Tuesday, May 30, 2023

Fanny Hesse, the mother of microbiology

There are unsung heroes in the scientific world. They do things behind the scenes in every lab to support the scientists in companies, academia, or government research institutes. They wash the glassware like beakers and flasks. They sterilize materials like medical operating tools. They lay things out for lab lessons. Because of their roles, they go unnoticed and unnamed, although sometimes if they are technicians, a researcher who presents his data at a conference might end his slideshow with their names and faces with a hearty thanks.

This article is about one of those heroes whose name should have been in the limelight for her single contribution to the world of microbiology. Her name is Angelina Fanny Eilshemius. Fanny was the oldest of ten children. She was born on June 22, 1850 in New York City to an import merchant. Her father was Dutch but moved to the U.S. from Germany only 8 years before Fanny was born. He was so successful that he was able to afford to send Fanny to a finishing school in Switzerland at the end of the Civil War, when she was 15. She had already learned cooking and housekeeping from her mother and servants, so the purpose of the finishing school was to teach her French and economics.

photo from alchetron.com

Walther Hesse, her future husband, was a German physician who spent a year in the medical corps. His brother introduced him to the Eilshemius family including Fanny in 1871. A year later, Fanny and her family went on vacation to Europe, and she met up with Walther again in Germany. They were married in 1874, so obviously they had hit it off from the start.

Walther was appointed as a county physician in a uranium mining town on the border of Germany and Czechoslovakia in 1877. (Not long after that, the nearby mines provided ore to Marie and Pierre Curie for their investigations on radium in the ore.) Dr. Hesse spent 10 years there mainly treating miners with lung cancer. He grew deeply interested in environmental hygiene, especially concerning dust contamination and carbon dioxide in the mines, homes, and schools. He was first introduced to the science of microbiology when he became responsible for smallpox vaccines in the community.

His and Fanny's big move was in 1881 when Walther's interest in studying bacteria caused him to take a sabbatical at the Imperial Health Agency in Berlin. The man in charge there was Robert Koch, one of the giants in the field of microbiology then. Koch had already discovered the cause for anthrax, cholera, and tuberculosis before Hesse arrived, and that was perfect timing for both people. With other researchers there, they pioneered many lab techniques in use today.

This is where Fanny enters the picture.

In addition to taking care of their sons, Fanny helped out in Walther's lab as he worked under Koch. Not only did she draw images from his microscopic views (a talent inherited from her grandfather, painter Louis Léopold Robert), but she was also a technician to prepare the broths to grow bacteria. One problem that everyone encountered was specific to growing bacteria that they were studying.

Fanny and Walther Hesse around 1872

Researchers used liquid broths that were rich in nutrients, but in order to find just one type of bacteria, they had to grow them on something hard. That way, if they were spread out in a diluted solution, each bacteria would grow separated from the others and make a tiny blob called a colony. That was a pure growth of just one type of bacteria, exactly what the researchers needed. 

Bacterial colonies from a cough on a Petri dish (from microbiologysociety.org)

Koch started doing this with thin slices of spoiled potatoes when he saw that they had bacteria and mold growing on them. But they didn't grow everything. People had already known that things grow naturally on foods. Bartolomeo Bizio investigated a "bloody bread" epidemic in Italy around 1820 and identified the bacteria growing on it. In 1872, Joseph Schroeter used potato, coagulated egg white, meat, and bread as surfaces that some bacteria would grow on. But using food was imprecise, and Koch was a stickler for precision.

White splotches on the right half are bacterial colonies on a potato slice.

So, Koch took his liquid broths and made them a little harder by adding gelatin. The problem Koch found was that when they were put into test tubes and incubated at body temperature, the gelatin melted back into a liquid form. Some bacteria can also digest gelatin and make it liquid. Hesse was trying to study bacteria growing from air samples at the same time, but hot summer temperatures also melted the gelatin. Hesse smeared a thin layer of gelatin on the inside of test tubes for his air contamination experiments, but he was frustrated when they easily melted and ran down the tube into a pool at the bottom instead of staying as a smooth flat layer where he hoped to count and identify what had grown there.

Walther then noticed that Fanny's puddings and jellies at home didn't suffer in the heat, so he asked what she did to prevent that. She told him she had replaced the gelatin with agar. As a child in New York City, while she was learning to cook, a neighbor who had immigrated from Java told her about agar, an extract from red algae used as a gelling agent in warm climates. (Agar is also called agar-agar in Malay language.)

Red algae (Wikipedia)

Walther quickly tested it and found that nutrient broth with agar added could be sterilized, and that bacteria did not eat it, plus it could be stored for a long time. That was what was needed, especially for some experiments with slow-growing bacteria like in tuberculosis. This was the solution (no pun intended) he and Koch needed!

The picture below show 3 ways agar can be used to grow bacteria, now and back in the days of Hesse and Koch. One is on a flat covered plate called a Petri dish. Another (left) is a deep tube, where you stab a needle with bacteria on it and see where it grows -- near the top where there is more oxygen, or near the bottom where there isn't any. If you pour agar into a tube and tilt it at an angle before it hardens, you get a slant (right). Putting bacteria on that surface allows it to grow like on a Petri dish but taking up less space. The middle tube has no agar in it; it's just a liquid broth which is good for bacteria that can swim.

Koch and other researchers developed different ways to grow bacteria on agar that was put into Petri dishes. Sometimes they wanted to count how many were there, so they took a broth and spread it on top of agar or mixed it with liquid agar before it hardened. If they had a sample of something and wanted to get just one colony growing from a single bacteria, they could also streak the sample with a wire loop onto the surface of the agar That way, if the sample was mixed with other bacteria, each one could be seen by its color or texture. These techniques are used today.

Results of 3 types of agar plate growth of bacteria

Fanny Hesse's simple home cooking advice about agar revolutionized how researchers could study bacteria. In fact, after agar was introduced to Hesse, it took Koch less than a year to use the technique and discover the bacteria that causes tuberculosis. In his paper, though, he only casually mentioned changing from gelatin to agar and never explained why. Neither Fanny nor Walther was given any credit for it, either. When Koch wrote up his landmark research on tuberculosis where he used agar to culture the bacteria, here is all that he said about this new method:

“The tubercule bacilli can also be cultivated on other media…they grow, for example, on a gelatinous mass which was prepared with agar-agar, which remains solid at blood temperature, and which has received a supplement of meat broth and peptone.”

Walther Hesse's grandson Wolfgang told this story and more, and he said that Fanny was so unassuming that she never mentioned this to the family. It wouldn't have been "proper". Her original drawings and Walther's notes have been kept by his descendants to this day. 


Here is a video showing how to streak an agar plate.

Here is Wolfgang Hesse's biographical account of Walther and Fanny.