1860-1979 1980-1991 1991-1993 1993-1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Autism/Thimerosal Timeline 1860-1979

Excerpt from Autism Facts.com

1860's
The first methylmercury compounds were synthesized in a chemical laboratory in London in the 1860's. Two of the laboratory technicians died of methylmercury poisoning. This so shocked the chemical community that methylmercury compounds were given a wide berth for the rest of the century.

Early 1900's

The potent anti-fungal properties of mercury were discovered, leading to applications to seed grains, especially for cereal crops. Despite the widespread use, few cases of poisoning were reported for the first half of the twentieth century.

1920's
Thimerosal was developed by Dr. Morris Selig Kharasch, a chemist and Eli Lilly Pharmaceutical Company fellow.

June 27, 1927
Dr. Morris Selig Kharasch filed for a patent for what he described as an alkyl mercuric sulfar compound (Thimerosal), which he felt could be used as an antiseptic and antibacterial product.

June 5, 1928
The patent for Dr. Morris Selig Kharasch's new product, Thimerosal, was issued.

1929
Dr. K. C. Smithburn, out of sheer desperation of having nothing to cure his patients, injected 22 patients who were dying of meningitis with Thimerosal. The patients received up to 10 mgs. of Thimerosal per kilogram intravenously. Two of the patients developed phlebitis or sloughing of the skin. Sloughing of the skin is essentially the break down of the skin itself. The study was not meant to examine toxicity. Seven of the 22 patients died within one day. The specific clinical assessments were not described and no laboratory studies were reported. All of the patients died from the meningitis and the doctor reported that they did not develop symptoms of shock before they died.

October 1929
Eli Lilly and Company registered Thimerosal under the trade name "Merthiolate".

1930
Dr. Powell and Dr. Jamieson of Eli Lilly refer to Dr. Smithburn's study of injecting meningitis patients with Thimerosal in their published paper titled, "Merthiolate as a Germicide" which appeared in the "American Journal of Hygiene" and acknowledge that Dr. Smithburn felt that:

• "...beneficial effects of the drug were not definitely proven."

They also noted that:

• "...a wide range of toxicity and injury tests should be done."

The study did not examine toxicity, nor were any clinical assessments or laboratory studies reported. Still, they used Dr. Smithburn's experience as proof that Thimerosal was safe for humans
.
Eli Lilly never allowed the Food and Drug Administration to see the study and never informed the FDA of the highly questionable methods they used to determine the safety of Thimerosal, which was based on Dr. Smithburn's injection of Thimerosal into the dying patients. Because the patients all died, some very quickly after receiving Thimerosal, there was no time to evaluate side effects or reactions.

April 24, 1930
An Eli Lilly intra-office memo from Retter to Rhodebamel stated:

• "...in view of our experience with the merthiolate solution, we have to know pretty definitely what to expect from merthiolate ointment and jelly before they are put on the market...Can we expect to have the stronger ointment and jelly used without complaint which attended the use of solution in the same strengths?...Our experience with the solution ought to serve as a warning and certainly in the face of that warning we ought not to advocate the use of the stronger products without some pretty definite evidence that we will not repeat our solution experience."

1931
Some vaccines begin to contain Thimerosal.
Dr. Kharasch filed a new patent application because he reformulated the product to:

• "...stabilize Merthiolate due to its tendency to acquire "certain burning qualities"."

September 1932
In a paper published by Eli Lilly researchers titled, "Merthiolate as a Skin Disinfectant", one researcher noted adverse reactions:

• "Reimann has reported that some individuals display a sensitiveness to thio [thimerosal] compounds, which is characterized by reddening of the treated area and the appearance of small papules and vesicles."

September 31, 1934
An article appears in "The American Journal of Hygiene" called "The Bactericidal and Antiseptic Action of Preservatives Frequently Used in Biological Products, and the Effect of these Preservatives on the Potencies of These Products" by Dr. Carolyn Rosenstein:

• "...little is known about the mercuric compounds when innoculated (injected) into humans. It is therefore preferable to use the minimum amount of this preservative necessary to maintain the sterility of the product."

1935
A study of the effectiveness of Thimerosal in killing staphylococcus bacteria on chick tissue is done. The study determined that Thimerosal was 35 times more toxic to the heart tissue it was meant to protect than the bacteria it was meant to kill.

July 22, 1935
The Director of Biological Services of the Pittman-Moore Company to Dr. W.A. Jamieson, Director of Biological Services at Eli Lilly stated:

• "We have obtained marked local reaction in about 50 percent of the dogs injected with serum containing dilutions of Merthiolate varying from 1 in 40,000 to 1 in 5,000, and we have demonstrated conclusively that there is no connection between the lot of serum and the reaction. In other words, Merthiolate is unsatisfactory as a preservative for serum intended for use on dogs. I might say that we have tested Merthiolate on humans and find that it gives a more marked local reaction than does phenol and tricresol."

During the 1930's
Both doctors Leo Kanner and Hans Asperger begin observing a newly discovered neurological disorder found in children. Leo Kanner called it Autism and he described what we know today as more severe or Classic Autism. Hans Asperger, a french doctor in Austria, reported less severe symptoms with normal to high intelligence levels. His discovered disorder is called Asperger's Syndrome.

1940's
There was a recognition of the toxicity of inorganic mercury in calomel used to treat ailments. Before this point, calomel-based teething powders caused many cases of mercury poisoning in infants and children in what was called acrodynia, or pink disease.

Children were receiving the DTP and smallpox vaccines. The DTP, Flu and Tetanus vaccines contain Thimerosal at 25 mcgs. of mercury per shot. The DTP was the only mercury containing vaccine routinely given to young children. The rabies vaccine was only given as needed.

December 1941
Dr. J. H. Mitchell in a lecture before the American Academy of Dermatology in New York stated that he had observed a number of cases of severe dermatitis following the treatment of dermatophytosis with preparations of Merthiolate.

1942
An Army doctor in Baltimore, MD, Dr. Francis A. Ellis published a paper raising concerns about Thimerosal:

• "We have investigated 5 patients with dermatitis due to Merthiolate and found that 4 were sensitive to Merthiolate and not to any other organic or inorganic mercury compounds with which they were tested...in performing routine patch tests with 10% ammoniated mercury ointment and 10% salicylic acid ointment he obtained relatively few positive reactions, but if the two were combined, then 50% of all patients tested gave positive reactions."

1943
Dr. Leo Kanner, child psychologist, described in a published study 11 cases of a new mental disorder in children that he described as being self-absorbed, detached from other people and using repetitive and bizarre behaviors. Kanner and other doctors believed it was an early-onset adult-type psychoses due to its similarities to adult schizophrenia. Kanner theorized that "Refrigerator Mothers" were the cause of autism. He called the disorder "early infantile autism". Pediatricians blamed mothers for decades.

Dr. Francis Ellis published a case report in the "Archives of Ophthalmology" stating that Merthiolate is capable of causing an inflammation of the mucous membrane in patients who are sensitive to the drug. He recommended that Merthiolate ophthalmic ointment should not be used in or about the eye unless a patch test shows the patient is not sensitive to the ointment and that the package insert should be labeled to warn consumers that such tests should be used before using the ointment. Since a patient may become sensitized to Merthiolate while using the ointment, it may be advisable to withdraw this product from the market before a case of permanent ocular damage occurs.

1944
Hans Asperger published his paper on a group of children he described as being of normal to high intelligence who were naive, having an intense interest in particular subjects, poor coordination and inappropriate social approaches to others. He believed his syndrome was separate from Kanner's but noted many similarities.

1947
A Paper titled, "The Sensitizing Factor in Merthiolate" published by Dr. Francis A. Ellis, reported that Merthiolate was causing dermatitis in his patients. He concluded:

• "No eruptions or reactions have been observed or reported to Merthiolate internally, but it may be dangerous to inject serum containing Merthiolate into a patient sensitive to Merthiolate."

1948
A paper titled, "Reaction Following the Use of Tr. Merthiolate" from Eli Lilly's files by an Arizona doctor, H.D. Cogswell, reported the case of a woman who suffered repeated multiple reactions to Merthiolate applied to her skin prior to surgery. She reportedly suffered chills and fevers and had small vesicles and erythema in the area of her Merthiolate applications. After her recovery, the patient indicated that the ulcer for which she was being surgically treated appeared after repeated application of a tincture of Merthiolate. She continued applying the Merthiolate until her skin became too raw and painful to continue use, and then sought medical care.

A study is published in the "Journal of the American Medical Association" titled, "The Bacteriostatic and Bactericidal Actions of Some Mercurial Compounds on Hemolytic Streptococci" in which the authors argued that Thimerosal was ineffective as a disinfectant, germicide, and antiseptic. They cited 8 studies from 1928, 1935, 1937, 1938 and 1944 which all held the same conclusions.

1950
In Eli Lilly's files, a New York Academy of Sciences article by Dr. John H. Brewer entitled, "Mercurials as Antiseptics" found that Merthiolate:

• "...is toxic when injected parenterally and therefore cannot be used in chemotherapy."

1953
Dr. Josef Warkany and Donald Hubbard in Cincinnati, Ohio reported a study on acrodynia, Pink disease, caused by mercury poisoning. They stated:

• "In several children of our series and in some recently reported, various immunization procedures preceded the onset of acrodynia in addition to mercurial exposure. This could be purely coincidental or the vaccination material may play a role as an accessory factor. It is noteworthy that many vaccines and sera contain small amounts of mercury as preservatives which are injected together with the biological material."

1954
Kanner, realizing that evidence showed that the brothers and sisters of autistic children were often well-adjusted, high functioning children, began to waver in his blaming the mothers. He believed that the development of autism was also genetic, as well as from bad parenting. But, psychoanalyst Bruno Bettleheim insisted that the autistic child was behaving in abnormal ways in retaliation against a rejecting mother who failed to provide enough love or attention.

Late 1950's
Evidence emerged of environmental damage with the use of mercury-treated grain. It was observed in Sweden that predatory birds were developing neurological disorders after consuming small animals that consumed the seed grain. The analysis of the birds indicated a sharp rise in mercury levels.

The Japanese health authorities in Minimata knew for some time that fisherman and their families were suffering with neurological disease and had signs of incoordination, constricted visual fields, and numbness in the extremities. A visiting Scotish physician recognized the neurological signs and symptoms as the same as occupational methyl mercury poisoning he had seen in England in 1939. Eventually the source was traced to a factory manufacturing acetaldehyde, where mercury compounds were used as a catalyst. The producers were unaware that the process converted some of the mercury to methylmercury which was discharged into Minimata Bay. The methylmercury released into the ocean bay contaminated the fish that were caught by the fishermen.

Late 1950's and 1960's
Serious outbreaks of alkyl mercury poisoning (methylmercury) erupted in several developing countries with seed grains treated with mercury.

1960's
Researchers in Europe and the United States began to believe that autism was caused by developmental disorders that were either present from birth or that developed early in childhood.

1963
The measles vaccine was introduced. It did not contain Thimerosal.

1964
Bernard Rimland, Ph.D. and father of an autistic child disproved the "rejecting parent" theory in his landmark book, "Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior", having documented the similarities between brain injured children and autistic children. His work pointed research toward investigating the biological mechanisms underlying the brain and immune dysfunction symptoms.

1965
Bernard Rimland, Ph.D. establishes the Autistic Society of America.

1967
The mumps vaccine was introduced. It did not contain Thimerosal.

Bernard Rimland, Ph.D. established the Autism Research Institute and began distributing questionnaires to parents of autistic children.

Autism appeared for the first time in the 8th edition of ICD Codes for diagnosing. It listed "infantile autism" as a form of schizophrenia.

Nelson and Gottshall with the Division of Biologic Products, Bureau of Laboratories, Michigan Department of Public Health published a study called, "Enhanced Toxicity for Mice of Pertussis Vaccines When Preserved with Merthiolate" in "Applied Microbiology". They stated:

• "Pertussis vaccines preserved with 0.01% Merthiolate are more toxic for mice than unpreserved vaccines prepared with the same parent concentrate and containing the same number of organisms....An increase in mortality was observed when Merthiolate was injected separately, before or after an unpreserved saline suspension of pertussis vaccine."

The Medical/Science Department of Eli Lilly & Company requests that the claim "non-toxic" on Thimerosal labels be deleted in the next printing run.

The draft label for Eli Lilly & Company's Thimerosal label changed to "non-irritating to body tissues" and non-toxic was omitted.

1968
Rho-GAM is introduced as a shot given to women who are Rh-Negative. The shot is to be given once after giving birth. The shot contains 10.5 mcgs. of mercury from Thimerosal.

1969
The rubella vaccine was introduced. It did not contain Thimerosal.

Public health concerns about methylmercury in the edible tissue of fish suddenly erupted when fish from Lake St. Clair bordering Michigan were found to have high levels.

April 1969
An Eli Lilly memo from W. R. Gibson to Dr. J. M. McGuire regarding the possible use of Thimerosal in contact lens solution states:

• "When Merthiolate breaks down, are the degradation products toxic or irritating? Our files yield no test information on the irritancy of degraded merthiolate."
• "Would we recommend the use of merthiolate solution and sterilize contact lens? In the absence of appropriate data, a positive recommendation could not be made, this use does not seem unreasonable and probably would not be hazardous."

Early 1970's
Studies done in London show that children with autism had families with various backgrounds of religion, race, financial status, social, and ethnic groups.

1971
The MMR vaccine was introduced containing vaccines for the Measles, Mumps and Rubella. The DTP, MMR and Polio vaccines were being given to children. The DTP is still the only vaccine that contained Thimerosal at 25 mcgs. of mercury per shot. The MMR and Polio vaccines were both live virus vaccines. Routine smallpox vaccination ceased.

Kanner admitted that Mothers were not to blame for autistic children.

Bay-Rho, by Bayer Corporation, was introduced for women who are Rh-Negative. The shot is to be given directly after giving birth. Bay-Rho contained 35 mcgs. of mercury from Thimerosal.

Winter of 1971 – 72
The largest and most serious outbreak of alkyl mercury poisoning occurred in Iraq. The outbreak was caused by preparing homemade bread with treated seed grains. The warning labels were not written in the local language and symbols such as the skull and crossbones to indicate poison held no meaning to rural Arabs. A red dye to indicate the presence of a fungicide was washed away by the victims with them thinking they had also washed away the poison. The insidious properties of methyl mercury were also contributing as there is a long latent period between exposure and the first symptoms. Some 6,000 cases were admitted to hospitals. An epidemiology study to follow-up on the outbreak suggested that as many as 40,000 individuals may have been poisoned.

1972
The federal government halted the use of mercury compounds for many industrial uses because the mercury had leached into the environment and found its way into the human food chain.

From Eli Lilly files, the British Medical Journal reported that mercury is known to act as a catalyst and to cause aluminum to burn rapidly. They said that the manufacturers of vaccines have been informed. (Aluminum is used in vaccines combined with Thimerosal)

Dr. Axton reported in a paper, "Six Cases of Poisoning After a Parenteral Organic Mercurial Compound (Merthiolate)" the case histories of four children and two adults severely poisoned by accidental exposure to Thimerosal. Five of the six cases died.

Eli Lilly received an article stating that mercury in vaccines caused 6 deaths. Symptoms and course of the 6 patients suggest mercury poisoning.

December 4, 1972
An internal Eli Lilly memo from Robert L. Stone to Dr. A. F. Crumley concerning the study of Thimerosal on dying meningitis patients candidly notes the study's shortcomings:

• "Considering the type of patient involved, one might question these observations (the appearance of no deleterious action) as providing adequate indication of any harmful effects of high doses of Methiolate in humans, in particular, more long term effects."

December 14, 1972
A memo titled, "Merthiolate in Parenteral Products" in Eli Lilly files by Robert L. Stone to Dr. A. F. Crumley states:

• "A review of some data being generated by the current concern for mercury in the environment suggests it would be advisable to obtain data on the metabolic deposition of Merthiolate..."

By this time, Federal Government agencies recognized that mercury was a cumulative poison that damaged brain cells.

1973
In Eli Lilly's files is an article entitled, "Dangers of Skin Burns from Thimerosal" which reported the case of a woman who received severe burns resulting from a chemical interaction between Thimerosal and aluminum. The article suggested that Thimerosal and aluminum should not be used together.

Dr. T. Suzuki reported a case of human poisoning that occurred from infusion of large volumes of plasma containing Thimerosal as a preservative in a paper titled, "Metabolic fate of ethylmercury salts in man and animal."

Suzuki reported levels of total and inorganic mercury in the tissues of a 13 year old boy who died 5 days after receiving infusion of artificial human plasma containing thimerosal as a preservative. The infusion of plasma took place over 6 months with a total estimated dose of 284 - 450 milligrams of mercury.

The levels of total mercury from high to low were in the following order: liver, kidneys, skin, brain, spleen, and lowest in plasma. A significant fraction of total mercury in both gray and white matter of the brain was inorganic mercury in the order of 30 to 40%. The kidney cortex had the highest percentage.

February 14, 1973
The FDA requested additional data on Merthiolate from Eli Lilly. Lilly's Director of Regulatory Affairs, E. A. Burrows, refused and responded with a defense of Lilly's product:

• "...due to the length of time this product has been on the market, its efficacy and safety have been proven by over forty years of use throughout the world. Because of this long period of use, it would be difficult to get recognized researchers to conduct new studies for safety or efficacy. They believe that over forty years of wide usage has proven efficacy and safety beyond that which could be done in special studies."

August 15, 1973
An internal Eli Lilly memo entitled, "Merthiolate Toxicity" by W. R. Gibson to M. J. Landes acknowledged:

• "The effects of long term, intravenous use in man is not known, no long-term toxicity tests have been performed."

November 16, 1973
Lilly's legal department recommended new labeling language for Thimerosal products:

• "Do not use when aluminum may come in contact with treated skin."

Unfortunately, Thimerosal and aluminum were used together in the DTP and DTaP vaccines for years. This did not change.

1974
Eli Lilly ceased its production of vaccines.

The FDA undertook a comprehensive review of the safety and effectiveness of over-the-counter medicines. The FDA asked their Over-The-Counter (OTC) Review Panel to conduct a massive review of OTC products. The panel opted to divide the task into categories, one of which was a review of OTC products containing ethylmercury.

May 1974
A study by E. Elkhouly and R.T. Yousef called, "Antibacterial Efficiency of Mercurials" in the "Journal of Pharmaceutical Sciences" looked at the effectiveness of mercury containing agents on Staphylococcus aureus and Pseudomonas aeruginoea. They stated:

• "...thimerosal was the least (effective)."

1975
The Advisory Review Panel on Over-the-counter Miscellaneous External Drug Products began the review for the FDA.

Dr. Blair states in a study in "Toxicology" that ethylmercury can be converted to inorganic mercury, which then preferentially accumulates in the kidneys and brain. The paper was titled, "Tissue Concentrations of Mercury After Chronic Dosing of Squirrel Monkeys With Thimerosal." The distribution of the mercury was the same as found in a 13 year old boy reported 2 years earlier by Dr. Suzuki.

1976
Rexall Drug Co. made efforts to place the following label on mercury products:

• "Frequent or prolonged use or application to large areas may cause mercury poisoning."

Eli Lilly objected to this warning stating that they are not aware of any incidence of mercury poisoning.

Thimerosal is given approval by the FDA for safety and use.

March 1977
In Russia, Dr. Mukhtarova published a paper on Thimerosal called, "Late After-Effects Of The Nervous System Pathology Provoked By The Action Of Low Ethyl-Mercuric-Chloride Concentrations." They concluded:

• "The pathology of the nervous system presented certain peculiarities by comparison with the early period. In evidence were changes in the sympatico-adrenal system function, vascular lesions of the brain after the type of transient derangements of the cerebral circulation in the vertebro-basilar basin and angiospasms, diffuse changes in the nervous system with the predominant involvement of the hypothalamic cerebral structures and in some cases psychic disturbances were on record."

December 1977
Dr. Fagan reported in a study that was funded by the National Institutes of Environmental Health Sciences titled, "Organ Mercury Levels in Infants With Omphaloceles Treated With Organic Mercurial Antiseptic" that between 1969 and 1975, there were 13 cases of exomphalos in infants treated by Thimerosal as a topical antiseptic. Exomphalos occurs when the abdomen fails to close around the base of the umbilical cord during the early development of the baby. Ten of the infants died and their tissues were analyzed for mercury content.

• "The results showed that thiomersal can induce blood and organ levels of organic mercury which are well in excess of the minimum toxic level in adults and fetuses."

   
He concluded that Thimerosal:

• "...has similar toxicological properties to methyl mercury and the long term neurological sequelae produced by the ingestion of either methyl or ethyl-mercury-based fungicides are indistinguishable."

He observed that:

• Mercury and mercury-containing compounds are highly toxic.
• Alkyl mercury compounds penetrate intact membranes.
• Equally effective and far less toxic broad spectrum antifungal and antibacterial antiseptics were available.

October 25, 1978
William R. Gibson wrote a letter to Dr. Alan Baskett of the Commonwealth Laboratories in Victoria, Austria regarding a concern that Thimerosal in the Australian pertussis vaccine was linked to intersucception, a painful blockage of the intestines, in mice. He noted that data relating to Thimerosal's safety and pharmacological effects in animal models are sparse.

1979
Heyworth and Truelove stated in their study, "Problems Associated With The Use of Merthiolate As A Preservative In Anti-Lymphocytic Globulin":

• "For many years, merthiolate was known to have anti-microbial activity. When it was first introduced as an anti-microbial preservative, little information about the fundamental biological effects of organic mercury compounds was available. We should like to request that merthiolate should now be regarded as an inappropriate preservative for anti-lymphocytic globulin preparations and other materials which are intended for administration to human subjects."