Medicine Matters - April 21st, 2023, by Dr. Mark Mosley

History Matters  Friday,  April 21, 2023

Syphilis & crimes against humanity -He who knows syphilis, knows medicine.” -William Osler MD

Historical Origins

• An unresolved debate exists about whether syphilis existed in Europe before Columbus but was confused with leprosy; or whether Columbus and his men brought it back from the “West Indies” (1492).

• First epidemic of syphilis recorded in 1495 during the French invasion of Naples Italy (referred to as the “French disease” by Italians; and the French called it the “Neapolitan (Naples) Disease”). Syphilis was also called the “Great Pox” and lues venerea (lues means “plague”)

• In 1527, Jacques de Bethancourt in his work New Litany of Penance introduces the term “venereal disease” (Morbus venerus)- the malady of Venus (Roman goddess of love) since the disease arises from illicit love.

• The name “syphilis” was first used in a 1530 poem by Italian poet-physician named Girolam Francastoro, who referenced the Greek shepherd Syphilus (from the Roman Poet Ovid) who led a revolt against the sun god and was stricken with a disgusting and odorous disease. Francastoro coins the word gumma (like resin or gum leaking from a tree) describing the hard abscesses and scars (found in tertiary syphilis).

• Henry VIII of England (1491 -1547) became so concerned about this new epidemic that he closed down all the brothels (“stews”) and bath houses; and mixed bathing was outlawed (1546)

Syphilis Pathophysiology

• 1789 the term “snuffles” is found describing the newborn nasal drainage characteristic of congenital syphilis. Hutchinson in 1863 describes the triad of pointy incisors, deafness, and the bullous skin rash associated with congenital syphilis. Also found with syphilus was cartilage and bone deterioration especially of the nose called a “saddle nose” deformity. These physical deformities could show up in the first 2 years of life “early congenital syphilis” or after 2 years “late congenital syphilis”. The rash, malnourished state, and deformities of congenital syphilis are pictured in Edvard Munch’s painting Inheritance.  ( a diseased “Madonna & Child”)(1897-99).
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• Prior to 1905, “venereal disease” (VD) was thought of as a single disease without demarcating between syphilis and gonorrhea.

• In 1905, the spirochete bacterium, Treponema  palladum  was identified as the causative micro-organism of syphilus. In 1906, a German bacteriologist, Paul von Wasserman, an assistant of Robert Koch (Koch’s postulate that disease is caused by bacteria)- developed a test to find the spirochete bacterium called the “Wasserman reaction.”

• 1910 - Phantom of the Opera is written. The mask is due to saddle nose deformity and facial deformity from congenital syphilis.

• Primary & Secondary stages of Syphilis- Treponema palladum is passed only among humans. Primary stage is a painless sore(s) usually on the penis, vagina, or rectum called a “chancre” (meaning “cancer”) appearing about 3 weeks after exposure. This is passed during intercourse or to the newborn in utero. This sore lasts about 3-6 weeks. If left untreated, it advances to secondary syphilis with swollen lymph nodes (buboes) , fever and rash. The genital sores become painfully abscessed with fevers and horrific night “bone pains.”

• Latent and Tertiary syphilis- if left untreated, the syphilis goes quiescent with no symptoms—and about 15-30% of people decades later with end up with hard abscessed sores and ulcerations (gumma), ocular syphilis or neurosyphilis resulting in headache and discordination (tabes dorsalis), delirium, dementia and death (“general paralysis of the insane”). The idea that a sexual transmitted disease which was fairly ubiquitous in the population could decades later cause brain disease (eg. neurosyphilis) was not considered until the descriptions of “tabes dorasalis” in which syphilus destroyed the spinal cord causing imbalance. (1913). People did not think of dementia or delirium as a brain disease. “Going “mad” was a mental disorder which was disconnected from brain or spinal cord disease. Brain disease and Mind disorder were not connected. There was a non-specific term called “paralysis of the insane” which was connected with syphilis and other disorders but this was a moral ailment, particularly ostracized and shunned as a direct punishment from God for sexual sins.

Syphilis Treatments

•  Paracelsus (1493-1541) promoted the metal mercury as a treatment for syphilis. After many deaths of people drinking elixirs of mercury; he modified it to an inunction (ointment) rubbed on the skin or suffumigation (inhaling it) during a bath. Mercury often caused renal failure, neuropathies, ulcers, loss of teeth and death. (“a night with Venus leads to a lifetime with Mercury!”). In 1894, mercurials were tried by injection. The mercurial treatments were often not helpful, extremely painful, and resulted in significant morbidity and mortality from mercury poisoning.

• Gabriele Falloppio was an Italian Catholic priest, physician, and very famous anatomist (from whom we get the name Fallopian tube). He also coined the term “vagina”. On his treatise on syphilis in 1564, he describes the first use of condoms for syphilis which he claims to have invented—a linen sheath soaked in a chemical solution and held on to the glans with a pink ribbon (to appeal to the female’s acceptance). He conducts a clinical experimental trial in 1100 men and reported than none acquired syphilis. Falloppio dies at the age of 40, two years before the publication of his treatise and most of his other works. He writes:

                “I tried the experiment (the use of condoms) on 1,100 men, and I

                        call immortal God to witness that not one of them was infected.”

• In the 1640’s condoms made of animal bladders were used by soldier’s of King Charles’ army. King Charles’ physician, the Earl of Condom, used an oiled sheath from sheep intestine to prevent the King from getting syphilis. The physician discouraged his name be connected with the device. (at least we don’t call them “Earls”)

• English physician, Daniel Turner, in 1717 argued against the use of a condom for syphilis based on the premise that there were not failsafe and could encourage more illicit sexual activity, and thereby paradoxically increase the spread of syphilis. The 18th century, in particular saw increasing moral arguments against condoms based both upon grounds of increasing illicit sexual activity as well as issues surrounding birth control.

• “Comstock laws” (named after Anthony Comstock) were a set of federal acts passed March 3, 1873 criminalizing the usage of the US Postal Service to delivery contraceptives, abortifacients, obscenity, and sex toys— this would preclude condoms.

• In 1906, Paul Ehrlich, a famous German physician used an organic arsenic compound called Salvarsan. Once the treponium was discovered, Paul Ehrlich coined the term “magic bullet” (an apt war image) and systematically tested compounds until he came across #606 which was found to be successful. He was awarded the Nobel Prize in 1908 for his discovery. By 1910, Salvarasan, also called 606, was on the market—and was modified to be less caustic (and less successful) as Neo-salvarsan in 1914. These treatments were regular injections for a year or more with a high degree of non-compliance.

Syphilis & World War I  (1914-1918)

• During WWI (1914-1918), syphilis was the second most common cause of disability and absence from duty. Greater than 10,000 men were discharged due to syphilis with over 7 million lost-person-days.

• During WWI, condoms were not allowed to be distributed due to the US government’s Comstock laws.

Tuskegee Syphilis Experiment (1932 -1972)

• The 1918 Chamberlain-Kahn Act required the Public Health Service (PHS) to “study and investigate the cause, treatment, and prevention of venereal disease.”

• The United States Public Health Service conducted a clinical study beginning in 1932 to document the natural history of untreated syphilis (Penicillin had not yet been invented. Only Salvarsan existed—and it did not treat tertiary syphilis).

• Investigators enrolled 600 impoverished African American male sharecroppers from Macon County, Alabama—399 had syphilis and 201 were the controls that did not.

• The African American men were not told they had syphilis. They were not told the nature of the study. They were only told they were being tested by the US government for “bad blood.” “Bad blood” was the most common cause of death in the South among the African American community and was a vague term which included many things such as anemia, fatigue, and syphilis. In response to them “volunteering”; the men would receive free meals on test days, free medical care for common ailments, and a free burial plot! (that might be a tip off)

• The original plan designed by Taliafero Clark, for the Tuskegee Syphilis Experiment was a 6-9 month study. The group, under the direction of John Heller Jr who was the US Public Health Service Director of the division for venereal disease, voted not to tell the participants the nature of the study based upon the following reasoning : 1) the men had acquired the disease themselves; 2) there was no treatment against tertiary syphilis; 3) “further education would not reduce their inherent sex drive.” and 4) “they were unlikely to seek out treatment otherwise on their own.” The committee also voted to extend the study for longer than 6-9 months. Clark disagreed on both accounts and quit in 1933.

• As World War II began (1939- 1945), understanding syphilis became even more important for American soldiers and the war effort. In 1938, Congress unanimously passed the National Venereal Disease Control Act appropriating  $3,000,000 for anti-VD public health measures. (this was a very large amount especially during the time of the Great Depression). At the forefront was Surgeon General, Dr. Parran, and the Public Health Service (PHS).

Syphilis & WWII (1939-1945)

• 1919 the Comstock laws, at least at the state level, were found to be haphazard and many of the laws overturned.

• Among Americans in 1923-25, syphilis was the 10th most common cause of death in the US. 1927-1931, condoms became standard issue for military soldiers.

• During WWII, venereal disease had disabled and killed more soldiers than the war. 18,000 soldiers a day were incapacitated due to VD (gonorrhea and syphilis). Slogans like “A German whore is more deadly than a German bullet” were common.

• British and American soldiers were given VD kits which included propaganda in addition to condoms. Whoever could “scare the pants on”  their soldiers would have the manpower to win the war.

• 1941- “May Act” -a federal offense to solicit sex near a military base.

• The following is an often told tale which proved to be a hoax-“Adolf Hitler ordered the Borhold Project in which sex dolls called gynoids named Lilli dolls would be produced to deter his soldiers from seeking out French whores. After about 50 dolls were produced, the program was axed in 1942” …But the following is not a hoax:  “Lilli dolls” could be found in nightclubs around Germany. In 1956,  Americans Ruth Handler and her daughter, brought back one of these Lilli dolls to the US and it became the template for their invention of the Barbie doll.

• As another aside, it is often attributed that Adolf Hitler had tertiary syphilis which he talked about incessantly in Mein Kampf (1925), referring to it as the Jewish Disease.”

• One of the PHS duties had been the operation of hospitals for the care of merchant seaman, including its facility on Staten Island under the direction of Dr. John Mahoney. It was under the direction of Dr. Mahoney that penicillin was first successfully used in rabbits with syphilis. (1941). This allowed for human clinical trials by the same group.

• Penicillin was first used clinically in humans in June 1943, when four US soldiers with syphilis were injected with penicillin at a US Marine Hospital on Staten Island. Six IM penicillin injections each day for 8 days! The military found 21 drug companies to make enough penicillin to have by June 6, 1944, D-day. . On June 26th, 1944, the Army adopted penicillin treatment for syphilis as a routine treatment. On March 1st, 1944, Pfizer opened the first commercial plant for large-scale production of penicillin. An antibiotic that cured syphilis helped to win WWII. And syphilis was the instigator of our discovery and use of antibiotics. Dr. John Mahoney was awarded the prestigious Lasker Award for clinical research in 1946 for “distinguished service as a pioneer in the treatment of syphilis with penicillin.”

Tuskegee Syphilis Experiment (post- WWII)

• The Tuskegee Syphilis Experiment was still being performed. Not only were the participants never told they had syphilis,; they were not treated with penicillin by researchers—and actively withheld from getting penicillin treatment made available to underserved communities-as to not skew the experiment’s results.

• These men continued to be untreated until 1972 when a whistle blower by the name of Peter Buxton leaked this experiment to the press. Out of the 400 poor black males in this experiment, 28 died as a direct result of syphilis and 100 died of related complications. Forty of their wives contracted syphilis and nineteen of their children were born with congenital syphilis.

• The Tuskegee Syphilis Study was arguably the most infamous biomedical research study in US history.  This study was being conducted simultaneously as the whole world watched the Nuremberg Trials (November 20, 1945 to October 1, 1946) in horror to find out about the unethical medical experiments done by German Nazi physicians. The Nuremberg trials lead to the international “Nuremberg Code” in which research on disadvantaged human subjects without informed consent is immoral and deemed “a crime against humanity.”

• Also ironic, was the fact that this was the same Tuskegee that had given WWII the famous African American Fighter Pilots (Tuskegee Airmen- 1941) who played an extraordinary role in helping the Allies win the war.

• Because of the press reports in late 1972, the Tuskegee Experiment was ended. Congress enacted the National Research Act in 1974 followed by the Belmont Report in 1979 which required the current “informed consent” laws and  institutional review boards (IRBs) for all medical research conducted in the US. President Clinton on May 16, 1997 offered a formal apology on behalf of the US government.

        “What was done cannot be undone. But we can end the silence . We can stop turning our heads away.

            We can look at you in the eye and finally say on behalf of the American people, what the United States

             government did was shameful, and I am sorry…To our African American citizens, I am sorry that your

            federal government orchestrated a study so clearly racist.”

Five of the eight study survivors attended the White House Ceremony. This public acknowledgement lead to the National Center for Bioethics in Research and Health Care at Tuskegee, Alabama which officially opened in 1999. 51.8 million in damages as well as free medical care for life was provided to the surviving participants and surviving family members.

• However, if one sees the Tuskegee Syphilis Experiment only as a historical wrong concerning race and science; they miss the enigmatic complexity which makes this even more disturbing. This US government partnered with Tuskegee University, a black college, to perform these experiments. The President of Tuskegee Institute was Robert Russa Moton. The head of John Andrews Hospital that performed the testing which included regular spinal taps was Eugene Dibble MD. Both of these men are African American. Most intriguing is Eunice Rivers, an African American RN, who was the primary contact for all of these participants throughout the entire 40 years of the study. It was her relationship with them that kept them going in the studies.

• The Tuskegee Syphilis Experiments were not secret. People at the Tuskegee Institute as well as government officials and people across the nation were aware of this experiment. There were a few voices (Irwin Schatz who was only 4 years out of medical school) who called out the unethical nature of these experiments on unknowing poor men; but the bewildering piece is how many people white and black that stood by for 40 years and said nothing. One can argue that perhaps they did not understand the full story of what was happening, but this is a difficult explanation over many different administrative changes.  John Charles Cutler Jr. was a surgeon, assistant surgeon general of the US (1958), and oversaw the Tuskegee Syphilis Experiment from 1960-1972. He maintained the necessity of not telling these men that had syphilis and not treating them up until the experiment ended. (See his interview on the 1993 NOVA documentary “The Deadly Deception”). Unfortunately, these vulnerable men and their families have paved the ugly path to why we have informed consent and IRBs today.

Terre Haute (1943-1944)

Dr. John Charles Cutler joined the Public Health Service in 1942. In 1943, he worked in the US Public Health Venereal Disease Research Laboratory on Staten Island. His director for general disease research was Dr. John Mahoney.  The experiment involved 241 prisoners from the US Penitentiary in Terre Haute, Indiana. They were given $100, a certificate of merit, and a letter of commendation to the parole board if the researchers could infect them by depositing various strains of gonorrhea into the urethra of their penises. The method of infection proved too unreliable. But here, experimental research on VD had moved from observing already infected men and not treating them, to actively infecting human subjects who were at a disadvantage to take a bribe.

Guatemala Syphilis Experiment (1946-1948)  *2005

• In 2005, Susan Reverby, a Wellesley College professor, while doing research on the Tuskegee Syphilis Experiments, discovered what we now know as the Guatemalan Syphilis Experiments of 1946-48. The goal of this experiment was to find a more suitable prophylaxis for VD. Could penicillin be used prophylactically to prevent syphilis?  This experiment had the support of Dr. Thomas Parran, Executive Officer of the US Army Medical Corps, as well as Dr. John Mahoney and his young associate Dr. John Charles Cutler who was placed in charge of the Guatemala Syphilis Experiment. Clearly, Guatemala was chosen to avoid the ethical constraints related to ethical individual consent, adverse legal consequences and bad publicity.

• The researchers paid prostitutes infected with syphilis to have sex with Guatemalan prisoners and comparing them to subjects who were directly injected with the bacterium. Free cigarettes were given to participants. A total of 1,308 people were involved in the experiments. The age range of subjects were from 10 years old to 72 years of age and included orphans, inmates, psychiatric patients, and school kids. Samples were collected on patients up until 1953. 87% of the syphilis subjects received some form of treatment but 13% could not be located. 83 individuals died during the course of these experiments. These experiments on healthy people remained secret even from Guatemalan officials until 2005. These experiments were funded by the US National Institutes of Health.

•  October 2010, President Barack Obama apologized to President Alvaro Colom and called the experiments “a crime against humanity”—which was the intentional echo of the words at the Nuremberg Trials.

EDITORIAL- What this teaches us about COVID-19?

• Syphilis was a disease used to ostracize groups of people based upon their race (French, Italian, Jewish, German, African-American).  It is vital to understand how this plays out historically, so that one can understand how morally reprehensible it is to call COVID-19 the “Chinese Disease.”

• Syphilis, like many diseases in history (but more) reveals the tension between an individual’s right to their own body and actions; and the public health of a society and its communities. COVID-19 is no exception with regard to masks and physical distancing.

• In disparate situations, “trying something” like mercurials is usually NOT better than not trying something that can kill you. (“One night with Venus is a lifetime with Mercury”).Chloroquine and hydroxychloroquine, and Remsidivir (and the “eye of a newt”) are not worth “trying” blindly without understanding that these kind of desperate blind attempts are almost always a failure, and often harms.

• Using potentially effective treatments ,if associated with socially disapproved behaviors, have always been argued as potentially allowing people to worsen their bad behavior. Historically, this is rarely born out to be true. When “universal masking” was adopted in the US; there were heated arguments in the administration that this will cause people to disregard the 6 foot rule and give people a false sense of protection. Ultimately, universal masking was recommended. If you were concerned enough to mask, this did not make one careless about the 6 foot rule.

• Crisis is a catalyst for changes that might not occur expediently otherwise. With syphilis and WW II, it was the condom and open discussions about the epidemic of venereal disease in the US. For COVID-19, it remains to be seen, but no question we will see widespread changes in the way education, healthcare, business and many other services will be done with less physical contact (“physical distancing”).

• Syphilis “allowed” millions of lives to be saved by forcing the development and widespread production of penicillin. COVID-19 may do that for anti-virals (even more than HIV) and vaccine use.

• We have much required government paperwork with “informed consent” today and IRBs which makes research very difficult to perform because 600 disadvantaged African American men believed their government was protecting them.

• Satan is an Angel. History is complicated. The worst war the world has ever known gave us the greatest medicine the world has ever discovered.   Arguably, World War II could not have been won without African American men from Tuskegee. (Tuskegee Airmen).  Arguably, the greatest US medical ethical atrocity was committed against African American men from Tuskegee.  Dr. John Mahoney, deserves as much historical credit as Fleming and Florey in bringing penicillin, as the first antibiotic, into this world. He should forever be given credit for the countless lives he saved by  his clinical studies at Staten Island. And he should be forever stained with the blind cruelty of what happened at Tuskegee, Terre Haute, and Guatemala. While Americans stood in judgement of Nazi doctors at Nuremberg for “crimes against humanity”; our US Public Health Service was committing “crimes against humanity” among poor African Americans, against US prisoners, and against the most vulnerable of people in Guatemala.

references

1. Parascandala, Sex, science and sin- a history of syphilis in America.
2. Reverby, s Examining Tuskegee: the infamous syphilis study and its legacy.
3. Ethically impossible: STD research in Guatemala from 1946-1948. Presidential commission for the study of bioethical issues.
4. The Deadly Deception (NOVA 1993)

* for fascinating reading on neurosyphilis and the disconnect between brain disease and mental illness, read “When the brain lost it’s mind” (2019) -