Corrado Nai

To study microorganisms in laboratory settings, scientists often rely on a perhaps surprising medium: agar, a jelly-like substance that, when mixed with other nutrients, supports the growth of bacteria and similarly small living things.

But agar hasn’t always fulfilled this function. Prior to the late 19th century, it was more commonly used as an ingredient in desserts and soups. At the time, researchers lacked a method to easily grow microorganisms (also known as microbes) as pure cultures isolated from other species—a crucial step in finding a cure for the diseases caused by these organisms. Solid substances like potato slices and coagulated egg whites presented several drawbacks, chief among them their high opacity. Gelatin offered some advantages, but it was easily consumed by microbes and melted at the high temperatures needed to cultivate bacteria. Adding agar to a nutrient-rich mixture avoided these problems, providing a transparent growth medium that wouldn’t be degraded by bacteria.

Agar’s introduction to the life sciences dates to a hot summer day in 1881, when Fanny Angelina Hesse proposed an unexpected replacement for the gelatin her husband, Walther, was using to study microbes in the air. According to a 1939 journal article, “the maddening liquefaction of gelatin ruined many of the experiments, and finally [Walther] began to seek new solidifying agents.” Hesse, in turn, suggested agar, “which she had been using for years in her kitchen in the preparation of fruit and vegetable jellies.”

Portrait of Fanny Angelina Hesse
In his 1992 biography of Hesse, Wolfgang wrote, “The author is proud to possess his grandmother’s original drawings.” Courtesy of Ursula Angelina von Stockhausen
A circa 1892 portrait of the Hesse family
A circa 1892 portrait of the Hesse family Courtesy of Ursula Angelina von Stockhausen

Many puddings made in Indonesia contain agar, a gelling agent that, unlike gelatin, doesn’t melt at the blistering temperatures typical in the Southeast Asian country. Though not Indonesian herself, the American-born Hesse had learned about agar’s culinary uses from a neighbor who once lived in the then-Dutch colony.

A complex sugar obtained from red algae, agar (a name derived from “agar-agar,” meaning “jelly” in the Malay language) is so important to scientific research that during World War II, when faced with import restrictions from Japan, the substance’s main producer at the time, the United Kingdom recognized the shortage as a national emergency. Across the U.K., citizens started foraging alternative seaweeds in an effort to safeguard the production of vaccines and antibiotics.

Despite agar’s significance, few remember Hesse’s key role in microbiology history. Much of the available information about her life comes from two sources: the 1939 paper about the introduction of agar into bacteriology (the study of bacteria), co-written by Arthur Parker Hitchens and Morris C. Leikind, and a short biography published in 1992 by the couple’s grandson, Wolfgang Hesse. Popular articles about Hesse tend to portray her chiefly as a housewife, but newly resurfaced documents shared by Wolfgang’s children and detailed here for the first time reveal her skill as a scientific illustrator and scholar in her own right. The records will be soon deposited at the Museum at the Robert Koch Institute in Berlin.

“Those kinds of materials are a historian’s dream,” says Colleen Puterbaugh, an archivist and public historian at the Center for the History of Microbiology Archives.

A close-up view of one of Hesse's 1906 illustrations
A close-up view of one of Hesse's 1906 illustrations Courtesy of Ursula Angelina von Stockhausen

I first heard Hesse’s story around 2012, at a workshop in Berlin. What surprised me, over the years, was the realization that even people who use agar every day tend not to know her name. I became determined to learn more about the woman who changed the world thanks to an Indonesian pudding. This quest eventually led me to Hesse’s great-granddaughter, Ursula Angelina von Stockhausen. “Oh, joy of joy,” von Stockhausen wrote in an October 2023 email. “We found what we were looking for”: 11 original illustrations created by Hesse in the summer of 1906. Next year, my colleagues and I hope to build on these drawings and similarly overlooked sources to publish an original graphic novel about Hesse’s many contributions to microbiology.

Hesse (often called Lina) was born Fanny Angelina Eilshemius in New York on June 22, 1850. Her father was a wealthy Dutch merchant who immigrated to the United States as a young man, while her mother, a cousin of the Swiss painter Louis Léopold Robert, was born in Lugano.

Hesse’s parents married in 1849 and had ten children, five of whom survived to adulthood. Hesse was the oldest of the siblings. The artistic spirit ran in the family: She followed in her second cousin’s footsteps by creating scientific illustrations, and her brother Louis Michel Eilshemius found success as a painter in New York City.

A circa 1890 or 1891 photograph of Walther and Fanny Angelina Hesse, plus their colleagues and friends
A circa 1890 or 1891 photograph of Walther and Fanny Angelina Hesse, plus their colleagues and friends Courtesy of Ursula Angelina von Stockhausen

Despite living in the U.S., the family had strong ties to Europe. After the upheaval of the Civil War, wealthy Americans frequently visited Europe in the summers, with Germany—particularly the city of Dresden, sometimes referred to as “Florence on the Elbe”—emerging as a popular destination. In September 1865, at the age of 15, Hesse was sent to a finishing school in Neuchâtel, Switzerland, to learn French, home economics and decorum, as was common for elite young women of the time.

Back home in the U.S., the family knew the German doctor Richard Hesse, who’d moved to Brooklyn to practice medicine. Richard introduced the Eilshemiuses to his Dresden-based brother, Walther, who’d served as a physician on a German ship traveling to and from New York in the winter of 1872 and 1873. Walther later drew on this experience to write a report on seasickness.

After meeting in New York, Walther and Hesse reconnected in Dresden. The couple married in Geneva in 1874, then settled in the German state of Saxony. A common cause united the duo: the desire to understand the invisible forces that make people fall ill.

As a county physician in the town of Schwarzenberg, near Dresden, Walther investigated the mysterious lung disease afflicting workers in nearby silver, cobalt and uraninite mines. Two decades before Marie Curie’s discovery of radium in 1898, radioactivity and its pernicious health effects remained poorly understood. Instead, Walther focused his attention on hygiene and dirt particles in the air.

An illustration by Hesse that was previously published in one of her husband's articles about microbes in the air
An illustration by Hesse that was previously published in one of her husband's articles about microbes in the air The Humboldt University of Berlin

To further his research, Walther studied under hygienist Max von Pettenkofer in Munich in 1878 and 1879. His next position was with Berlin-based bacteriologist Robert Koch, who advised him on the study of microbes in the early 1880s. It was through this final, long-lasting medical interest of Walther’s that the power of agar—and of Hesse’s insight—came into full force.

“Berlin was the Mecca of medical research in the 1880s,” says Benjamin Kuntz, director of the Museum at the Robert Koch Institute. “When Walther joined his lab, Koch was an unknown physician, and he’d just settled down as a young scholar. The house where Koch and Walther worked is still there.”

Agar is the breeding ground that allows microbes to grow, rendering them visible without a microscope. These tiny organisms were first observed in 1674, when Dutch merchant and self-taught scientist Antonie van Leeuwenhoek spotted what he called “little animals” in plaque scraped from his tooth. “There are more living animals in the unclean matter in the teeth in one’s mouth than there are men in a whole kingdom,” he declared after viewing the specimen under a rudimentary microscope. But seeing doesn’t equate to understanding. Up until the early 1880s, physicians hotly debated whether microbes could cause disease or if they were just byproducts of sick cell tissue.

According to Wolfgang’s 1992 biography, Hesse was Walther’s “major supporter in many different projects,” creating drawings of microscopic samples for her husband’s published papers and aiding him in the lab. In the summer of 1881, Walther, who was attempting to study airborne microbes, grew frustrated with the gelatin used to coat his lab’s glass tubes. “One day, [he] asked Lina why her jellies and puddings stayed solid at these temperatures,” Wolfgang wrote. “She told him about agar-agar.” Stable at high temperatures, resistant to degradation, and easily sterilized and stored for lengthy periods of time, agar enabled long-term cultures, in which microbes can reproduce under controlled conditions, making them easier to analyze.

Petri dish cultures created by plating microbes on agar
Petri dish cultures created by plating microbes on agar Rizzelli Stefania via Wikimedia Commons under CC BY-SA 4.0

Walther sent a letter detailing the discovery to Koch, who was trying to determine the cause of tuberculosis, an infectious disease then killing roughly 1 in 7 infected people in Germany. On March 24, 1882, Koch held a highly praised presentation in which he proved that tuberculosis is caused by a bacterium, paving the way for better diagnosis and treatment of the disease. (The anniversary is commemorated annually as World Tuberculosis Day.) A few years later, in 1890, Koch wrote, “One could also indulge in the hope that in the not-too-distant future, the pathogens associated with all contagious diseases could be found.”

Popular accounts of microbiology history sometimes attribute the first use of agar in laboratory settings to Koch. The Nobel Prize website, for example, notes that the scientist “invented new methods … of cultivating pure cultures of bacteria on solid media such as potato, and on agar.” In his 1882 lecture, Koch mentioned agar’s role in discovering Mycobacterium tuberculosis but failed to acknowledge the Hesses’ contributions to his research. The couple themselves never wrote a report about agar, which might explain why their names are virtually unknown today.

Though Koch publicized agar’s applications, he didn’t immediately recognize its superiority as a microbial growth medium. For years, scientists (Walther included) continued to debate the merits of gelatin versus agar. At a time when women had no place in the lab (and almost nowhere beyond the kitchen), Hesse’s achievement was unassuming, everlasting and—as is often the case in scientific disciplines—gradual.

“In the Hesse family, this contribution to bacteriology was hardly ever mentioned,” Wolfgang wrote. “Lina never spoke about it, probably because she was a very unassuming person.”

Wolfgang and Fanny Angelina Hesse are seated on the left side of this photograph, taken in Dresden in 1930.
Wolfgang and Fanny Angelina Hesse are seated on the left side of this photograph, taken in Dresden in 1930. Courtesy of Ursula Angelina von Stockhausen

Hesse died in December 1934, 23 years after her husband, who died in July 1911. The 1939 journal article offered a brief overview of her pioneering career but noted, “We know little of her early life.” The 1992 biography, based on a longer unpublished account written in German, was stripped of many personal details during editing and its translation into English. The cover of the journal in which the essay appeared features one of Hesse’s stunning scientific illustrations.

An unassuming parenthetical in Wolfgang’s biography alludes to these artworks’ existence, stating, “The author is proud to possess his grandmother’s original drawings.” This sentence eventually led me to Wolfgang’s children, who shared 11 illustrations drawn by Hesse for Walther’s last publication. A series of plates with splashes of watercolor, the images document the dilution of fecal samples to quantify intestinal bacteria growing on a nutrient-rich agar plate. Though they look hastily created, they’re accurate and informative.

The Hesse family also shared unseen family portraits, as well as the full biography written by Wolfgang. To tell his grandparents’ story, Wolfgang drew on scientific and personal documents preserved by Hesse, as well as his own memories of his grandmother. (Walther died before Wolfgang was born in 1915.) The unpublished biography brings to light new details about Hesse’s early and late life. From Wolfgang’s perspective, readers meet a loving grandmother who enjoyed telling stories and spending time with her grandchildren, often surprising them at Christmas with her special puddings.

One of Hesse's unpublished scientific illustrations
One of Hesse's unpublished scientific illustrations Courtesy of Ursula Angelina von Stockhausen

The newly uncovered materials paint a portrait of a placid, humble woman who took care in preserving her husband’s life’s work. Hesse never spoke about her role in introducing agar to the life sciences, though at least one scholarly work linked her name to agar during her lifetime. This might explain why her mark in collective memory has been so different from others who introduced great innovations or made grand discoveries—and didn’t hesitate to act upon their grandeur. Koch, for one, lamented in his 1905 Nobel Prize lecture that his warnings regarding tuberculosis had “been unheeded.” Leeuwenhoek added the prestigious-sounding suffix “van” to his name after he achieved fame.

Agar is still essential today. It has been the breeding ground for countless world-changing discoveries, from antibiotics to gene editing tools like CRISPR. Recent shortages of seaweed due to overharvesting sent waves of alarm through the scientific research community, which lacks real alternatives to agar. No one knows this better than lichenologists, who study the symbiosis between fungi, algae and other microbes that form lichens. “Culturing is a crucial skill for lichenologists,” says Lucia Muggia, a scientist at the University of Trieste in Italy. “For a study published in 2018, we tested an alternative gelling agent, alginate. And while we didn’t see many changes in how lichens formed under these lab settings, agar was still more practical to handle, so we stuck with it.”

Hitchens and Leikind, the authors of the 1939 journal article, pointed out that “lesser innovations and discoveries are commemorated with the name of the innovator.” A short report published in 1887 by Julius Petri, for instance, made that scientist a household name, forever associated with the glass dishes that often hold an agar-based growth medium, despite the fact that other scholars boast stronger claims to the invention.

“Could not ‘plain agar’ from now on be designated as ‘Frau Hesse’s medium?’” Hitchens and Leikind asked. “Her contribution to bacteriology makes her immortal.” The authors might have been more successful if they’d suggested calling agar plates “Hesse plates”—the counterpart of Petri dishes. Eighty-five years after the article’s publication, Hesse’s name is sadly still unknown to most.

Editor's Note, July 9, 2024: This article has been updated to identify Fanny Angelina Hesse's mother as a cousin, not the daughter, of the Swiss painter Louis Léopold Robert.

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Corrado Nai

Corrado Nai is full-time parenting and part-time writing. He has a PhD in microbiology and used agar every day for over ten years. He is currently writing a graphic novel about Fanny Angelina Hesse’s story and legacy, which can be supported through Kickstarter.