# Maud Menten

Maud Leonora Menten
Born20 March 1879
Port Lambton, Ontario
DiedJuly 17, 1960 (aged 81)
Alma materUniversity of Toronto
Known forMichaelis-Menten equation, contributions to enzyme kinetics and histochemistry
Scientific career
Institutions
ThesisThe Alkalinity of the Blood in Malignancy and Other Pathological Conditions; Together with Observations on the Relation of the Alkalinity of the Blood to Barometric Pressure (1916)

Maud Leonora Menten (March 20, 1879 – July 17, 1960) was a Canadian bio-medical and medical researcher who made significant contributions to enzyme kinetics and histochemistry. She is primarily known for her work with Leonor Michaelis on enzyme kinetics in 1913.[1] The paper has been translated from its original German into English.[2][3]

Maud Menten was born in Port Lambton, Ontario and studied medicine at the University of Toronto (B.A. 1904, M.B. 1907, M.D. 1911, Ph.D., 1916). She was among the first women in Canada to earn a medical doctorate.[4] She completed her thesis work at University of Chicago. At that time women were not allowed to do research in Canada, so she decided to do research in other countries such as the United States and Germany.

In 1912 she moved to Berlin where she worked with Leonor Michaelis and co-authored their paper in Biochemische Zeitschrift[1][5] which showed that the rate of an enzyme-catalyzed reaction is proportional to the amount of the enzyme-substrate complex. This relationship between reaction rate and enzyme–substrate concentration is known as the Michaelis–Menten equation.[6]

After studying with Michaelis in Germany she entered graduate school at the University of Chicago where she obtained her PhD in 1916.[7] Her dissertation was titled "The Alkalinity of the Blood in Malignancy and Other Pathological Conditions; Together with Observations on the Relation of the Alkalinity of the Blood to Barometric Pressure". Menten worked at the University of Pittsburgh (1923–1950),[8] becoming Assistant Professor and then Associate Professor in the School of Medicine and head of pathology at the Children's Hospital of Pittsburgh. Her final promotion to full Professor, in 1948, was at the age of 69 in the last year of her career.[7][9] Her final academic post was as a research fellow at the British Columbia Medical Research Institute.

## Early life and work

The Menten family moved to Harrison Mills, British Columbia, where Maud's mother worked as a postmistress. After completing secondary school, Menten attended the University of Toronto where she earned a bachelor of arts degree in 1904 and a master's degree in physiology in 1907. While earning her graduate degree, she worked as a demonstrator in the university's physiology lab.

As Menten wanted to further her medical research, she found that opportunities in Canada were scarce for women at the time. As a result she accepted a fellowship at the Rockefeller Institute for Medical Research and left for in New York City in 1907; there she studied the effect of radium bromide on cancerous tumors in rats. Menten and two other scientists published the results of their experiment, producing the Rockefeller Institute's first monograph.[10] Menten worked as an intern at the New York Infirmary for Women and Children. After a year at the Institute, Menten returned to Canada and began her studies at the University of Toronto where in 1911 she became one of the first Canadian women to qualify as a medical doctor.[9]

## The Michaelis-Menten Equation

In 1912, Menten came back to medical research, working with renowned surgeon George Crile, in whose honour the Crile crater on the Moon is named, on the control of acid-base balance during anaesthesia.[11] Around this time she became acquainted with Leonor Michaelis, who was known then as one of the world-leading experts in pH and buffers.[12] Menten became attracted to Michaelis' early work in enzyme kinetics, despite his modest laboratory establishment in Berlin, and made the difficult decision to cross the sea to work with Michaelis.

Michaelis and Menten expressed the relationship they were investigating as an equation:

${\displaystyle v={\frac {Va}{K_{\mathrm {m} }+a}}}$

for a steady-state rate ${\displaystyle v}$ in terms of the substrate concentration ${\displaystyle a}$ and constants ${\displaystyle V}$ and ${\displaystyle K_{\mathrm {m} }}$ (written with modern symbols). Victor Henri had included an equivalent equation in his thesis, but he did not use it and did not appreciate the importance of the steady state or the simplification that would result from considering the initial rate.[12] [13] The equation shows not only that each enzyme is specific for its substrate, but also that the rate of reaction rate increases to saturation as the substrate concentration increases. The constant ${\displaystyle K_{\mathrm {m} }}$ used in expressing this rate is now called the Michaelis constant.[14] The paper deriving the Michaelis–Menten equation is Menten's most famous work.[1]

## Other work

After her research in Berlin, Menten enrolled in University of Chicago, where in 1916 she obtained a PhD in biochemistry.[15] In 1923, she still could not find an academic position for women in Canada; she took a position as part of the faculty of the medical school at the University of Pittsburgh while serving as a clinical pathologist at Children’s Hospital in Pittsburgh. Despite the demands both jobs had, Menten found time to maintained an active research program,[16][17][18] authoring or coauthoring more than 70 publications. Although her promotion from assistant to associate professor was timely, she was not made a full professor until she was 70 years old, within one year of retirement.[14]

As part of extensive work on alkaline phosphatase,[19][20][21] Menten invented the azo-dye coupling reaction, which is still used in histochemistry. This was described in a major textbook of the 1950s[22] in the following terms:

It is not too much to say that the use of this principle was a stroke of genius.

She characterised bacterial toxins from B. paratyphosus, Streptococcus scarlatina and Salmonella ssp. that were used in a successful immunisation program against scarlet fever in Pittsburgh in the 1930s - 1940s.[23] She also conducted the first electrophoretic separation of blood haemoglobin proteins in 1944.[24] In this she anticipated the results of Linus Pauling and his collaborators[25] by several years, but he is usually credited with the discovery. She worked on the properties of hemoglobin, regulation of blood sugar level, and kidney function.[26]

She continued to work on cancer, especially in children,[27] as well as other illnesses of children.[28][29]

After her retirement from the University of Pittsburgh in 1950, she returned to Canada where she continued to do cancer research at the British Columbia Medical Research Institute (1951–1953).[30]

Poor health forced Menten's retirement in 1955, and she died July 17, 1960, at the age of 81, in Leamington, Ontario.[9][4]

## Personal life

Rebecca Skloot portrays Menten as a petite dynamo of a woman who wore "Paris hats, blue dresses with stained-glass hues, and Buster Brown shoes."[9] She drove a Model T Ford through the University of Pittsburgh area for some 32 years and enjoyed many adventurous and artistic hobbies. She played the clarinet, painted paintings worthy of art exhibitions,[4] climbed mountains, went on an Arctic expedition, and enjoyed astronomy. By the time of her death, she mastered several languages, including Russian, French, German, Italian, and at least one Native-American language, Halkomelem.[31] Although Menten did most of her research in the United States, she retained her Canadian citizenship throughout her life.[31]

## Honors

Throughout her career Menten was affiliated with many scientific societies.

At Menten's death, colleagues Aaron H. Stock and Anna-Mary Carpenter honored the Canadian biochemist in an obituary in Nature: "Menten was untiring in her efforts on behalf of sick children. She was an inspiring teacher who stimulated medical students, resident physicians and research associates to their best efforts. She will long be remembered by her associates for her keen mind, for a certain dignity of manner, for unobtrusive modesty, for her wit, and above all for her enthusiasm for research."[26]

In 1998 she was posthumously inducted into the Canadian Medical Hall of Fame.[4] She was also honored at the University of Toronto with a plaque and at the University of Pittsburgh with memorial lectures and a named chair.[9] Port Lambton, Canada, where Menten was born, installed a commemorative bronze plaque about her in 2015.[32]

## References

1. ^ a b c Michaelis, L.; Menten, M.L. (1913). "Die Kinetik der Invertinwirkung" [The kinetics of invertin action]. Biochemische Zeitschrift. 49 (17): 333–369.
2. ^ Michaelis, L.; Menten, M.L. (2013). Translated by Boyde, T.R.C. "The kinetics of invertin action". FEBS Lett. 587 (17): 2712–2720. doi:10.1016/j.febslet.2013.07.015. PMID 23867202.
3. ^ Johnson, Kenneth A.; Goody, Roger S. (2011). "The Original Michaelis Constant: Translation of the 1913 Michaelis–Menten Paper". Biochemistry. 50 (39): 8264–8269. doi:10.1021/bi201284u. PMC 3381512. PMID 21888353.
4. ^ a b c d "Dr. Maud Menten". The Canadian Medical Hall of Fame. Retrieved 14 October 2014.
5. ^ Srinivasan, Bharath (2021-07-16). "A Guide to the Michaelis‐Menten equation: Steady state and beyond". The FEBS Journal: febs.16124. doi:10.1111/febs.16124. ISSN 1742-464X. PMID 34270860.
6. ^ Srinivasan, Bharath (2020-09-27). "Words of Advice: teaching enzyme kinetics". The FEBS Journal. 288 (7): 2068–2083. doi:10.1111/febs.15537. ISSN 1742-464X. PMID 32981225.
7. ^ a b "Leonor Michaelis and Maud Menten". Science History Institute. June 2016. Retrieved 20 March 2018.
8. ^ Menten, M. (1919). "A Study of the Oxidase Reaction with alpha-Naphthol and Paraphenylenediamine". The Journal of Medical Research. 40 (3): 433–458.3. PMC 2104435. PMID 19972493.
9. Skloot, Rebecca (Oct 2000). "Some called her Miss Menten" (PDF). University of Pittsburgh School of Medicine magazine. Retrieved 14 October 2014.
10. ^ Jobling, J W; Flexner, Simon; Menten, Maud L (1910). Tumors of animals. Rockefeller Institute for Medical Research.
11. ^ Menten, M.L.; Crile, G.W. (1915). "Studies on the hydrogen-ion concentration in blood under various abnormal conditions". Am. J. Physiol. 38 (2): 225–232. doi:10.1152/ajplegacy.1915.38.2.225.
12. ^ a b Deichmann, U.; Schuster, S.; Mazat, J.-P.; Cornish-Bowden, A. (2014). "Commemorating the 1913 Michaelis-Menten paper Die Kinetik der Invertinwirkung: Three perspectives". FEBS Journal. 281 (2): 435–463. doi:10.1111/febs.12598. PMID 24180270. S2CID 5183178.
13. ^ Cornish-Bowden, A.; Mazat, J.-P.; Nicolas, S. (2014). "Victor Henri: 111 years of his equation". Biochimie. 107: 161–166. doi:10.1016/j.biochi.2014.09.018. PMID 25252213.
14. ^ a b "Leonor Michaelis and Maud Leonora Menten". December 12, 2017.
15. ^ Menten, M.L. (1919). "A study of the oxidase reaction with a-naphthol and paraphenylenediamine". J. Med. Res. 40 (176): 433–U22.
16. ^ King, CG.; Menten, ML. (1935). "The influence of vitamin C level upon resistance to diphtheria toxin I. Changes in body weight and duration of life". J. Nutrition. 10: 129–140. doi:10.1093/jn/10.2.129.
17. ^ Menten, ML (1927). "Changes in the blood sugar of the cod, sculpin, and pollock during asphyxia". J. Biol. Chem. 72: 249–253. doi:10.1016/S0021-9258(18)84376-9.
18. ^ Menten, ML (1922). "Pathological lesions produced in the kidney by small doses of mercuric chloride". J. Med Res. 43 (3): 315–321. PMC 2104460. PMID 19972572.
19. ^ Menten, ML.; Janouch, M. (1946). "Changes in alkaline phosphatase of kidney following renal damage with alloxan". Proceedings of the Society for Experimental Biology and Medicine. 63 (1): 33–37. doi:10.3181/00379727-63-15482. PMID 20274252. S2CID 45215943.
20. ^ Menten, ML.; Junge, J.; Green, MH. (1944). "Distribution of alkaline phosphatase in kidney following the use of histochemical azo dye test". Proceedings of the Society for Experimental Biology and Medicine. 57: 82–86. doi:10.3181/00379727-57-14706. S2CID 87059085.
21. ^ Menten, ML.; Junge, J.; Green, MH. (1944). "A coupling histochemical azo dye test for alkaline phosphatase in the kidney". Journal of Biological Chemistry. 153 (2): 471–477. doi:10.1016/S0021-9258(18)71989-3.
22. ^ Pearse, AGE (1953). Histochemistry: Theoretical and Applied (1st ed.). London: Churchill.
23. ^ "Scarlet fever deaths avoided in city". The Pittsburgh Press. May 19, 1942.
24. ^ Andersch, MA; Wilson, DA; Menten, ML. (1944). "Sedimentation constants and electrophoretic mobilities of adult and fetal carbonylhemoglobin". Journal of Biological Chemistry. 153: 301–305. doi:10.1016/S0021-9258(18)51237-0.
25. ^ Pauling, L; Itano, H A; Singer, S J; Wells, I C (1949). "Sickle cell anemia, a molecular disease". Science. 110 (2835): 543–548. Bibcode:1949Sci...110..543P. doi:10.1126/science.110.2865.543. PMID 15395398.
26. ^ a b Stock, Aaron; Carpenter, Anna-Mary (1961). "Prof. Maud Menten". Nature. 189 (4769): 965. Bibcode:1961Natur.189..965S. doi:10.1038/189965a0.
27. ^ Neale, AE.; Menten, ML. (1948). "Tumors of the thymus in children". American Journal of Diseases of Children. 76 (1): 102–108. doi:10.1001/archpedi.1948.02030030109012. PMID 18117553.
28. ^ * Menten, ML.; Fetterman, GH. (1948). "Coronary sclerosis in infancy - report of 3 autopsied cases, 2 in siblings". American Journal of Clinical Pathology. 18 (10): 805–810. doi:10.1093/ajcp/18.10.805. PMID 18889323.
29. ^ * Troll, MM.; Menten, ML. (1945). "Salicylate poisoning - report of 4 cases". American Journal of Diseases of Children. 69: 37–43. doi:10.1001/archpedi.1945.02020130044006.
30. ^ Menten, ML.; Willms, M.; Wright, WD. (1953). "Nucleic acid content of splenic lymphocytes in normal and leukemic mice". Cancer Research. 13 (10): 729–732. PMID 13094687.
31. ^ a b Cornish-Bowden, Athel; Lagnado, John (December 2013). "Maud Leonora Menten: A woman at the dawn of biochemistry" (PDF). The Biochemist. 35 (6): 46–47. doi:10.1042/BIO03506046. Retrieved 10 April 2019.
32. ^ Hnatyshyn, Carl (9 Oct 2014). "Plaques for historical figures approved for St. Clair Twp". Wallaceburg Courier Press. Postmedia Network. Retrieved 2 June 2015.