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Judah Folkman

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Judah Folkman
Born(1933-02-24)February 24, 1933
Cleveland,Ohio
DiedJanuary 14, 2008(2008-01-14)(aged 74)
Denver,Colorado
CitizenshipAmerican
Alma materOhio State University
Harvard Medical School
Known forAngiogenesis
AwardsCharles S. Mott Prize(1997)
Massry Prize(1997)
Keio Medical Science Prize(1998)
Scientific career
FieldsPediatric surgery
InstitutionsHarvard Medical School

Moses Judah Folkman(February 24, 1933 – January 14, 2008)[1]was an American biologist and pediatric surgeon best known for his research on tumorangiogenesis,the process by which a tumor attracts blood vessels to nourish itself and sustain its existence. He founded the field of angiogenesis research, which has led to the discovery of a number of therapies based on inhibiting or stimulating neovascularization.[2]

Early life[edit]

Born in 1933 in Cleveland, Ohio, Judah Folkman accompanied his father, arabbi,on visits to hospital patients. By age seven, he knew he wanted to be a doctor rather than follow in his father's footsteps, so he could offer cures in addition to comfort. His father replied, "In that case, you can be a rabbi-like doctor," words his son took to heart.[3]

Folkman graduated fromOhio State Universityin 1953, and thenHarvard Medical Schoolin 1957.[4]While a student at Harvard Medical School, he trained underRobert Edward Gross[5]and also worked on a prototypepacemaker,work that he never published.[6]

In 1960, his residency was interrupted when he was drafted in theUnited States Navyand did research for the Navy until 1962 at theNational Naval Medical CenterinBethesda, Maryland.During that time, he studied the use ofsilasticfor the sustained release oflipophilicdrugs; the 1964 publication of that work helped inspire the technological development of theNorplantimplantable contraceptive at thePopulation Council.[7]: 117 [8]

The navy research was focused on developing artificial blood; in the course of testing potential products to see if they could keep alive thymus glands taken from rabbits, he noticed that tumors in the gland could not grow as they did if the glands were perfused with blood. His curiosity as to why led to his work on angiogenesis.[3]

After his two years work for the navy, Folkman completed his residency at Massachusetts General Hospital. He worked as an assistant surgeon at Boston City Hospital, then trained further in pediatric surgery at Children's Hospital of Philadelphia underC. Everett Koop.[5]

Career[edit]

In 1967 he was appointed surgeon-in-chief ofChildren's Hospital Bostonat the age of 34. Folkman was appointed the Julia Dyckman Andrus Professor of Pediatric Surgery at Harvard Medical School in 1968, where he was also Professor of Cell Biology. He was the youngest full Professor at Harvard Medical School in history.[3]In addition to directing the Children's Hospital Boston Surgical Research Laboratories, which grew to become the Vascular Biology Program, for nearly four decades, he was the Scientific Director of the hospital's Vascular Anomalies Center.[3]

In 1971, he reported in theNew England Journal of Medicinethatsolid tumorsareangiogenesis-dependent.[5][9]He hypothesized that there was an unknown "factor" that tumors secreted to help it increase its blood supply, and that if that factor could be blocked, tumors would wither and die. Though his hypothesis was initially disregarded and treated with skepticism by most experts in the field, Folkman persisted with his research.[4]He and collaborators, who includedBert L. Vallee,soon identified the already-knownfibroblast growth factoras an angiogenic factor, but the team's work showed that there were additional, unknown factors.[2]To help accelerate the work, Folkman started collaborating with industry.[5]In 1974 Harvard University andMonsantosigned a ten-yearindustrial-funded research grantto support his cancer research, which at that time was the largest such arrangement ever made; medical inventions arising from that research were the first for which Harvard allowed its faculty to submit apatent application.[4][5]Robert Langerworked as a postdoc in Folkman's lab during this time, concentrating on usingsilasticand other materials to deliver drugs.[5]

In the mid to late 1980s, two other angiogenic factors were identified by other labs that had been inspired by his work:angiogeninandVEGF.[5]With the factors identified,drug discoverycould begin. When the Monsanto agreement (which yielded no products for Monsanto) ended, Folkman started receiving research funding fromTakedaand then from a startup company,Entremed,that put half its venture capital funding into research in the Folkman lab.[5]

Donald E. Ingbersoon discovered that a fungus,Aspergillus fumigatus,secreted a chemical,fumagillin,that inhibited angiogenesis. Takeda performedmedicinal chemistryto optimize it, leading to development of TNP-470.[5]Folkman's team later tested it in adults withhemangiomas;they also usedinterferon alpha,an already approved drug that they had already shown to be an angiogenesis inhibitor, to treat infants with hemangiomas in some of the first clinical trials of angiogenesis inhibitors which were published in 1992.[10]In these trials they also studied the levels offibroblast growth factorin the urine of the trial subjects and published that work in 1994; these were some of the first explorations of the use ofbiomarkersin clinical trials assurrogate endpoints.[5][11]

In 1991 Michael O "Reilly, working in the Folkman lab with Entremed funding, discovered the first endogenous angiogenesis inhibitor,angiostatinand then another,endostatin.Entremed began developing them and soon struck a collaboration withBristol-Myers,which caught national interest and spurred further investment in angiogenesis inhibitors by other pharma companies.[5][12]

In 1993 he surprised the scientific world by hypothesizing that angiogenesis is as important inblood cancersas it is in solid tumors,[13]and the next year he published work showing that abiomarkerof angiogenesis was higher in all people with cancer, but especially high in people with blood cancers, and other evidence of the role of angiogenesis in blood cancers emerged as well.[13]Meanwhile, a member of his lab, Robert D'Amato, was looking forangiogenesis inhibitors,and discovered thatthalidomideinhibited angiogenesis in 1994.[14][15]Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas.[10]Folkman convinced the patient's doctor to try thalidomide, and that doctor ended up conducting a clinical trial of thalidomide for people with multiple myeloma in which about a third of the subjects responded to the treatment.[10]The results of that trial were published in the New England Journal of Medicine in 1999.[10][16]

In 2004, the first angiogenesis inhibitor,bevacizumab(Avastin), was approved by the FDA, as a treatment for colon cancer. It is arecombinanthumanizedmonoclonal antibodythat was discovered and developed byNapoleone Ferrara,a scientist atGenentech.[17][18]A similar drug,Lucentis,was later approved for treating macular degeneration.[3]After further work was done by Celgene and others, in 2006 the U.S. Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosedmultiple myelomapatients.[10][19]

Awards[edit]

Folkman was a member of theNational Academy of Sciences,theInstitute of Medicine,the American Academy of Arts and Sciences, and theAmerican Philosophical Society,among others. He was the author of some 400 papers and more than 100 book chapters and monographs and received scores of United States awards and honors for his research as well as numerous international awards, including theGeorge Ledlie Prizefrom Harvard, Canada'sGairdner Foundation International Award,Israel'sWolf Prize,Germany'sErnst Schering Prize,the United Kingdom Society for Endocrinology's Dale Medal in 2000,[20]Prince of Asturias Award,the Golden Plate Award of theAmerican Academy of Achievement[21]and Switzerland's Dr. Josef Steiner Cancer Research Award.[22]In 2005 he was awarded theScientific Grand Prize of the Lefoulon-Delalande Foundation.[23]

He was awarded theMassry Prizefrom theKeck School of Medicine,University of Southern Californiain 1997. On May 29, 1998, Folkman received anhonorary doctoratefrom the Faculty of Medicine atUppsala University,Sweden[24]

Personal life[edit]

Folkman died of a heart attack in Denver on January 14, 2008, at the age of 74 en route to deliver the 2008 Keynote Address at the Keystone Symposium (Molecular Mechanisms of Angiogenesis in Development and Disease) inVancouver, British Columbia.[25]

He was survived by his wife, Paula, whom he met and married while doing his surgical residency,[5]two daughters, and a granddaughter.[25]

Further reading[edit]

  • Cooke, Robert; Koop, C Everett (2001).Dr. Folkman's War: Angiogenesis and the Struggle to Defeat Cancer.New York: Random House.ISBN978-0-375-50244-6.
  • Judah Folkman (2001).Cancer Warrior(.MP3)(Video). PBS NOVA.RetrievedAugust 25,2007.
  • "Folkman's Foresight".CR magazine.Fall 2008. Archived fromthe originalon October 23, 2008.RetrievedOctober 16,2008.
  • Judah Folkmanbiography and inspiration for theTobin Project
  • Lam, Andrew. Saving Sight: An eye surgeon's look at life behind the mask and the heroes who changed the way we see. Bokeelia, FL; Irie Books, 2013ISBN978-1617203794

References[edit]

  1. ^"Judah Folkman, MD".Department of Ophthalmology.Harvard Medical School.RetrievedFebruary 18,2019.
  2. ^abCao, Yihai;Langer, Robert(September 9, 2008)."A review of Judah Folkman's remarkable achievements in biomedicine".Proceedings of the National Academy of Sciences of the United States of America.105(36): 13203–13205.Bibcode:2008PNAS..10513203C.doi:10.1073/pnas.0806582105.PMC2533169.PMID18772371.
  3. ^abcdeChildren's Hospital BostonRemembering Judah Folkman: Biography
  4. ^abcHarvard Medical SchoolBio at Harvard Medical School
  5. ^abcdefghijklPatricia K Donahoe.Judah Folkman: 1933–2008. A Biographical MemoirNational Academy of Sciences, 2014
  6. ^Academy of Achievement. June 17, 2010Judah Folkman Biography, Foundations for Cancer TherapyArchivedJanuary 19, 2008, at theWayback Machine
  7. ^Laura J. Frost and Michael R. ReichAccess: How Do Good Health Technologies Get to Poor People in Poor Countries?ArchivedFebruary 12, 2016, at theWayback MachineBibliomotion, Inc., 2014.ISBN9781629560304
  8. ^Folkman J, Long DM (March 1964). "The Use of Silicone Rubber as a Carrier for Prolonged Drug Therapy".J Surg Res.4(3): 139–42.doi:10.1016/s0022-4804(64)80040-8.PMID14130164.
  9. ^Folkman, J (1971). "Tumor angiogenesis: therapeutic implications".New England Journal of Medicine.285(21): 1182–1186.doi:10.1056/NEJM197111182852108.PMID4938153.
  10. ^abcdeBielenberg DR, D'Amore PA (2008). "Judah Folkman's contribution to the inhibition of angiogenesis".Lymphat Res Biol.6(3–4): 203–7.doi:10.1089/lrb.2008.1016.PMID19093793.
  11. ^Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J (March 1994). "Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers".J. Natl. Cancer Inst.86(5): 356–61.doi:10.1093/jnci/86.5.356.PMID7508518.
  12. ^John Crewdson for the Chicago Tribune. April 11, 1999Crucial Test For Cancer Drug
  13. ^abFolkman J (December 2001). "Angiogenesis-dependent diseases".Semin Oncol.28(6): 536–42.doi:10.1016/s0093-7754(01)90021-1.PMID11740806.
  14. ^D'Amato RJ, Loughnan MS, Flynn E, Folkman J (1994)."Thalidomide is an inhibitor of angiogenesis".Proceedings of the National Academy of Sciences of the United States of America.91(9): 4082–4085.Bibcode:1994PNAS...91.4082D.doi:10.1073/pnas.91.9.4082.PMC43727.PMID7513432.
  15. ^Ribatti D (2008)."Judah Folkman, a pioneer in the study of angiogenesis".Angiogenesis.11(1): 3–10.doi:10.1007/s10456-008-9092-6.PMC2268723.PMID18247146.
  16. ^Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B (November 1999)."Antitumor activity of thalidomide in refractory multiple myeloma".N. Engl. J. Med.341(21): 1565–71.doi:10.1056/NEJM199911183412102.PMID10564685.S2CID45150547.
  17. ^Andrew Pollack for the New York Times. February 27, 2004F.D.A. Approves Cancer Drug From Genentech
  18. ^Ribatti D (2008). "Napoleone Ferrara and the saga of vascular endothelial growth factor".Endothelium.15(1): 1–8.doi:10.1080/10623320802092377.PMID18568940.
  19. ^"FDA Approval for Thalidomide".National Cancer Institute. Archived fromthe originalon January 28, 2012.RetrievedJanuary 8,2012.
  20. ^"Society for Endocrinology Medal Winners"(PDF).Archived fromthe original(PDF)on May 16, 2013.
  21. ^"Golden Plate Awardees of the American Academy of Achievement".www.achievement.org.American Academy of Achievement.
  22. ^"The Dr. Josef Steiner Cancer Research Foundation".Archived fromthe originalon November 29, 2011.
  23. ^"Historique".Fondation Lefoulon-Delalande Institut de France.April 12, 2012.RetrievedDecember 12,2017.
  24. ^Naylor, David (June 9, 2023)."Honorary doctorates – Uppsala University, Sweden".www.uu.se.
  25. ^abPollack, Andrew (January 16, 2008)."Judah Folkman, Researcher, Died at 74 on January 15, 2008".The New York Times.RetrievedApril 11,2010.

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