may be used for – 1) the creation of a human embryo or embryos for research purposes; or 2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death.” This executive order seeks to fund embryo-destructive with federal funds, which is a direct violation of the Dickey-Wicker amendment.

Secondly, the executive order does nothing to limit reproductive cloning. It trades on the alleged distinction between “therapeutic” and “reproductive” cloning, but there is no difference between these two types of cloning when it comes to what is made. Cloning is a form of asexual reproduction, which is essentially what happens during twinning. Yet we do not set twins aside for destructive research. The fact is that all cloning creates a human being and this executive order approves the production of human beings solely for the purpose of killing them. This is simply barbaric.

Third, even though the order says that it will “lift the ban on federal funding for promising embryonic stem cell research,” there never was a ban on such research, only a ban on research that destroyed new embryos to make new lines. The pejorative manner in which this is phrased might make good copy, but it is historically disingenuous.

Finally, the order states that embryonic stem cell research will be funded “only when it is …scientifically worthy.” The problem is the induced pluripotent stem cells are putting classically made embryonic stem cells out of business. None of this embryo-destructive research is necessary.

New NIH Guidelines for Embryonic Stem Cell Research

Melinda Penner evaluates the new NIH guidelines for embryonic stem cell research and this site: here.  It is a very interesting evaluation.

The guidelines allow the use of surplus embryos from in vitro fertilization cycles for the production of embryonic stem cells.  These embryos were originally made for reproductive purposes, but research that will end their existence is allowed on them.  Embryos that were made by somatic cell nuclear transfer are usually made for the purpose of research.  However the guidelines prohibit research on such embryos that were originally made for research.  In others the guidelines allow research on embryos originally not made for research and prohibit funding for research on embryos made for the purpose of research.  In this regard the guidelines are inconsistent.

However, the guidelines seem to regard embryos as expendable.  That creates a society where the weakest members of our species are perpetually at risk.  To justify killing them, we use arguments like “they are going to die anyway.”  Such are argument was used by Scrooge in Charles Dickens “A Christmas Carol.”  When asked for a donation to help the poor at Christmas time, Scrooge said that the poor and homeless should hurry up and die and “decrease the surplus population.”  We would regard such an attitude and inhumane, but when it comes to those who are a little younger than the rest of us, it is somehow perfectly acceptable to destroy them.  I refuse to call such reasoning “moral progress” or such a policy “wise.”