1893
Alfred Werner proposed the theory of metal-ligand binding (“the pincer-like fashion”), which provided the foundation for modern chelation chemistry and development of treatment.

1930s
The textile industry required a chelating agent to remove calcium during textile processing and this led to the synthesis of polyamino-carboxylic acids, one of which was EDTA. A patent was filed for EDTA in Germany in 1935.

1940s
Martin Rubin, PhD, professor at Georgetown University, who was involved in getting a patent for EDTA (along with chemist Frederick Bersworth), discovered its biological effects on calcium homeostasis. This led to its laboratory use as an anticoagulant, for which it is still used today (“purple-top tubes”).  Dr. Rubin helped to achieve approval by the FDA  for the treatment of lead poisoning (CaEDTA) and hypercalcemia (disodiumEDTA), and later collected the world literature on chelation.

1950s
Norman E. Clarke, Sr. and Albert Boyle separately published several articles showing improvement in patients with heart disease who were being treated for lead poisoning.

Foreman reported that high doses of disodium EDTA over a short period of time can cause kidney damage, leading to the development of safe treatment protocols.

1960s
In 1960, Dr. Marvin Seven and other authors edited a book entitled “Metal Binding in Medicine”, which contained papers on chelation that had been presented at two major symposia. Dr. Seven, who was associated with the National Institutes of Health, was killed in auto accident in 1961. This was considered by many to be a major blow to the development of EDTA chelation therapy, because he was a leading advocate of the therapy.

Kitchell and Meltzer wrote several articles reporting on positive effects of EDTA treatment for heart disease but their last article had a negative conclusion(not supported by their reported data), which discouraged further research by conventional doctors. A 1980’s re-examination and critique pointing out glaring errors in this negative article, by Cranton and Frackelton, was ignored by mainstream medicine.

Ray Evers and Carlos Lamar each collected huge volumes of anecdotal data showing vascular improvements with chelation therapy.  Lamar published his experiences in a series of articles, particularly documenting the salvage of legs with diabetic peripheral vascular disease.  Evers won a precedent-setting court case establishing that once a drug is approved for any purpose, it can be used for other indications at the discretion of a physician, which allowed the use of EDTA for vascular disease as well as for the use of dozens of other drugs by all American specialists.

In 1969, Abbott’s patent for EDTA expired, which resulted in decreased motivation to promote EDTA as a treatment for cardiovascular disease.

1970s
The American Institute of Medical Preventics, later called the American College for the Advancement in Medicine (ACAM), was formed in 1973 by Harold Harper, Ross and Garry Gordon and others to promote and teach chelation therapy. Since that time, ACAM has sponsored conferences and workshops on cutting edge subjects involving nutritional medicine and chelation therapy twice a year. Many physicians were trained in the safe administration of EDTA chelation therapy.

Garry Gordon and Robert Vance wrote an article about the mechanisms of action of EDTA chelation therapy.

Bruce Halstead wrote the book Scientific Basis of Chelation Therapy, This book was later updated by Ted Rozema.

1980s
Richard Casdorph, a practicing cardiologist, showed improvements in ejection fractions of the heart and in cerebral blood flow with chelation therapy in several articles.

McDonagh, Rudolph, and Cheraskin published about 30 articles documenting various positive effects with chelation therapy, including improvement in lipids, carotid blood flow, and lung function and no adverse effect on bone density.  This group and Cranton each wrote articles showing no problems with kidney function in patients treated with EDTA according to the published protocol.

The American Medical Association called for studies to see if chelation worked.  At the same time, conventional cardiologists wrote several editorials against the therapy.

The American Board of Chelation Therapy in 1983 was formed to certify doctors who give the therapy. It was later called the American Board of Clinical Metal Toxicology. ACAM also certified doctors who took its workshop on chelation therapy and passed its written and oral examinations.

The Great Lakes College of Clinical Medicine, later called the International College of Integrative Medicine (ICIM) was formed in 1983 to teach and do research on chelation and other integrative therapies.

After complex negotiations, in the late 1980’sWalter Reed Army Hospital agreed to do a randomized clinical trial on EDTA chelation therapy, but part way through the study it was discontinued, allegedly because the investigators were called to serve in the Gulf war and did not return to complete the study.

Frackelton and Cranton published a landmark study about free radical control as the primary mechanism for chelation therapy in 1984.

Olszewer and Carter published a study in in 1988 in Medical Hypothesis documenting 87% of vascular patients showing improvement with chelation therapy.  They later published a small cross-over clinical trial in 1990, documenting significant results in peripheral vascular disease, in the Journal of the National Medical Association.

Arlene Brecher lectured throughout the country and wrote a popular book (Forty Something Forever) promoting chelation therapy from the patient’s point of view.

Blumer and Cranton raised the possibility that EDTA therapy might prevent cancer in a population exposed to environmental lead exposure in a study with an 18-year follow-up.

1990s
Three groups of cardiovascular surgeons published small clinical trials on chelation therapy.  None had enough subjects to come close to clinical significance.  All were severely criticized in letters to the editor because of procedural errors.  All came to negative conclusions.  One even admitted that their purpose was to disprove the therapy.  At the initiative of Claus Hancke, the Guldager study was criticized for its shortcomings by the Danish supreme court.  Hancke and Flytlie published an article showing that 58/65 patients on the waiting list for cardiac bypass and 24/27 peripheral vascular patients also on a surgical waiting list were able to cancel their surgeries after receiving EDTA chelation therapy.

Peter van der Schaar, a Dutch cardiovascular surgeon, published several favorable studies and wrote a massive textbook on the therapy, recently in its 10th edition.

Michael Schachter had an article published titled: “Overview, Historical Background and Current Status of EDTA Chelation Therapy for Atherosclerosis” in 1996.

Elmer Cranton published a Textbook on Chelation Therapy, into its 2nd edition in 2001.

Terry Chappell published two meta-analyses summarizing the literature to date and coming to the conclusion that treatment with EDTA chelation therapy was very closely correlated to measurable improvement in vascular function

Opponents of chelation therapy, as well as almost all alternative therapies, call themselves “quackbusters”.  This small group of doctors has infiltrated the Federation of State Medical Boards and travels around the country making formal complaints about doctors who provide the therapy.

They tried to outlaw the therapy in California.  ACAM testified in defense of chelation and the California Medical Board voted down the proposal.

The Federal Trade Commission filed a complaint against ACAM for making a claim in a brochure that chelation was effective for vascular disease.  ACAM submitted almost 100 articles in support of the claim, but the FTC insisted that a large randomized trial was required to make that claim.  ACAM finally gave up after spending a million dollars in legal fees and signed a consent order saying they would not make such a claim any more, based on the evidence at that time.

Articles began appearing in the conventional medical literature that too much heart surgery was being done in the United States.  The outcomes from medical therapy were just as good for many patients, if not better.

Steve Olmstead, a research cardiologist from the University of Washington Medical School, wrote a 100 page monograph discussing in detail the mechanisms, chemistry, and scientific evidence on chelation therapy.  One of his conclusions was that the preponderance of the evidence was in favor of the therapy for peripheral vascular disease.  This document was distributed to every medical school library in the United States.

2000s
Representative Daniel Burton, chairman of the Congressional Oversight Committee held a hearing with testimony from the NIH and from experienced chelation physicians.  The conclusion was that a large study was clearly indicated.  Subsequently, the NIH sent out a call for proposals.  A review panel turned down the first proposal, but approved the second one, called the Trial to Assess Chelation Therapy (TACT).  The chief investigator is Gervasio A. Lamas, who is a world-renowned researcher.  Several prominent medical schools (Miami, Duke, Harvard) and experienced chelation physicians agreed to participate.

Several articles appeared in major journals showing that even small amounts of lead can increase the risk for hypertension and vascular disease.

Lin and Lin Tan published a leading article in the New England Journal of Medicinethat chelation can improve moderate non-diabetic kidney failure, presumably by removing lead and improving circulation to the kidneys.

Terry Chappell and seven colleagues published a study showing that patients with known vascular disease treated with chelation therapy had a much lower incidence of subsequent cardiac events, such as heart attacks and the need for surgery, than a comparable group of patients treated with conventional cardiac care.  These were the same end points as TACT, but the study was much smaller and was not a randomized, double-blind study.

2010s
It was reported by the Center for Disease Control (CDC) that a child died after receiving the wrong medication, disodium EDTA, in a short intravenous push.  It is very important to know that calcium EDTA, which is approved to treat lead toxicity can be given as a short IV push, but that disodium EDTA, which has been described in this timeline as a potential treatment for vascular disease, must always be given by a slow intravenous drip, at a rate no more than 1 gram per hour. Otherwise, the calcium blood level can drop dangerously fast.  The unfortunate child was given the wrong preparation, and that is the reason for the death.

Because many cardiologists discouraged patients from participating in TACT, enrollment proceeded slowly.  For several months, the study was delayed because a complaint by the “quackbusters” saying that it should be stopped immediately. The same group convinced a reporter from the Chicago Tribune to write a negative article about the study, even though no data had yet been released.  However, after seven years the study was finally completed on October 31, 2011.  The findings of the study are to be presented at the American Heart Association meeting in Los Angeles on November 4, 2012.  All we know at this point is that over 1700 patients enrolled nationwide, and the safety committee, which was active throughout the study, found no concerns for safety, using the study protocol.

Virtually all of the studies noted in the timeline used intravenous disodium EDTA with various vitamins and minerals.  The protocol for the safe administration of intravenous EDTA chelation therapy has been published by ACAM and ICIM in their training courses, and is used in certifications by ACAM and ABCMT.  Despite numerous claims, that oral EDTA might be similarly effective, there is no published evidence that oral EDTA might be helpful for treating vascular disease. Oral EDTA is only about 5% absorbed, which might make it useful for prevention for those exposed to high levels of lead on an ongoing basis, but most doctors who utilize intravenous disodium EDTA for vascular disease do not recommend oral EDTA for primary treatment.

The references for the articles cited in this timeline are available in Schachter’s historical article, in Chappell’s meta-analysis, and from L. Terry Chappell at P.O. Box 248, Bluffton, Ohio 45817 or at lterryc@wcoil.com.  A good number of additional articles and events were not included in the timeline for lack of space.