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"Discovery in pharmaceuticals – like everything else – favors those who go searching in the right places." -- formerly on the website of Eli Lilly and Company (largest manufacturer of insulin)
Preface Sometimes good things have a long gestation period. Insulin potentiation therapy (IPT) has been around for a long time. First developed in 1928, its chief practitioners, three generations of the Drs. Donato Perez Garcia, called it cellular therapy or Donatian therapy or cellular therapy for the change of the physicochemical constants of the blood. SGA, M.D. gave it the name IPT in the 1970s or 1980s. A good brief history of IPT from a doctor's point of view is at the beginning of Dr. SGA's first published IPT paper. Dr. SGA has written another unpublished history. I have drawn much material from these, as well as from documents, emails, and conversations with Dr. Perez Garcia y Bellon 2 and Dr. Perez Garcia 3. I will make corrections and additions as they come to my attention. This only a sketch, not a definitive history of IPT.
Discovery It was 1926, and insulin was hot new medical technology. A Canadian, Frederick Grant Banting, had discovered it at age 30 in 1921, and had received a Nobel Prize in 1923. Diabetes had suddenly become a curable disease, and insulin was just starting as a lucrative franchise for the Eli Lilly company. As so often happens at the beginning of an era, there was a broader range of experimentation before concepts and rules gelled and hardened. Although most of the attention was, of course, focused on the use of insulin for diabetes, a few doctors explored other possibilities of this new drug. Apparently one obscure application explored was the use of insulin for management of non-diabetic malnutrition. Donato Perez Garcia, MD 1 was then a young, 28-year-old military doctor in Mexico City. He read about insulin, and was particularly interested in this obscure application for malnutrition. He had suffered from a chronic gastrointestinal condition for several years, and was below his ideal weight. So he decided to try intravenously injecting himself with small amounts of insulin before each meal. He would become very hungry, and would eat with gusto. After several weeks of this, his digestive problems went away, and he gained weight to a more normal level. Discontinuing the insulin, he continued in a good state of health. Synthesizing his experience and the
scientific understanding of insulin to date, he theorized that the insulin had
accomplished two tasks: He wondered: If insulin enhances uptake of nutrients, would it also enhance uptake of other substances, including drugs, for improved treatment results? In particular, he wondered if insulin could help in treatment of syphilis. Like AIDS today, syphilis was the infectious worldwide scourge of the time, terrorizing society and taking the lives of the poor and the rich, the unknown and the famous. Antibiotics had not yet been discovered. Using extremely toxic heavy metal drugs, mercury and arsenic salts, doctors could often successfully treat the disease in its early stages. But there were serious side effects, and the patents' health suffered. And when syphilis reached its final or tertiary stage, entering the central nervous system (CNS), there was little the doctors could do. They could not get enough drugs into the CNS without killing the patient. Dr. Perez Garcia 1 theorized that insulin might help deliver these drugs better, and perhaps in smaller doses. As Banting did for the discovery of insulin, Dr. Perez Garcia 1 tried his idea out first with dogs. In his experiment, he prepared one group of dogs by injecting them intravenously with insulin. A second group of dogs received no insulin. After the first group developed symptoms of hypoglycemia (low blood sugar), he injected both groups with a mixture of mercury and arsenic salts in hypertonic glucose (sugar) solution. He found that the mercury and arsenic concentration in brain and spinal cord of the insulin treated animals was approximately the same as it was in their blood. In the control animals, drug concentration in brain and spinal cord was much less. Apparently the system of insulin, hypoglycemia, and glucose had breached the blood-brain barrier, getting the drugs for the first time into the normally inaccessible CNS. Dr. Perez Garcia 1 then tried this protocol in human syphilis patients in 1928 with amazing success. He could successfully treat an otherwise incurable common disease. He found that he could actually use larger doses of the toxic mercury and arsenic drugs, not only getting them into the CNS, but also getting them out of the body afterwards. He also began to try this insulin potentiation method for treatment of other diseases, again with remarkable success. In all his work, Dr. Perez Garcia 1 was ahead of the science of his time. His procedures were developed empirically. He followed hunches, he found what worked, and he followed and extended it. He developed theories based on what he saw in his patients. He thought that drugs were flushed through membranes into the cells, perhaps adsorbed onto glucose molecules. He thought that the hypoglycemic pulse somehow helped detoxify the body, and somehow transformed the biochemistry to generally improve health. But it would not be until the biochemical and molecular biological understandings of the 1970s and 1980s that some of the mechanisms of insulin potentiation would be understood.
Fame Things were going Donato's way. He was at the top of his world and climbing. In 1930 his son Dr. Perez Garcia y Bellon 2 was born. In 1935 he applied for a US patent for this method of treating syphilis, and it was granted in 1939. And he published a report of his work in dogs and humans in the June, 1938 edition of Revista Medica Militar (Mexico).
In 1935, Donato was invited by Harvard University to discuss his technique and his results. In 1937 he was sent by the Mexican government to San Antonio, Texas, for a year to demonstrate his technique. At Austin State Hospital he demonstrated rapid and complete return to health in seven patients with syphilitic paralysis and dementia. [ I have copies of the record sheets and can add them to this site later.] During his year in San Antonio, Dr. Perez Garcia 1 treated almost 600 cases of mostly syphilitic neurological disease. Just before going to Washington DC to give further demonstrations, he was interviewed in San Antonio in June of 1938 by a reporter for a Spanish language newspaper. I do not know what happened in Washington. But apparently Dr. Perez Garcia 1 did not make a big enough impression to have any permanent results. In my imagination, he was like a passing comet, citizen and embodiment and harbinger of a larger world, a future world, noticed in its brilliance by a few, understood by fewer, and then quickly forgotten.
Dr. Perez Garcia 1 mentioned the name Sakel in the interview. Apparently someone by that name had claimed to have discovered insulin potentiation. Interestingly, during this time, a group of doctors in the US, networked by "snail" mail, a slow forerunner of today's Internet listservers, explored other nondiabetic uses of insulin (see Huggins 1977). They were focused on local injection and topical application of insulin for treatment of wounds and infections, and apparently they never came up with the efficient systemic hypoglycemia protocol that Dr. Perez Garcia 1 developed. But it is clear that in those early days, interest in nondiabetic uses for insulin was alive in scattered locations on the globe. Dr. Perez Garcia 1 began to use insulin potentiation to treat wealthy and famous people (as well as many normal people) in Mexico, not only for syphilis, but also for such complaints as ulcers, gallstones, and even appendicitis. Patients who had experienced great success referred their friends to him, and his practice grew. He treated movie stars, the director of the Mexican Ballet, a real Mayan princess, Mexican presidents, other high government officials and their families, and people from all over the world who heard about him and came to Mexico City.
I love the news photo above, which catches Dr. Perez Garcia 1 during this exciting period. From left to right: (leftmost is unidentified); Pancho Segura, a famous boxing manager; Dr. Bolanos Cacho, a well-known doctor who treated many Mexican sports professionals; a laughing Dr. Perez Garcia 1; and famous Mexican actor Palilli. Note the earnest gratitude in Palilli's face. Dr. Perez Garcia 1 has just saved him from an otherwise incurable and fatal disease (my guess is it was neurosyphilis).
In 1939, the Mexican Secretary of Health signed a declaration that Dr. Perez Garcia 1's therapy, based on results to date, was deserving of further study. Perhaps encouraged by that recommendation, the Mexican Army established that year an experimental clinic to investigate the merits of IPT. The results in treating syphilis and many other diseases were spectacular, as certified in a 1940 statement signed by the Secretary for National Defense, and the Heads of the Technical and Sanitary Sections of the Army. Read this statement, in English. Things were going incredibly well for Dr. Perez Garcia 1. On a visit to Tijuana and San Diego in spring of 1944, he successfully treated many patients who had diseases ranging from syphilis to malaria. He even successfully treated a general's wife's gall bladder disease. His trip was celebrated in a short article in Time Magazine, April 10, 1944.
Obscurity... and Productivity
In the 1930s and early 1940s, the national government of Mexico was run by the military. This gave Dr. Perez Garcia 1 a lot of connections and advantages. Riding high on his successes, he was favored to be the next Minister of Health for Mexico. And if he had gotten that position, no doubt IPT would have gained much more support at that time, and would probably be in much wider use today. But the military lost the national election in 1944, and his hopes were dashed. As I recall hearing, one of his medical school classmates got the job instead, and later used his position to suppress and discredit Donato's work. World War II came, and brought with it the widespread use of penicillin (which was discovered in 1928, the same year he first developed IPT). Suddenly Donato's syphilis treatments and patent were obsolete. But his insulin protocol was still uniquely effective in treating other diseases. And Donato found that it even delivered penicillin (and later, other antibiotics) better, and made it more potent. In 1945 he demonstrated for the first time that IPT could be used to treat cancer. In 1947, Dr. Perez Garcia 1 made one more trip to the US to demonstrate IPT and share it with the world. I have another article from a San Antonio newspaper. Apparently, despite his unsurpassed medical results, Donato's technique did not catch on. Was it because of his national origin? Was it because he could not give a satisfactory scientific explanation of why it works? Was it because insulin was already pigeonholed by doctors as a drug only for diabetes? Was it because it offered no profit motive to pharmaceutical companies, and in fact could hurt short-term profits by reducing the necessary dose? Were people just not ready for it? Whatever the reason, Dr. Perez Garcia 1 returned to Mexico City and continued to practice medicine out of his private clinic. Ignored in the US, shunned as a quack in Mexico, he was nevertheless a quiet hero to his patients, who brought him more referrals. |
