THE MICROSCOPIC WORLD

Modern health care’s creation was triggered by the observations of a Dutch man named Van Leeuwenhoek.  Like the fictional Gulliver he became the first to make the voyage, the first to gaze at the unknown world through a powerful lens.

  A contemporary of Rembrandt and Vermeer, Leeuwenhoek was born in 17th century Delft.  It’s a town in Western Holland known for cool, foggy summer mornings, numerous boat filled canals, wide streets connected by wooden bridges, and blue and white pottery.  In his day horses and carts clattered across the stones in front of a large open air market, narrow rows of houses surrounded the town square, and food and wood were weighed before it was sold.  Leeuwenhoek’s mother came from a well-to-do brewer’s family and Van Leeuwenhoek first worked as a draper’s apprentice.  While there he used the lenses of the day to check the quality of a fabric’s thread.  Later in life he was politically active.  He became a civil servant and was a chamberlain of one of the assembly chambers at city hall.  At age 40 he made one, and later many incredibly powerful, tiny magnifying lenses. Once he had created the devices he started exploring the microscopic world, and he saw sights that had never before been seen or suspected.  He drew pictures and sent them to the National Geographic of his day, the Royal Society.  His images of bacteria, red blood cells and sperm seemed fictional to some contemporaries who looked through ordinary polished and ground glass lenses.  Others believed.  During his life Leeuwenhoek made an additional 500 magnifiers.  One person, then another became aware of a microscopic world and learned it was often unfriendly. To this day no one really knows how he made his lenses.  His process died with him. 

 Back then people had long known that when someone develops smallpox and survives they don’t get it again.  That’s why some in ancient China and Africa blew crusts of a diseased person’s scab up the nose of an uninfected person.  They hoped the illness they were causing would be mild, or at worst it wouldn’t be deadly.

In 1796 Edward Jenner, a British doc proved there was a safer way to prevent the disease.  He heard that milkmaids who were infected by cowpox didn’t’ develop small pox, and he checked it out.  He took material from the pussy scabs on a young woman’s hand and “inserted it into small incisions he made in a boy’s skin.”  Much as cats and tigers are members of the same species, the viruses that cause cowpox and small pox are related.  Each can cause pustular lesions.  People who develop cowpox sometimes run a fever and are sick for a week, but the illness is mild and when a person recovers (or is vaccinated) their body is protected from the oft lethal disease

Jenner submitted his findings to the Royal Society and they were rejected, so he self published and became famous. Thomas Jefferson and James Madison read about his findings, and in 1813 Congress passed the Vaccine act.

In1853 the British Parliament made childhood vaccination with modified cowpox compulsory. 

After widespread immunization contained the illness, people in the U.S. stopped vaccinating.  In the19th century there were outbreaks, and states attempted to enforce existing laws or pass new ones.  The disease finally disappeared from North America in 1952 and from Europe in 1953.  As recently as 1967 (according to the CDC) 10 to 15 million people in Africa, Asia, Indonesia, and Brazil were contracting Smallpox each year. That year 2 million died and many were scarred for life.  The World Health Organization started a program of worldwide vaccinations.  Their efforts to eliminate the terrible disease seem to have succeeded.  The bug’s last known “natural” victim was infected in 1977.

In 1848 hand washing was little more than a cultural or religious ritual.  No one (best I can tell) connected “germs” and sanitation with infectious illnesses.  That year a Hungarian physician, Ignaz Semmelweis, was working at a hospital in Vienna and was troubled.  Women whose babies were delivered by doctors and medical students developed a fever and died 4 times more often than women whose babies who were delivered by midwives.

Semmelweis investigated and learned that the medical students in question came from the dissecting room to the maternity ward without cleaning 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 Budapest, his hometown.  In 1881 he published a book on “childbed fever.”  When he was in his late 40s he was overcome by paranoia and dementia and he was committed to a psychiatric institution.  It took a generation before his teachings were widely accepted.

While Semmelweis was investigating sanitation in Vienna, Louis Pasteur, a French chemist was graduating and becoming a researcher.  When he was young Pasteur was an average student who loved to draw and paint.  Then he got his act together and “won first prize in physics.”  He eventually studied chemistry and physics at the prestigious Ecole Normale.

At age 26 Louis 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.

Pasteur was 32 when he 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, bacteria, caused fermentation.  We call it the germ theory. In 1863, working for the French emperor, Napoleon III, Pasteur proved it was possible to eradicate harmful bacteria at a temperature well below boiling.  He prevented wine from contamination by heating fermented grape juice to 50–60 °C (120–140 °F). .  We call the process Pasteurization.   

In 1879 he and his assistants injected chicken cholera bacteria into some of his birds.  The germs had been sitting on the shelf for a while, the infections they caused were mild, and the infected chickens were subsequently resistant to the bug.  Pasteur realized it was possible to weaken a pathogen to the point where it wasn’t harmful but it still triggered an immune response.  He exploited the phenomenon to develop vaccines for chicken cholera, and anthrax. 

In 1885 a rabid dog bit a 9 year old French child. We now know that after it enters a person’s body, the virus that causes Rabies infects an axon, the “long slender projections of nerve cells that conduct electrical impulses.”  The infectious agent then travels up the axon to the brain and eventually kills the person or animal.    

The oft repeated story says the young man was bitten 15 times and two days later his mother came knocking.  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 animal.  Upon the second creature’s death, part of its spinal cord was injected into a third animal.  With each passage the agent became less virulent.  Using the technique in reverse 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.  Doctors started using similar extracts to treat people who were bitten by a rabid creature. The vaccines of the twenty first century contain inactivated virus that was grown in human or chick embryo cells.

          The Rabies virus is still responsible for the deaths of 59,000 humans a year. Ninety percent of the cases in Africa and Asia are caused by dogs. In this country we worry about bats and wild animals, and 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.

In the early 1800s the quality of microscopes was variable.  Then a few craftsmen started making clear, powerful magnifying lenses.  One of them, Carl Zeiss, came from a German family of artisans and he apprenticed with a maker of fine tools.  In 1846 he opened a workshop in Jena, a river valley town in the “green heart” region of eastern Germany.  The first dozen years his technicians under the supervision of a short tempered, authoritarian foreman, made single lens precision microscopes.  Eleven years later Zeiss introduced scopes with two lenses.  Scientists could now look into the upper curved glass, peer down a tube and view an object that was just below a second lens.  With the help of Ernst Abbe, a mathematician, the company used calculations to determine the optical characteristics of their lenses, and it improved the illumination system. Smaller and smaller objects came into view.  Doctors from Germany and beyond bought one of their scopes.  Carl’s first wife died shortly after she gave birth to their first son.  She was 22 at the time.  Carl married two more times and out lived one of the women.  All three of them were, in his words, “spiritually very much country folk.”

Robert Koch the German “father” of the germ theory, once wrote that his Zeiss scope was responsible for a large part of his success.  Koch was born 21 years after Pasteur.  He was a gifted child and could read a newspaper when he was 5.  In Germany he ran a medical practice and spent hours peering into a microscope.  When he was a district medical officer he investigated a pasture where the cows that ate the grass got sick and died. He collected blood from one of the dead animals, injected it into a mouse, and the rodent died.  Koch found rod shaped microscopic creatures in the soil, grew them in a rabbit’s eye, and allowed them to dry out.  They looked innocuous, but they were just dormant. When their survival was threatened the bacteria surrounded themselves with a protein coat, become spores, and vegetated.  They were able to endure harsh conditions, and when and if conditions permitted they emerged.  In the twentieth century these spores—anthrax—became one of the agents bioterrorists use. 

Koch’s life as a researcher started after he returned from the 1870 war with France.  When the conflict started Koch, “a 5 and a half foot tall man with a stern face and thin high voice,” tried to become an army physician.  He was rejected because he was nearsighted.  As the conflict wore on he re-applied and became a military doctor. He was with the German troops that besieged Orleans.  It’s the city on the Loire River where, in 1429, Joan of Arc famously fought the English.  Koch was troubled by the damaged bodies he had to deal with.  He once observed that in war time human life becomes “worthless.”

Years later Koch was a famed researcher.  When he was 47years old he met the other “germ theory father” in London.  At the time Pasteur was 68 and partially paralyzed.  The encounter was cordial, tense, and controversial.  Both men were doing research on anthrax.  After Pasteur presented the results of his research Koch was judgmental.   Neither man spoke the other’s language.  Letters were exchanged, and one of Pasteur’s remarks was translated as a comment on “German arrogance.” After the apparent insult each man started criticizing the work of the other.24  

Once doctors had good microscopes they learned how to categorize bacteria by drying and dyeing tissue and sputum that contained germs.  Koch used special stains on infected human and bovine (cow) tuberculosis and identified the bacillus that caused the disease.  “A plodding worker and a careful seeker of facts”, Koch dazzled a group of colleagues on a Friday evening in 1882.  He proved that the tubercle bacillus was transmissible and that it was the cause of TB in man. 

Much as people in 2020 are investing our hopes and fortunes into vaccine that will force our immune systems to reject the coronavirus– Koch tried to energize the (poorly understood) immune systems of people with tuberculosis.  He isolated a glycerine extract of the TB bacillus and injected it into the skin of a person with an active TB infection.  The fluid caused chills, fever and an aggressive skin reaction.  When it was instilled into infected guinea pigs it seemed to “completely cure animals in the late stage of the disease.” 

Koch unveiled his new treatment when he addressed the crowd at a Berlin auditorium.  “I have at last hit upon a substance which has the power of preventing the growth of the tubercle bacilli not only in a test tube but in the body of an animal.” In the subsequent months he began giving regular tuberculin injections to a number of patients with advanced disease who were in Berlin’s Charite hospital. 

Conan Doyle, the Scottish physician who created Sherlock Holmes admired Koch and wanted to meet and hear the great man.  On November 16th he arrived in Berlin by train.  When the British Embassy was unable to get him a seat at one of Koch’s demonstrations he went to Koch’s house.  He knocked on the door, and the butler showed him into the living room.  While Doyle was waiting, letters were dumped on a nearby desk and on the floor.  Doyle would later characterize them as pleas for help from people with “sad broken lives and wearied hearts who were turning in hope to Berlin.”  The next day Doyle visited the clinic where the infected were being treated.  He saw people who were febrile, quite ill, and suffering as a result of the injections.  Disappointed and dubious he wrote about his visit and misgivings and returned to Scotland. 

Koch’s supply of his “remedy” was “scarce”, but by the end of 1890 over two thousand people with advanced disease had been treated. Most of the people who received tuberculin were not improved and only 28 were cured. 

Facing public scorn because his treatment failed, the now 47 year old Koch left his wife and married Hedwig, an 18 year old art student who was “fascinated with his studies.”  He traveled to Egypt and wrote his 18 year old lover, “If you love me I can put up with anything, even failure.  Don’t leave me now.”  When Koch inoculated himself with tuberculin, she volunteered to be injected too.” 

During his later years, his reputation now diminished, Koch traveled the globe with Hedwig and weighed in on various issues– often to his detriment.  He, for example, didn’t believe milk that contained bovine (cow) TB was harmful and opposed the pasteurization of milk.  He also promoted the use of an arsenic containing medicine to treat sleeping sickness.  When he was 67 he had a massive heart attack.

During Koch’s lifetime many who had Tuberculosis spent a year in a sanatorium.  Breathing clean air and leading a healthy life helped some of them go into a remission.  The first antibiotic that killed TB, Streptomycin was discovered in 1943.  Like penicillin it was being used by a soil organism to defend itself from the bacteria that surrounded it.  Over time streptomycin resistant bacteria started to emerge.  In 1953 it was joined by INH –isoniazid.  The medication was a chemical that a PhD student in Prague synthesized in 1912.  It was probably sitting on a shelf somewhere when, in the 1940s industry researchers decided to test hundreds of random chemicals on mice with Tuberculosis. The third powerhouse, Rifampin, became available in 1963.  It was a chemical that was produced by a soil organism, and it was isolated and modified by Italian researchers.

.  By the 1950s and 60s doctors were able to successfully treat most TB infections with a combination of the medications.  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 tuberculosis would disappear.  Unfortunately poverty, HIV, and bacterial resistance reversed the trend, and the incidence of T.B. started to rise.

At some point in their lives one of 4 people alive today, was or will be infected by the cough of a person with tuberculosis. 90 percent mount a cell mediated immune response.  Their body encases and imprisons the bug, but doesn’t always kill it.  Years later the bacillus sometimes escapes, grows, and spreads.  In 2019 ten million people worldwide developed an active infection and 1.4 million died.  

Koch and Pasteur had challenged the belief that diseases were the result of some mysterious force in the miasma.  They used live organisms to energize the immune system and with others demonstrated that germs cause disease and cleanliness matters.  

In the mid 1800s Joseph Lister, the man who was called 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.” In time he 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, Lister was the surgeon for the Glasgow infirmary.  He noticed that half the people who had a limb amputated became septic and died.  By that time he had read about Pasteur and germs, and he started treating raw wounds with carbolic acid, a foul-smelling antiseptic that was used to clean sewers.  His surgical infection rate dropped to 15%, and the Scots were impressed.  Their doctors started cleaning and sterilizing the tools they used.  Doctors in England 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 Over time he wrote articles and influenced his peers.  At age 56 he was named a Baron.

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, or 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.” Then a sanitary commission, set up by the British government arrived and they flushed 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 once wrote: “Sufferings were the result of too little “fresh air, light, warmth, quiet, or cleanliness.”