Alan Hofmann

Alan Hofmann
Born	(1931-05-17)May 17, 1931 Baltimore, Maryland, U.S.
Died	September 7, 2021(2021-09-07) (aged 90) La Jolla, California, U.S.
Known for	Research on bile acids & digestion
Spouse	Heli Hofmann
Children	2
Scientific career
Fields	Medicine Gastrointestinal physiology Biochemistry
Institutions	Johns Hopkins University University of Lund Rockefeller University Mayo Medical School University of California, San Diego

Alan Frederick Hofmann (May 17, 1931 – September 7, 2021) was a gastrointestinal physiologist, biochemist and clinician who was notable for his extensive basic, translational and clinical research on bile acids and lipid digestion. From 1977, he was a member of the Division of Gastroenterology at University of California, San Diego.^[1] He influenced and mentored a large number of researchers with his ideas, knowledge and support.^[2]

Career

He was born and grew up in Baltimore, MD, where he attended the Johns Hopkins University gaining an AB in 1951, and MD in 1955. He was a medical intern and resident at Columbia-Presbyterian Medical Center, New York. From 1959 to 1962, he was a National Foundation Research Fellow, working with Bengt Borgström at the University of Lund, Sweden. This was an inspirational time for him and established his lifelong work in lipid digestion and bile acids.^[3] After continuing his research at Rockefeller University, New York, in 1966 he moved to the Mayo Medical School, Mayo Clinic, Rochester, Minnesota. In 1977 he relocated to University of California, San Diego, where he was Professor of Medicine in the Division of Gastroenterology, with Emeritus status from 2002.

Research

Hofmann reviewed his 50-year research career up to 2009.^[3] He made many advances in the chemistry and biology of bile acids, helping understand and treat various liver, biliary and digestive diseases.^[4][2]

His research includes many aspects of lipid digestion and absorption, bile acid evolution, pathobiology, and pathochemistry, bile secretion, cholelithiasis, biliary physiology and pharmacology, and the diagnosis and treatment of various digestive and hepatobiliary diseases.^[1][2] Together with his longtime collaborator, Lee Hagey, he has written a comprehensive history of bile acid research.^[5] Making the most of his proximity to the San Diego Zoo, his publications helped define the wide bile acid diversity found in different vertebrates.^[6]

His early studies on the role of bile acids in the formation of micelles, the structure of the mixed micelle, and bile acid metabolism in humans, led to pharmacokinetic models of lipid digestion.^[7][8]

He was instrumental in the development and evaluation of the use of bile acid therapy to dissolve cholesterol gallstones, first using chenodeoxycholic acid.^[9][10]

He published fundamental work on the enterohepatic circulation of bile acids and how disturbances in ileal function such as those found in Crohn's disease can produce chronic diarrhea.^[11][12][13]

Publications

He has numerous scientific publications dating from 1960 to 2021. His initial publications in 1960 characterized his future research: Exchange of iodine-131-labeled chylomicron protein in vitro in the American Journal of Physiology ^[14] and the next (also a sole author publication) was in Nature on Micellar solubilization of fatty acids and monoglycerides by bile salt solutions.^[15]

He published over 500 articles, including original research and many invited contributions and reviews. His most highly cited publications are on the liver bile salt export pump (over 1100),^[16] the first description of gallstone dissolution by bile acid therapy (over 800),^[9] on the properties of bile salts (over 700),^[17] and the mechanisms whereby bile acids produce secretion in the colon (over 500).^[18] His articles have been widely cited, with an H-index of 111.^[19]

Awards and honors

He received many awards recognizing his achievements, including honorary degrees and visiting lectureships.

• Distinguished Achievement Award, American Gastroenterological Association, Functions and dysfunctions of bile acids,1970
• Sir Arthur Hurst Memorial Lecturer, British Society of Gastroenterology, 1974
• Eppinger Prize (Falk Foundation, W. Germany), 1976
• Harvey Society Lectureship, 1978
• William Beaumont Prize in Gastroenterology of the American Gastroenterological Association, 1979
• Honorary Doctorate, University of Bologna, Italy, 1988
• Julius M. Friedenwald Medal, American Gastroenterological Association, 1994^[2]
• Davenport Medal, American Physiological Society, 1996
• Fellow of the Royal College of Physicians, London, U.K., 1996
• Klatskin Lectureship, Yale University, 1997
• Distinguished Achievement Award, American Association for the Study of Liver Diseases, 1997
• Distinguished Alumnus Award, Mayo Clinic and Mayo Foundation, 2001
• Recognition as Distinguished Mentor, Digestive Health and Nutrition Foundation, 2004
• Herbert Falk Medal, Falk Foundation, 2010.

Influence

Many leading physicians and investigators have cited the benefits of his influence and mentorship.^[2] These include Ian Gilmore^[20] and Aldo Roda.^[21] Together with Gustav Paumgartner in 1972, he helped establish the biennial series of international meetings on bile acids, sponsored by Dr. Herbert Falk and the Falk Foundation.^[22] These have been key in bringing together bile acid researchers and advancing knowledge of their actions and therapeutic value.^[5]

He endowed an annual lectureship at the Johns Hopkins University Gastrointestinal Division in 2005 as he was grateful to Hopkins for providing him with the scholarships which allowed him to attend college and medical school. This lecture has become the highpoint of the academic year, inviting a major GI scientist who is a role model as an academic investigator for faculty and fellows.^[23] Recipients have included James Boyer, Tachi Yamada, Monty Bissell, Jeff Gordon, and Anna Mae Diehl.

Personal

He lived in La Jolla California and was married for 43 years to the artist Heli Hofmann.^[24] He is survived by two children from his first marriage, Anthea Phillips and Cecilia McKenzie, five grandchildren, and two stepdaughters. He remained scientifically active into his 90th year, but suffered from multiple system atrophy. He died peacefully at home in La Jolla on September 7, 2021.^[25]

References

1. "UCSD Faculty: Alan Hofmann MD". Retrieved 8 May 2014.
2. Isenberg JI, Phillips SF (December 1994). "Presentation of the Julius M. Friedenwald Medal to Alan F. Hofmann, M.D., Ph.D". Gastroenterology. 107 (6): 1590–4. doi:10.1016/0016-5085(94)90796-x. PMID 7958668.
3. Hofmann AF (May 2009). "Bile acids: trying to understand their chemistry and biology with the hope of helping patients". Hepatology. 49 (5): 1403–18. doi:10.1002/hep.22789. PMID 19296471. S2CID 11286451.
4. Hofmann AF (1999). "The continuing importance of bile acids in liver and intestinal disease". Arch. Intern. Med. 159 (22): 2647–58. doi:10.1001/archinte.159.22.2647. PMID 10597755.
5. Hofmann AF, Hagey LR (May 2014). "Bile Acid Chemistry, Biology, and Therapeutics During the Last 80 Years: Historical Aspects". J. Lipid Res. 55 (8): 1553–1595. doi:10.1194/jlr.R049437. PMC 4109754. PMID 24838141.
6. Hofmann AF, Hagey LR, Krasowski MD (February 2010). "Bile salts of vertebrates: structural variation and possible evolutionary significance". J. Lipid Res. 51 (2): 226–46. doi:10.1194/jlr.R000042. PMC 2803226. PMID 19638645.
7. Hofmann AF (October 1963). "The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts". Biochem. J. 89: 57–68. doi:10.1042/bj0890057. PMC 1202272. PMID 14097367.
8. Hofmann AF, Borgström B (February 1964). "The intraluminal phase of fat digestion in man: the lipid content of the micellar and oil phases of intestinal content obtained during fat digestion and absorption". J. Clin. Invest. 43 (2): 247–57. doi:10.1172/JCI104909. PMC 289518. PMID 14162533.
9. Danzinger RG, Hofmann AF, Schoenfield LJ, Thistle JL (January 1972). "Dissolution of cholesterol gallstones by chenodeoxycholic acid". N. Engl. J. Med. 286 (1): 1–8. doi:10.1056/NEJM197201062860101. PMID 5006919.
10. Thistle JL, Hofmann AF (September 1973). "Efficacy and specificity of chenodeoxycholic acid therapy for dissolving gallstones". N. Engl. J. Med. 289 (13): 655–9. doi:10.1056/NEJM197309272891303. PMID 4580472.
11. Hofmann, AF (1967). "The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy". Gastroenterology. 52 (4): 752–7. doi:10.1016/S0016-5085(67)80140-9. PMID 5337211.
12. Hofmann AF, Poley JR (August 1969). "Cholestyramine treatment of diarrhea associated with ileal resection". N. Engl. J. Med. 281 (8): 397–402. doi:10.1056/NEJM196908212810801. PMID 4894463.
13. Hofmann, AF (2009). "Chronic diarrhea caused by idiopathic bile acid malabsorption: an explanation at last". Expert Review of Gastroenterology & Hepatology. 3 (5): 461–4. doi:10.1586/egh.09.49. PMID 19817666.
14. Hofmann AF (Sep 1960). "Exchange of iodine-131-labeled chylomicron protein in vitro". Am. J. Physiol. 199 (3): 433–6. doi:10.1152/ajplegacy.1960.199.3.433. PMID 13715094.
15. Hofmann AF (June 1961). "Micellar solubilization of fatty acids and monoglycerides by bile salt solutions". Nature. 190 (4781): 1106–7. doi:10.1038/1901106a0. PMID 13715095. S2CID 4164411.
16. Gerloff T, Stieger B, Hagenbuch B, Madon J, Landmann L, Roth J, Hofmann AF, Meier PJ (April 1998). "The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver". J. Biol. Chem. 273 (16): 10046–50. doi:10.1074/jbc.273.16.10046. PMID 9545351.
17. Hofmann AF, Small DM (1967). "Detergent properties of bile salts: correlation with physiological function". Annu. Rev. Med. 18: 333–76. doi:10.1146/annurev.me.18.020167.002001. PMID 5337530.
18. Mekhjian HS, Phillips SF, Hofmann AF (August 1971). "Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man". J. Clin. Invest. 50 (8): 1569–77. doi:10.1172/JCI106644. PMC 442055. PMID 4938344.
19. "Alan Hofmann". Google Scholar. Retrieved 24 September 2021.
20. "My working day: Ian Gilmore". Journal of the Royal Society of Medicine. 102 (7): 304–305. 2009. doi:10.1258/jrsm.2009.09k033. PMC 2711193.
21. Pfeifer, Andrea; Jarosz, M.; Roda, A.; Sanz-Medel, A.; Gauglitz, G.; Garrigues, P.; Heumann, K.; Wise, S.; Jinno, K. (2012). "Meet the Editors of an Outstanding Journal — An interview - Springer". Analytical and Bioanalytical Chemistry. 402 (1): 7–13. doi:10.1007/s00216-011-5505-2. PMID 22127576.
22. Paumgartner G (April 2010). "Biliary physiology and disease: reflections of a physician-scientist". Hepatology. 51 (4): 1095–106. doi:10.1002/hep.23472. PMID 20373364. S2CID 28158017.
23. Johns Hopkins Medical Center. "Endowed Hofmann Lectureship". Archived from the original on 1 May 2018. Retrieved 3 July 2014.
24. "Heli Hofmann - Post-Impressionism - Oil Painting - About artist". Archived from the original on 2014-07-14.
25. "Alan F. Hofmann: Obituary". New York Times. Retrieved 20 September 2021.

External links

• "UCSD Faculty: Alan Hofmann MD". Retrieved 8 May 2014.