A Brief History of Testosterone
A Cowardly Act in Bank Lick, Kentucky
Dr. Henry Reseding had been looking for a victim for quite some time. Believing he had found the perfect person to experiment on, he plunged the syringe into the old man’s arm and walked away. As a coward, Reseding would only prey upon those who had no ability to advocate for their own health. After all, if he really had the elixir of life in his hands, the old man would start to show signs of increased strength. And if the whole thing was a scam, well… at least he hadn’t hurt himself in this whole endeavor.
Writhing in agony, the old man died a few days later. Infection seeped from the injection site and into his blood, slowly poisoning each of his body organs. His family and friends were infuriated – a white doctor had used an elderly African American man as a guinea pig, and murdered him.
The community of Bank Lick, Kentucky was enraged and sought justice on the cruel doctor. Henry Reseding prepared to flee the country, but disappeared a few days later and was never seen again. His fate has never been confirmed, but it is assumed he met justice when the population of Bank Lick found him. (Source: Poverty Bay Herald, Volume XVI, Issue 5581, 28 September 1889, Page 2.)
The Discovery of the "Elixir of Life"
A short time before Reseding’s cowardly act of victimizing the innocent in the name of “research,” Dr. Brown Sequard was busy experimenting on himself.
Interested in what caused a digestive problem known as “rumination” (having partially digested food come up to be chewed and swallowed again), he swallowed a sponge on a string. This allowed him to investigate the properties of human digestive fluids and stomach contents.
Dr. Sequard’s great discovery, however, came from a hypothesis formed on his observation of eunuchs:
''There is no need of describing at length the great effects produced on the organization of man by castration, when it is made before the adult age. It is particularly well known that eunuchs are characterized by their general debility and their lack of intellectual and physical activity."
Sequard also believed that the release of “spermatic fluid” led to a general decline in physical and mental abilities. Sequard correlated strength and vitality to this fluid, and guessed that the loss of vitality in old age must be due to a loss of some mysterious material created in the testicles of men.
Since Sequard used his own body for research, he took a mortar and pestle and tried to extract various fluid types from the testicles of dogs and guinea pigs. At the age of seventy two, he was beginning to feel the effects of old age. After proving the effect of this elixir on elderly rabbits and dogs, Sequard prepared to experiment on himself:
"I have made use, in subcutaneous injections, of a liquid containing a very small quantity of water mixed with the three following parts : First, blood of the testicular veins ; secondly, semen ; and thirdly, juice extracted from a testicle, crushed immediately after it has been taken from a dog or a guinea-pig."
Throughout the months of May and June in 1889, Sequard gave himself ten injections of this elixir. While Dr. Sequard’s health was quite good in consideration of his age, he did have extreme exhaustion upon ending his day’s work, and suffered from rumination and muscular rheumatism, a common type of muscular pain and weakness in the elderly.
Almost immediately after starting the injections, Dr. Sequard felt an increase in strength and endurance. He was able to work on his feet for hours at a time, and was no longer exhausted after arduous work. He could literally run up the stairs to his lab, and objective testing showed that his arm strength had increased by an astonishing degree.
Early Experiments with the Elixir of Life
The scientific world quickly took note of this seemingly miraculous discovery, and dubbed it the “elixir of life.” Experiments were started all over the world, in the hopes of confirming and replicating the amazing chemical that appeared to turn back the hands of time.
All over the world, doctors took syringes in hand and injected the supposed “elixir of life” into various patients. Not all “research participants” were informed of the experiment being performed, as in the case of Reseding’s victim in Bank Lick.
In San Francisco, an appeal for volunteers was made for a public test of the elixir. The director of the testing program selected a likeable, seventy year old man named James Gamble. Using an elixir made from a lamb’s testicles, Gamble was injected with the fluid, exclaiming,
“Why, that does not hurt at all! Just a prick of the needle and a little tingling is all!”
After a few days, Gamble reported that he was more limber, had better digestion, and felt more vigorous than he had in years. Objective tests showed an improvement in grip strength.
Once news of the successful experiment was leaked, local livestock dealers in San Francisco could not keep guinea pigs in stock. Local doctors were buying the animals in record numbers to perform what was known as the “Brown Sequard Operation.”
Skepticism over the Elixir of Life
In Kansas City, two doctors were experimenting with the Brown Sequard elixir at a home for the aged. The doctors noted a marked improvement in one of the patients, but suggested that a combination of brandy, cocaine, and opium would have the same effect.
Doctors around the nation reported mixed success with the elixir, and some doctors decided the positive responses to the elixir were “mental excitement.” The experiments of the mid 1800s eventually stalled, and the use of Sequard’s elixir began to die out.
Reviving the Experiment: The Elixir Gets a Name
It wasn’t until the 20th century that the idea of a male chemical causing vitality was revived. The stockyards of Chicago provided an enormous amount of animal material for experimentation, and Fred Koch at the University of Chicago put the animals to use. Koch obtained 40 pounds of bull testicles, and managed to extract 20mg of a pure substance from the material.
Koch obtained capons - roosters castrated at a young age – and injected them with the material. Capons never develop the ability to crow or other secondary sexual characteristics, so they were an excellent choice for Koch’s experiment on virility. After injecting the capons with the extract, cock-a-doodle-doo’s were heard all over the laboratory. Koch’s experiment was a success.
The chemical was dubbed testosterone, and scientists were excited by the possibilities. Dr. Brown Sequard was simply ahead of his time – the supposed “elixir of life” was real, and while the hormone could not truly reverse the hands of time, it could endow extra strength and endurance.
In the 1930s, the world was engaged in full-scale research on the hormone, now known to be a steroid. In 1935, the first attempts to synthesize testosterone from cholesterol were made. By 1939, the Nobel Prize was issued to Butenandt and Ruzicka for the discovery of how to synthesize testosterone from cholesterol – this ushered in the Golden Age of steroid chemistry, which lasted through the 1950s.
The Chemical Structure of Testosterone
The Use of Testosterone in the Clinical Setting
Once testosterone was isolated in its pure form, it was put into clinical use almost immediately. Regulatory agencies did not control or monitor the use of drugs in the same way they do today, and testosterone injections were given to those who had hypogonadism (underdeveloped testes).
By the 1950s, scientists were able to formulate a longer acting form of the hormone, and could tailor the effect of the steroid to be anabolic or erythropoetic (to stimulate red blood cell growth) - these versions of the hormone were not used for those with hypogonadism, but were used for increasing strength or to increase the rate of production for red blood cells. At this point in time, testosterone had to be given through injection or by subcutaneous pellet, as the hormone was not effective if taken orally.
In 1958, scientists began to inject testosterone into ill patients, to help them gain weight.
In the 1970s, a versoin of testosterone called undecanoate was developed. Undecanoate could be taken orally, ushering in a new age of testosterone treatment.
Finally, in the 1990s, a transdermal patch form of testosterone was developed to treat hypogonadism, and in the 2000s, a transdermal gel became the standard delivery system (in the United States).
Only a small proportion of the population has hypogonadism, but testosterone has found other uses for those with biologically low levels of testosterone (also called "low-t").
Steroid Use Rises
Abuses of Testosterone
In Nazi Germany, it is widely believed that anabolic steroids (derived from testosterone) were administered to German soldiers to increase aggressiveness. There are some reports that Adolf Hitler administered injections of testosterone to himself.
The Soviet Union noted the increased physical strength, aggression, and endurance gained by the German army via the use of steroids, and began experimenting with the steroid in the 1950s. It is quite possible the Soviets used anabolic steroids during the 1952 Olympic Games.
The introduction of anabolic steroids into the United States is attributed to the physician of the US weightlifting team, who saw the effects on the Soviet performance at a competition in Vienna. Dr. John Ziegler was impressed with the increase in strength demonstrated by the Soviet competitors, and began experimenting with a few U.S. weight lifters. Shortly after this period of time, the anabolic steroid Dianbol was introduced – it offered the increased strength of testosterone, with fewer side effects.
The Olympic Games held in Melbourne, Australia in 1958 were filled with weight lifters using anabolic steroids. The German Democratic Republic consistently won medals in various sports, despite the small size of their country, due to a program to synthesize new steroids for their athletes.
In 1967, a ban on the use of anabolic steroids was announced by the International Olympic Council. By the 1970s, most major national sports followed suit and implemented a ban on the use of steroids to improve athletic performance.
To enforce the ban, a test had to be developed – the “epitestosterone test” was first utilized by the Olympic Council in the 1982 games. If an athlete’s testosterone level was more than six times greater than their epitestosterone level, then they were using an anabolic steroid to improve performance.
Thus began a cat-and-mouse game of steroid development and ways to detect their presence in an athlete's body. Anabolic steroids that could be excreted from the body quickly were developed, rendering the epitestosterone test obsolete. As new steroids are developed, new tests must be developed to detect a presence in the body. In 2003, the chief executive of the United States Anti-Doping Agency discovered a new anabolic steroid (tetrahydrogestrinone, or THG) in wide use among athletes. A new test was developed, and athletes were warned that a positive result would bar them from performing in the 2004 Olympic Games in Athens, Greece.
The Testosterone Factor: National Geographic
The Effect of Testosterone on Development
Testosterone may have a link to handedness, or the dominant hand a person uses. Increased testosterone levels are linked with left handedness, though some claim this is a correlation rather than a causation.
The length of the ring finger may be an indicator of testosterone levels: females tend to have a ring finger length which matches their index finger, while males have ring fingers that are longer than their index fingers.
A study performed on the androgen receptor gene showed that a decrease in testosterone resulted in an increase in left handedness. The length of the androgen receptor gene has been positively correlated with lower androgen levels and an increased level of left-handedness.
While it is difficult to prove a direct causative effect of testosterone on handedness, the effects of the hormone are “felt” in other ways in the womb.
Mice typically give birth to litters of several pups, and the position of a pup in the womb can determine behavioral characteristics after birth. A female pup may be surrounded by male pups, and the testosterone produced by the male pups will transfer to the neighboring female pup. This effect is known as intra-uterine position, and the female pups show partial masculinization.
Effect of Intra Uterine Position on Female Mouse Pups
Female Mice/No Male Neighbors
Female Mice Surrounded By Males
Sexually dimorphic hypothalamus
Distance between anus and genitalia
Female testosterone concentration
Mating and Fertility
Mounting Other Females
Early Testosterone Exposure: A Poll
Which finger is longer - your index finger or ring finger?
The Effect of Testosterone on Human Development
In human beings, testosterone is produced during the seventh gestational week in males. The surge of hormones causes the male genitalia to develop and causes specific areas of the male brain to develop. In the absence of testosterone, the fetus will retain female characteristics (the default sex).
There is a rather interesting genetic condition known as 5-alpha-reductase deficiency. This condition results in a rather startling situation: babies are labeled as “female” at birth, but begin to develop male genitalia at puberty!
The condition only affects those who are phenotypically XY males – while the babies appear to be “female” at birth, the genetic sex of the individual is male. 5-alpha-reductase is a hormone that converts testosterone into dihydrotestosterone (DHT). Dihydrotestosterone is the form of the hormone required by the fetus to initiate the development of masculine physical characteristics. In the absence of this hormone, male genitalia do not develop.
These children are often raised as females, though they often self-identify as male. While the physical appearance of a child with this condition is female, the child has (recessed) testicles, male gonads, and are completely fertile.
At puberty, the male body requires testosterone (but not dihydrotestosterone) to complete growth. At this stage in life, an individual with 5-alpha-reductase deficiency experiences a rapid growth of the male genitalia and often become phenotypically male. Since DHT is far more potent than testosterone, the virilization of the affected person may not be complete at puberty due to insensitivity to the hormone. 5-alpha –reductase deficiency is classified as an intersex condition .
Testosterone (or, more correctly, dihydrotestosterone) is also responsible for male-pattern baldness. Individuals lacking DHT (including those with 5-alpha-reductase deficiency) do not experience male pattern baldness.
From the early discovery of the “elixir of life” to the abuse of anabolic steroids, the history of testosterone is a fascinating into humanity. The same hormone which grants strength and endurance also makes us lose our hair . Its effect on fetal development is still being explored, but testosterone is obviously responsible for the primary male sexual characteristics, and may be an influence on which hand is dominant.
The documentary series below demonstrates the effect of the hormone bath in utero on human beings: while we may be male and female, each person carries a unique level of "maleness" and "femaleness."