Planned Parenthood and Fetal Tissue Procurement


Unless you have been without any internet access for the past month or so, you have probably heard about the undercover videos made by David Daleiden of the Center for Medical Progress that feature the chief medical director of Planned Parenthood, Dr. Deborah Nucatola,  discussing the sale of fetal tissue that results from an abortion, and Dr. Mary Gatter, the Medical Directors’ Council President for Planted Parenthood doing essentially the same thing.

The emotional impact of these videos are immense, but I would like to try to step back from that and discuss the legal side of these videos.  Fetal tissue procurement is heavily regulated by the Federal government.  The specific laws that regulate human fetal tissue procurement are shown below:

42 U.S. Code § 289g–2 – Prohibitions regarding human fetal tissue
a) Purchase of tissue
It shall be unlawful for any person to knowingly acquire, receive, or otherwise transfer any human fetal tissue for valuable consideration if the transfer affects interstate commerce.
(b) Solicitation or acceptance of tissue as directed donation for use in transplantation
It shall be unlawful for any person to solicit or knowingly acquire, receive, or accept a donation of human fetal tissue for the purpose of transplantation of such tissue into another person if the donation affects interstate commerce, the tissue will be or is obtained pursuant to an induced abortion, and—
(1) the donation will be or is made pursuant to a promise to the donating individual that the donated tissue will be transplanted into a recipient specified by such individual;
(2) the donated tissue will be transplanted into a relative of the donating individual; or
(3) the person who solicits or knowingly acquires, receives, or accepts the donation has provided valuable consideration for the costs associated with such abortion.
(c) Solicitation or acceptance of tissue from fetuses gestated for research purposes
It shall be unlawful for any person or entity involved or engaged in interstate commerce to—
(1) solicit or knowingly acquire, receive, or accept a donation of human fetal tissue knowing that a human pregnancy was deliberately initiated to provide such tissue; or
(2) knowingly acquire, receive, or accept tissue or cells obtained from a human embryo or fetus that was gestated in the uterus of a nonhuman animal.
(d) Criminal penalties for violations
(1) In general
Any person who violates subsection (a), (b), or (c) shall be fined in accordance with title 18, subject to paragraph (2), or imprisoned for not more than 10 years, or both.
(2) Penalties applicable to persons receiving consideration
With respect to the imposition of a fine under paragraph (1), if the person involved violates subsection (a) or (b)(3), a fine shall be imposed in an amount not less than twice the amount of the valuable consideration received.
(e) Definitions
For purposes of this section:
(1) The term “human fetal tissue” has the meaning given such term in section 289g–1 (g) of this title.
(2) The term “interstate commerce” has the meaning given such term in section 321 (b) of title 21.
(3) The term “valuable consideration” does not include reasonable payments associated with the transportation, implantation, processing, preservation, quality control, or storage of human fetal tissue.

If we wade through the legalese, we can see that you cannot sell fetal tissue.  It has to be donated and it cannot come from a pregnancy whose sole purpose was to provide a source of fetal tissue.  You may not sell it for a profit.  You may also not transplant it.  All of this is meant to prevent women from having babies so they can sell their parts for money.  For this reason, abortion clinics may not use the possibility of fetal tissue donation as an inducement to persuade women to have an abortion.

In both of these videos, Planned Parenthood executives, not people who run individual centers, medical directors, which makes this official Planned Parenthood policy, actively discuss the prices of fetal organs.  That reflects an intent to sell fetal organs and that means that these videos reflect an intent to break a Federal law.  If this reflects routine Planned Parenthood policy and/or practice, then they are routinely breaking the law.

As you can see, at the very least, this deserves an investigation.  If Planned Parenthood clinics routinely charge biotechnology companies beyond their normal administrative and medical costs for fetal tissue, then they are breaking the law.  Maybe that is not the case (I highly doubt it frankly, but that’s my take), but we do not know without an investigation.  The Justice Department should become involved quickly and all federal funding of Planned Parenthood should be suspended pending full cooperation with a Federal investigation.  This should be the minimal results of these troubling videos.

StemCells, Inc., Sued by Former Employee Who Says Their Stem Cell Treatment is Unsafe


A California stem cell company, StemCells, Inc., that is developing cell-based therapies for several different neurological and eye conditions, is being sued by a former employee (whistleblower) who claims that the company did not follow proper protocols in the preparation of their treatments. Rob Williams, who was once a senior manager at StemCells, Inc., has alleged that the company fired him after he brought these problems to the attention of senior management.

According to the Courthouse New Service, Williams in the lawsuit stated that he “noted poor sterile technique, failure to adhere to current Good Manufacturing Practices in the company’s manufacturing process, and substantial deficiencies in the company’s Manual Aseptic Processing of HuCNS-SC (Human Central Nervous System Stem Cells) cell lines—failure and deficiencies that put patients at risk of infection or death during ongoing clinical trials.”

Ken Stratton, who serves as the general counsel for StemCells, Inc., has told the California Stem Cell Report that Williams’s employment “was terminated for performance deficiencies, and [the company] finds no merit to the allegations.” Stratton also said that “the elements of manufacturing practices that concerned Mr. Williams were immediately and carefully reviewed by the company.”

It might be worth noting that this lawsuit coincides with the departure this past April or May of StemCells, Inc.’s Executive VP of Manufacturing Operations and Regulatory Affairs, Stewart Craig, who took a position at Sangamo Biosciences.

Unfortunately for StemCells, Inc., this particular lawsuit comes soon after a second bit of bad press. Embryologist Alan Trounson led the California Institute for Regenerative Medicine (CIRM) until June of this year, but has joined the board of StemCells, Inc., shortly after leaving the state stem cell research funding agency. According to an opinion article written by Ron Leuty, who is a reporter for the San Francisco Business Times, Trounson has recused himself from discussions regarding a loan StemCells, Inc., received from CIRM in 2012 because of his close relationship with the company’s founder. “But the speed of his appointment to the StemCells board has raised questions” about a possible conflict of interest, Leuty wrote.

CIRM has been marred by conflicts of interest accusations since California voters in 2004 birthed CIRM through Proposition 71 and the subsequent sale of $3 billion in state bonds. Now it has one more strike against it.

Leuty called the situation an embarrassment for CIRM. “If the public perceives that individuals—researchers or CIRM employees or company executives—are feeding at the trough of the semiautonomous public agency, it isn’t going to help CIRM get more cash from that very same public that foots the bill.”

New Pluripotent Stem Cell Production Protein Identified


Large scale production of stem cells requires an intimate knowledge of the genetic networks that convert adult cells into induced pluripotent stem cells (iPSCs). The original protocol established by Shinya Yamanaka and his colleagues used four genes all clustered on a retrovirus vector, but there are safer, more technically subtle ways to make iPSCs.

Because iPSCs are made from a patient’s own cells, they are less likely to be rejected by the patient’s immune system. They also show tremendous developmental flexibility, they can potentially be differentiated into any adult cell type in the body.  The problem with iPSCs comes from the difficulty of making large quantities of them in a reasonable amount of time.  However, a new research publication from scientists at the University of Toronto, the University for Sick Children and Mount Sinai Hospital, in collaboration with colleagues from the United States and Portugal, identifies specific proteins that play central roles in controlling pluripotency that may mean a potential breakthrough in producing iPSCs.

Researchers discovered these proteins by using something called the “splicing code.”  Benjamin Blencowe discovered the splicing code a few years ago.  “The mechanisms that control embryonic stem cell pluripotency have remained a mystery for some time.  However, what Dr. Blencowe and the research team found is that the proteins identified by our splicing code can activate or deactivate stem cell pluripotency,” said Brendan J. Frey, from the University of Toronto Departments of Electrical Engineering and Medicine, who published with Benjamin Blencowe the paper that deciphered this splicing code (see Nature 2010 465: 53-59).  While a complete recipe for producing iPSCs may not be available yet, it is beginning to look more likely, according to Frey.

In this paper, Blencowe and his collaborators identified two proteins known as muscleblind-like RNA binding proteins, or MBNL1 and MBNL2.  These proteins are conserved and direct negative regulators of a large program of cassette exon alternative splicing events that are differentially regulated between embryonic stem cells and other cell types.

RNA splicing occurs in plant, animal, fungal, and protist cells (only very, very rarely in bacteria), and involves the removal of segments of primary RNA transcripts.  When RNA molecules are transcribed in eukaryotic cells, they are engaged by cellular machinery called the RNA spliceosome.  The RNA spliceosome removes segments known as “introns” and the excised introns are degraded and the remaining RNA segments, which are known as “exons, are ligated together to form a mature messenger RNA.

mRNA splicing

Some introns are removed from primary RNA transcripts by all cells, but others are removed in some cells but not others.  This phenomenon is known “alternative splicing” and it is responsible for the differential regulation of particular genes.

alternative_splicing

Alternative splicing is mediated by sequences called splicing enhancers and splicing silencers that are six to either nucleotides long and bind proteins that either induce or repress alternative splicing in those cells that express the proteins that bind these splicing enhancers or silencers.

Alternative RNA splicing mechanism

MBNL is one of these proteins that bind to RNA splicing silencers.  If the quantity of MBNL proteins in differentiated cells is decreased, then these cells switch to an embryonic stem cell-like alternative splicing pattern for approximately half of their genes.  Conversely, overexpression of MBNL proteins in ES cells promotes differentiated-cell-like alternative splicing patterns.  Among the MBNL-regulated events is an ES-cell-specific alternative splicing switch in a protein-coding gene called the forkhead family transcription factor FOXP1.  FOXP1 controls pluripotency, and consistent with a central and negative regulatory role for MBNL proteins in pluripotency, knockdown of MBNL significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming.

Thus MBNL proteins should be one of the main targets for the mass production of iPSCs.

Federal Court Rules in Favor of Federal Funding for Embryonic Stem Cell Research Legal


On August 24, 2012, a three-judge panel ruled that the government had properly interpreted a law that bans the use of federal funds research that destroys human embryos. Many legal observers, however, opined that this ruling will not end the controversy over this issue, and one of the judges on the three-judge panel importuned Congress to clarify what the government could and could not do with respect to human embryos.

This ruling upholds the dismissal of the case by the US Court of Appeals for the District of Columbia Circuit. The case, Sherley v. Sebellius, 11-5241, sought to prevent the US Department of Health and Human Services from using federal money to fund human embryonic stem cell research. The plaintiffs contended that funding human embryonic stem cell research would violate the Dickey-Wicker Amendment, which was passed as a rider to other legislation in 1996.

Predictably, biotechnology companies interested in embryonic stem cell-based treatments and other more academic embryonic stem cell researchers were quite pleased with the ruling. For example, Gary Rabin of Advanced Cell Technology said: “This court ruling should be of considerable benefit to our embryonic stem cell-based clinical programs. It effectively removes major speed bumps for the National Institutes of Health in terms of approving the several stem cells lines that we have submitted for their consideration for funding. We expect that a number of our embryonic stem cell lines will be approved for funding in coming months.”

The plaintiffs in this case were: a) James L. Sherley, who is a former a former member of the MIT faculty, but presently works as a senior scientist at the Boston Biomedical Research Institute; b) Theresa Deisher, who is the founder, managing member, and research and development director of AVM Biotechnology; and Nightlight Christian Adoptions, which is a non-profit, licensed adoption agency dedicated to protecting and finding adoptive parents for human embryos conceived through in vitro fertilization; c) the Christian Medical Association, a non-profit association of doctors dedicated to improving ethical standards of health care in the United States and abroad.

The main argument put forward by the plaintiffs in this lawsuit is that the present NIH Guidelines for the funding of embryonic stem cell projects violate existing federal law that bans the use of federal funds for the destruction of human embryos. Because the NIH created and sent its guidelines with a preconceived determination to fund human embryonic stem cell research and without considering scientifically and ethically superior alternatives, the guidelines are invalid regulations that violate the federal Administrative Procedure Act and, therefore, should be struck down.

With respect to the merits of the plaintiff’s case, it seems rather obvious, to me at least, that the NIH guidelines violate federal law. The Dickey-Wicker amendment was sponsored by former Congressman Jay Dickey (RAK) and Senator Roger Wicker (R-MS) who was then a member of the House of Representatives)], and applied to every Health and Human Services (“HHS”) appropriations bill governing the National Institutes of Health (NIH) since 1995. The bill states, “None of the funds made available by this Act may be used for . . . research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 C.F.R. § 46.204(b) and section 498(b) of the Public Health Service Act (42 U.S.C. § 289g(b).” Even for lawyer-speak, that seems pretty clear to me. Embryonic stem cell research includes the derivation of new embryonic stem cell lines from human embryos.  The derivation process destroys the embryo, which is precisely the thing that the Dickey-Wicker amendment prohibits the NIH from funding with federal money.

However, the federal judges did not see it that way for one reason:  funding for embryonic stem cell research also includes work on already established embryonic stem cell lines.  These lines are already in existence that the decision to kill the embryos has already occurred.  Therefore, the judges thought that the Dickey-Wicker amendment was simply not specific enough on the matter to merit stopping all funding for embryonic stem cell work.

While this argument has merit, it dodges the fact that embryo-destroying research will be funded by the NIH because of this ruling and some of this research will include laboratories that destroy embryos to make embryonic stem cells.  This is clear, since several sources have noted the increase in embryonic stem cell lines approved for NIH funding.  For example the Nature Medicine blog had this to say:  “Since the beginning of the month, the NIH has quietly kept adding ES cell lines to its registry, bringing the total tally up to 128.”  Thus the NIH funding policy has definitely led to the destruction of more embryos.

Where did this legal battle originate?  It began in 1994, during the presidency of Bill Clinton.  Before 1994, there was a ban on human embryo experimentation.  The Clinton Administration took steps to reverse this ban, and allow embryo-destructive research on donated embryos left over from fertility clinics while still prohibiting research that created its own embryos for research purposes.;  This policy shift was in response to the recommendation of an advisory committee known as the Human Embryo Research Panel (“HERP”).  This was an ad hoc committee formed to address the question of embryo research.  The phrase “ad hoc” is a Latin phae that means “for this.”  It simply means that this committee was formed for to address this particular question.  In testimony before the House Appropriations Committee, NIH Director Varmus stated that NIH would have funded six out of nine applications for grants involving embryo-related research “if the NIH had been able to proceed according to the recommendations and the President’s directive.”  Varmus also stated that he “firmly agree[d]” with particular sections of the HERP report, and further told the Committee that NIH was currently deciding whether to go forward with funding embryo-destructive research on donated human embryos.

However, before NIH was able to approve any grants that funded embryo-destructive research, Congress passed the Dickey-Wicker Amendment for the first time.  Opponents of the amendment argued that prohibiting federal funding of embryos research would push such research into the dark recesses of private industry where it would not be properly regulated.  Also, the understanding of the amendment was universal throughout Congress: it would prohibit ALL federal funding of embryo-destructive research.  Democratic senator from California, Barbara Boxer, understood the Dickey-Wicker Amendment as creating “a total prohibition of Federal funding for human embryo research,” and Republican Congressman John Porter understood the amendment in this way as well.  In fact Porter tried to pass an alternative rider to the Dickey-Wicker Amendment that would have prohibited federal funding for only creation of new embryos, but not other types of embryo-destructive research with donated embryos, but his rider was defeated.

Even more significantly, the NIH understood the amendment that way from 1996-1999 when they enforced it.  DNA research with DNA from human embryos that did not necessarily kill the embryos was prohibited from receiving federal funding under the NIH’s understanding of the Dickey-Wicker Amendment.  In a 1996 letter (October 10)  to Georgetown University Medical School researcher Mark Hughes who was using federally funded equipment to conduct tests on DNA derived from embryos, NIH “clarif[ied] . . .the NIH position on embryo research.” The agency explained that “analysis from DNA derived from a human embryo” violated the federal prohibition on research involving embryos and that NIH equipment “may not be used for embryo work of any kind.”

However, four years later, the NIH altered its position and issue Guidelines authorizing the funding of human embryonic stem cell research (65 Fed. Reg. 51976, Aug. 25, 2000).  Before the 2000 Guidelines were published, then-HHS General Counsel Harriet S. Rabb issued a memorandum on January 15, 1999, that supported the National Institutes of Health (NIH) claim that the Dickey-Wicker Amendment ought to be re-interpreted to ban federal funding of the derivation of embryonic stem cells – the procedure by which human embryos are destroyed to harvest their embryonic stem cells – but not research utilizing the derived embryonic stem cells.  This is in direct contradiction to the clear understanding of the Dickey-Wicker amendment put forward by Congress.

To remedy this reinterpretation of the Dickey-Wicker Amendment (DWA), seven senators sent a letter to then Secretary of Human Health and Services, Donna Shalala.  In that letter they stated that “Congress never intended for the National Institutes of Health to give incentives for the killing of human embryos for the purpose of stem cell research.”  The warnings of the senators and the comments from many dissenting parties were ignored by the NIH.

When President Bush took office, he rescinded the Clinton rules and upheld the original interpretation of the DWA.  This ended when Barak Obama became president in 2008.  President Obama revoked President Bush’s Executive Order 13435 (June 22, 2007) and ordered NIH “support and conduct responsible, scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent permitted by law.”

This was the reason for the lawsuit filed by Sherley and his co-plaintiffs.  They wanted the Federal government to simply recognize the law as it was originally written and interpreted.  Unfortunately, the judges ignored all that and went with their own shtick.  This is sad, and it should be remedied, but for now the situation seems to be that Congress’ laws do not mean what they originally say.

New Skin for Claudio


Michele De Luca from the University of Modena and Reggio Emilia in Italy specialize in culturing skin cells to make sheets of skin layers in culture that can be transplanted onto the bodies of patients with skin injuries or skin diseases. Patients with full-thickness burns or other types of injuries can benefit greatly from this type of therapy. Dr. De Luca is also interested in a genetic disease known as epidermolysis bullosa (EB). EB is really a group of diseases of the skin characterized by blistering in response to minor injury, heat, or friction from rubbing, scratching or even adhesive tape. There are four main types of EB and most of them are inherited.

Dr, De Luca had a patient named Claudio who suffered from EB. Claudio had been tortured all his life with huge open wounds all over his body. Dr. De Luca was able to grow Claudio’s skin in culture and form large sheets of skin, but, unfortunately, these skin sheets were just as abnormal his Claudio’s native skin, and the transplanted sheets would have done little good.

To solve this problem, Dr. De Luca used gene therapy to fix the genetic problem in Claudio’s skin cells. Claudio suffered from a mutation in the gene that encodes Laminin 5, a cell adhesion protein that is essential for getting the skin layers to stick together.  In order to fix this mutation, De Luca used a completely novel method for placing genes into cells that included viruses that inactivate themselves once they insert into the genome of the cultured cells, but the inserted gene is still under the control of sequences that cause it to be expressed only in skin cells.

After introducing a normal copy of the laminin 5 gene into Claudio’s cultured skin cells, Dr. De Luca was able to grow Claudio’s skin in cultured into tough, resilient, skin sheets that were then transplanted onto Claudio’s legs. The transplanted skin provided large swaths of normal skin that did not suffer from open wounds or pain. The grafts have now been in place and stable for several years.

The combination of two technologies, gene therapy and tissue engineering gave Claudio a new lease on life. Unfortunately, because genetically engineered cells are, legally speaking, drugs, many new safety criteria must be met before this technology is ready for use in an off-the-shelf kind of treatment for patients.

Wall Street Journal Opines on FDA and Stem Cells


Scott Gottlieb (physician) and Coleen Klasmeier (attorney) have penned an excellent op-ed piece in the Wall Street Journal that tasks the FDA for their unbending regulatory caprice and unwillingness to adapt to the new advances in medicine. It is definitely in line with what Centeno has been saying for these long years. Read it here.

They are reasonable troubled by the DC court’s uncritical acceptance of the FDA’s arguments and note:

“The FDA has repeatedly sought to blur the line between manufacturing medical products and practicing medicine whenever new techniques emerge. But the standard for regulation isn’t whether the agency feels a technique is novel but whether it meets the definition of being a medical product.

Federal regulators have stretched that definition to the point where a reasonable limit no longer exists. The law provided a clear impediment to unrestrained exercise of FDA authority. Something needed to be an “article”—not a medical procedure—in order to become a drug. The constraint that a drug needed to be a “thing” has been read out of the law by FDA, and the district court appears to have accepted that position.

If the FDA’s victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency’s reach.”

They also sadly note:  “Most of the science of using adult stem cells for regenerative medicine is unfolding in Britain, Singapore and Israel precisely because of the FDA’s bent to hold with misgiving anything novel in medicine.”  Reform the FDA.  To do that we need a new president.

Centeno Responds to the FDA: Part 3


In the last post, we saw that Centeno responded to the FDA by noting that in their own history, the FDA regarded cells as drugs by changing the wording in a statute in a manner that did not conform to standard legislative practice and by making a deal with a drug company that involved assigning a status to that product (fast-track) for which it did not qualify. The next cog in the FDA’s regulatory wheel is that of evidence-based medicine (EBM). This is a tough one for me to visit because EBM represents as large part of my own training in research and biomedical sciences. Therefore, Centeno will be calling me to challenge many of my own presuppositions.

A formal definition of EBM isa method that attempts to apply the best available evidence gained from the scientific method to clinical decision-making. EBM does this by assessing the degree of risks and benefits of treatments or a lack of treatment, and diagnostic tests. The ultimate goal of EBM is to help clinicians understand if a treatment will do more good than harm.

This sounds wonderfully academic and objective, and surely EBM provides an excellent method for developing and evaluating new medicines, procedures and devices. However, EBM asserts that this is the ONLY way to perform medical studies.

Centeno at this point makes a very profound historical point. The history of medicine is filled with discoveries that did not utilize the methods of EBM. He gives the following example: Emergency Medicine. Car crash victims are treated with methods that have not been vetted by EBM. If EBM were the rule in the emergency room, most emergency medicine physicians and nurses would have to stand there with their hands tied while the patient on the table dies before them. This suggests that there is more than one way to acquire medical knowledge and test the quality of it.

Historically, there were two schools of thought as to how one should interpret scientific findings. The Bayesian and Frequentist school differed in their approaches to such data. The Bayesian approach comes from Thomas Bayes who argued that future decisions should be dictated largely by past experiences. Thus, for Bayesians, the best way to make a decision lies in mathematical probability calculations that tell you if A is more likely to work better than B, or something like that. Frequentism comes from the work of thinkers such as Aristotle who said that the probable is “that which, for the most part, happens.” The frequentist looks for those events that occur frequently under the controlled conditions found in a laboratory.

In the 1930s, the debate between frequentism and Bayesianism came to a head when Sir Harold Jeffreys, and theoretical physicist who used mathematical models to study the Earth and its solar system, and Sir Ronald Fischer, a population geneticist. Jeffreys used Bayesian probability to construct forma theories of scientific reasoning, but Fischer used frequentism. Because frequentism is very “on” and “off” with respect to its assertions, it seemed more certain. Because frequentism seemed to make a complex work simpler, it won the day because of its perceived explanatory power and elegance. Bayesianism, was viewed as wish-washy and not worth the time of the researcher.

Frequentism works quite well in the laboratory where the conditions are well controlled. However, once the clinical trials go from the laboratory into inbred animals that all have the same genetic background, to people who can differ wildly in their metabolism, digestion, absorption, or receptor binding, receptor densities, or response to receptor binding, such scientific reasoning does seem to represent reality accurately. In order to deal with the shortcomings of frequentism, some clinical researchers has suggested using so-called “adaptive clinical trials” in which the data gathered as the trial progresses are used to change some aspect of the trial midstream.

The real problem with frequentist thinking in medicine is that it tends to cultivate a one-size-fits-all mentality. Centeno uses the following analogy: The average height for men in the US is 5 feet, 9.5 inches. Therefore, if this information was used to make men’s clothes, it would be an unmitigated disaster.

Centeno thinks that this is the entire problem with EBM – its application to medicine that essentially says that there is no other way to treat a patient, and that if the physician does not follow that recommendation, then you are a quack, instead to tailoring your treatment to the individual patient’s needs.

Frequentist thinking also leads to long, massively expensive drug trials that are often unsuccessful that wastes not only gazillions of dollars, but precious time that very sick patients to not have. Furthermore, since universities receive large sums of money from the National Institutes of Health (NIH), they are married to the frequentist system, as are large pharmaceutical companies. Therefore, these two institutions tend to oppose major reform of the FDA.

One other point at this time is this – socialized medicine is frequentism on steroids. If we take the British National Health Service for example, this institution publishes treatment guidelines for a variety of maladies. If the doctor deviates from the treatment protocol, then the NHS will not pay for it. Also, the NHS also specifies who will receive these treatments. It is a cost-analysis that determines if you get treated and what kind of treatment you get, individual variation in patients be damned.

Many medical breakthroughs that led to things such as in vitro fertilization, modern open-heart surgery, and the surgically-implanted plates and screws that stabilize fractures were all developed outside the frequentist system. Instead of working on a narrow clinical trial that includes a handful of people, why not share information about particular drugs and procedures, which the internet allows, and run clinical trials that make sense the observations of a global village of physicians?

An example might be helpful. Hyaluronic acid (HA) is a complex, charged carbohydrate that acts as a lubricant for joints. Arthritis can be treated by injections of HA into arthritic joints and this “WD-40” for the joints help relieve the pain of arthritis and the inflammation associated with it. Physicians who have used HA have shown that it works well for arthritic hips and shoulders as well as knees. According to Centeno, there are some 104 research studies on the use of HA in the hip. However, the FDA will not approve the use of HA outside the knee unless it goes through the same lengthy, expensive trials in which arthritic patients are given placebos that do not help them. Clearly physician experience has shown that HA works outside the knee. Instead of approving it on a limited basis and then subjecting it to past-marketing research, the FDA is stuck in its frequentist way of thinking and this keeps them from seeing the light when it comes to HA.

There is another factor at play here and this is beautifully covered by an article by the Independent Institute. The FDA is motivated to delay or deny potentially useful drugs because of the exposure of their work. Consider the following scenario: If the FDA approves a drug that turns out to be dangerous, victims are hurt and they appear in the press and television. The FDA repents, fires someone and then pulls the drug. If, however, they do not approve a good drug that can save lives, there are no victims, no sob stories in the press and no terrible news stories on MSNBC. Nevertheless these delays have genuine victims. Robert Goldberg of Brandeis University has stated (how exactly he calculated this remains a mystery to me) that the delays in drug and device approvals have cost around 20,000 lives over the past 30 years.

Thus we have a FDA that works with a system that cannot handle the 21st century and the medical advances it will bring.

Centeno Responds: Part 2


In the last post, we saw that the FDA’s illegal fast-track approval of Genzyme’s cell-based Carticel product as a drug set a precedent that cells had to be treated as drugs and any cell-based therapy had to go through the extensive, expensive and invasive approvals for other types of pharmaceuticals.

This move put the kibosh on the development of cell-based therapies, since such therapies would have been massively expensive.

Centeno thinks that the FDA’s move stifled a potential renaissance in American medicine that would have been on par with the discovery of antibiotics. This might be a severe overstatement, but it seems clear to me, at least, that the FDA’s move did slow down the development of cell-based therapies.

Professional societies were no at all pleased with this regulatory move, since it would slow down the availability of therapies for patients. For example, te Society of Clinical Oncology, which represents 30,000 cancer specialists, sent a letter to the FDA on August 10, 1998 that read: “A striking aspect of the FDA’s proposal to regulate stem cell procedures is the virtual absence of any justification for the initiative. The principal “concerns” previously cited by the FDA in support of the new regulatory apparatus are preventing the transmission of communicable diseased and assuring that stem cell procedures are safe and effective.”

Certainly, these are valid concerns, but the letter continued: But, the FDA has adduced no evidence whatever to suggest that communicable diseases are presently being spread through stem cell procedures, or that stem cell transplants are unsafe or ineffective. Instead, the FDA has proposed to subject physicians and facilities performing stem cell procedures to an extraordinarily burdensome and restrictive regulatory regime based solely on theoretical issues.”

Wow! In other words, “your concerns are not real.” Furthermore, “you have no evidence to document your concerns and they only exist as possibilities.” In other words, according to these cancer specialists, the FDA created a policy to fix a problem that did not exist.

Certainly, the FDA could make the argument that the regulation guarantees that such problems will not pop up anytime soon, this misses the point of regulation – to address actual problems and not imaginary ones.

At this point Centeno makes a horrible historical blunder when he mentions the “Bush Administration’s ban on embryonic stem cell research.” For the umpteenth time, “THERE WAS NO BAN ON EMBRYONIC STEM CELL RESEARCH DURING THE BUSH ADMINISTRATION.” There I got that out. There was a moratorium on the use of federal funds for research that derived new embryonic stem cell lines, since such work required the destruction of human embryos. Private funding could fund such work, and embryonic stem cell research that used already established, approved ESC lines was eligible for federal funds. In the meantime, work on adult stem cells advanced during this time and some treatments became available.

Centeno thinks that drug companies supported by universities wanted to offer embryonic stem cells (ESCs) in vials, which would be administered and approved by the FDA in the way any drug would. Adult stem cells, on the other hand, came from the patient’s own body, and therefore, had a rough time fitting into this paradigm. The FDA, therefore, decided the alter the wording of a statute to include adult stem cells.

21 CFR 1271 regulations allowed any cells that came from a patient’s own body (autologous) to be regulated as a transplant or not at all. Therefore, any competitor of Genzyme could simply use their adult stem cell procedures without going through the lengthy and extensive approval process. It also meant that physicians, who are not directly regulated by the FDA, could start their own stem cell procedures without any FDA oversight.

The FDA however, solved this problem by altering one word in the statute from “into another human” to “into a human.” This change was apparently made without the public comment period required by the law. Even though this change seems minor, it means that cells from your own body cannot be placed into you without the FDA’s approval. In this manner, the FDA inserted itself into the lives of doctors.

Mary Ann Chirba, J.D., D.Sc., M.P.H. at the Boston College Law School gave the FDA a screen-full when she used her keyboard to critique the FDA’s language change. She said of this regulatory change that “in revising §1271.3(d) without the benefit of public input, the FDA has fashioned a regulation that imposes real and extensive burdens on patients and providers while achieving little if any benefit — at least with regard to low-risk, autologous adult stem cell therapies.” Not everyone is taking this change lying down.

One point Chirba makes is quite telling. She notes that the FDA has no such regulatory strategy when it comes to in vitro fertilization (IVF) therapies for infertile couples. IVF involves the harvesting of oocytes (eggs) from the presumptive mother and sperm from the presumptive father, the use of these cells to achieve fertilization in the laboratory, culture of the embryos outside the body, and then reintroduction of the cultured embryo into the mother’s body. Note the similarities of this treatment with autologous stem cell treatments – retrieval of cells from the patient, culturing the cells to make something different, but related to the originally harvested cells, and then the transplantation of those cells into the patient. The similarities are uncanny except that the FDA regulates autologous stem cell treatments but not iVF. Confused? Maybe you should be, because I am too.

If the FDA regulated IVF, they would achieve little in the way of safety, but the cost of the procedure would explode (however, the embryos might be better protected, but the FDA seems little concerned with human embryos these days, but that’s for another post).

The contradictory nature of this regulatory change has generated some terrific contradictions. For example, the FDA does not regulate bone marrow transplants, and in some cases, umbilical cord blood is used for such therapies instead of bone marrow.  By 2009, there had been 15,000 cases of umbilical cord blood transplantation, and cord blood was saving lives and was relatively unregulated by the FDA.  Then in 2009, the FDA changed tack and decided that cord blood was a drug and required approval.  Cord blood “drugs” received approval in 2011, but nothing changed with regard to its safety profile and use.  First it’s not a drug then it is; what’s up?

Another example is fat tissue used by plastic surgeons.  Plastic surgeons have been using fat for transplantation for years without FDA approval, but now, according to the FDA, is the fat is broken down in any way before it is reintroduced, then it is a drug.  Your own fat is now a drug!  Ridiculous?  You bet it is!  Then there is Cytori Therapeutics who have designed and manufacture a machine that isolates fat-based stem cells from fat.  According to the FDA, this machine manufactures and drug and must be vetted like a drug.  The machine is approved in Europe, but not in the US because the FDA is too busy sending warning letters to Cytori telling them to cease and desist unless the almighty FDA tells them they can proceed.

There are also some genuine tragedies that come with this stunt pulled by the FDA.  For example, Allosource and Parcell Laboratories process cadaver bone for bone transplants.   However, because the bone contains stem cells, according to the FDA, they are making a drug and require the huge piles of money it takes to receive FDA approval.  Then there is Provenge, a revolutionary treatment for prostate cancer that takes white blood cells from your own body and then reprograms them in culture to attack the prostate cancer.  Thanks to the excessive regulation of the FDA, one dose of Provenge costs $93,000.  Then there is the very sad case of Reprogenesis, who made a stem cell-based treatment for children with Vesicoureteral Reflux or VUR.  Even though the treatment uses the patient’s own stem cells to build a new urinary valve in the ureter, the FDA said that they were making a drug and needed approval for it.  Reprogenesis went bankrupt thanks to the FDA and children with VUR do not have that therapy.

If this sounds nuts, that’s because it is.  Don’t get me wrong, we need the FDA and we need an agency to safeguard the safety and efficacy of the medicines we take, but the FDA is working on a model that is 3-4 decades out of date.  American medicine is missing the renaissance in science because of overregulation and unwise regulation.  It needs to change.

 

Centeno Responds to The DC Court Decision: Part 1


The DC court case that ruled that cells = drugs upheld an injunction placed upon Regenerative Sciences by the FDA to not provide their Regenexx-C treatment unless they sought official FDA approval. Dr. Centeno, one of the major shareholders in Regenerative Sciences and its chief spokesperson, who also developed many of the treatments used at the Colorado clinic, has responded to the court ruling and the FDA in an ebook entitled “The Stem Cells They Don’t Want You to Have.” In our next few posts, we will discuss his response.

According to Centeno, in this country, there are two layers of regulation for medical procedures, treatments, and devices. Federally, the FDA has device and drug laws that they enforce. Their laws dictate what drugs and devices are approved and the clinical uses of these drugs a devices. Secondly, each state has regulations that direct the practice of medicine within their borders.

The FDA regulates those drugs and devices that are used throughout the nations and across state lines. Physicians, however, are not regulated by the FDA. This is an important point, because the FDA does dictate how the physician practices medicine. The state regulates the practice of medicine within its boundaries, but the FDA regulates the drugs and devices used across state lines. These two layers are regulation are meant to provide checks and balances to the regulation of medicine.

The importance of these checks and balances is that the physician is meant to do whatever is necessary to save your life, improve your health, or reverse a particular illness. The FDA does not have to like it, but they do not traditionally have the authority to do anything about it.

The FDA, however, has tried in the past to buck this system. For example, there is a practice in clinical practice known as “off-label” usages of drugs. Such usages involve prescription of a drug for a malady for which the FDA did not provide approval. For example, proton, pump inhibitors, such as omeprazole, for acid reflux disease, have been prescribed off-label because some physicians have noticed that they can quell severe diarrhea. Why they would do this is unclear, but it is the observation that they do. Therefore they are prescribed for such purposes. The FDA is not always alright with that, and in 1978, in United States v. Evers, the FDA sued Dr. Ray Evers for his use of calcium disodium versenate, a drug normally used in metal poisoning, as a treatment for arteriosclerosis. The court found for Evers in this case even though the weight of expert opinion was against the efficacy this drug as a treatment of arteriosclerosis. The Evers case established the ability of physicians to prescribe drugs off-label. In the words of Centeno, the court “preserved as sacred the right of your doctor to prescribe any drug in any way to save your life.”

The FDA, however, is not happy with this arrangement, and has been seeking ways around it. In the 1990s, the FDA attempted to crack down on pharmacies and physicians that “compounded” drugs. If a patient has a medical need that is not met by the available formulations of medicines, then the physician may ask to pharmacy to modify the formulation or combine it some other component. For example, if a medicine is pelleted with a tablet that contains gluten but the patient does not tolerate gluten, then the doctor can ask the pharmacist to prepare a gluten-free version of the medicine. Alternatively, if the patient is an infant and extremely low doses are required for a particular drug, then the doctor may ask the pharmacist to cut the drug with something else to lessen the dosage, or produce very tiny dosages in the traditional form. The FDA attempted to add a section to the Food, Drug and Cosmetic Act to regulate compounding, but they were defeated after a consortium of compounding pharmacies sued the FDA.

In the 1990s, when cells were used to treat patients, the FDA tried a different tact, since it seemed unlikely that they could properly regulate cells. After all, cells are neither drugs nor medical devices. This came to a head in 1995 when Genzyme began to culture the cartilage cells from patients to make a product known as Carticel. Carticel consisted of a patient’s own cells that had been cultured outside the body. Then they would give the cultured cells to a surgeon for implantation into the knee. How could these be regulated as a drug?

The FDA was concerned because culturing cells could introduce animal viruses into them or some other contaminant that could harm people. Therefore, there had to be some way to regulate this product in order to safeguard the health of patients. As you can see, the FDA are not monsters. They do want to help patients, but they are simply overstepping their bounds, according to Centeno.

Back to Carticel. Initially one division of the FDA had granted Genzyme clearance to market Carticel as a medical device. However, another branch of the FDA called the Center for Biologics Evaluation and Research or CBER told Genzyme that they had to have full and clear FDA drug approval in order to market Carticel.

What could Genzyme do? Without FDA approval, they were stuck, but getting FDA approval would require years and millions of dollars. Why FDA required drug approval for something that was not a drug was a mystery, but Genzyme was in no mood for a brawl with the FDA. They had a promising technology, but without approval, they could not sell it, and if they did not sell it, another company would pick up the technology and make it work with the FDA.

Therefore, Genzyme made a deal with the FDA. CBER wanted to call the cell drugs, but they ran into lots of opposition from powerful opponents: The Red Cross, The American Society of Clinical Oncology, The Society for Reproductive Technologies, and the BioPharma Association. According to Centeno, a Genzyme lobbyist told the FDA that they had to regulate cells, otherwise, Genzyme would have no way to protect its investment. The FDA acquiesced with the proviso that it would fast-track Carticel if the FDA was able to regulate cells as drugs.

It was this “Midnight deal,” according to Centeno, that paved the way for the FDA to call cells drugs and regulate them accordingly. Carticel was approved in nine months when the regular time for drug approval was seven years. There was a problem with this fast-track approval: The 21 CFR 601 statute was meant for the approval of drugs for treating critically ill patients. Carticel did not meet this requirement, which makes the use of fast-tracking in this case illegal.

As a result of this deal, other drug companies that developed or were developing cell-based therapies simply fell in line behind Genzyme and went through the FDA process for drug approval of their non-drug-based therapies.  FDA drug approval became, in the words of Centeno, the “gold standard” for cell base-products.

An evaluation of this situation will be discussed in a later post.

DC Court Says that Stem Cells are Drugs


On the 23rd of July, 2012, the US District Court in Washington DC acknowledged the right of the Food and Drug Administration (FDA) to regulate clinical therapies that are made from the patient’s own processed stem cells. This case answered the question, “Does the court agree with the FDA that stem cells are drugs?”

According to the judge, the FDA is right and stem cells cultured outside the body are drugs. This ruling upholds the injunction brought by the FDA against Regenerative Sciences, the Broomfield, Colorado-based clinic that offers the Regenexx stem cell treatment procedure.

The Regenexx procedure uses mesenchymal stem cells that are isolated from patients’ bone marrow. These stem cells are then processed and injected back into the patients to treat joint pain. The FDA has labeled this procedure the “manufacturing, holding for sale, and distribution of an unapproved biological drug product.” In August 2010, the FDA ordered Regenerative Sciences to stop offering the treatment, since they were offering a drug without FDA approval

According Nature magazine science reporter, David Cyanoski, investigations by the FDA that led to the injunction showed that there were flaws in the cell processing protocol that violated the FDA’s regulations that refer to “adulteration.” These regulations are meant to ensure the safety of patients who receive the therapy.

Not surprisingly, academics are praising the decision and a shot across the bow of any enterprising physician who wants to offer stem cell treatments. For example, Jeanne Loring, a regenerative-medicine scientist at the Scripps Research Institute in La Jolla, California, has said that this court decision will send a warning to others who want to offer unapproved stem-cell treatments. In her words: “So many people want to start these companies. They say, ‘FDA? What FDA?’.”

Chris Centeno, the medical director of Regenerative Sciences and one of two majority shareholders, told Nature that he plans to appeal against the ruling. Centeno has replied to the ruling in an internet book entitled “The Stem Cells They Do Not Want You To Have.” Centeno’s main objection during the trial was that the ‘Regenexx’ procedure does not significantly modify the mesenchymal stem cells before they are reinjected into the patient. Therefore, the procedure should be considered a routine medical procedure. The company also argued that because all the processing work is done in Colorado, the procedure should be subject to state law, rather than to regulation by the FDA.

Unfortunately for Centeno, the Ninth Circuit court disagreed with both arguments. According to the court: “the biological characteristics of the cells change during the process.” This and other considerations mean that the cells are more than “minimally manipulated,” which makes them a drug a subject to regulation by the FDA. .

University of Minnesota bioethicist Leigh Turner, agrees with the court on this one. Turner noted: “It is much too simplistic to think that stem cells are removed from the body and then returned to the body without a ‘manufacturing process’ that includes risk of transmission of communicable diseases,” he says. “Maintaining the FDA’s role as watchdog and regulatory authority is imperative.”

The FDA injunction only applies to one of the Regenexx stem-cell products; the Regenexx-C procedure. In this procedure, the bone marrow mesenchymal stem cells are processed for 4–6 weeks. The Regenexx-C procedure will still be available, since after the 2010 injunction, the company moved its treatment location to an affiliated Cayman Island clinic.

Centeno plans to continue providing the other three procedures; Regenexx-SD, Regenexx-AD, and Regenexx-SCP, for joint pain, in the United States. In those treatments, the cells are reinjected within one-two days. Centeno claims that those cells are “minimally manipulated”, and that the FDA sees them as the “practice of medicine” and “has no issues” with them.

According the Nature’s David Cyanoski, until July 25th of this year, a graphic on the Regenerative Sciences website claimed that these three other procedures were “FDA approved.” However, the FDA has not approved these three procedures, and Centeno was not able to provide documentation to support his claims that the agency views the three treatments as outside its purview. This graphic was removed from the Regenexx website after Nature’s enquiries.

Stem-cell ethics and regulation expert, Doug Sipp, who is at the RIKEN Centre for Developmental Biology in Kobe, Japan, is concerned that this ruling will simply drive entrepreneurs to move their stem cell clinics outside the United States to avoid regulation. Indeed, Regenerative Sciences has done just that by setting up their Regenexx-C procedure in the Cayman Islands. According to Sipp, “Other US stem-cell outfits have close ties with partner clinics in Mexico and other neighboring countries, which are traditionally regulatory havens for other forms of fringe medicine as well. I suppose it will be business as usual in such places,”
We will have more to say about this in the days to come, but for now, this is it.

Letter from a Nurse With MS – FDA’s Cells = Drugs Hurts People


At the Regenexx Blog site is a letter from a Registered Nurse who has Multiple Sclerosis. The drugs for MS do little to stop the progression of the disease and they have remarkably bad side effect. On top of that they are very expensive. Despite some exceedingly robust results with animals models with a form of MS and stem cell treatments, and human clinical trials with a patient’s own mesenchymal stem cells, the FDA has yet to budge because according to your FDA cells = drugs and they get to regulate them into the ground.

This letter from the nurse really nails it on the head and shows how the FDA’s policy is a) crap, and b) actively hurting sick people. Read about it here, and then write your Congressperson.

British Hospital Refuses to Hydrate a Dehydrated Patient: Hospital Administrators Hide and the Patient Died


I lived in Great Britain for three years (1994-1997) and have first-hand experience with the National Health Service. Needless to say, I was not impressed. They do fine with child-birth and then abandon older people to their own fate. Nationalized health care is rationed health and do not let anyone tell you differently. When you become old enough, the health service you spent your whole life paying into abandons you in your time of greatest need. Now we have a stark example of this.

Wesley Smith has a blog entry on this. It will make you sick. According to the British newspaper, The Daily Mail, a desperate hospital patient died after he was denied hydration by the hospital. To get hydration, he called the police and begged them to bring him a drink. The patient, Kane Gorny, 22, needed drugs to regulate his hormone levels after successfully beating brain cancer months earlier. However, during a further hospital stay nurses forgot to give him his medication and he became so delirious he was forced to call 999 (the UK equivalent of 911) to ask for help. The police officers went to St George’s Hospital in Tooting, south London, but were turned away by staff who insisted that Mr Gorny was fine. Gorny had been admitted in May 2009 to undergo hip replacement surgery after his bones became brittle. This was a side-effect of his prescribed steroids. Kane’s mother, Rita Cronin, said she spent hours trying to convince hospital staff that Kane needed urgent attention but was repeatedly “told he was alright.” See http://www.dailymail.co.uk/news/article-2167643/Patient-dying-thirst-rang-999-Inquest-hears-mothers-fury-nurses-neglected-son.html for the article.

An inquiry into the matter has been initiated by the Crown Prosecution Service at the behest of Gorny’s parents.  Kane Gorny had surgery on his pituitary gland, and he had problems regulating his levels of salt and water in his system.  Pituitary surgery commonly damages that back part of the pituitary gland and this prevents the release of antidiuretic hormone (ADH, also known as vasopressin).  Without ADH, patients have a condition called diabetes insipidus, and they need to take exogenous ADH.  Without exogenous ADH, the patient will urinated themselves to death.  The nurses failed to give him his medicine, and dismissed his concerns and the concerns of his mother.  Because he was so dehydrated, Kane called the police to get some fluid, but the nurses at the hospital dismissed them.  He died from dehydration and abnormally sodium levels.  His death was almost certainly a painful one.

The inquiry will probably result in some nurses being sacked (British for fired), but the status quo will probably be maintained.  This kind of abuse is more routine in the British Health System than they would probably admit.  Doctors have even started to prescribe water to elderly patients to prevent them from dying from dehydration.  Is this what we want for the US?

Obamacare: The Aftermath


Since many have asked my what I think about Obamacare and the recent Supreme Court ruling, I thought that I might provide my views on the topic.

In the first place, the law is obviously unconstitutional. The federal government cannot compel you to buy something. There is simply no universe in which someone can read our Constitution and come to the conclusion that the Constitution gives the government that power over its citizens.

Secondly, if Obamacare is a tax, then the lawsuit before the Supreme Court would have been dismissed, because according to the Anti-Injunction Act Donald Verrilli argued before the Supreme Court that the individual mandate is NOT a tax. However, in order to find the bill constitutional, Roberts had to treat it as though it was a tax. But wait a minute. The Anti-Injunction Act says that you cannot contest a tax bill until the tax is paid. Therefore, if Obamacare was a tax, then the case should have been dismissed til the tax was collected. Thus for the sake constitutionality, Obamacare is a tax, but for the sake of litigating it, it is not a tax. Roberts tried to have it both ways, but he can’t. This is the reason why legal pundits all over the US are troubled by Robert’s garbled, self-contradictory opinion. If this was a principled ruling then why did it make no internal sense.

Third, Obamacare is unworkable. In the words of Holman Jenkins of the Wall Street Journal, Obamacare is “upheld and doomed.” The problems with Obamacare are four-fold and they are :

1. Taxes

Besides being a massive federal power grab, Obamacare contains one of the largest tax increases ever imposed on the American economy. These tax increases come at a time when job growth should be the nation’s number one priority.. The tax sections of Obamacare begins with an increase in the Medicare payroll tax of 0.9 percent for individuals with incomes above $200,000 ($250,000 for couples) in 2013. Needless to say, this tax will depress the demand for labor at a time when job creation is critical in order to for jump-start the economy. Some might think that this tax will not hit the middle class because of the relatively high initial income thresholds, but they are wrong. These income thresholds were purposely not indexed to inflation. Therefore, as the years pass, more and more middle-income families will cross the thresholds because of normal wage growth.

Obamacare also includes an additional 3.8 percent tax on investment income; a new 2.3 percent excise tax on medical devices that will reduce the size of the industry. It also includes taxes on the drug and insurance industry that will be passed on to consumers in the form of higher premiums; and a tax on high-premium insurance plans that will also be passed on to consumers.

2. Deficits and Debt

Obamacare will exacerbate our nation’s already alarming entitlement spending and debt crises. The dramatic rise in spending on Medicare and Medicaid already is pushing the federal budget to the breaking point. Obamacare makes the problem much worse since it adds two new additional entitlement programs in the form of a massive Medicaid expansion and a new premium credit entitlement for households with incomes between 138 percent and 400 percent of the federal poverty level. These two entitlement expansions are expected to add a minimum of 35 million Americans to the entitlement rolls when phased in, at an expense of more than $200 billion annually by the end of the decade (CBO, Letter to House Speaker Nancy Pelosi, March 20, 2010, Table 4.).

Obamacare was sold by means of offsetting cuts in Medicare that supposedly would pay for it. Unfortunately, the Medicare cuts have been exposed as unrealistic because they would result in Medicare paying even less for medical services than Medicaid does today. (John D. Shatto and M. Kent Clemens, “Projected Medicare Expenditures Under Illustrative Scenarios with Alternative Payment Updates to Medicare Providers,” Office of the Actuary, Centers for Medicare and Medicaid Services, May 18, 201). This would severely jeopardize seniors’ access to care. Even worse, the offsetting cuts were made, the savings are double-counted under Obamacare, and are used once to pay for future Medicare commitments that are today counted as unfunded governmental liabilities, and then a second time to supposedly cover the costs of Obamacare’s entitlement expansions (Charles Blahous, “The Fiscal Consequences of the Affordable Care Act,” The Mercatus Center of George Mason University, 2012). Since money cannot be used twice, Obamacare will add hundreds of billions of dollars in new debts this decade, and trillions over the longer term (James C. Capretta, “The Medicare Trustees’ Report and the $8.1 Trillion Double-Count,” The Weekly Standard Blog, April 24, 2012).

3. Individual Mandate

The individual mandate hands immense regulatory power to the Department of Health and Human Services (HHS). According to Obamacare, HHS controls just about every aspect of the nation’s health system. In January 2012, the Administration announced that it planned to use that power to impose new benefit requirements on all employer-sponsored insurance in the name of “preventive health services” (now frequently termed the “HHS mandate”).

Additionally, the regulations issued by the Administration in this regard would require all employers, including religious employers such as Catholic hospitals and universities, to cover abortifacient products, contraceptives, and sterilization procedures in the health plans they offer to workers. By requiring all employers to offer these products and services in their health insurance policies, they would directly violate the religious liberty rights of thousands of religious institutions around the country.

4. The Bureaucratic Micromanagement of American Health Care

The bulk of Obamacare is based on the theory that the federal government has the capacity and know-how to micromanage American health care. This is the basis for the provisions that establish an unaccountable and unelected board—the Independent Payment Advisory Board (IPAB)—to oversee all aspects of how Medicare is run. It is also the theory behind Accountable Care Organizations (ACOs), which are authorized in Obamacare to give the federal government a new role in influencing how doctors and hospitals are organized to deliver care to seniors.

Unfortunately and contrary to socialistic preconceptions, the government is NOT adept at micromanaging how health care or any other aspect of people’s lives. When the government is given this much authority and discretion, it does not result in higher-quality care for patients. Instead, it leads to price controls and one-size-fits-all regulations that misallocate resources and lead to access problems. Obamacare compounds the problem since it creates massive new and costly bureaucracies at the federal and state levels of government that will become permanent and unresponsive centers of power. The IRS and HHS will grow. A new agency in HHS is slated to spend $10 billion supposedly testing new ideas, but already there is indication that the money is being wasted on projects driven more by politics than substance.

Obamacare is also pours hundreds of millions of dollars into the states to coax them into building the “exchanges” that will become the foundation of the Obamacare edifice. These exchanges, far from fulfilling the supposed mission of fostering a dynamic marketplace, will be the means by which the federal government will extend its reach to every corner of the health sector. Every American who does not obtain his or her insurance through an employer will have little choice but to go through Obamacare’s exchanges.   It will only be a matter of time before the federal government uses its new powers to impose even more top-down cost controls on the health system, to the detriment of the quality of American health care.

Obamacare is a disaster. Had the Supreme Court ruled properly, we would be out of this mess, but as it sits now, repeal – complete and total repeal – is the only answer.

The FDA is Responsible for the Drug Shortages


The Food and Drug Administration (FDA) has implemented extremely restrictive drug policies that are generating drug shortages across the nation. According to the Regenexx blog, clinicians all over the United States have been feeling the effects of this pinch for some time.

Centeno gives the following example: “we were paying about $1 a bottle for local anesthetic, now when we can find it-that same bottle is often $4 a bottle.” As you might guess, this is having a significant effect on patient care, since surgery centers cannot get their hands on certain drugs. Cancer patients have been dramatically affected, since stocks of cheap, generic drugs are drying up.

On his blog, Centeno predicted that these shortages were due to “an ascendant hyper-regulatory FDA.” As it turns out, Centeno’s instincts were dead on. A Congressional hearing has confirmed that the FDA is responsible for the drug shortages. The “new FDA” focuses on reducing the so-called “type 1 regulatory” errors. Type 1 regulatory errors occur if a dangerous drug is allowed to go through market. It is certainly a proper function of the FDA to prevent type 1 regulatory errors. However, by overly focusing on type 1 regulatory errors, the agency is guilty of type 2 errors, in which good drugs are from the market.

The number of people harmed by type 2 errors is very large indeed. One estimate puts the number at 82,000 lives a year. Forbes Magazine documented the enormous rise in Warning Letters issued by the FDA. These Warning Letters have essentially shut down the production of generic drugs. These factories were shut down not because there was an actual problem, but because of theoretical risks due to current Good Manufacturing Practice violations.

The FDA employees that issued the letters did not take into account the consequences of their actions; namely that entire factories would have to shut down. A fair number of these manufacturers may or may not be able to reopen their production lines for these cheap medications because of the increased regulatory costs. Some of these companies may even have had to build new facilities. Many companies will simply drop the production line and this means less generic drugs. Also for many of these drugs, there are no brand name alternatives anymore, and the consequences of all this is that our hyper-regulatory FDA that has chosen to focus on reducing one type of regulatory error and by being only focused in one direction, they place the public’s health at risk.

What is the solution? We need a FDA that is as concerned with type 1 errors as they are with type 2 errors. This will balance these concerns so that the public is as protected from bad drugs as much as it’s protected from delays in promising therapies or shortages of generic drugs.

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’S IND FOR SPINAL CORD INJURY PLACED ON HOLD


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.”