"Toxicologists have long known that 'the dose makes the poison.'"
RADIATION HORMESIS AFTER 85 YEARS
Background Radiation is Good for You (21/8/88)
[This file downloaded from Ken Seger's excellent BBS in St. Louis, Mo., tel. 314-821-2815. No author given, but I seem to recognize the masterful pen of Marshall Brucer, M.D. (Note by P.B.)]
Why does your pancreas secrete only when food has passed through the stomach? In 1902, an English physiologist, E. Starling, dis- covered that an acid estract of duodenum contained "secretin" that, when discharged into blood, stimulated the pancreas to secrete. By 1904, he coined the word "hormone" to designate any substance produced in small amounts, but carried in blood to influence some other organ. It is from the Greek "Hormo," meaning, "To excite."
A pharmaceutical principal practiced by the ancients was: A weak stimulus might stimulate what the same, but stronger, stimulus inhi- bits. No medieval poisoner would dare kill somebody without first tasting the poison. Alchemists all knew that a poison taken in small dosage was dangerous. A few generations ago, physicians carried strychnine in their bags for aged 50 year old patients. Only in high dose was it considered a harmful poison; prescriptions were intended to be for a stimulating tonic.
Toxicity is a Matter of Dose.
No substance is without toxic effects at improper dose. Consider the most dangerous substance known to man: Oxygen. It adversely affects the body at 5% too low a concentration. Moderate oxygen defi- ciency however, stimulates RBC production. Many common substances, such as nicotine, caffeine, alcohol, and even water, have mild effects in low doses, but are deadly with large dosage.
For a hundred years, pharmacologists gave groups of animals various doses and plotted the percent killed against the dosage. The amount of a drug that killed 50% of the animals became the drug's LD-50 (Lethal Dose for 50%). The complete curve was sigmoid, but an LD-90 could be "statistically significant" in a very small population. With few dead at LD-10, it took many animals and lots of time to find "significance." Hence, the low end of the curve was often "approximated." Few pharmacologists paid attention to very low-dose effects.
The Word "Hormesis" is Introduced.
However, physiological chemistry (biochemistry's proper name during the 1920's) blossomed around vitamins and hormones, both low dose materials. C. Southam and J. Erlich found that concentrations of oak bark extract inhibited fungal growth, but in low dose it stimu- lated fungal growth. Publishing in Phytopathology 33:517, 1943, they modified Starling's word to "Hormesis" which described stimulation by low doses of agents that are harmful, even lethal at high dose.
After World War II, antibiotics were released to agricultural chemists. During the 1950's, T. Luckey and colleagues were feeding antibiotics to livestock, expecting that the suppression of intestinal flora would decrease growth. Instead, they discovered that low dose dietary antibiotics caused a surge in growth. Since then, feeding antibiotics has become standard practice for poultry, pigs and cattle. Experiments in germ free birds demonstrated a true chemical hormesis. In surveying the literature, T. Luckey found that hormesis was common, particularly when the "dose" was of ionizing radiation.
One of the first studies in radiobiology (1898) found that X-irradiated algae grew faster than unirradiated control groups. Stimulated growth was noted in trees (1908) and increased life span in invertebrates (1918) and insects (1919). X-Rays stimulated seedlings (1927), plant growth (1937), along with guinea pigs, rabbits and mice (1940's). Increased life span was the rule in low dose irradiated rats, dogs, and even house flies (1950's). In a 1981 monograph (CRC Press), T. Luckey revived the term "hormesis," but this time with ionizing radiation and backed it up with a review of over 1250 articles from 85 years of experimental biology.
Takes the Spotlight
Before 1900, about ten articles mentioned a probable hormetic response to X-rays, then two or three articles were published each year, until the death, in 1906, of an English radiotherapist from overexposure caused the first radiation hysteria. (ArRR, 1906-1910) Skin damage to number of German and French radiotherapists led to a new emphasis on protection from damage. Before World War I, and into the thirties, about ten articles a year mentioned a hormetic effect, but the idea did not grow.
Why Didn't Hormesis Take Hold?
A Russian histologist, Alexander Gurwitsch, had discovered in 1923 that living cells gave off a form of radiant energy that stimulated other growing tissues. (RA 100:11, 1923) "Gurwitsch" rays were confirmed outside of Russia, then denied. During the 1930's, major WPA radiobiology programs studied these "mitogenetic rays," but with World War II, geneticists and biologists dismissed the idea with shame. The rays taught radiobiologists how to juggle numbers and live off a government dole.
In 1925, H. Martland described 18 female radium dial (like those glow in the dark watch faces, etc.) painters. After tipping brushes with their lips for five years, these high dose recipients developed necrosis of the jaw bones and profound anemia. Other high dose patients, including possible osteosarcomas were, and still are, de- scribed in tabloid scandal sheets. No newspaper ever featured the 30 year followup of 1155 low dose radium dial painters who had fewer cancers than the general population and lived longer.
In 1926, H. Muller published his work on genetic damage from irradiation of fruit flies. X-rays soon became standard for producing fruit fly mutations. In the 1930's, "Radiation" became synonymous among geneticists, with chromosome damage. Chromosome defects of unknown significance occur in man after high dose, but postulated mutations after low dose are all mathematical extrapolations from data on fruit flies and mice.
Health Physics is Invented.
The Manhattan Project expected large amounts of radioisotopes. Robert Stone gathered a new group, that he called Health Physicists, to monitor this largely unknown, possibly dangerous phenomenon. Their first experiment, rasing mice in an atmosphere of uranium dust, showed exposed mice living longer than controls. They set up an arbitrary Maximum Permissible Dose (MPD) after proving that mice in radiation fields ten times the MPD lived longer than controls. Thus Health Physics began with a high MPD, and ended the war with record safety.
After World War II, almost 20 articles per year mentioned a hor- metic effect in spite of a budding fallout hysteria. Health Physi- cists soon learned that their livelihood depended upon scaring the pants off Congress. H. Muller predicted a genetic catastrophe from A- Bomb exposure in a 1955 flurry of headline publicity. [No publicity was given the disproof 35 years later.] This was (at least for the media) scientific proof that radiation cause such things as two headed babies. In 1957, a fire in a power reactor at Windscale, England, released 20 curies of I-131 into the atmosphere. Newspapers predicted thousands of thyroid cancers in end-of-the-world headlines (but failed to mention, 25 years later, that no biologic effect has ever been detected).
Health Physics and Genetics were supported lavishly by radiation hysteria, and Radiation Biology was the most intensely researched science in history. At the 1955 Atoms-for-Peace conference an English geneticist uttered heresy at the opening session. Background radiation, he said, was probably the cause of most mutations throughout evolution, and the human race had not done too bad. He was almost read out of science for this heresy. Every Genetics budget meeting, from 1955 to 1981 opened its request for funds with an anti-nuclear litany. In spite of this atmosphere, during the 1960's and 1970's, about 40 articles per year described hormesis. In 1963, the AEC repeatedly confirmed lower mortality in guinea pigs, rats and mice irradiated at low dose. In 1964, the cows exposed to about 150 rads after the Trinity A-Bomb in 1946 were quietly euthenized because of extreme old age.
A Little Radiation
Is Good for You.
In 1981, T. Luckey revived a very obvious radiation hormesis. No experimental evidence of damage at low-dose existed; self-serving extrapolations from high-dose data dominated Health Physics. One New York Health Physics bureaucrat passed off hormesis as a "theory" similar to evolution. But, in 1983, M. Brucer published an article in the Health Physics Newsletter entitled "Radiation is Good For You," and over 200 reprint requests indicated agreement with his position. In August 1985, a Conference on Radiation Hormesis in Oakland, California, recognized the reversal in concepts of radiation effects. Its Proceedings, published in the Health Physics journal in 1987, finally recognized that low dose radiation is not only good for you, it is essential to life. But how will Health Physicists now earn a living?
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