The Most Wonderful Human Being in the World

Dr. Maud Menten, ca. 10-1915. Courtesy, Archives Services Center, University of Pittsburgh

Dr. Maud Menten, ca. 1910-1915. Courtesy, Archives Services Center, University of Pittsburgh

In July of 1912 an extraordinary young scientist named Maud Menten visited Russell Coles at Cape Lookout, N.C.

Other scientists visited the legendary shark hunter too, but none impressed him like she did.  After spending a week assisting her with a research project, Coles wrote a colleague at the Smithsonian, saying “Dr. Menten is unquestionably the most wonderful human being in the world.”

This is chapter 7 of Shark Hunter: Russell J. Coles at Cape Lookout.

Unlike the other scientists, Menten was not even an ichthyologist or any other kind of marine biologist.

She was a brilliant young medical doctor and biochemist. She sought out Coles because she was looking for live specimens of a special kind of fish, the Brazilian electric ray (Narcine brasiliensis), for an experiment involving the effects of exhaustion on nerve cells.

At the time she visited the North Carolina coast, Menten had already earned her M.D. at the University of Toronto and was a fellow at Western Reserve University Medical College  (now Case Western Reserve University Medical School) in Cleveland.

She had already done important work on the distribution of chloride and potassium ions in nerve cells, and she had also co-authored a book on tumors in animals.

While at Western Reserve, Menten worked in the lab of a famous surgeon named Dr. George Washington Crile at the H.K. Cushing Laboratory of Experimental Medicine.

Today Crile is remembered most often for co-founding the Cleveland Clinic and for having been the first surgeon to do a successful blood transfusion, which he did at Lakeside Hospital in Cleveland in 1906.

When Menten traveled to the North Carolina coast, it was to obtain specimens of electric rays for another of Crile’s research projects.

Crile had a longtime interest in the physiological changes that stress, trauma and exhaustion cause in the human body. As one component of that research, he did a series of animal studies involving the effects of exhaustion on nerve cells.

In that research, he examined the nerve cells of animals that had been driven to exhaustion either as part of their normal life cycle or because of human intervention– foxes that hunters had chased, for instance, or salmon after they had migrated upriver to spawn.

The Path to Morehead City

In addition, with Dr. Menten’s help, Crile was able to study the effect of exhaustion on the nerve cells of the Brazilian electric ray. It is a species of ray found in coastal areas from North Carolina to the northern part of Argentina.

Electric rays make up the order Torpediniformes. As a group, they have the capacity to  produce an electric shock that ranges from eight to 220 volts, depending on the species.

The rays use this electric discharge to stun prey and to protect themselves.

Dr. Celia Bonaventura, a biochemist who is an emeritus professor at the Duke University Marine Lab in Beaufort, N.C., explained to me that electric rays generate an electric discharge by enabling a movement of ions (electrically charged atoms or groups of atoms) across the membranes of cells called “electrocytes.”

The electrocytes, she told me, are actually stacked in columns of many cells, like people stacked Delco batteries in the early 20th century to power lights and machinery before electric lines reached rural areas.

An electrical charge– Menten’s generation of biochemists discovered—results from minuscule differences in pH across the cell membrane, but in the rays the tiny charge adds up because the stacked electrocytes contain a large number of cells.

Eventually, as the electric ray gives off its charge, carbon dioxide builds up and ion concentration increases with the result that the cells become more acidic and are driven toward exhaustion.

“Setting the stage for that discovery”

I’m getting a little ahead of my story, but I think it’s worth pointing out here that determining pH and protein concentrations in cells was at the core of Menten’s research throughout her professional life.

Scientists now understand that it is the very small pH differences across cell membranes that drive the production of ATP (adenosine triphosphate), which is the primary energy currency used for cellular functions in all living organisms.

“All the work that Menten and others did on the effects of pH set the stage for that discovery,” Dr. Bonaventura told me.

She explained that it was a tremendously important advance in biochemistry and medicine.

Dr. Bonaventura also noted that nerve impulses similarly rely on ion concentration differences that are controlled by cell membranes .

Crile eventually published his findings in a six-part series called “Studies in Exhaustion” that appeared in the Archives of Surgery between 1920 and 1924.

In the second part of the series, in July 1921, he highlighted his research on the Brazilian electric rays and other animals in an article simply called “Studies in Exhaustion II. Exertion.”

(Other parts of the series featured exhaustion due to other factors– sepsis, bleeding, emotional trauma, etc.)

In the July 1921 article, Crile acknowledged Menten’s assistance in acquiring 12 Brazilian electric rays on the North Carolina coast.

Coles with a group of 8 unidentified rays probably on the beach at the Promise Land in Morehead City ca. 1912-15. Photo courtesy of Walter Coles, Sr., Coles Hill, Va.

Coles with a group of 8 unidentified rays at Cape Lookout ca. 1912-15. Photo courtesy of Walter Coles, Sr., Coles Hill, Va.

The Smithsonian’s assistant curator for fishes, Barton Bean, had recommended to Menten that she seek out Coles as the surest way to find the electric rays that Crile wanted for his research.

In a letter to Bean that my daughter Vera and I found at Coles Hill (Russell Coles’ ancestral estate in Virginia) dated June 28, 1912, Menten noted simply that she was going to see Coles “relative to some work on elec. Ray.”

Coles knew his stuff when it came to the rays at Cape Lookout. He had been observing electric rays there for roughly a dozen years, and he had been collecting them and recording their numbers and on what day he caught them since 1909.

He summarized that information in an article in the Bulletin of the American Museum of Natural History in 1913.

Brazilian electric rays (Narcine brasiliensis) are found on reefs from the North Carolina coast to northern Argentina. From Shark-References.com

Brazilian electric rays (Narcine brasiliensis) are found in reef environments from the North Carolina coast to northern Argentina. From Shark-References.com

In the article, Coles noted that Brazilian electric rays appeared to migrate north into Cape Lookout Bight every summer. Judged by the ray’s appearance in his nets and in the nets of the local fishermen who shared information about their catches with him, the date of arrival of the rays was remarkably consistent.

In the three summers from 1909 to 1911, he and his crew caught their first Brazilian electric rays on June 29 and their last one on the 4th of July.

Based on that knowledge, Coles and Menten timed their rendezvous in Morehead City for June 28, 1912. They began collecting electric rays the next day.

The Unstoppable Miss Menten

Maud Menten was a force of nature.  She was a small woman who had a penchant, one writer has noted, for “Paris hats, blue dresses with stained-glass hues, and Buster Brown shoes.”

She was born in Port Lambton, a village 50 miles northeast of Detroit, Michigan, in the Canadian province of Ontario, in 1879.

When she was 11 years old, the Mentens moved 2,000 miles west and were among the founding settler families of Harrison Mills, a village in southwestern British Columbia, at the juncture of what newcomers called the Fraser and Harrison rivers.

Harrison Mills ca. 1920. Courtesy, Fraser Historical Society

Harrison Mills ca. 1920. Courtesy, Fraser Historical Society

Her mother, Emma, operated a general store, hotel and post office there. Her father, William, was a riverboat captain.

Colonized by Europeans mainly during a gold rush and a timber industry boom in the last half of the 19th century, the area around Harrison Mills was the ancestral territory of two Indigenous peoples, the Sq’éwlets (Scaulits) and the Sts’ Ailes (Chehalis). They spoke different dialects of Halq’eméylem, the language of the Indigenous peoples in the Fraser Valley.

I don’t know how young Maud Menten learned the language, but she was said to be a fluent speaker of Halq’eméylem as a child and apparently remained fluent in the language throughout her life.

When she was a girl, she took a ferry across the Fraser River every morning to attend the village school in Chilliwack, a somewhat larger town. (Harrison Mills had no school.) At the time of her graduation in 1897, the average class attendance at the school in Chilliwack was 14 students.

According to a recent exhibit at the Kilby Historic Site in Harrison Mills (curated by University of British Columbia student Nina Payne), Menten taught briefly at a local elementary school before traveling back to Ontario to attend the University of Toronto in 1900.

Maud Menten, age 7, ca. 1885. Courtesy, Kilby Historic Site, Harrison Mills, BC

Maud Menten, age 7, ca. 1885. Courtesy, Kilby Historic Site, Harrison Mills, BC

Maud Menten graduated with honors in 1904 and then enrolled in the university’s medical school in the first class that did not exclude women. She earned a bachelor’s degree in medicine in 1907 and her M.D. in 1911, becoming one of the first women physicians in the country.

Finding medical research institutions willing to accept a woman, no matter how well qualified, was even more difficult than finding a medical school that accepted women students.

Nevertheless, over the next several years, Menten succeeded in finding short-term research opportunities at the Rockefeller Center for Medical Research in New York City, the University of Toronto and Western Reserve University in Cleveland.

At the time she came to the North Carolina coast, she had become one of the first women researchers in either Canada or the U.S. in the field of biochemistry.

Maud Menten in her cap and gown. Courtesy, Kirby Historic Site, Harrison Landing, BC

Maud Menten in her cap and gown. Courtesy, Kirby Historic Site, Harrison Mills, BC

She was indefatigable. Throughout her career, she was known for her 18-hour workdays, her relentless pace, her dogged perseverance and her unwillingness to suffer fools gladly.

Yet she also had other passions and clearly had a light heart. She played the clarinet, painted seriously and was an avid amateur astronomer. She liked outdoor adventures and once joined an Arctic expedition.

Courtesy, University of Pittsburgh Medical Center

Painting by Maud Menten. Courtesy, University of Pittsburgh Medical Center

In an article for a university alumni magazine, the science writer Rebecca Skloot referred to her as the “unstoppable Miss Menten.”

In the article, Skloot observed that other physicians and scientists—most particularly the men that ran research labs and hospitals– often put up obstacles to her as a woman in a field in which women were a tiny minority. They failed to promote her, refused to fund her research and sometimes claimed credit for her work.

Many tried to change how she approached scientific problems as well.

In response, Skloot wrote, “Menten, whose petite frame and sea-blue eyes projected only tenderness, would smile sweetly and keep right on doing it her way.”

“The very problem of life itself”

She was 33 years old when she visited Russell Coles in North Carolina. That week she swept him up into a frenzy of activity.

The whole week was a whirlwind. Coles later wrote Bean that he “slept less than three hours in every 24” that week.

Menten brought a large array of lab equipment with her. On her arrival, Coles helped her to set up a temporary lab in a room in Morehead City that he had outfitted for his dissections.

In a letter to Bean that he wrote after Menten’s departure, Coles recalled how he “hauled big net nearly all night and worked nearly all day with her in laboratory…. “

Images of a variety of rays in the genus Torpedo (which, yes, is the source of the word torpedo). Known since Antiquity and often ascribed magical powers, torpedo rays were even used by the ancient Greeks to treat pain. From http://biophysics.sbg.ac.at/ra

Images of a variety of rays in the genus Torpedo (which, yes, is the source of the word torpedo). Known since Antiquity and often ascribed magical powers, torpedo rays were even used by the ancient Greeks to treat pain. From http://biophysics.sbg.ac.at/ra

Coles was not a humble man and his letters do not make him seem especially respectful of women in general, at least not those he met at Cape Lookout. Nevertheless, in the correspondence that Vera and I read at Coles Hill, he seems to have felt highly privileged to have been in Menten’s company and more than a little in awe of her.

On July 24, he wrote Bean, “I never could have accomplished what she has . . . it is wonderful and I am very glad that you aided in getting her here.”

Coles felt as if Menten had discovered the secret of life.

“She is the first and only one to have discovered and proven the very problem of life itself,” he exulted.

He wrote, “She has found the chemical ingredients and the muscular action which brings these ingredients together and produces electricity”—by which he meant the chemical and pH changes in nerve cells that shape neural pathways.

He was of course giving her more credit than any one scientist was due—but in a way it was understandable. Menten was part of a generation of scientists that had begun to reveal the biochemical foundations of life and Coles was getting a crash course in their discoveries.

It was all new and revelatory to him. He had not had a biology class since his brief stint at VMI in the 1880s. At that time, his professor had probably been trained before the Civil War.

Menten, on the other hand, had just earned her M.D. at the University of Toronto and was already a gifted biochemist– she would later complete a Ph.D. in biochemistry at the University of Chicago as well.

Her view of living organisms went far beyond the kind of taxonomic descriptions, anatomical studies and field observations that Coles had learned from the marine scientists with whom he had worked at Cape Lookout—her outlook was grounded in chemical pathways and molecular interactions involving enzymes, pH balances and the like.

To say the least, Coles was enthralled. His letters and diaries generally show a predatory view of women—as objects to be hunted, conquered and then cast aside, not wholly unlike his attitude towards sharks.

Not true with Menten. In speaking of the week of hospitality and energy he devoted to Menten, he referred only to her work and to her ideas.

On July 24, 1912, he wrote Bean at the Smithsonian, “I will feel well repaid in having been able to make Dr. Maud Menten’s great work . . . a success.”

It was in that same letter that he wrote, “Dr. Menten is unquestionably the most wonderful human being in the world.”

Tiny Chemical Machines

When she visited the North Carolina coast, Maud Menten was at the beginning of a brilliant career. Only a year later, in 1913, she and a German biochemist named Leonor Michaelis derived a landmark mathematical model for determining the rate of enzyme reactions.

Enzymes are a kind of protein, the “tiny chemical machines,” to quote Science Boreali’s chemistry editor, Dr. Chantal Mustoe, that exist by the thousands in every cell of the human body. While other proteins have other functions, enzymes catalyze nearly all the body’s metabolic processes.

Studying an enzyme called invertase, which breaks down sugars, she and Michaelis found, to quote Mustoe again, that “the complex sugar (sucrose) and the simple sugars (fructose and glucose) absorb a special type of light differently.”

Measuring that light absorption, Michaelis and Menten could tell the rate “at which sucrose disappeared and fructose and glucose appeared.”

From that work, the two scientists were able to derive a mathematical model describing that process, which came to be known as the Michaelis–Menten Equation and gave birth to the study of Michaelis–Menten Kinetics.

Mustoe continues:

“If their mathematical modelling of enzyme activity applied only to invertase, their findings might have faded with the years. But the equation is not specific to invertase. In a given environment, the Michaelis-Menten equation applies to any protein that binds and interacts with something else (even the proteins that “read” our DNA).”

Michaelis–Menten saturation curve; Plot by Thomas Shafee CC BY 4.0

The Michaelis-Menten Equation has been an essential tool in the development of vaccines and other medicines, and it remains a core tool in biochemical and medical laboratories around the world. Today scientists cite the pair’s original paper more frequently than ever.

Beyond the Michaelis-Menten Equation

While most often remembered for the Michaelis-Menten Equation, Menten went on to have a long and accomplished career as a clinician, medical researcher and biochemist.

She joined the faculty in the Department of Pathology at the University of Pittsburgh School of Medicine in 1918. She remained there for 32 years, while also serving as a clinical pathologist at Pittsburgh’s Children’s Hospital.

During that time, her research spanned a broad range of topics in pathology and biochemistry: kidney function, properties of hemoglobin, tumors in children’s thyroids, the regulation of blood sugar levels and more.

Dr. Celia Bonaventura, professor emeritus, Duke University Marine Lab, Beaufort, N.C

Dr. Celia Bonaventura, professor emeritus, Duke University Marine Lab, Beaufort, N.C

Dr. Bonaventura told me that she came to admire Menten deeply as she studied her research papers on my behalf.

She was aware of course of the Michaelis-Menten Equation, which every biochemist and medical student learns at some point. She was not aware, however of Menten’s later work, though it turned out that she had used laboratory techniques pioneered by Menten throughout her research career. One was the development of what is called the azo-dye coupling reaction for alkaline phosphatase, which Menten did in 1944 and in the process opened the field of enzyme histochemistry.

Enzyme histochemistry uses special dyes to identify specific proteins within cells and on tissues, which remains an essential part of medical and biochemical research in many fields today.

Dr. Bonaventura was deeply impressed by Menten’s perseverance and by the exactitude of the lab techniques that were necessary to identify such dyes, especially with the limited tools available at the time. She compared Menten’s work in this area to, in her words, “Edison’s perseverance in finding the right filament.”

Dr. Bonaventura was also impressed to learn that Menten had accomplished the first electrophoretic separation of blood hemoglobin proteins.

She said, “Menten showed the world the importance of the positive and negative charges carried by proteins. That’s really a lot. Her demonstration that you can isolate and separate proteins based on their charge among the thousands of component parts of cells has had a tremendous number of applications in many different fields of biochemical and medical research.”

Dr. Bonaventura, whom I think is now the co-president of the Maud Menten Fan Club (with me), added “ Menten’s pioneering work was foundational for the understanding we now have of how different cell types use specific ions. New discoveries are continuing to be made along these lines.”

“For example,” she told me, “Menten and Crile documented the presence of chloride in nerve cells, a feature which is currently being intensely investigated for its significance in memory.”

Dr. Bonaventura concluded, “Maud Menton was an outspoken and talented scientist. She walked a path that was not at all common for her time. She’s a role model we can all learn from as we continue to explore how an organism’s biochemical pathways are affected by its activity and its environment.”

A new generation of women scientists and iconoclasts of all kinds have been re-discovering Menten. Maud Menten, linocut, by Ele Willoughby, 2018.

A new generation of women scientists and iconoclasts of all kinds have been re-discovering Menten. Maud Menten, linocut, by Ele Willoughby, 2018.

Menten retired as a full professor and chair of the Department of Pathology at the University of Pittsburgh’s School of Medicine in 1950. She later did cancer research back in British Columbia, until health issues forced her to retire in 1954.

She died in Ontario in 1960, but she had her ashes returned to her family’s burial plot in British Columbia.

I would have loved to see Menten and Coles out at Cape Lookout together: I imagine them waist-deep in the water, the lighthouse in the distance, Coles hanging on her every word, hungry to know her world, both of them looking in their own way to understand the mysteries of life.

-To be continued-

 

4 thoughts on “The Most Wonderful Human Being in the World

  1. I am preparing, actually just reading, about Harlowe Canal, as I prepare for my 5th challenge of circumnavigation of Cedar Island on a windsurfer race board. I read a few of your articles and the last one on the Quakers and Slaves and all the history and map explanations, the most challenging and dreaded portion being through the Harlow. That article, linked me to this your essay page and…. All so very fascinating and enriching. Thank you for my first read of your essays, and Menten. Going to read all of them…. Also going to forward Menten’s to my daughter who studied Biology at UNC….

    Liked by 1 person

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