Moses Judah Folkman (February 24, 1933 – January 14, 2008) was an American
medical
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practic ...
scientist
A scientist is a person who conducts scientific research to advance knowledge in an area of the natural sciences.
In classical antiquity, there was no real ancient analog of a modern scientist. Instead, philosophers engaged in the philosoph ...
best known for his research on tumor
angiogenesis, 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.
Early life
Born in 1933 in Cleveland, Ohio, Judah Folkman accompanied his father, a
rabbi
A rabbi () is a spiritual leader or religious teacher in Judaism. One becomes a rabbi by being ordained by another rabbi – known as ''semikha'' – following a course of study of Jewish history and texts such as the Talmud. The basic form of ...
, 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.
[Children's Hospital Bosto]
Remembering Judah Folkman: Biography
/ref>
Career
Folkman graduated from Ohio State University
The Ohio State University, commonly called Ohio State or OSU, is a public land-grant research university in Columbus, Ohio. A member of the University System of Ohio, it has been ranked by major institutional rankings among the best publ ...
in 1953, and then Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
in 1957.[Harvard Medical Schoo]
Bio at Harvard Medical School
/ref> While a student at Harvard Medical School, he trained under Robert Edward Gross[ and also worked on a prototype pacemaker, work that he never published.][Academy of Achievement. June 17, 201]
Judah Folkman Biography, Foundations for Cancer Therapy
After his graduation, he started his surgical residency at Massachusetts General Hospital.
In 1960 his residency was interrupted when he was drafted in the United States Navy
The United States Navy (USN) is the maritime service branch of the United States Armed Forces and one of the eight uniformed services of the United States. It is the largest and most powerful navy in the world, with the estimated tonnage ...
and did research for the Navy until 1962 at the National Naval Medical Center
National may refer to:
Common uses
* Nation or country
** Nationality – a ''national'' is a person who is subject to a nation, regardless of whether the person has full rights as a citizen
Places in the United States
* National, Maryland, ...
in Bethesda, Maryland
Bethesda () is an unincorporated, census-designated place in southern Montgomery County, Maryland. It is located just northwest of Washington, D.C. It takes its name from a local church, the Bethesda Meeting House (1820, rebuilt 1849), which in ...
. During that time, he studied the use of silastic Silastic (a portmanteau of 'silicone' and 'plastic') is a trademark registered in 1948 by Dow Corning Corporation for flexible, inert silicone elastomer.
Composition
The Silastic trademark refers to silicone elastomers, silicone tubing and some cr ...
for the sustained release of lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...
drugs; the 1964 publication of that work helped inspire the technological development of the Norplant
Levonorgestrel-releasing implant, sold under the brand name Jadelle among others, are devices that release levonorgestrel for birth control. It is one of the most effective forms of birth control with a one-year failure rate around 0.05%. The d ...
implantable contraceptive at the Population Council
The Population Council is an international, nonprofit, non-governmental organization. The Council conducts research in biomedicine, social science, and public health and helps build research capacities in developing countries. One-third of its res ...
.
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 couldn't grow as they did if the glands were perfused with blood. His curiosity as to why led to his work on angiogenesis.[
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 under ]C. Everett Koop
Charles Everett Koop (October 14, 1916 – February 25, 2013) was an American pediatric surgeon and public health administrator. He was a vice admiral in the U.S. Public Health Service Commissioned Corps, and served as the 13th Surgeon Ge ...
.[ Patricia K Donahoe]
Judah Folkman: 1933–2008. A Biographical Memoir
National Academy of Sciences, 2014 In 1967 he was appointed surgeon-in-chief of Children's Hospital Boston
Boston Children's Hospital formerly known as Children's Hospital Boston until 2012 is a nationally ranked, freestanding acute care children's hospital located in Boston, Massachusetts, adjacent both to its teaching affiliate, Harvard Medical Sch ...
at 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.[ 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.][
]
Work on angiogenesis
In 1971, he reported in the ''New England Journal of Medicine
''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one.
His ...
'' that solid tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s are angiogenesis-dependent.[ 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.][ He and collaborators, who included Bert L. Vallee, soon identified the already-known ]fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...
as an angiogenic factor, but the team's work showed that there were additional, unknown factors.[ To help accelerate the work, Folkman started collaborating with industry.][ In 1974 Harvard University and ]Monsanto
The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in ...
signed a ten-year industrial-funded research grant to 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 a patent application
A patent application is a request pending at a patent office for the grant of a patent for an invention described in the patent specification and a set of one or more claims stated in a formal document, including necessary official forms and re ...
.[ ]Robert Langer
Robert Samuel Langer Jr. FREng (born August 29, 1948) is an American chemical engineer, scientist, entrepreneur, inventor and one of the twelve Institute Professors at the Massachusetts Institute of Technology.
He was formerly the Germeshau ...
worked as a postdoc in Folkman's lab during this time, concentrating on using silastic Silastic (a portmanteau of 'silicone' and 'plastic') is a trademark registered in 1948 by Dow Corning Corporation for flexible, inert silicone elastomer.
Composition
The Silastic trademark refers to silicone elastomers, silicone tubing and some cr ...
and other materials to deliver drugs.[
In the mid to late 1980s, two other angiogenic factors were identified by other labs that had been inspired by his work: ]angiogenin
Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ''ANG'' gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular ...
and VEGF
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
.[ With the factors identified, drug discovery could begin. When the Monsanto agreement (which yielded no products for Monsanto) ended, Folkman started receiving research funding from and then from a startup company, Entremed, that put half its venture capital funding into research in the Folkman lab.][
]Donald E. Ingber
Donald E. Ingber (born 1956) is an American cell biology, cell biologist and bioengineering, bioengineer. He is the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University,Crow, James Mitchell (19 Janua ...
soon discovered that a fungus, '' Aspergillus fumigatus'', secreted a chemical, fumagillin, that inhibited angiogenesis. Takeda performed medicinal chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...
to optimize it, leading to development of TNP-470.[ Folkman's team later tested it in adults with ]hemangiomas
A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the ski ...
; they also used interferon alpha
The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyt ...
, 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. In these trials they also studied the levels of fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...
in the urine of the trial subjects and published that work in 1994; these were some of the first explorations of the use of biomarkers
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, pa ...
in clinical trials as surrogate endpoints In clinical trials, a surrogate endpoint (or surrogate marker) is a measure of effect of a specific treatment that may correlate with a ''real'' clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of He ...
.[
In 1991 Michael O"Reilly, working in the Folkman lab with Entremed funding, discovered the first endogenous angiogenesis inhibitor, ]angiostatin Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels). Clinical trials have been undertaken for its use in antic ...
and then another, endostatin
Endostatin is a naturally occurring, 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.
Endostatin is a broad-spectrum angiogenesis inhibi ...
. Entremed began developing them and soon struck a collaboration with Bristol-Myers
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...
, which caught national interest and spurred further investment in angiogenesis inhibitors by other pharma companies.[John Crewdson for the Chicago Tribune. April 11, 199]
Crucial Test For Cancer Drug
/ref>
In 1993 he surprised the scientific world by hypothesizing that angiogenesis is as important in blood cancers
Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...
as it is in solid tumors, and the next year he published work showing that a biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
of 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.[ Meanwhile, a member of his lab, Robert D'Amato, was looking for ]angiogenesis inhibitors An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels ( angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...
, and discovered that thalidomide
Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications o ...
inhibited angiogenesis in 1994. 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.[ 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.][ The results of that trial were published in the New England Journal of Medicine in 1999.]
In 2004, the first angiogenesis inhibitor, bevacizumab (Avastin), was approved by the FDA, as a treatment for colon cancer. It is a recombinant humanized monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ...
that was discovered and developed by Napoleone Ferrara
Napoleone Ferrara (born 26 July 1956, Catania), is an Italian-American molecular biologist who joined University of California, San Diego Moores Cancer Center in 2013 after a career in Northern California at the biotechnology giant Genentech, ...
, a scientist at Genentech.[Andrew Pollack for the New York Times. February 27, 200]
F.D.A. Approves Cancer Drug From Genentech
/ref> A similar drug, Lucentis
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment ( Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related ...
, was later approved for treating macular degeneration.[ 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 diagnosed multiple myeloma patients.][
]
Awards
Folkman was a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society
The American Philosophical Society (APS), founded in 1743 in Philadelphia, is a scholarly organization that promotes knowledge in the sciences and humanities through research, professional meetings, publications, library resources, and communit ...
, 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 the George Ledlie Prize The George Ledlie Prize is awarded by the "President and Fellows of Harvard College" for contributions to science.
George Ledlie
George Hees Ledlie was born at Palatine Bridge, New York and attended private schools and colleges to prepare for Ha ...
from Harvard, Canada's Gairdner Foundation International Award
The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a ...
, Israel's Wolf Prize
The Wolf Prize is an international award granted in Israel, that has been presented most years since 1978 to living scientists and artists for ''"achievements in the interest of mankind and friendly relations among people ... irrespective of nati ...
, Germany's Ernst Schering Prize, the United Kingdom Society for Endocrinology's Dale Medal in 2000, Prince of Asturias Award
The Princess of Asturias Awards ( es, Premios Princesa de Asturias, links=no, ast, Premios Princesa d'Asturies, links=no), formerly the Prince of Asturias Awards from 1981 to 2014 ( es, Premios Príncipe de Asturias, links=no), are a series of a ...
, the Golden Plate Award of the American Academy of Achievement
The American Academy of Achievement, colloquially known as the Academy of Achievement, is a non-profit educational organization that recognizes some of the highest achieving individuals in diverse fields and gives them the opportunity to meet ...
and Switzerland's Dr. Josef Steiner Cancer Research Award. In 2005 he was awarded the Scientific Grand Prize of the Lefoulon-Delalande Foundation. In 2006, Folkman was one of seven people appointed by President Bush to the National Cancer Advisory Board of the National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
.
For his discoveries which originated the concept and developed the field of angiogenesis research, Folkman was awarded the Wolf Prize in Medicine
The Wolf Prize in Medicine is awarded annually by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The ...
in 1992.
He was awarded the Massry Prize
The Massry Prize was established in 1996, and until 2009 was administered by the Meira and Shaul G. Massry Foundation. The Prize, of $40,000 and the Massry Lectureship, is bestowed upon scientists who have made substantial recent contributions in ...
from the Keck School of Medicine, University of Southern California
, mottoeng = "Let whoever earns the palm bear it"
, religious_affiliation = Nonsectarian—historically Methodist
, established =
, accreditation = WSCUC
, type = Private research university
, academic_affiliations =
, endowment = $8.1 ...
in 1997.
On May 29, 1998 Folkman received an honorary doctorate
An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or ''ad hon ...
from the Faculty of
Medicine at Uppsala University
Uppsala University ( sv, Uppsala universitet) is a public research university in Uppsala, Sweden. Founded in 1477, it is the oldest university in Sweden and the Nordic countries still in operation.
The university rose to significance during ...
, Sweden
Death
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) in Vancouver, British Columbia
Vancouver ( ) is a major city in western Canada, located in the Lower Mainland region of British Columbia. As the most populous city in the province, the 2021 Canadian census recorded 662,248 people in the city, up from 631,486 in 2016. The ...
.
He was survived by his wife, Paula, whom he met and married while doing his surgical residency,[ two daughters, and a granddaughter.][
]
References
Further reading
*
*
*
Judah Folkman
biography and inspiration for th
Tobin 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, 2013
External links
M. Judah Folkman papers, 1907–2012 (inclusive), 1950–2006 (bulk). H MS c365. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.
{{DEFAULTSORT:Folkman, Judah
1933 births
2008 deaths
Bexley High School alumni
Members of the United States National Academy of Sciences
American biologists
American surgeons
Jewish American scientists
Cancer researchers
Harvard Medical School alumni
Harvard Medical School faculty
Ohio State University alumni
People from Boston
Scientists from Cleveland
United States Navy officers
Wolf Prize in Medicine laureates
Massry Prize recipients
20th-century surgeons
20th-century biologists
Jewish physicians
20th-century American Jews
21st-century American Jews
Military personnel from Massachusetts
Members of the National Academy of Medicine