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The Discovery of Kryptopyrrole and its Importance in Diagnosis of Biochemical Imbalances in Schizophrenia and in Criminal Behavior

© Abram Hoffer M.D., Ph.D 
(Excerpted from Journal of Orthomolecular Medicine)


In this issue Dr. Richard T. Kraus describes a notorious serial killer who is serving a 250 year sentence for the murder of eleven women. Unfortunately, serial killers are not a threatened species. On the contrary, they threaten society more and more, and with modern weapons of destruction seem to be even more effective. This case report may be the first in which four main factors which determine human behaviour are discussed in detail. Dr. Kraus describes "...a matrix of genetic, biochemical, neurological and psychological deficits”. I am particularly interested because the kryptopyrrole (kp) which was found in this person’s urine was originally discovered in Saskatchewan about 1960 when I was Director of Psychiatric Research. The main biochemical research was completed in Saskatchewan by Dr. D. Irvine,(1) and in New Jersey by Dr. C. C. Pfeiffer (1) and his research group of biochemists.

This report provides a model of how criminal behaviour ought to be explored, with numerous references to the medical literature for all of the four variables. I will discuss mainly the biochemical findings and provide a brief history of its discovery. The presence of kp in urine is a valuable diagnostic aid especially for determining more specific treatment. It is most closely related to the schizophrenias but cuts across all diagnostic categories. I think it could become an important differential diagnostic test. It is simple to do, any competent medical laboratory can do it. The laboratory in Victoria has been running them for me since 1976.

By 1960 the biochemical unit of the psychiatric research program in Saskatchewan was gearing up to investigate any possible relationships to the schizophrenias. One of the studies involved examining urine for several fractions and comparing the urine of patients and controls. We were then treating many alcoholics using psychedelic therapy. D-lysergic acid diethylamide (LSD), the hallucinogen, was well studied as a compound which could induce a model psychosis or a psychotomimetic experience. It occurred to me that inasmuch as LSD produced something very similar (but not identical with) schizophrenia, perhaps it might also generate in the body of a person (not schizophrenic) the same type of biochemical abnormality which we thought was present in the patients. I asked Dr. N. Payza to examine the samples of urine obtained from an alcoholic who had been given LSD as part of his treatment. The first morning specimen was obtained and another one around noon, usually the height of the experience. My idea was that if something appeared after LSD which was not present before, this might give as a lead. We were fortunate because the first patient we tested had a large amount of a substance that was not present in the morning specimen.

We soon showed that it was not a breakdown product from the LSD itself, which meant it was created in the body by the impact of the hallucinogenic drug upon one of the biochemical systems. After we had improved the assay procedure we began to test patients. One day I took into the laboratory 12 specimens of urine. Six were obtained from schizophrenic patients, five were obtained from normal subjects and one was a blank. The code was kept secret. I asked the biochemical team to analyze these samples and to tell me which of the 12 were obtained from the schizophrenic patients. They accurately spotted all the schizophrenic samples. I concluded that schizophrenic patients, not given LSD, had the same substance in their urine as did some alcoholics who had been given LSD, but that it was not present in normal controls.



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     by Abram Hoffer

In pursuing this research we were the first physicians in America to conduct double blind controlled tests, and we were later the first to recognize and to publish its many defects and flaws. By 1967 we had established ...more

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