Showing posts with label microbiology. Show all posts
Showing posts with label microbiology. Show all posts

Sunday, September 17, 2023

A Dutchman Spies Invisible Creatures With his Gizmo

                    Antonie van Leeuwenhoek

On September 17, 1683 Antonie van Leeuwenhoek wrote a letter to the Royal Society in London describing animalcules—tiny one celled animals invisible to the naked eye now known as protozoa.  In doing so he inadvertently founded a new branch of sciencemicrobiology.

Leeuwenhoek was an unlikely scientist.  At the time most scientific investigation was the sole providence of gentlemen who had the education, leisure time for investigation, and the fortune to support the cost of their work.  He was neither a gentleman nor particularly well educated.    He came from a family of tradesmen or what the English called skilled mechanics.  His father was a basket maker and his mothers family were brewers.  They were from Delft, a reasonably prosperous small city in the Netherlands province of South Holland.

As a young man Leeuwenhoek became a draper.  He also worked as a surveyor, wine assayer and as a municipal official.  His occupations made him comfortable, if not wealthy, and he was a respected member of the community.  He was friends with and almost the exact contemporary of Delft’s most famous resident the painter Johannes Vermeer and was an executor of his estate when the master died in poverty in 1675.

His commercial success allowed Leeuwenhoek the time to pursue his growing interest in science.  An avid reader, he had read Robert Hookes illustrated book Micrographia.  Hook was working with primitive compound microscopes using two lenses.  But the technology of these devices was primitive and could only magnify objects 20 to 30 times.  Around the mid-1660’s he began to grind lenses in an attempt to create more effective instruments.

My high school science text credited Leeuwenhoek as the inventor of the microscope.  As you can see, he was not.  Compound microscopes had been around for nearly 40 years.  His devices had single lenses, but the quality of the lenses was so high that he was able to achieve documented magnification of over 200 times.  And evidence from his detailed observations indicates that some of the devices that he constructed may have neared a power of 500.

One of van Lueeuwenkhoek's deceptively simple but effective microscopes.

Leeuwenhoek’s breakthrough—and a closely guarded secret in his lifetime—was not discovered until 1957 when scientists discovered that he used finely drawn thread of molten glass to create perfect small spheres which became his lenses.  The small lens would be set in a brass or silver plate in front of which would be a pointed rod on an adjustable screw which would hold the object being studied.  Leeuwenhoek, working in the brightest natural light, would hold the device close to his eye. 

Leeuwenhoek constructed at least 500 different devices, only a handful of which still survive.  He often crafted new microscopes specifically for the specimens he wished to examine.

A Dutch edition of the book Sequel of the letters written to the widely renowned Royal Society of London.

He made careful, extraordinarily detailed written observations of what he saw.  These observations are so clear modern scientists can often identify the exact species of microbe he was observing.  Since his drawing skills were poor, he later also hired a professional illustrator to make drawings to be enclosed in his letters to the Royal Society and other scientists.

His correspondence with the Royal Society continued for more than 50 years through his final illnesses.  The Society frequently published his findings translated from Dutch to English or Latin in the Philosophical Transactions of the Royal Society, the most important scientific journal in the world at the time.

Among his main discoveries were infusoria, the unicellular animals in pond water now mostly classified as protists; bacteria from the human mouth; vacuoles, important structures in the cells of plants, fungi, and some protia; spermatozoa; the banded structure of mussel fiber; and the blood flow in capillaries.

Leeuwenhoek commissioned a professional artist to illustrate many of his observations for the Royal Society including these animalcules.

In his later years Leeuwenhoek was famous.  He was visited by William of Orange and other notables who he let make their own observations with his equipment.  He even presented a microscope to Peter the Great of Russia when he was invited to visit the Tsars ship.

Active to the end, he died in Delft in 1723 at the age of 90.

In 1981 Leeuwenhoek’s original specimens, sent to the Royal Society were discovered in a remarkable state of preservation along with many of his handwritten notes in Dutch. 

His life and work are a testament to the talent and persistence of a common craftsman. 

 

Thursday, March 25, 2021

The Cup Cake Downfall of Dr. Koch, the Consumption Bug, and Popular Culture

                        Dr. Robert Koch at work in his laboratory.

Consumption, as it was then widely known, was a pervasive and enduring near world-wide epidemic that had no identifiable beginning or foreseeable end.  It brought slow, sure death to millions.  Most pervasive among the urban poor crowded together in fetid slums and the lowest levels of the rural peasantry whose large, multi-generational families often lived together in crowded hovels.

But consumption was no respecter of class privilege.  Those who read biographies of notables from the 17th to early 20th Centuries as well as literature from the same period are struck by the frequent references to the White Plague and its devastating effects.  Take, for instance, just the highly educated and largely affluent literary elite of Boston and the New England Renaissance.  Ralph Waldo Emerson saw a beloved brother, his child bride Ellen Louisa, and other friends and relatives succumb to the disease.  Theodore Parker was just one of several other leading figures of the Transcendentalist movement who died of it.  It was suspected to run in families—we would call it hereditary today—largely because devoted family members would tenderly nurse stricken kin giving them the long, close exposure we now know is necessary to transmit the disease.

In the 1938 weeper Three Comrades Margaret Sullivan dies beautifully, with self-sacrificing heroism of consumption in a mountain sanitarium leaving behind her grieving husband Robert Taylor, and his surviving World War I comrade Franchot Tone who also worshiped her.  Tragic death by consumption was a frequent theme of novels, plays, and film for generations.

The very memory of the disease haunted people even after it was on its way to being controlled.  Every movie goer knew that a cough in the first reel was certain foreshadowing of a tragic death bed scene in the last.

Consumption was commonly assumed to rise spontaneously, be caused by miasmas or foul air—and thus to be treatable by exposure to clean, fresh air in sanitariums away from the city—or, as noted, be hereditary.

On March 24, 1884 Dr. Robert Heinrich Herman Koch, Germany’s most distinguished physician and the Father of Microbiology published a paper sweeping away all of those suppositions and rendering them mere superstitions and as outdated in medicine as bleeding.  Consumption, or as he called it tuberculosis, was caused by a bacterium which he had isolated and named Mycobacterium tuberculosis.

Dr. Koch, of course, could not offer a cure for the dread disease, but by proving that it was a communicable infectious disease he laid the groundwork for eventual effective public health preventative measures and eventually treatment.  Infection rates began to decline in Europe and North America after World War I.  But it wasn’t until the development of the antibiotic streptomycin in 1948 that an effective treatment of the active illness was achieved.  That was followed by other effective antibiotics.

The development of a Tubercular skin test led to the discovery that many more people carry the infection in a latent, but communicable form.  Only 10-15% of those with latent infection get the active disease, generally when the immune system has been weakened by other illness, injury, and infection, or due to chronic malnutrition. 

By the turn of the 21st Century rates of active tuberculosis infections in the advanced industrialized nations had plummeted to near zero.  Most new reported cases involved immigrants and visitors.  Even high rates of infection in the Third World were coming down, albeit slowly.  Then in 2007 international rates began a sharp increase, particularly in sub-Saharan Africa and much of Asia.   Increases are blamed on the rapid development of anti-biotic resistant strains, tuberculosis as a secondary infection in those with HIV/AIDS, over whelmed and underfunded public health services in desperately poor and often politically unstable countries.  Drug resistance has even caused rates to begin to creep up in Europe and the U.S.

Internationally there were in 2012 8.6 million active chronic cases were, 8.8 million new cases diagnosed, and 1.20–1.45 million deaths, most of these occurring in developing countries.  Of these about 350 thousand occurred in those also infected with HIV.  That means that tuberculosis today is far more deadly than the widely reported panic infections of recent years until the Coronaviris struck down 2.7 million over the last 18 months.

Deadly Tuberculosis bacteria first isolated and identified by Dr, Kosh using the techniques and protocols that he invented and which are still the standard for microbiological research.

But back to Dr. Koch.  His breakthrough discovery, for which he was honored with the Nobel Prize for Medicine in 1905, was the result of years of work in microbiology and the development of his famous Four Postulatesfour conditions, all of which must be met, that prove any disease is directly caused by an identifiable microbe.

Robert Koch was born in Clausthal, Hanover, Germany to a middle class family on December 11, 1843.  A very bright child, he reportedly taught himself to read from his parent’s books and magazines before he entered school in 1848.  At gymnasium—the equivalent of high school but with higher academic standards than in America—he excelled in math and science.  Koch entered the University of Göttingen at age 19 where he studied natural science for two years before switching to medicine.

Even as an undergraduate Koch’s proclivity for research and laboratory work drew notice.  He was asked to assist Jacob Henle, a noted anatomist who had published a pioneering theory of contagion in 1840, to participate in his research project on uterine nerve structure.  The next year he was conducting independent research into succinic acid secretion at the Physiological Institute culminating in his lauded dissertation. Koch graduated medical school in January 1866 with the highest honors and a bright future ahead of him.

In the summer of 1867 Koch married Emma Adolfine Josephine Fraatz and they had a daughter, Gertrude, the following year.  In 1870 he was called away from his established medical practice and family to serve as a surgeon in the Franco-Prussian War.

Dr. Koch examining a sheep for anthrax.

After the war Koch turned his attention to research in various plagues which he was convinced were communicable diseases.  His first break through came with anthrax, the deadly disease that annually did major economic damage by infecting herds of cattle and other domestic ruminants.  He identified the cause, the bacteria Bacillus anthracis.  He also discovered that spores of the bacteria could remain dormant for long periods of time and become activated under optimal circumstances.  Koch used microscopy, including dyeing his samples for examination on a slide, and identifying agar as an ideal culture medium in which to grow specimens for examination.  These became the standard techniques for microbiological research to follow.

Even more important was his development of the Four Postulates based on his experience with anthrax.  The postulates are

1)      The organism must always be present, in every case of the disease.

2)      The organism must be isolated from a host containing the disease and grown in a pure culture.

3)      Samples of the organism taken from pure culture must cause the same disease when inoculated into a healthy, susceptible animal in the laboratory.

4)      The organism must be isolated from the inoculated animal and must be identified as the same original organism first isolated from the originally diseased host.

Even using more advanced equipment and techniques than Koch had available, modern epidemiologists employ these same criteria and methods.

Dr. Koch about the time he gained fame for his breakthrough identification of the anthrax pathogen, 

The isolation of Bacillus anthracis was the first time in history a specific microbe had been identified as the cause of a disease and thus gave strong support to the still controversial germ theory and was a nail in the coffin of outdated ideas like spontaneous generation.

Koch was widely acclaimed for his discovery and it led to his appointment as a professor of medicine and an administrator at Berlin University.

He next turned his attention to a disease that regularly erupted, especially in semi-tropical and tropical regions in devastating epidemics—Cholera.  Koch collected samples and did field research during epidemics in Egypt and India.  He isolated and identified Vibrio cholera.  It turned out that in 1854 Italian anatomist Fillipo Pacini had isolated the same bug but had not widely published his findings nor definitively identified it as the cause of Cholera.

On the strength of these achievements Koch was recruited as an advisor to the Imperial Department of Health in the newly consolidated German Empire.  It was during this time that he performed his research on tuberculosis and published his result in 1882.  It was the apex of a brilliant career.  Not only would he be awarded the Nobel Prize for this discovery but also the Prussian Order of Merit in 1906.  In 1908 with support of a gift of 500,000 gold Marks from American philanthropist Andrew Carnegie the Robert Koch Medal and Award was established to be awarded annually to the scientist who does the most to advance research and discovery in microbiology.  The criteria of the judges is said to be, “What would Robert Koch be working on if he was alive today?”

Dr. Koch created a scandal when he divorced his wife of 25 years to marry his much younger mistress, actress Emma Hedwig Freiberg.

In 1893 he ended his 25 year marriage to Emma after becoming involved with a beautiful and much younger actress, Hedwig Freiberg who he had been seeing as early as 1889.  Indeed his scandalous involvement with her may have led to a not entirely voluntary retirement from Berlin University in 1890.  Koch married Hedwig after his divorce.

Had it not been for the scandal Koch might have been as celebrated in America as his contemporary, the Frenchman Louis Pasteur. Certainly their accomplishments and advancement of modern medicine were at least comparable.  But the deep Puritanical strain of Americans would never allow that level of adoration for an open and unapologetic adulterer.

In the 1930 film classic The Blue Angel, nightclub singer Lola Lola--Marlena Dietrich--was the cause of the downfall and ruin of a distinguished professor--Emile Jannings--said to be modeled on Dr, Koch.

Their story is said to have inspired the 1930 German film Der blaue Engelshot simultaneously in an English version, The Blue Angel—and released by Paramount in the U.S.  The movie featured the fall of a distinguished professor played by Emile Jannings when he becomes infatuated by night club singer Marlene Dietrich in the memorable role that made her an international star.  The movie was based on Heinrich Mann’s novel Professor Unrat published in 1905 when Koch’s scandal was still in people’s minds. 

Ironically Jannings would go on to portray Koch is a German 1939 bio-pic.  The Nazi-era film was a propaganda piece celebrating the achievements of good Aryan science.

Luckily Koch’s fall was not as complete or lethal as the professor in the book and movie.  He accepted his major awards with Hedwig at his side.  She remained there until he died on May 22, 1910 as the health spa of Baden-Baden of a heart attack at 66 years of age.  He had been in declining health for years.