THE EVOLUTION OF THE HEALTH CARE WE ENJOY
The characteristic of scientific progress is our knowing that we did not know. (Adapted from French philosopher Gaston Bachelard.)
AMERICAN MEDICAL CARE—A HISTORY
I’m not the only person who has attempted to tell medicine’s story–not a historian by profession, but my medical knowledge is deep seated. When I entered medical school doctors made house calls and people who were having a heart attack were put in a quiet room where they wouldn’t be bothered. I spent the last 40 plus years caring for sick people, interacting with the system, and teaching part time. The world I entered 60 years ago has changed– a lot. I hope you find my approach and insights thoughtful and very real.
A few years back the chairman of the history department at Washington U., St. Louis contacted me. Before I went to medical school I graduated from the University as a history major. A member of the current faculty, he explained, had recently published a book about my craft’s rich tradition. He wanted to know if I was still interested in what 20th century British Historian E. H. Carr called the “unending dialogue between the present and the past.”
The book is the story of a 200 year long journey into the microscopic world that surrounds us. It tells of scientific, institutional, and mechanical advances —big money and politics—and the struggle to deliver care.
Prior to the last two centuries physicians in the West often relied on the teachings of the ancients, like the Greek physician Hippocrates, who concluded that illness, was “due to an imbalance of blood, phlegm, black bile, and yellow bile2;” the Roman Galen who dissected monkeys and wrote about their anatomy.
Over millions of years the creatures that populate our planet have developed defenses against microscopic invaders. Our immune systems are powerful, and our bodies know how to heal fractures, limit blood loss, and much, much more.
Healers, herbalists, prayers, the laying-on of hands, acupuncturists, skilled therapists—and, of course, attitude, fitness, and life’s circumstances have long played, and continue to play an important role in our health and well being.
For most of man’s time on earth, our doctors often served the ill best when they stepped aside or heeded the dictum: “first do no harm.” Even today they aren’t needed very often.
The development of the health care that people in all corners of the world (to a greater or lesser extent) currently enjoy was triggered by discoveries made by a Dutch man named Leeuwenhoek. A contemporary of Rembrandt and Vermeer, he was born in 17th century Delft, a town in Western Holland known for cool foggy summer mornings, numerous boat filled canals, and wide streets connected by wooden bridges. In his day horses and carts clattered across the stones in front of a large open air market. Food and wood were weighed before it was sold. Narrow rows of houses surrounded the town square. Leeuwenhoek’s mother came from a well-to-do brewer’s family, and he started his work life as a draper’s apprentice. He used lenses, such as they were, to check the quality of a fabric’s thread. Over time he became politically active, and spent 40 years as the chamberlain of a city hall assembly chamber.
At age 40 he invented a totally new technique for making lenses. His microscopes were tiny, powerful and revealed a world man had never before seen or suspected. As a result of his decision to keep the process for developing his lenses a secret, some who worked with ordinary polished and ground glass didn’t believe him. He was the earliest man who ever observed tiny bacteria and the first person that visualized and described red blood cells. As he watched this previously unknown world, he drew pictures and sent them to the Royal Society. They published his letters. 4
In 1796 Edward Jenner, a British doc, proved an old wives tale true. He took material from the pussy scabs on a milkmaid’s hand and injected it into the skin of another person. The illness it caused was mild, and the “treated” person was now immune to the highly lethal viral disease, smallpox. Thomas Jefferson and Madison read about Jenner’s findings and Congress passed the Vaccine act in 1813.
During the centuries that preceded Jenner’s revelations, some in parts of Africa, Asia, and later Europe were intentionally infected with live small pox (or technically the variola virus.) Material from”scabs were blown into a person’s nose” or Variola rich pus was dried and scratched into skin. When done right it caused a milder form of the disease.
Two decades before Jenner published his cowpox observations, George Washington watched his defeated troops enter the high, flat ground south of the Schuylkill River at Valley Forge. It was 6 days before Christmas. The skies were grey and foreboding, and a cold wind was most likely blowing off the river. Washington worried about a smallpox outbreak. The disease had recently “raged through Boston.” Most of the British troops were city boys who had been exposed when they were young, and they were immune. Washington’s soldiers were commonly farmers and had not been present during the Smallpox outbreaks that periodically occurred in cities. Battlefield flare-ups had caused deaths, and had contributed to at least one defeat. The continental forces besieging Quebec in 1775 were weakened by a smallpox outbreak and had to withdraw.
The retreating men that Washington observed entering Valley Forge were “without clothes to cover their nakedness, without blankets to lay on, and without shoes.” They walked “through frost and snow without a murmur.” Shelters were just being erected. They had been defeated, would have to fight again, and Washington decided to act. On his orders medical personnel gathered pus from active smallpox lesions and rubbed it into freshly created wounds in each soldier. As Washington explained in his journal, “The need for secrecy was great, as the British would have had a significant advantage had they known of the debilitated condition of the American troops who were recovering from induced smallpox.” The inoculations are said to have caused the deaths of 4 of every 500 soldiers.9
I find the fatality numbers a little hard to believe. Twenty five percent of the men who spent the winter in the valley died. Before they were immunized they were already in a weakened state. People with smallpox are really sick and in epidemics the disease often has a thirty percent mortality rate.
In 1848, one hundred twenty three years after Leeuwenhoek demonstrated the existence of microscopic creatures, no one (best I can tell) connected “germs” and sanitation with infectious illnesses. Washing hands was little more than a cultural or religious ritual. That year a Hungarian physician, Ignaz Semmelweis was working at a hospital in Vienna and was troubled because the women whose babies were delivered by doctors and medical students developed a fever and died 4 times more often than those whose babies were delivered by midwives.47
Semmelweis investigated and learned that the medical students who delivered babies came from the dissecting room to the maternity ward without washing their hands. He introduced hand washing and the death rate plummeted. Unfortunately his fellow physicians continued to believe that the high rate of childbed fever was due “miasmas”, clouds of invisible matter, and Semmelweis lost his job. The son of a prosperous grocer he returned to his hometown, Budapest, and in 1881 published a book on “childbed fever.” In his late 40s, overcome by paranoia and dementia, he was committed to a psychiatric institution. It took a generation before his teachings were widely accepted.11
1848 was also the year that the Frenchman, Louis Pasteur graduated and became a chemistry researcher. An average student as a youth, Louis loved to draw and paint. When he was a teenager he “won first prize in physics” and he went on to study chemistry and physics at the prestigious Ecole Normale. Pasteur was 26 when he married 23 year old Marie Laurent. “According to legend he spent the morning of his wedding day in the lab and became so wrapped up in what he was doing that he had to be reminded to go to church.23”
When he was 32 Pasteur became a professor of chemistry at the University in Lille, a market city near the Belgian border whose streets were paved with stones and whose skies were often grey and rainy. In Lille, and 3 years later in Paris, Pasteur showed his fellow scientists that living organisms, called bacteria caused fermentation. We call it the germ theory. In 1863, working for the French emperor, Napoleon III, Pasteur learned that the contamination of wine could be prevented by heating fermented grape juice to 50–60 °C (120–140 °F). The process of eradicating harmful bacteria at a temperature well below boiling, Pasteurization, bears the scientist’s name.
In 1879 he and his assistants discovered that a culture of bacteria that had been sitting around for a month lost most of its virulence. When injected into a chicken it created a mild infection, and the chicken was subsequently resistant to illness caused by the bug. In the following years his group learned how to weaken a pathogen to the point where it wasn’t harmful, but triggered an immune response.
Could that be what’s happening to the Coronavirus. More people are getting sick but fewer are dying.
Pasteur exploited the phenomenon and developed vaccines for chicken cholera, and anthrax.
In 1885 a rabid dog bit a 9 year old French child. After it enters the body, the Rabies virus infects an axon, the “long slender projections of nerve cells that conduct electrical impulses.” It travels up the axon to the brain and is uniformly lethal.
The oft repeated story says the young man was bitten 15 times and his mother was knocking at Pasteur’s door two days later. Prior to this incident Pasteur had, for some time, been injecting the agent that caused rabies into a series of animals. When the first infected animal died, dried extracts of its spinal cord were harvested and injected into a second, and later a third animal. With each passage the agent became less virulent. Using this technique Pasteur injected the boy with a series of 14 increasingly virulent fragments of dried homogenized rabbit spinal cord.
The boy survived, and Pasteur’s fame grew. For decades thereafter doctors used similar extracts to treat people who were bitten by a rabid creature. .
The Rabies virus is still responsible for the deaths of 59 000 humans a year. 90 percent of the cases in Africa and Asia are caused by dogs. In this country we worry about bats and wild animals, but the U.S. has less than 5 confirmed cases a year. In his later years Pasteur had a series of strokes and he died when he was in his 70s.1
Born 21 years after Pasteur, the other “father” of the germ theory, Robert Koch, seemed destined for greatness since his childhood. He was a star student, and it is said he was reading newspapers at the age of 5. In Germany he simultaneously ran a medical practice, was a district medical officer, and spent hours peering into a microscope. Ultimately isolating the bacterium that causes anthrax in mice, he proved the disease was caused by a germ.
Once doctors had good microscopes they learned that when they dyed objects before they viewed them, it was easier to identify bacteria. Koch stained tissue infected with human and bovine (cow) tuberculosis with his special stains and was able to identify the bacillus that caused each disease. “A plodding worker and a careful seeker of facts, Koch dazzled a group of colleagues one Friday evening in 1882 by proving that the tubercle bacillus was transmissible and that it was the cause of TB in man.” Later he isolated tuberculin, a protein derivative of the bacillus, and he thought it would be curative. (It isn’t) He announced his “cure” in a Berlin auditorium that seated 8000. Some of “the rich and famous sought the treatment. The mystery writer Conan Doyle noted a pile of letters four feet wide and two feet deep on the floor of Koch’s office. All contained pleas for the miracle cure.”
When his “cure” failed and he faced public scorn he wrote his young lover: “as long as you love me I cannot be beaten down.”56 At age 47 he left his wife and married the 18 year old woman who was fascinated with his studies.” “When he inoculated himself with tuberculin, she volunteered to be injected too.”
Before 1870 Germany was a group of kingdoms, and they had been humiliated by Napoleon. In 1870 Germany became a nation and invaded and defeated the once proud French. A few years later the two germ theory “fathers”, Koch and Pasteur were introduced to one another in London. Koch was 47 years old and Pasteur 68 and partially paralyzed. The meeting was cordial, tense, and controversial. Later, in part due a mistranslation of what one said or wrote, each started criticizing the work of the other.24
In 1848, the year Pasteur was a novice chemist, Joseph Lister, the father of modern antisepsis began his medical studies. ” A humble Scotsman with an athletic build he became the surgical apprentice of James Syme, “the greatest surgical teacher of the day.” Lister later married Syme’s eldest daughter and adopted her religion. Born a Quaker he became a Scottish Episcopalian. A few years after he completed his training, he was the surgeon for the Glasgow infirmary and he noticed that half the people who had a limb amputated became septic and died. He’d been reading about Pasteur and germs, and he started treating raw wounds with carbolic acid, a foul-smelling antiseptic that was used to clean sewers. The infection rate dropped to 15%, and the Scots were impressed. They started cleaning and sterilizing the tools they used at the time of surgery. English doctors weren’t convinced until Lister went to London and operated on a fractured kneecap. He wired the bone together, closed the incision, and the wound didn’t become infected.29 At age 56 Lister was named a Baron.20
Florence Nightingale took our awareness of cleanliness up a notch. Born in Florence Italy, hence her name, she was the rebellious daughter of wealthy Brits who didn’t want her to become a nurse. During the disastrous Crimean War between Britain and Russia, (1853-6), she worked at a small hospital in London. A world away in Turkey a muckraking reporter visiting the front lines stopped at a British Military hospital. He found the conditions “appalling”, which no doubt meant poor sanitation; gaping wounds; and bad smells. His newspaper articles detailed what he saw, and his fellow countrymen were incensed. Then a high official made it possible for Florence to get involved, and she and 38 other nurses sailed to Turkey.
At the military hospital in Scutari, sanitation was “neglected and infections were rampant.” There was no clean linen. The clothes of the soldiers were swarming with bugs, lice, and fleas. The floors, walls, and ceilings were filthy, and rats were hiding under the beds. There were no soap, towels, nor basins, and there were only 14 baths for approximately 2000 soldiers. Nightingale purchased towels and provided clean shirts and plenty of soap. She brought food from England, scoured the kitchens, and set her nurses to cleaning up the hospital wards.” A sanitary commission set up by the British government, arrived to flush out the sewers. She may not have had the drugs, blood, or modern day ‘tools’ that can turn an illness around, but she showed that diseased bodies have a remarkable ability to mend themselves. As Florence later wrote, “Sufferings were the result of too little “fresh air, light, warmth, quiet, or cleanliness.”1
Early in the First World War, 8 of every thousand wounded British troops in France developed tetanus, also known as lockjaw. When dirt got into their wound and the skin healed, bacteria were trapped. The germs that didn’t require oxygen thrived. One of the common soil organisms, clostridium tetani, didn’t usually cause a terrible infection but a produced a lethal toxin. After an average of 8 days, after enough of the poison had entered a person’s body, jaws tightened, muscles became rigid, breathing and swallowing became difficult.
The development of a toxoid, an antibody that blocks the venom and prevents “lockjaw” was the result of research performed by 2 men. One, a physician named Shibasaburo Kitasato, was born in a mountainous village on the southern Japanese island, Kyushu. He became a microbiologist and the Japanese government sent him to Berlin, to Koch’s lab. He was the first to grow a pure culture of the tetanus bacillus. In 1890 he and another researcher “injected sub-lethal doses of tetanus toxin into rabbits.” They produced an antitoxin that, when injected, blocked the poison. They did not, however, develop the vaccine that prevents the disease.
It was created in 1924 by a French veterinarian, Gaston Ramon. He inactivated the deadly poison with formaldehyde. Then he added an “adjuvant” a chemical that boosts the immune response to the now weak and no longer lethal toxin.15 His creation, which also led to the development of the injection that prevents diphtheria, saved countless lives and he was nominated for the Nobel Prize 155 times. He never won.
By the time the U.S. entered the Second World War the army was routinely using the vaccine for tetanus. Though there were over 2.5 million wounded soldiers during the conflict only 12 developed cases of lockjaw–tetanus. Four of those individuals probably didn’t get all three shots.
SAFE DRINKING WATER. SANITATION. PARASITES
As a freshman med student I attended a weekly class and was introduced to a large number of bizarre appearing microscopic creatures. I don’t recall a final exam, but I’ll never forget the take home message. It was written on the chalk board by the good natured Japanese professor and is probably the only thing that most of the giggling medical students remember to this day. DES. Don’t Eat Shit.
By the time I entered school the discoveries of Pasteur, Koch, and Lister were ancient history and a whole new class of invaders called parasites had been identified. Dozens of scientists had isolated and studied the life cycle of one creature after another. We learned that when people defecate in the open (and half a billion people in India still do) bacteria and parasites are deposited in the dirt and they get into our rivers. Some of the organisms can enter the bodies of the animals and fish that we sometimes eat raw. When we walk barefoot on ground where someone previously defecated, parasites can penetrate the soles of our feet.
Humans currently co-exist with 90 common species of parasites. Most are mainly found in the tropics. Some were apparently inherited from our primate ancestors in Africa. The tape and round worms that live in our intestines and thus share our meals were visible to the naked eyes of Hippocrates and physicians of Rome, China, and the first millennium of the Arab Empire.
Most of the parasite life cycles were worked out by researchers all over the globe before the Second World War. There are a number of drugs with a variety of toxicities that have been developed and can kill the creatures. They aren’t needed much in our world. Parasites are not a major problem in most places that have good sewage, vector control, and clean water. But a problem may be brewing. Close to 200,000 Americans sleep outside most nights and the government doesn’t provide adequate facilities to protect them, and in turn protect us from the microscopic creatures.
Patented in 1975 by Smith Kline, the drug that’s used to kill the parasites that live in the intestines of many was created by Robert J. Gyurik and Vassilios J.Theodorides, after Vassilios read an article, had a sudden insight, and sketched the chemical structure of the future medication. Raised in a small Greek village near the Macedonian border, the drug’s inventor, Vassilios, starts the tale of his youth on the morning in 1941 when 400 German soldiers surrounded his town and marched its 1600 occupants to the village center. He was 10 years old. The soldiers told everyone to bring out their guns. Then they searched the houses. Finding shotguns in two homes they tied the owners of the weapons to a tree and publicly shot them. Later that day a German soldier was searching Vassilios house. He saw a shotgun behind a door and motioned to Vassilios–hide it. When he left Vassilios threw the gun in the bushes and was grateful. To attend school the young man had to walk an hour and a half to another village. He was in that nearby town the day in 1947 that Communist soldiers burned his village and killed 48 people. Some were relatives. A good student, Vassilios found school to be easy and interesting. After he finished high school, planning to become a mathematician, he visited the university office and asked where the mathematics school was. The clerk asked: what’s wrong with the Veterinary school? And he decided to give it a shot. As a veterinary student he developed an interest in research and decided he needed a PhD. His future wife’s family emigrated to Boston and Vassilios decided to follow her. He came to the U.S., married the girl, earned a PhD, and worked for Pfizer in Terra Haute Indiana for two years. There were only two Greek families in town. The other Greek was the mayor. Vassilios’ wife was unhappy and they moved to Pennsylvania where he got a research job at Smith Kline and French laboratories.
A few years later he read an article, and had an “aha” moment. Unexplainably he somehow “knew” the steps he would have to take to create the chemical that became Albendazole. (Quoting Pasteur he explained “God helps the minds that are prepared.”) Introduced in 1977, the medication was initially given to animals in Australia and New Zealand, but it was not approved for people in the U.S. Someone at the FDA decided it was carcinogenic. Vassilios met with people at the agency and showed them that their “mathematical approach in evaluating its potential carcinogenicity was incorrect.” They agreed and humans started using it in 1982.
Twenty eight years later the company that owned the drug had merged with 2 other pharmaceutical giants and was called GlaxoSmithKline, (GSK). It had offices in over 100 countries, and was headquartered in Brenford, a “town” in greater London where Julius Caesar crossed the Thames River during his 54 BC invasion of Britain. In October 2010, the drug had become a financial loser and the company dumped/sold it. The marketing rights for albendazole, a major anti-parasitic drug was picked up by Amedra pharmaceuticals, a small American drug company. The details of the deal were not disclosed (or at least I couldn’t find them on the web.) As part of the agreement GSK agreed to continue manufacturing the drug for Amedra in the short run. They also renewed their pledge to the World Health Organization. They would continue to give the organization 600 million tablets per year as their contribution to the struggle to free the world from Lymphatic Filiariasis.
As explained by the CDC: “Lymphatic Filiariasis (LF) is a mosquito-borne parasitic disease caused by microscopic, thread-like worms. They “inhabit the lymphatic and subcutaneous tissues” and prevent liquid from flowing through the lymphatic vessels. The country roads of the body, these vessels flow in an upward direction and pass through lymph nodes that filter toxins. The fluid within them transports infection fighting white cells and empties into the large veins on either side of the neck.
Filiariasis affects 120 million people in 80 countries. People develop swollen limbs, breasts and scrotums and their skin becomes thick and hard.” The Global Alliance is trying to rid the planet of the condition by annually giving albendazole and Ivermectin to all of the occupants of communities that are at risk.3
The year after Amedra bought Albendazole, Teva, stopped manufacturing the drug’s only U.S. competitor, Mebendazole (brand name-Vermox) and Amedra became the only U.S. player in the intestinal parasite business. With the U.S. rights in their pocket, its new owner raised the cost dramatically. In late 2010, the average wholesale price for the medication was “$5.92 per typical daily dose”. By 2013 it had jumped to $119.58.
In India Albendazole commonly sells for $18. According to Wiki, in some countries it costs a penny to 6 cents a dose.
The parasites albendazole targets, helminthes, live in the intestines of a billion people. Usually acquired in childhood, the creatures are sometimes ingested with tainted food and water. When mature, some can penetrate the skin of a child or adult who walks “barefoot on contaminated soil.” Much as a butterfly spends part of its existence as a caterpillar, the parasites who camp in our bodies have a life cycle. Some spend part of their existence in a cow, pig or fish and gain entrance when people eat raw meat or uncooked fish. As Giovanni Grassi, an almost world famous Italian researcher (he should have shared the Nobel Prize for Malaria) demonstrated in 1881, the worms can go directly from man to man. He started his experiment by examining his feces to prove he wasn’t infected. Then he ate ascaris eggs. A bit later he found the parasite in his feces. In 1922 a Japanese pediatrician, Shimesu Koino one-upped Grassi when he ingested ascaris eggs and found worms in his sputum. Such, as they say, is how research on parasites was performed.
Medicaid spent less than $100,000 per year on Albendazole in 2008, and more than $7.5 million in 2013. Doctors in this country are prescribing it more often because the CDC thinks we should presume that refugees that come here from poor countries have parasites in their intestines, and we should treat them. Part of the increased spending is the result of increased demand.
One day when my grandson, who had never lived in a third world country, was 3 or 4, he passed a worm. My daughter checked the internet, identified the creature and put it in a jar. When she showed it to her doctor he was taken aback– amazed. His nurse, on the other hand, merely shrugged. No big deal. She had grown up in a village in the Philippines. We still have no clue as to where or how the worm got in the kid’s body.
In the early part of the 19th century objects seen through the microscopes of the day were sometimes blurry or distorted. A century earlier Van Leeuwenhoek had learned how to magnify objects 250 fold with a single tiny lens. He produced 500 gadgets but didn’t teach others how to make them and no one knew how to make “his kind” of lens. Robert Hooker, his British contemporary used a different type of magnifying device when he studied plants. Looking through a pair of lined up pieces of glass, his ability to see tiny objects depended on the quality of his lenses. A jack of many trades, Hooke was also a surveyor and, as an architect, helped design the buildings that replaced those destroyed by the Great Fire of London in 1666.
The quality of the microscopes produced during the early 1800s was variable. Then two German mechanics independently started to manufacture really good lenses and microscopes. One of them, Carl Zeiss, came from a German family of artisans and apprenticed with a maker of fine tools. In 1846 he opened a mechanical workshop in Jena, a river valley town in the “green heart” region of eastern Germany. His microscopes were simple. Lenses were the result of trial and error. Poor quality scopes were destroyed. 20 years later a mathematics professor, Ernest Abbe joined the company. He introduced mathematical modeling (whatever that is) and the company started producing microscopes that allowed observers to see tiny objects clearly, and a number of parasites that had not, previously, been visible were identified.
In the late 1880s Charles Laveran, a French military doctor, was gazing through a powerful microscope and saw pigment and motionless bodies in the red blood cells of some people with Malaria. He was stationed, at the time, in Bone Algeria, a colonial city on the Mediterranean coast. Thinking what he saw might be significant he “meticulously examined the blood of 200 patients and observed crescent bodies in all cases of malaria” but never in the blood of people who didn’t have malaria. Lavern presented his findings to his fellow doctors, and many thought he was seeing disintegrating red blood cells. By 1884 Italian researchers looking through advanced microscopes were also able to “observe amoeboid movement of the organisms” and Laveran’s findings were validated.
The parasite that causes Malaria lives in the liver and attacks oxygen carrying red blood cells. Historically a major cause of death and disability the disease has been around for hundreds of years. In 1898 the Italian, Giovanni Grassi proved that “mosquitoes that fed on infected patients transmitted the parasite to uninfected individuals. About the same time Richard Ross performed similar studies in India. A British physician who preferred to spend his time writing novels and poetry, Ross didn’t believe in the mosquito theory, but he kept receiving bothersome letters promoting the mosquito hypothesis from a Scottish physician he met in London named Patrick Manson. In 1898 Ross finally did the research, and failed because he used the wrong mosquito. Eventually Ross proved that mosquitos carry the infection from one person to another and he received the Nobel Prize. The Italians who made a similar finding weren’t honored. And there were doubters. To convince nonbelievers Manson shipped a number of infected mosquitos from Rome to the middle of London. The trip by ship took 48 hours and some of the mosquitos died en route. When they arrived Manson allowed one of the mosquitos to infect his son. The young man got sick, but was cured with quinine.
Malaria remains a huge worldwide problem. In 2019, 228 million people were infected with the parasite. 400,000 of them, two thirds of which were children died. That year there were only 2000 cases in the U.S. Most occurred in immigrants or people returning from an at-risk area.
Over the last century and a half, we’ve learned a lot about the illness. Many generations of drugs have been developed. But the disease is only absent from much of the world because most countries that are politically and technically able, are controlling the vectors that spread it.
When the French tried to build a canal between the Atlantic and Pacific Oceans at Panama in the late 1800s no one knew that Malaria and another tropical disease, Yellow Fever, were transmitted from one person to another by mosquitos. Then an American military doctor had a theory and performed a study.
The research was conducted in 1900 in Cuba. At the time the island was occupied by U.S. soldiers. America had won a war with Spain in 1898, and had freed the island from the European colonizer. Cuba would become independent in 1902. In 1898 there was an outbreak of Yellow Fever among American soldiers who were stationed on the island.
Doctors currently believe the virus that causes the infection originally came from the rain forests of Africa, was around for centuries, and was brought to the New World by slave traders. Infected people develop headaches, fever, and bleed easily. Many develop shock and die. The doctors who cared for the sick soldiers in Cuba apparently thought the illness was caused by mysterious “fomites.”
The U.S. government sent Major Walter Reed to the island of rum and cigars to investigate. A military physician who had spent 17 years in the arid American West, Reed suspected Yellow Fever was transmitted by mosquitos. He met with the doctors caring for the ill, and they were willing to check out his theory. Volunteers, some of whom were ill and others who were well, were housed in a barracks. Mosquitos were collected and the insects were allowed to use the tip of their straw-like mouth to pierce each person’s skin.
One of the apparently skeptical doctors conducting the investigation “submitted to the bite of a creature that had fed on an infected soldier.” He joked “if there is anything to the mosquito theory, I should have had a good dose.” A week later his life was in the balance for three days.
A fellow doctor who brought the mosquitoes from one soldier to another noticed a bug on his hand. He allowed it to suck his blood. A week later he became febrile, delirious, started vomiting, had seizures and died. As one of the infected who survived put it: “such is yellow fever.”
We now know the illness is caused by a virus and there is an effective vaccine. But Yellow Fever still annually causes 200,000 infections and 30,000 deaths in central Africa and South America.
A few decades before doctors knew mosquitoes transmit malaria and yellow fever, French promoters were encouraged by the creation of the Suez Canal. It took ten years to build and the waterway opened in 1869. The promoters decided to build an ocean to ocean passage way in Panama. Convincing investors that the task wouldn’t be very expensive or difficult, they raised money from over 200,000 people. After 20,000 workers from the West Indies were recruited, a Frenchman named Jules Dingler was put in charge. When he went to Panama, Dingler brought his family. He “is credited with having said that “only drunkards and the dissipated contract yellow fever and die.” During his early years on the job Dingler’s son, daughter and wife each contracted the infection. None of them survived. Dingler returned to France a man broken in mind and body. Unlike Suez, the Panama terrain turned out to be challenging. Between 1881 and 1889 over 20,000 laborers who toiled in the thick rain forests died. That year the company funding the project declared bankruptcy and the French abandoned the project.42
In 1904, when the U.S. started building the Panama Canal, the people in charge knew that the mosquito transmitted Malaria and Yellow Fever. Engineers “drained pools of water, cut all the brush and grass near villages, and constructed drainage ditches. Larvae were oiled and killed with an insecticide. Screens were placed on windows and doors, and “collectors were hired to gather the adult mosquitoes that remained in the houses and tents during the daytime.”
A totally different kind of parasite lives in the bodies of millions of people in sub-Saharan Africa, some South American countries, parts of the Caribbean, and a few countries in Asia. It’s called Shistosomiasis, and in 1960 the U.S. Army had a research lab in Puerto Rico that was studying the creature. I spent one med school summer on the balmy island of Puerto Rico, working in a research lab on a bluff overlooking the Caribbean. A fellow student and I would drive to an inland body of water, put on protective hip boots and trudge into the ponds. The snails of Puerto Rico are part of the life cycle of a parasite. An intermediate life form of the creature penetrates the skin of people who wade in the island’s fresh water ponds. They make their way to a person’s liver and dig in, sometimes causing significant damage. We scooped the snails up with a net, carried them back to the lab, and placed them in sunlight. They discharged “shed” miniscule worms. We gathered the worms, they are called cercareiae. And we put them into test tubes. Then we dipped the tails of mice into the liquid. Weeks later we studied the infected mice.
In the 20th century we learned of at least one malaria like parasite that is transmitted by a tick. Called Babesiosis, it enters bodies when the tick bites and it invades red cells, causing chills and fever. It can be lethal.
The most common infection that ticks spread is caused by a bacteria that’s technically a spirochete. Called Lyme disease it is named for the town in Connecticut where it was identified. In the mid 1970s Mrs. Murray, an artist who had been living in a house near a picture post card rural country road for 15 years, developed rashes, painful swollen joints, and numbness and weakness. Over the years she got worse. She was hospitalized three times and unable to paint. Some thought she was a hypochondriac. Then her son developed joint pain and he couldn’t smile. He had Bell’s palsy and his facial muscles didn’t work. Another son developed a rash behind his knee and others in the town got ill. It took a while before a young Yale physician and others discovered that some ticks carry a bacteria– a spirochete. When the ticks bite the spirochetes are injected into a person’s body. It often takes decades before the creatures causing Lyme have done their worst.
During the last century we’ve learned, one by one, about the diseases that are transmitted by the bites of a ticks hiding in the long grass we hike through, the nearby woodlands, or the fur of a four legged companion. The brown dog tick can carry the bacteria responsible for Rocky Mountain spotted fever. It’s an infection that makes people quite ill but thanks to doxycycline is only lethal one time in 200. The bite of black legged ticks of the North East and Great Lakes area can introduce our bodies to Anaplasmosis, a bacterium that causes chills and fever and responds to antibiotic. And there are others.
Cities in Western Europe and the U.S. didn’t have running water until sometime in the 1800s. Initially there was only one tap per neighborhood or large apartment building.22 Some claim that the chlorination of our drinking water may be “the most significant public health advance of the millennium.” The practice was prompted by the realization, in the late 1800s, that bacteria were the cause waterborne infections like typhoid fever, dysentery, and cholera. About the same time scientists learned that the element chlorine kills bugs. When a municipal water sand filter failed in a city in England in 1905 there was a typhoid outbreak, and the city started adding chlorine to their municipal water. Three years later Jersey City, New Jersey started chlorinating city water. Chlorine is currently added to “over 98 percent of all U.S. municipal water,” and outbreaks of typhoid fever have been virtually eliminated. (Chlorine does not kill parasites like Giardia and Cryptosporidium.)
In the last century we’ve learned a lot about diarrheal diseases and their treatment. But the slums of many third world cities don’t have good plumbing. Much of the world’s fresh water is contaminated. For half of the world’s people governments haven’t been able to solve the problem.44 One in 9 childhood deaths are the result of diarrhea and the culprits responsible include bacteria like E. coli, salmonella, shigella, and cholera.
In addition to the drinking water, E.coli was recently found in Romaine lettuce grown downstream from an area where cattle were confined. In 1987 sewage from farm animals infected with the parasite cryptosporidium overflowed in Georgia and 13,000 people developed diarrhea.43
When I was a freshman med student a biochemistry professor who looked like the movie star Robert Wagner was trying to prove that water didn’t just seep into our bodies through the wall of the small intestine. Salt and water are sometimes pushed in by a biochemical pump fueled by glucose.63
I took notes and passed the exam, but I didn’t get it. Why would a person spend years of his life working on the way salt and water moves across a membrane. ?
Years later I learned that when the cholera bacteria infect the small bowel the bug causes a huge amount of fluid to leak into the intestines. People don’t absorb liquid normally, they develop watery diarrhea, and many die of dehydration.
Our lecturer, Robert Crane showed that if a teaspoon of salt and two tablespoons of sugar are added to a liter of clean water, the solution is absorbed and the person can be rehydrated. His simple formula has saved more lives than most of the $100,000 a year drugs being advertised on television. Somebody bottled it and called it Pedialyte.
Self described as a problem solver, Crane was born in New Jersey and didn’t develop an interest in science until he was a freshman in college. During the Second World War he was a deck officer on a navy destroyer that took a bomb at the battle of Leyte Gulf and was later part of the screen of ships that carried Douglas MacArthur back to the Philippines. He got his PhD in chemistry at Harvard, married a biochemist, and spent more than a decade performing research in St Louis. In 1978 he was awarded the Nobel Prize .
Cholera has only been a problem in the western world for a little over 200 years. It first came to our attention after an epidemic in 1817 started in the Ganges Delta of India and it was spread by ships trading goods in Thailand, China, and Japan. Millions got sick. Three decades later the third world wide cholera pandemic struck. There were outbreaks in Europe and the Americas. At the time people in London didn’t have piped in drinking water or flush toilets. Most got their water from communal pumps. Sewage and untreated human waste was dumped in the Thames and the river smelled.
The epidemic of 1854 started in the Soho district of London. John Snow a physician lived nearby. A vegetarian and teetotaler who liked to swim, Snow suspected the source of the infection was contaminated water. He mapped the location of the people who got sick and convinced town officials that the Broad Street pump was the source of the epidemic. They removed the pump handle and the epidemic “almost immediately” trickled to a stop. Snow, not surprisingly, was subsequently disbelieved and denounced.
In 1991 a massive Hurricane blew across Hispanola, the Caribbean island that is shared by the Dominican Republic and Haiti. At the time there hadn’t been cases of cholera in the country for more than a hundred years. The U.N. brought in relief workers from Bangladesh and they lived with the people. 70% of Haitian households had either rudimentary toilets or none at all. A few months after the volunteers arrived, the water people drank contained the kind of Cholera bacteria that infects the people of Bangladesh. 665,000 Haitians were infected and over 8000 died. 15 years later a non-profit called SOIL is supplying compostable toilets and trying to help solve the island’s waste problem.62
In recent decades the Center for Disease control has been informing all about common and rare conditions with concise, disease specific posts on the internet. They have a free newsletter, the Morbidity and Mortality Weekly report.
Located in Atlanta Georgia, the federal agency was created a little over 70 years ago. In its early days it concentrated on mini epidemics. I recall a hepatitis outbreak in 1963. It affected a number of the doctors and nurses who worked at the hospital where I was an intern. The CDC sent a young sleuth. He checked our plumbing, drew our blood, and inspected our kitchens. It took a month but he figured out where and how the illness started. When I was in the military a friend who was sent to help immunize a tribe of Native Americans in the state of Washington came through town. My brother-in-law was sent overseas to help determine the dose of gamma globulin that would keep soldiers in Viet Nam from getting hepatitis. Currently a $6.6 billion a year department of the public health service, the agency collects data on acute and chronic diseases and makes recommendations. Their epidemiologists investigate outbreaks, and they provide the laboratory and pharmacy of last resort for rare infectious diseases. According to the Kaiser Health news, experts say that “under President Donald Trump, the CDC has become a non-entity in the battle against the coronavirus.“59
In the early 1900s house calls were common. People who had suffered heart attacks, strokes, or major trauma were often cared for at home. Adequate anesthesia made elective surgery painless. But in the decades that preceded blood banking and antibiotics, cutting a body open was risky.
As always, in addition to physicians mankind had healers– people whose trained hands can detect and correct displaced bones; experts who know how to turn certain plants and herbs into balms— how certain foods affect some ailments– or how to therapeutically massage muscles or stimulate acupressure points. Gurus and religious leaders employed prayer, meditation, and positive thinking to improve the lot of sufferers. There’s a mysterious and often powerful healing process we call the placebo effect. We become aware of it each time two groups of people are studied and one faction gets a potion that should promote healing–and the others get a sugar pill.—a placebo. Depending on what’s being studied, many in the placebo group often improve or get well.
In the late 19th and early 20th centuries a number of hormones were discovered and isolated. We learned what endocrine glands do and how they go wrong.
Hormones are chemical messengers. They are created in an “endocrine gland” then travel by blood and other mechanisms to parts of the body where they do their thing. If a man is given estrogens he grows breasts. If a woman is given male hormones she grows a beard.
Thyroid and adrenal hormones help regulate many of the body’s metabolic and other functions. When either is totally absent people wither and die. They are “vital.” Adrenal glands sit atop the kidney.
The thyroid gland is located in the middle of the neck, just below the voice box and above the chest. The story of the gland and the hormones it produces is both old and new, and is complex enough to deserve a chapter or a book. (and that’s not where I’m going.)
When a body lacks iodide the gland enlarges, looks like a tumor, and is called a goiter. Thousands of years ago Chinese physicians successfully treated the protuberance with seaweed. Iodine is currently add to the salt in over a hundred countries, including Canada and Mexico. In the U.S. fortification is voluntary, companies don’t have to mention the iodine content of their product on the label, and processed foods use non iodinated salt, so it’s still a potential problem.64,65 The growth of newborns who don’t make enough thyroid hormone is stunted. They can develop physical deformities, and neurologic impairment.” The condition called cretinism was recognized over a number of years by a few physicians. In 1891 George R. Murray, a 26 year old physician who didn’t have a hospital or medical school appointment, obtained fresh sheep’s thyroid from a slaughterhouse, prepared an extract, and injected it under the skin of a woman who looked like she was markedly deficient in thyroid. When she improved he published his experience. Though others have probably used similar treatments in long ago China and Europe, Murray was the first rooster to crow and experts usually give him credit.60,61
During the last 200 years numerous observers have periodically peeled a bit more of the thyroid onion and progress has preceded stepwise. The major advance that garnered the attention of the Nobel Prize committee occurred in Bern Switzerland near the end of the 19th century. The mortality for the resection of the thyroid gland had been quite high and it dropped dramatically when a surgeon named Theodore Kocher performed the procedure. His operations were “meticulous with minimal blood loss. It was a rather slow procedure with occasional spectators becoming quite irritated. Not fast, but safe, was his advice to young surgeons. Using this technique, by 1912, Kocher had performed approximately 5000 thyroidectomy operations, with mortality being only 0.5%.” For this accomplishment and for his studies on the gland and how hormones function he received the Nobel Prize in 1909. Born in Bern Switzerland, Kocher studied, married, and spent his surgical career in the centuries old city encircled on three sides by the Aare River. A colonel in the Swiss militia he spent much of his non medical time trying to get the makers of weapons to create missiles that didn’t deform and were “intentionally less lethal.”
Three people got the Nobel Prize for cortisone. The first, Phillip Hench was a Mayo Clinic rheumatologist who loved Sherlock Holmes and had “one of the more remarkable Sherlockian libraries ever assembled.” He liked mysteries and wanted to understand why his patient with jaundice suddenly got well or a woman he was caring for who had severe rheumatoid arthritis improved dramatically when she was pregnant. Some hormone had to be responsible.
His “Watson” was Edward Kendall, Mayo’s chief of Biochemistry. Described as a charismatic man with a generous personality, by one writer—and as a person who “often didn’t get along well with his colleagues” by another he spent the greater part of his professional life standing before a lab bench. Working with 150 tons of adrenal glands, he extracted 9 million dollars worth of epinephrine for Parke Davis and kept the material the company didn’t want. Later he separated 5 cortical compounds from the organs.13
Collaborating with Hench, Kendall checked the people’s urine and blood and found adrenal compounds in both of the patients. Kendall gave Hench minute amounts of one his adrenal extracts and Hench gave it to volunteers with arthritis. It didn’t help.
About that time they met Tadeus Reichstein. He was a Swiss researcher who was born in Poland and had been named for Tadeusz Kościuszko, the Polish national hero who fought in the continental army during the American Revolution. Tadeusz had learned how to extract adrenal hormones from bile. I’m not sure what happened next but Dr Kendall and biochemists from Merck & Company produced 9 grams of adrenal “extract E.” In 1948 it was given to a patient with rheumatoid arthritis and “The resulting improvement was amazing,” all three were given the Nobel Prize.
In 1940 war seemed likely and the government funded cortisone research allegedly because they believed the hormone would allow pilots to fly up to 40,000 feet without oxygen. Cortisone and hydrocortisone became available after the Second World War: The hormone saved Jack Kennedy’s life.7 Kennedy was the 35th U.S. president and the son of a wealthy Irish immigrant. He was diagnosed as having Addison’s, having adrenal glands that didn’t make enough cortisone in the 1940s. People with the condition—Addison’s disease, are anemic, have abdominal pain, and lose weight. Some have weak muscles and get dizzy when they stand. The disease is usually the result of an immune system disorder. 20% of time Tuberculosis is the offender. When young Jack fought with his older brother he was always on the short end. As an adult Kennedy collapsed twice: once on a congressional visit to Britain and a second time at the end of an election campaign parade. That time “the diagnosing physician commented told one of Kennedy’s friends: “That young American friend of yours, he hasn’t got a year to live.35”
The body makes insulin in the islets of Langerhans, groups of cells that are scattered throughout the pancreas. The hormone allows sugar to enter muscles and fat. When sugar can’t get into the cells, the level of glucose in the blood rises. People with juvenile diabetes have, over months to years, lost the ability to make insulin because their immune system has destroyed their beta, insulin producing cells.
Prior to 1920 scientists knew where the hormone was made, but they didn’t know how to extract it. Most of the pancreas makes digestive enzymes. When activated they divide the bonds that link the amino acids together to form proteins. Insulin is one of many proteins that are “digested “when the pancreatic enzymes become functional. In the early 1920s two Canadian scientists tied off a dog’s pancreatic ducts and managed to keep the dog alive long enough for the pancreas to destroy itself. Then they removed the organ, chopped it into pieces, mixed it with saline, and filtered an extract. As they hoped, the activated enzymes had digested most of the pancreas, but they hadn’t destroyed insulin.3
The discovery was momentous. A fatal disease could be controlled. For complex reasons the Nobel Prize for the breakthrough was only awarded to Fred Banting one of the investigators who did the work. His student, Charles Best, performed most of the testing but, according to Banting, “was never credited with proposals that advanced the research.” The other half of the Nobel Prize for insulin was given to the head of the department, J.R. Macleod.
That bothered Best. He “developed a deep psychological hunger for recognition as a discoverer of insulin.” During the subsequent decades he and Banting worked together and “Banting developed an intense dislike of Best.” In 1940 Best was invited to come to London and Banting, now the head of the department, wouldn’t allow Best to go. Banting decided he would go instead. Before boarding the plane for war torn London, Banting’s last words were: “If they ever give that chair of mine to that son of a bitch, Best, I’ll roll over in my grave.” His plane crashed in Newfoundland, and he died.25
In 1935 a German physician and chemist discovered the first antibiotic, sulfa. (See chapter on FDA) Chloral hydrate, the first synthetic hypnotic was introduced in 1869, and in 1860 Albert Niemann, a German chemistry student “extracted cocaine from coca leaves and found and wrote that “when applied to the tongue it left a peculiar numbness.”
By the time I became a physician narcotics had long been used for pain control and had an age-old disreputable history. Mentioned 4000 years ago by Aristotle’s buddy Theophratus, the extract of the poppy plant, was long known as a drug that relieved pain, affected moods, and created a craving and an addiction.
In the 1700s the British developed a love for tea grown in China and the UK was shelling out a lot of silver for the leaves. Needing a commodity the Chinese would buy, the Brits grew poppies in India and peddled its extract, opium, in China. It sold well. Many got addicted and silver started flowing back to England. By the 1800s Chinese leaders, troubled by the way the drug affected the people and upset because so much silver was leaving the country, started the world’s first war on drugs. They forbade the British from trafficking opium. The Brits responded by sending 16 warships. They “arrived at Guangzhou, bombarded forts, fought battles,” and won the first opium war. As spoils of their victory, the English gained control of the island of Hong Kong and access to 5 Chinese ports.
In the early 1800s at a time when purified plant extracts were used as medicines, Wilhelm Serturner was an apprentice apothecary in Paderhorn. The town bordered Germany’s shortest river and had been founded by Charlemagne in the eighth century. After separating “morphine crystals from tarry poppy seed juice,” Serturner learned the crystals put stray dogs and rats to sleep. Taking “a small quantity” for a tooth ache, he “experienced tremendous relief.” A low dose made three volunteers “happy and light headed,” and at a higher dose caused “confusion.58” Over time Serturner became an addict. He was once described as a person with “aggravated hypochondriacal alterations in his frame of mind and quiet disturbances of mood.59”
In 1844 Francis Rynd, a Dublin physician who hunted foxes and was “in much demand at “fashionable dinner parties”, invented the hollow metal needle. A decade later a physician in Edinburg and another in France independently invented the syringe. In the process they helped people in pain and created an instrument that would lead to countless infections and the addiction of many.
In 1897 two traveling salesmen from North Carolina met at a train station in Texas and learned they had the same birthday. A decade later, now entrepreneurs, Beckton and Dickinson started the first U.S. facility that produced hypodermic needles and syringes.
In the 1930s German chemists almost accidentally discovered the first synthetic pain relieving and addicting drug, meperidine—Demerol. In the subsequent century chemists developed a number of additional synthetic narcotics. One was created in 1953 by a group of European chemists led by Paul Janssen of Belgium. They added carbons, benzene and other chemicals to the part of meperidine that causes sedation and analgesia and in 1960 came up with fentanyl. The drug is 100 to 200 times more potent than morphine. I used it on patients when I performed colonoscopies. Doctors like it. Owned by Johnson and Johnson, it has recently been the cause of a number of over dose deaths.
In June 1971 President Nixon declared the U.S. war on drugs. Over the subsequent decades the Federal Drug Enforcement Agency grew to a force of over 10,000. In 2016 about 200,000 Americans were incarcerated for Drug offenses. And In 2018, over 67,000 people in the U.S. died from a narcotic overdose.
D. THE SECOND WORLD WAR
Penicillin became available during the Second World War. It was discovered in the 1920s by Alexander Fleming, a Professor of Bacteriology at the University of London and a medical officer in World War I. He was known by colleagues because he once had a cold, dropped mucous into a petri dish full of bacteria, and left it there forgotten, for two weeks. “Not known for fastidious laboratory organization, he placed the dish among the clutter at his desk.26” When he came back he noticed that his bugs were gone. He investigated and discovered lysozyme, the enzyme in tears and saliva that was responsible. He wrote up his finding and his account was published.
On another occasion he noted that fluid coming from a penicillium mold growing in one of his Petri dishes killed the bacteria in the container. He tried to isolate the juice—which he called penicillin after the mold that produced it. He was only able to collect a small amount, but he did write another article and it was published in a medical journal.
A decade later a group of Brits led by Howard Florey (a pathology professor) and Norman Heatley got interested in Fleming’s fluid. They got hold of the Penicillium mold and extracted enough to treat a few lab animals. In May of 1940 “they infected eight mice with a fatal dose of streptococcus. Four of the creatures were then injected with penicillin. Hours later “the untreated mice were dead and the penicillin-treated mice were still alive…. Penicillin’s spectacular possibilities were obvious.” More needed to be done, but Britain was at war and Florey’s research could not proceed. That’s why he and Heatley brought some of the mould to the U.S. They convinced scientists at the agricultural research lab in Peoria Illinois to help them search for a Penicillium mold that would produce more than a trickle of the magic juice. One of the labs mycologists, Kenneth Raper, found the super mold growing on a cantaloupe in a nearby store. It was “50 times more potent than anything previously tested, and it became the primogenitor for almost all of the world’s penicillin.” The group then looked for companies that could generate large amounts of the antibiotic and Pfizer stepped up big time. Their engineers knew had learned how to ferment gluconic acid in deep tanks and Pfizer purchased an old ice plant in Brooklyn that contained fourteen 7,500-gallon tanks. Then they converted the building into a highly productive penicillin factory.65 After the war the company manufactured a second antibiotic, streptomycin, and later a third antibiotic, Terramycin.
In the decades before I entered the profession, students spent a lot of time learning about two of mankind’s chronic transmissible diseases: Syphilis and Tuberculosis. Scientists still aren’t sure if Syphilis arrived in the New World in the body of one of Columbus’ sailors or whether the bacilli was acquired from inhabitants of the Americas and, along with maize and potatoes, was brought to Europe. Some are still periodically examining the remains of ancient humans and looking for evidence.
In my days as a doctor syphilis was called the great imitator. If someone got sick and syphilis was the possible cause of the problem we were taught to always rule it out.
By the 1950s a blood test for its presence, the VDRL was drawn every time a person entered a hospital or obtained a marriage license. The test was invented before the World War I in a US public health service “venereal disease research lab”, hence its name. The test detects the antibody a person started making when they were infected by syphilis. Once penicillin, became available we could cure the disease and its incidence in the U.S. dropped. But it didn’t go away and “Syphilis still occasionally presents with non-typical features in a person who has another sexually transmitted disease, HIV.
The bacillus that causes the other chronic infection that has tormented mankind for thousands of years, tuberculosis, was identified in 1882 by the German physician, Robert Koch. Many seemed to cure their disease by spending a year in a sanatorium, breathing clean air and leading a healthy life. In the 1950s doctors were able to successfully treat most TB infections with a combination of antibiotics: streptomycin, discovered in 1943, INH in 1952, and Rifampin in 1963. Between 1954 and 1985 the number of infected people in the U.S. dropped from 80,000 to 20,000, and experts predicted that within a few decades TB would disappear. They were wrong. Poverty, HIV, and bacterial resistance reversed the trend, and the incidence of T.B. started to rise.
One of 4 people alive today, at some point in their lives was infected by the cough of a person with tuberculosis. 90 percent didn’t get sick. They mounted a cell mediated immune response and their body encased and imprisoned the bug, but didn’t kill it. It sometimes escapes. 10 million people currently have an active infection and a million and a half die each year.19
When I started medical school (1958), tuition was $600 a semester. By 2019 my school was charging $65,000 per year. With housing, food, and travel a student’s “estimated annual expenses were over $87,000.” They don’t say why they are selectively lowering tuition, but in 2019 the school plans to decrease fees by an average of $20,000 per student per year.7
In 1962, aside from antibiotics doctors had (in retrospect) relatively few medications to work with. We had aspirin, barbiturates, and a number of treatments that were largely the derivatives of plants, minerals and animals. (Colchicine, for example, was extracted from Colchicum autumnal…the meadow saffron and was used to treat gout and a few other maladies.) We worked with glass syringes and hypodermic needles made of steel. After they were utilized, the needles were washed, sharpened, sterilized and reused. When I was an intern (in 1963) we treated people who were stricken by a myocardial infarctions with “quiet and rest.” One fateful night I entered a room—the door was closed– to do an admission history and physical on a man who was having a heart attack. The patient was in trouble. He was confused, pale, sweating–dripping wet and barely had a blood pressure. He was in cardio-genic shock. I started an IV and infused the available drugs. Nothing helped and he died. Nowadays heart attack victims who don’t instantly die are rushed by ambulance to a nearby hospital where a cardiologist and team are waiting to catheterize their coronary arteries and to unblock and “stent” the occluded vessel. (Some of the improvements in care are not due to better drugs.)
By the 1950s physicians had digitalis, quinidine, nitrates for diseases of the heart. Excess fluid accumulation could be flushed by an injection of a mercury based diuretic; there was a new promising diuretic called chlorothiazide.
By my first year in med school, doctors could slow the coagulation of blood – and prevent and treat venous blood clots–with the anticoagulant Warfarin–Coumadin. Produced by certain fungi dicoumarol initially got people’s attention when it caused the death of a number of cows in the 1920s. The animals had eaten moldy sweet clover, it kept their blood from clotting normally, and they bled to death. Researchers spent decades trying to extract the responsible chemical and “in the dimness of dawn on June 28, 1939, after working all night, Harold Campbell at the University of Wisconsin (finally) saw crystalline dicoumarol on a microscope slide.” A few years later, led by the son of a Lutheran minister, Wisconsin researchers synthesized the chemical’s long acting derivative, called it Coumadin, and marketed it as an effective rat poison. On further thought the decided to use it as a medication for people.12
Maurice Hilleman, the scientist who ultimately created 40 vaccines, was born on a hot summer Montana day on a farm near the banks of the Yellowstone and Tongue River. His mother had eclampsia and died when he was 2 days old, but before she died she gave her baby to the childless couple down the road. Maurice claims he was put to work as soon as he was able to tell a weed from a seed. “Everyone in Montana had to earn their keep. “.On the farm they sold what they grew, and he picked berries, and watered the animals. As a teenager he worked at J.P. Penny’s in the nearby town and “helped cowpokes pick out chenille bathrobes for their girlfriends.” Deciding he didn’t want to go to the local college because he “didn’t want to be strapped down by the church dogma,” Maurice won a scholarship to Montana State University. Graduating first in his class, he was admitted to the PhD program in microbiology at the University of Chicago. “Despite receiving a scholarship, money was always in short supply. Hilleman lived in a squalid apartment and survived on a single meal each day. At 6 feet 1 inch tall, he weighed less than 140 pounds.14”
The Chicago University system, as he described it, was one where professors didn’t want to be bothered unless “you discover something. “While in school he determined that the bug that infected three million Americans a year and scarred the fallopian tubes of many women was not a virus. It was a bacterium, a Chlamydia that grew in cells and it could be killed with antibiotics. After he graduated his professors wanted him to stay in academia “I was not allowed to look for a job in industry; but I came from a farm. I wanted to do something—to make something38.”
In 1944 as a new employee of Squibb he developed a vaccine for Japanese Encephalitis Virus. It normally can be found in pigs in parts of South East Asia and it is transmitted by mosquitoes. Usually mild, the infection sometimes causes fever, seizures, and serious long term movement problems. In 1944 World War Two was raging, the U.S. was getting ready to fight the Japanese, and the army wanted a vaccine that would protect soldiers. Hilleman offered to make the vaccine for $3 a dose and he won the contract. Squibb gave him a horse barn and an engineer. An old farm boy, he bulldozed out the manure, painted the floor, and went to work. From U. of Chicago days Hilleman knew the virus would grow in the brain of a mouse so he did some testing. As he later explained to fellow “vaccinologist” Burt Dorman, making a vaccine is like getting the old tractor working. You fiddle with it. If that doesn’t work you fiddle with it some more. Once Hilleman figured out how to make the vaccine he assembled a crew of 30 women. They injected the virus into the skulls of mice and waited for it to grow. After a few days they killed the rodents with ether and “harvested 30,000 brains a day.” The organs were homogenized with a blender, washed, centrifuged, and washed again and again. The process was repeated until the solution contained pure viruses. The life forms were then inactivated with formaldehyde. Three months later Squibb had enough vaccine to immunize 200,000 troops.38
After the Second World War the U.S. military and the World Health Organization were on the lookout for the next influenza pandemic. In 1957 Hilleman was working at Walter Reed military hospital when he read about a flu outbreak in Hong Kong that infected ten percent of the population–250,000 people. He contacted an army physician in Japan who got an infected navy serviceman to gargle and spit into a cup. A month later Hilleman put the spit into a fertilized egg and a flu virus grew. He then checked the serum of hundreds of people and found that no one had antibodies to that strain of flu. Most of the humans alive had never been exposed to the virus. The only people who had antibodies were a few 70 and 80 year olds who had survived the flu epidemic of 1889-90.
Hilleman figured that a virus would arrive in the fall and it would be devastating. No one alive had ever experienced anything like it. He “sent out a press release and warned the world” but no one seemed to believe him. “Joe Bell” a prominent U.S. Public Health service epidemiologist, known for his attention to detail commented “what pandemic? What Influenza?” “How,” Hilleman wondered, “could people live in this world and be so stupid.” Eventually Hilleman went to a restaurant where the head of the U.S. influenza commission was eating. He interrupted the man’s meal, showed him the information, and told him that ignoring his findings was “a big mistake.” The commissioner checked the data and agreed; it was a pandemic virus.
Hilleman contacted 6 companies that produced flu vaccine. He cut the red tape, side stepped a few rules, and told chicken growers to NOT kill roosters. As a farmer he knew roosters were usually killed late in the hatching season and companies would need a lot of fertilized eggs. By late fall 40 million doses of vaccine were available and many people were immunized. The disease arrived in the U.S. that September in the body of a girl who attended a church conference in Grinnell Iowa and in the lungs of Boy Scouts from Hawaii who attended a jamboree at Valley Forge Pennsylvania. The 1957 flu killed 70,000 Americans and 4 million worldwide, but thousands of lives were saved.
In the 1950s Hilleman moved to the Merck Company and started a revolution of sorts. Over the years his group turned out products that prevented a staggering 40 animal and human diseases.
His vaccine for Hepatitis B was made using killed virus. To convince the public it was safe he asked Merck mid level executives to be the first to be injected. No one volunteered the first time so he brought the execs back and explained that “No” was not an option. Fearing the vaccine might have been contaminated with HIV some of the injected execs later admitted they took the shot but were “scared to death.”
When he later learned the vaccine production was being accelerated Hilleman met with the people making it. He had killed the viruses with formaldehyde, pepsin and urea. The process was effective but it was slow. When he heard the company was making it faster Hilleman assumed steps were being skipped. No one knew if it affected the vaccine’s safety. He gathered the production crew and told them someone was “changing the fucking process so he can get more yield and earn a bonus. Meatheads are everywhere.38”
In 2005, 3 years before he died Hilleman famously told his colleagues that “the most apt description of me was as a man who appeared to be a bastard, but if you looked deeper inside you still saw a bastard.”
The vaccines for measles mumps and chicken pox became available in the late 60s and early 70s. In 1957, the year before I graduated from med school, the people I interviewed all remembered their childhood illnesses, staying home for a week, fevers, rash, and a swollen jaw.8
In the 1950s Jonas Salk and Albert Sabin developed immunizations for polio. The studious son of immigrants, young Jonas Salk was “a perfectionist” and a good student. He went to medical school, became a research bacteriologist, and, instead of joining the army, assisted Thomas Francis, the man who developed a flu vaccine for the army. The son of a steel worker, Francis—they called him Tommy, was 41 when the U.S. entered the war. The nation remembered how the flu had killed more soldiers than the enemy during the prior conflict and the government didn’t want a repeat. Salk was military age but discovering a vaccine for flu was more important than another soldier with a gun.
In 1947, at age 33 Salk was given a laboratory at the University of Pittsburg and was funded by the March of Dimes. The official charity that supported the development of a vaccine was created and promoted by Franklin Roosevelt. He was the U.S. president during the depression of the 1930s and led the country during most of the Second World War years. Unable to walk without help after he developed paralytic polio at age 39, he had a disability that was public knowledge. The virus was feared. 1952 there was an outbreak of Polio in the United States and over 57,000 infections and 3145 deaths.
Salk’s vaccine used live virus that was chemically inactivated and injected. In the early ‘50s it was given as part of a placebo controlled trial to 2 million school children. In 1955 the study proved it was safe and effective, Salk became an instant icon, and his life changed. His celebrity status troubled his medical colleagues and affected his marriage of 28 years. He ended up divorcing his first wife and he married Francoise Gilot, a woman who had once been the “longtime lover of Pablo Picasso.” He founded a research institute in San Diego, was interviewed, and in a book was psychologically picked apart. His interviewer wrote that the man “movie stars came to visit and babies were named after” was “conceited but vulnerable–mild-mannered, but often arrogant and combative.39”
The other developer of a polio vaccine was born in Poland and was15 when he and his parents came to the United States. Albert Bruce Sabin eventually went to medical school and graduated in 1931. While studying Polio at the Children’s Hospital Research Foundation in Cincinnati, Ohio, he discovered that polio viruses lived in the small intestines before they attacked nerves. During the Second World War Sabin developed a number of vaccines for the army. When the war ended he returned to Ohio and he isolated a polio mutant that grew in the intestines and prevented infections with the wild virus. The U.S. at the time was committed to Salk and wouldn’t allow Sabin to test, produce, or administer his creation.
In 1955 the Russians founded a Polio Research Institute in Moscow, and in 1956 its head virologist Mikhail Chumakov visited Salk in Pittsburgh and Sabin in Cincinnati. Sabin spoke a little Russian, Chumakov a little English, and they became friends. The following year Sabin spent a month giving lectures in Russia, meeting with researchers, and promoting his vaccine. When he returned home the Salk vaccine was being widely used and an American researcher advised Sabin to toss his vaccine “in the sewer.” In 1958 Chumakov tested a vaccine made with Sabin’s seed virus on 20,000 Russian children. It was safe, easy to administer, and effective. Chumakov got permission from the public health chief of the Politburo and distributed the oral vaccine to more than 15 million Soviets and later to 23 million children in East Germany, Czechoslovakia, Hungary, Romania, and Bulgaria. An expert sent by the WHO agreed the vaccine seemed to be working but “definitive results would take time.”
Sabin refused to patent the Oral vaccine, and it is currently widely used in the poorer countries of the world.
On April 26, 1955 half of the 760,000 doses of Salk vaccine made by Cutter in Berkeley California, were recalled when the nation learned the vaccine was making some kids sick and was causing paralysis and a few deaths.
Thousands of kids developed a stiff neck and fever, 51 were permanently paralyzed, and 5 died. The formaldehyde in the vats had failed to inactivate the virus completely and the vaccine was pulled from the market. In 1961 the Sabin vaccine became available in the U.S. and was widely used. 26 years later the Salk, injectable vaccine was reintroduced. This time it was safe. Since 2000 the Salk product has been the only vaccine used in the U.S. and Europe. In the rest of the world “more than 10 billion doses of oral vaccine were given to 3 billion kids during the last 20 years. The World Health Organization thinks they have prevented 13 million cases of polio, but it’s also caused a few problems. Mutatants of the oral vaccine occasionally occur in a person’s intestine, and they have caused 760 cases of polio and can cause paralysis.40”
During the last half of the 20th century states started requiring kids who attended public schools to be immunized. Most families complied; the rest were usually shielded by “herd” immunity. If all or most kids in a community are protected, those who have not been immunized are unlikely to be exposed to the disease. The shots sometimes caused fever and joint aches, and one in a million kids developed encephalitis, a serious brain inflammation. The complications led to law suits and Pharma wanted to stop producing vaccines. In response, Congress passed the 1986 National Childhood Vaccine Injury Act, and the government started compensating the families of people who were harmed.
In 2020 a novel, sometimes lethal Coronavirus kicked off a terrible epidemic.
- Eminent Victorians by Lytton Strachey http://www.gutenberg.org/cache/epub/2447/pg2447.html
- (NY Times podcast: 1619, episode 4) ; https://www.britannica.com/topic/Freedmens-Bureau
- http://www.uefap.com/reading/exercise/ess3/pringle.htm
- https://www.newyorker.com/magazine/2009/01/26/getting-there-from-here
- https://www.va.gov/about_va/vahistory.asp
- NY Times podcast “1619” episode 4
- . The story of the isolation of cortisone from the adrenal glands of cows in 1935 and how they became basis for the cortisone preparations that were “used at the end of the 1940s to treat rheumatoid arthritis and other inflammations” will not be discussed in detail in this book.
“In the late 1930s, some of JFK’s physicians were astute enough to try the newly developed corticosteroid to help manage his colitis. Pellets were implanted under his skin and JFK’s nausea and diarrhea improved; the treatment allowed him to proceed with college.” Cortisone ultimately caused Kennedy’s bones to thin, caused osteoporosis.
http://clinchem.aaccjnls.org/content/56/8/1349
https://www.the-rheumatologist.org/article/the-tortured-path-to-the-cortisone-discovery/
It’s not clear when or where thyroid was
first used as a treatment.
George Murray, a Brit usually gets the credit because in 1891 he “obtained fresh sheep’s thyroid from a slaughterhouse and “injected it into a woman with most of the characteristic features of myxoedema—severe thyroid deficiency.” Desiccated thyroid was probably used by some in the late 1800s. In the 20th century the meat packer Armour extracted it from slaughtered animals and became one the hormone’s major suppliers. https://www.jameslindlibrary.org/articles/the-discovery-of-thyroid-replacement-therapy/
- “Starting with the 2019-20 entering class, the medical school “the school committed $100 million over the next decade.” ($10 million dollars/yr—divided by 492 students– that’s about $20,000 per enrollee per year.) Some students won’t get a break. “The money will allow “as many as half of its future medical students to attend tuition-free.” The university had a $3.4 billion endowment—accumulated donated money– in 2018. (Harvard had 10 times as much.) The “endowment” money was invested in the market and earned an average of 7.6 \% ($21 million a year) the last five years.7 https://mdadmissions.wustl.edu/how-to-apply/financial-aid/cost-of-education/
- Measles is still present in some parts of the globe and 2017 caused the deaths of more than 100,000. But, in the last decade it’s estimated that immunization saved the lives of 21 million. Dabbagh A, Laws RL, Steulet C, et al. Progress toward regional measles elimination — worldwide, 2000–2017. MMWR Morb Mortal Wkly Rep 2018;67:1323-1329.
Thanks in part to the World Health Organization, in 2018 86% of infants worldwide (116.3 million) received 3 doses of the vaccine for diphtheria-tetanus-pertussis, (DTP3), 84% of the world’s kids got three doses of the vaccine for hepatitis B, 86% received a dose of measles vaccine by their second birthday, and 85% of the planet’s infants had received three doses of the vaccine for polio. And that’s just part of the story. https://www.who.int/en/news-room/fact-sheets/detail/immunization-coverage https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.html
- http://www.sjsu.edu/people/ruma.chopra/courses/h174_MW_F11/s3/smallpox_GWarmy.pdf
`10. http://sitn.hms.harvard.edu/flash/special-edition-on-infectious-disease/2014/the-fight-over-inoculation-during-the-1721-boston-smallpox-epidemic/
- https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)60062-3.pdf
- The Discovery of Dicumarol and Its Sequels By KARL PAUL LINK, PH.D. https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.19.1.97
- https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA148#v=onepage&q&f=false/ https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA148#v=onepage&q&f=false/
- The Tortured Path to the Cortisone Discovery February 17, 2019 • By Thomas R. Collins https://www.the-rheumatolo gist.org/article/the-tortured-path-to-the-cortisone-discovery/ Cortisone by Edward C. Kendall. Charles Scribner’s Sons, 1971 https://pdfs.semanticscholar.org/0419/f2e829172a3864f861a49cb75b0d905c8d42.pdf Daria jadreskic
- https://www.famousscientists.org/maurice-hilleman/
- https://en.wikipedia.org/wiki/Tetanus_vaccine
- https://www.weforum.org/agenda/2019/04/gaston-ramon-vaccination-secret-weapon-adjuvanted/
- https://www.historyplace.com/worldwar2/timeline/about-blitz.htm
- https://www.famousscientists.org/louis-pasteur/https://www.vbivaccines.com/wire/louis-pasteur-attenuated-vaccine/
https://www.thelocal.fr/20171017/lille-why-would-anyone-want-to-live-there
- https://www.who.int/mediacentre/news/releases/2015/mtct-hiv-cuba/en/
- https://www.nobelprize.org/prizes/medicine/1905/koch/biographical/
- https://www.britannica.com/biography/Joseph-Lister-Baron-Lister-of-Lyme-Regis
- https://www.who.int/news-room/detail/05-12-2019-more-than-140-000-die-from-measles-as-cases-surge-worldwide
- http://exhibits.hsl.virginia.edu/hands/victorian/
- https://books.google.com/books?id=YNBjDwAAQBAJ&pg=PA25&lpg=PA25&dq=pasteurs+wedding+day&source=bl&ots=0lwF4g53mX&sig=ACfU3U1G-UjPjYi4kBzEI_lieShlRCztYQ&hl=en&sa=X&ved=2ahUKEwiquNS0vanoAhUFup4KHbjqBJ4Q6AEwFHoECBkQAQ#v=onepage&q=pasteurs%20wedding%2
24.https://www.sciencedirect.com/science/article/pii/S1201971210023143#bib23 Robert Koch and the ‘golden age’ of bacteriology
- Rewriting Medical History by Michael Bliss. https://watermark.silverchair.com/253.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlcwggJTBgkqhkiG9w0BBwagggJEMIICQAIBADCCAjkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM-R09g2HE8Z-EbJa5AgEQgIICCieV_xxElSH2KHjv4cVAftjwQ1_VSYrDrQwxOWQJJdFAugjXN_tctiK1mIkaWaIqeai3d-lwtH_lKC1QV8W0ls-z5JREFQooawMH80Yvn3__aicTaerWOrsJC7GpQ-sREmd0nlofqSpyUGJjFZp1b7pPDBNVwCHR0xJKUZPQkIJuaQQDUBqCzvyfgM827WSDFdSn1kCEigVwyyVhpYT9uvCQfJQGHTo1WUsaytfGrqnXuvXcI1SjaRFUBNgKNWAmo8OUSTaqCrI-Hg7Gc-ahkcUwzgE4J9_ZHOJu19YqFXxYFNtKAo2c1XyUw5dwrNq1UqzVc6-feV_MbdaQtlJL4WJpKKAfD88Ac0_ApGEefbPix38OCpa-XGHYG2hQDZd_k6j5mz9qDuSdfpefiDFF15unrLspBZoFSoS0J2btDeADHLPdseXQymR0n_PL8cVrkbUZOdcp7OuMoc7mH4piW0QqLxmRJOfq8ma0dhvMXisbvGSbtBNq0Oiou5kTbduSQqEUETzxiuLKTABXFQa98fGTG1KCuqHrSjKGeD6shGNxgHhO_t5cnOqemz5TT4OGqkjj8nLKvS9T4HZgb0p208ICRJyc9Ys4tzqM80YsBSGPefEU4d9B48NQO2mEwwRycJxEg-aFcjfuTNsXTyo1j6iUJM_EoPWP2n77DKMGdBeudJldM3WikdiyBw
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/
- https://www.who.int/news-room/fact-sheets/detail/tuberculosis
- https://www.nytimes.com/2015/12/16/health/hepatitis-c-treatment-egypt.html
- Dinzar Gothams of the Imperial College London “conservatively estimated the generic price of the newest TB drug, pretomanid could be $10.80–$34.09 per patient per month. The second (older) drug, Bedaquiline could be produced for $8–$17/month (current lowest price $136/month). And the third medication, linezolid could be produced for $4–$9/month (current lowest price $193/month). $23 to $60
- Dzintars Gotham Faculty of Medicine, Imperial College London, London, UK; et al. Estimated generic prices for novel treatments for drug-resistant tuberculosis Journal of Antimicrobial Chemotherapy, Volume 72, Issue 4, April 2017, Pages 1243–1252
- https://www.downtoearth.org.in/news/health/fda-approves-new-oral-three-drug-regimen-for-extensively-drug-resistant-tb-66179
- 30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217699/#ref1
- https://www.sciencehistory.org/historical-profile/jonas-salk-and-albert-bruce-sabin https://www.notablebiographies.com/Ro-Sc/Sabin-Albert.html https://libapps.libraries.uc.edu/liblog/2016/10/heloisa-sabin/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383764/
- https://www.nejm.org/doi/full/10.1056/NEJMp1808903
- https://onlinelibrary.wiley.com/doi/full/10.1046/j.1440-1843.2003.00518.x?sid=nlm%3Apubmed
https://www.who.int/csr/sars/country/table2004_04_21/en/
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30129-8/fulltext
- Yaseen M. Arabi, M.D., February 9, 2017; N Engl J Med 2017; 376:584-594 DOI: 10.1056/NEJMsr1408795
35. https://www.healio.com/rheumatology/practice-management/news/online/%7B74059ff3-579e-4540-b20f-d496eec0a7f0%7D/all-the-presidents-secrets-john-f-kennedy-and-addisons-disease
- https://pubmed.ncbi.nlm.nih.gov/15219556/
- https://www.referenceforbusiness.com/history2/76/American-Medical-Association.html
- Vaccinated by Paul Offit HarperCollins, 2007
- Jonas Salk a life byCharlotte DeCroes Jacobs, Oxford press 2015
- https://www.notablebiographies.com/Ro-Sc/Sabin-Albert.html https://www.sciencehistory.org/distillations/political-illshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589490/pdf/yjbm00059-0074.pdf
- https://www.nejm.org/doi/full/10.1056/NEJMoa1903869
- https://www.czbrats.com/Builders/FRCanal/failure.htm.
- https://www.usatoday.com/story/money/2018/08/07/large-cattle-farm-may-have-caused-romaine-lettuce-e-coli-outbreak/924063002/
- https://cmr.asm.org/content/15/4/59
- http://www .johnsnowsociety.org/john-snow.html https://www.history.com/topics/inventions/history-of-cholera
- Albendazole https://www.youtube.com/watch?v=p1JrtZQ-Ydw
- cowpox https://emedicine.medscape.com/article/1131886-clinical
- cortisone https://www.mayoclinicproceedings.org/article/S0025-6196(11)62920-0/pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296908/pdf/jrsocmed00020-0011.pdf
- Kocher . thyroid https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206627/
- OPIUM WARS https://asiapacificcurriculum.ca/learning-module/opium-wars-china
- Fentanyl https://www.jpain.org/article/S1526-5900(14)00905-5/pdf
- FRANCIS FLU https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(15)00317-3.pdf
- Cutter Berkley https://www.nejm.org/doi/full/10.1056/NEJMp048180
- Tetanus– https://prism.ucalgary.ca/bitstream/handle/1880/51826/9781552388655_chapter06.pdf;jsessionid=6B018FEE77F343A6F601D0AF647F4DF1?sequence=9
https://www.terumo.com/story/terumostory/1921_2001/cat1_1_3.html#:~:text=Kitasato%20succeeded%20in%20growing%20the,toxins%20that%20can%20cause%20convulsions.
- MICROSCOPES: https://royalsocietypublishing.org/doi/10.1098/rsob.150019
- Koch a plodding worker https://books.google.com/books?id=el2LDwAAQBAJ&pg=PT130&lpg=PT130&dq=was+robert+koch+a+showman&source=bl&ots=5vLQTaTbaU&sig=ACfU3U0h3exSZu02YnkjDQbKAY41K6jQJw&hl=en&sa=X&ved=2ahUKEwiwp6nB26LqAhVBMH0KHfYVCSUQ6AEwCnoECAYQAQ#v=onepage&q=was%20robert%20koch%20a%20showman&f=false
- Koch https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916274/
- Serturner https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125194/#ref1
- Serturner https://books.google.com/books?id=hzB9DwAAQBAJ&pg=PT196&lpg=PT196&dq=aggravated+hypochondriacal+alterations+in+his+frame+of+mind+and+quiet+disturbances+of+mood.&source=bl&ots=GkPrUkJ0ea&sig=ACfU3U2dtwCbjDzm4CQBOISY-cl8SH_zPQ&hl=en&sa=X&ved=2ahUKEwj_rNSR3q_qAhVDoZ4KHZNmAF0Q6AEwAHoECAoQAQ#v=onepage&q=aggravated%20hypochondriacal%20alterations%20in%20his%20frame%20of%20mind%20and%20quiet%20disturbances%20of%20mood.&f=false
- Trump covid https://khn.org/morning-breakout/cdc-used-to-be-one-of-worlds-preeminent-disease-fighting-bodies-but-agency-gutted-under-trump/
- Thyroid extract https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046199/
- 61 Before Murray https://www.jameslindlibrary.org/articles/the-discovery-of-thyroid-replacement-therapy/
- 62 Haiti https://www.nejm.org/doi/full/10.1056/NEJMp1012997
- Iodine in food. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509517/#B17-nutrients-04-01740
- Robert Crane https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.366
- Iodine https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509517/#B17-nutrients-04-01740
- Pfizer penicillin https://www.eurekalert.org/pub_releases/2008-06/acs-pwo061208.php#:~:text=They%20needed%20huge%20tanks%20that,opened%20on%20March%201%2C%201944.
