Sidney Farber

Biography

• Born September 30, 1903 Buffalo, New York
• 1923 – Graduated from the University of Buffalo after studying philosophy and biology
• 1924 – Completed first medical year at the Universities of Heidelberg and Freiburg before transferring to Harvard Medical School as a second-year student.
• 1927 – Graduated MD from Harvard Medical School.
• 1929 – Appointed instructor in pathology at Harvard Medical School. First full-time pathologist at Children’s Hospital Boston and inspired Lotte Strauss (1913–1985) to specialise in pediatric pathology
• 1937 – Published The Postmortem Examination, to help standardise autopsy practice
• 1938–1940 – Published studies on unexpected death in infancy, transposition of the great vessels and Eastern equine encephalitis.
• 1944 – With Harry Shwachman and colleagues, he helped define cystic fibrosis as a systemic disorder rather than an isolated pulmonary disease
• 1946 – Appointed chairman of the Division of Laboratories and Research at Children’s Hospital Medical Center
• 1947 – Appointed pathologist-in-chief and chairman of the staff at Children’s Hospital Medical Center. Assistant professor of paediatrics and pathology at Harvard. Investigated the effects of folic-acid conjugates in human malignancy.
• 1947–1948 – Helped establish the Children’s Cancer Research Foundation with the Variety Club of New England. The Jimmy Fund campaign followed the May 22, 1948 broadcast.
• 1948 – Appointed professor of pathology at Harvard Medical School.
• 1952 – Reported disseminated lipogranulomatosis, subsequently termed Farber disease.
• 1955 – Demonstrated that actinomycin D, particularly when combined with radiotherapy, could produce remission and control metastases in Wilms tumour.
• 1960–1967 – With paediatric pathologist Gordon F. Vawter (1923-1990), published a long-running series of clinical–pathological conferences from Children’s Hospital Medical Center in The Journal of Pediatrics.
• 1964 – Received the Variety Clubs International Humanitarian Award.
• 1966 – Awarded the Albert Lasker Clinical Medical Research Award for his pioneering work in paediatric cancer chemotherapy.
• 1968 – Elected president of the American Cancer Society and received the Oscar B. Hunter Award of the American Therapeutic Society for experimental therapeutics.
• 1969 – Expanded the Children’s Cancer Research Foundation’s charter to include adult patients and opened an adult cancer service within the institute.
• 1972 – Received the Gold-Headed Cane Award from the American Association of Pathologists and Bacteriologists
• Died suddenly of a heart attack on March 30, 1973

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Medical Eponyms

Farber disease (1952) [disseminated lipogranulomatosis]

Farber disease, or disseminated lipogranulomatosis, is an autosomal-recessive lysosomal storage disorder caused by ASAH1-associated acid ceramidase deficiency. Ceramide accumulation produces a classical triad of painful progressive joint contractures, subcutaneous or periarticular nodules and hoarseness caused by laryngeal granulomas, with variable neurological, pulmonary and visceral involvement.

1947 – Farber presented the first recognised case, a 14-month-old infant, during a Mayo Foundation lecture and termed the disorder disseminated lipogranulomatosis.

1952 – Farber published the first formal description of three affected children in A lipid metabolic disorder: disseminated lipogranulomatosis. He proposed that the condition combined features of Niemann–Pick lipid storage disease with the granulomatous inflammation seen in Hand–Schüller–Christian disease.

1957 – With Joseph Cohen and Leon Uzman, published the expanded clinicopathological account Lipogranulomatosis; a new lipo-glycoprotein storage disease. This paper established disseminated lipogranulomatosis as a distinct inherited storage disease and described the characteristic systemic granulomatous lesions, joint involvement, subcutaneous nodules and laryngeal disease

1967–1972 – Subsequent investigators demonstrated tissue accumulation of ceramide and identified deficiency of lysosomal acid ceramidase as the underlying biochemical defect.

1999 – Molecular characterisation of the human acid ceramidase gene (ASAH) confirmed pathogenic variants as the cause of the disorder now classified within the ASAH1-related acid ceramidase deficiency spectrum.

2007 – Ehlert and colleagues reported allogeneic haematopoietic stem-cell transplantation in four patients without significant neurological involvement. Transplantation produced near-complete resolution of granulomas and joint contractures with major improvement in mobility.

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Key Medical Contributions

Aminopterin and childhood acute leukaemia

Aminopterin is a synthetic folate antagonist that inhibits folate-dependent nucleotide synthesis and the proliferation of rapidly dividing cells. Farber’s studies provided the first reproducible evidence that systemic chemotherapy could induce remission in childhood acute leukaemia, although the responses were temporary and treatment was limited by severe toxicity.

1947 – Farber and colleagues reported that folate conjugates appeared to accelerate leukaemic proliferation in some children. They reasoned that antagonism of folate metabolism might suppress the malignant marrow.

Farber obtained experimental antifolate compounds developed by chemists associated with Yellapragada Subbarow at Lederle Laboratories and commenced treatment with aminopterin. The first patient, an eight-year-old boy with advanced acute leukaemia, received the drug on December 16 and subsequently entered clinical and haematological remission.

1948 – Farber, Louis Diamond, Robert Mercer, Robert Sylvester Jr and James Wolff published Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. Of 16 critically ill children treated, ten demonstrated temporary clinical and haematological improvement; five representative cases were reported in detail.

The responses included disappearance of blast cells, recovery of normal haematopoiesis and regression of hepatosplenomegaly. Severe stomatitis and marrow suppression demonstrated the toxicity of aminopterin, and all remissions were temporary.

1949 – Reviewing a larger experience with aminopterin and related compounds, Farber warned that there was no justification for describing the patients as cured. His work established antimetabolite chemotherapy as a viable treatment strategy and prompted the development of less toxic folate antagonists, particularly methotrexate.

No evidence has been presented which would justify use of the word ‘cure’ of acute leukemia…Further research for less toxic related compounds with even greater effectiveness… is imperative.

Faber, 1949

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Actinomycin D and multimodal treatment of Wilms tumour

Wilms tumour, or nephroblastoma, is an embryonal renal malignancy occurring predominantly in young children. Modern treatment combines surgery with systemic chemotherapy such as dactinomycin and vincristine, with additional agents for higher-risk disease. Radiotherapy is reserved for selected stages, histologies and metastatic sites.

Farber’s work with actinomycin D, now termed dactinomycin, provided the first convincing chemical regression of Wilms tumour and helped establish chemotherapy as an essential component of treatment for childhood solid tumours.

1955 – Farber reported the first chemical regression of Wilms tumour using actinomycin D in Carcinolytic action of antibiotics: puromycin and actinomycin D. This extended the principle of systemic chemotherapy from childhood leukaemia to a paediatric solid tumour.

1956 – With Donald Pinkel, Edward Sears and Rudolf Toch, he reviewed Advances in chemotherapy of cancer in man, including the activity of actinomycin D against Wilms tumour.

1959 – Giulio D’Angio, Farber and Charlotte Maddock demonstrated that actinomycin D potentiated the effects of radiotherapy on tumours and normal tissue. They also documented reactivation of reactions within previously irradiated areas and warned of severe toxicity when the two treatments were combined without dose modification.

1960 – Farber, D’Angio, Audrey Evans and Anna Mitus published Clinical studies on actinomycin D with special reference to Wilms’ tumor in children, consolidating its place alongside nephrectomy and radiotherapy.

Farber’s work helped establish the principle that chemotherapy could eradicate microscopic or metastatic disease beyond the primary tumour and transformed Wilms tumour treatment into a coordinated programme.

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Pancreatic insufficiency and cystic fibrosis

Cystic fibrosis is an autosomal-recessive multisystem disorder caused by pathogenic variants in CFTR, producing abnormal epithelial chloride and bicarbonate transport and dehydrated secretions in the respiratory, gastrointestinal, pancreatic, hepatobiliary and reproductive tracts.

1938 – Dorothy Hansine Andersen (1901–1963) published  Cystic fibrosis of the pancreas and its relation to celiac disease. She established cystic fibrosis of the pancreas as a distinct disorder and distinguished it from the heterogeneous group then termed the coeliac syndrome.

1943 – With Harry Shwachman and Charlotte Maddock, Farber investigated pancreatic enzyme activity in infants and children. Their studies helped distinguish cystic pancreatic fibrosis from idiopathic coeliac disease by demonstrating absent or markedly reduced pancreatic enzymes in duodenal secretions.

1944 – Farber linked pancreatic achylia with meconium ileus and published a pathological study of pancreatic insufficiency in early life. His observations of abnormalities in organs beyond the pancreas encouraged a broader interpretation of the disease.

1945 – Farber introduced the term muco-viscidosis, arguing that “cystic fibrosis of the pancreas” failed to reflect a generalised disorder of abnormally viscid secretions affecting the respiratory, intestinal, pancreatic and biliary systems.

Although the mucus-viscosity theory did not identify the underlying defect, Farber’s terminology helped move cystic fibrosis from an organ-specific pancreatic disease towards recognition as a systemic disorder. The molecular basis was established in 1989 with identification of the CFTR gene.

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“Total care,” the Jimmy Fund and national cancer advocacy

Farber recognised that effective cancer treatment required more than anticancer drugs. Through the Children’s Cancer Research Foundation and the Jimmy Fund, he brought laboratory investigation, clinical care, nursing, nutrition, social work and family support together within a dedicated paediatric cancer programme.

1948 – The national radio programme Truth or Consequences introduced Farber’s 12-year-old patient Einar Gustafson under the pseudonym “Jimmy.” The May 22 broadcast raised more than $200,000 and gave rise to the Jimmy Fund, providing public support for Farber’s research and clinical service.

1949–1952 – Fundraising supported construction of the Jimmy Fund Building, which brought laboratories, offices and outpatient treatment facilities together in one institution. The Children’s Cancer Research Foundation was formally incorporated in 1951, and the building opened the following year.

Mid-1950s – Farber developed the concept of “total care,” integrating anticancer treatment with nursing, nutrition, social work, psychological counselling and support for the patient’s family. This multidisciplinary structure became an important model for later paediatric oncology centres.

1955–1971 – Farber campaigned for federal investment in cancer research. Working with Mary Lasker and congressional and medical allies, he helped promote the National Cancer Institute’s drug-development and cooperative clinical-trials programmes and contributed to the advocacy movement preceding the National Cancer Act of 1971.

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Major Publications

• Farber S. The postmortem examination. 1937
• Farber S. Pathologic changes associated with pancreatic insufficiency in early life. Archives of Pathology. 1944;37:238–250.
• Farber S. The relation of pancreatic achylia to meconium ileus. J Pediatr. 1944;24:387–392.
• Farber S. Some organic digestive disturbances in early life. Journal of the Michigan State Medical Society. 1945;44:587–594.
• Farber S, Cutler EC, Hawkins JW, Harrison JH, Peirce EC 2nd, Lenz GG. The Action of Pteroylglutamic Conjugates on Man. Science. 1947 Dec 19;106(2764):619-21.
• Faber S, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med. 1948 Jun 3;238(23):787-93.
• Faber S. Some observations on the effect of folic acid antagonists on acute leukemia and other forms of incurable cancer. Blood. 1949;4(2):160-167.
• Farber S. A lipid metabolic disorder: disseminated lipogranulomatosis; a syndrome with similarity to, and important difference from, Niemann-Pick and Hand-Schüller-Christian disease. AMA Am J Dis Child. 1952 Oct;84(4):499-500. [Farber disease]
• Farber S. Carcinolytic action of antibiotics: puromycin and actinomycin D. Am J Pathol. 1955;31:582.
• Farber S, Pinkel D, Sears EM, Toch R. Advances in chemotherapy of cancer in man. Adv Cancer Res. 1956;4:1-71
• Farber S. Cohen J, Uzman LL. Lipogranulomatosis; a new lipo-glycoprotein storage disease. J Mt Sinai Hosp N Y. 1957 Nov-Dec;24(6):816-37.
• D’Angio GJ, Farber S, Maddock CL. Potentiation of X-ray effects by actinomycin D. Radiology. 1959;73:175–177.
• Farber S. Chemotherapy in the treatment of leukemia and Wilms’ tumor. JAMA. 1966 Nov 21;198(8):826-36
• Faber S. Newer Agents in the Treatment of Acute Leukemia. Lectures to the Laity. WNYC 1951

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References

Biography

• Vawter GF, Cohen J. Founders of pediatric pathology: Sidney Farber 1903-1973. Perspect Pediatr Pathol. 1988;12:1-9.
• Miller DR. A tribute to Sidney Farber– the father of modern chemotherapy. Br J Haematol. 2006 Jul;134(1):20-6.
• Ribatti D. Sidney Farber and the treatment of childhood acute lymphoblastic leukemia with a chemotherapeutic agent. Pediatr Hematol Oncol. 2012 May;29(4):299-302. 
• Wisnia S. Sidney Farber, Chemo Crusader. WNYC 2015
• Kumar Upadhyay A, Prakash A, Kumar A, Jena S, Sinha N, Sharma S. Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy. Cureus. 2024 Aug 31;16(8):e68286.
• Fresquet Febrer JL. Sidney Farber (1903-1973). Historia de la medicina 2014

Eponymous terms

• Li CM, Park JH, He X, Levy B, Chen F, Arai K, Adler DA, Disteche CM, Koch J, Sandhoff K, Schuchman EH. The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression. Genomics. 1999 Dec 1;62(2):223-31.
• Ehlert K, Frosch M, Fehse N, Zander A, Roth J, Vormoor J. Farber disease: clinical presentation, pathogenesis and a new approach to treatment. Pediatr Rheumatol Online J. 2007 Jun 29;5:15.
• Yu FPS, Amintas S, Levade T, Medin JA. Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis. 2018 Jul 20;13(1):121. 
• 75 years ago, a boy with cancer, Einar Gustafson, got the surprise of his life – and the nickname ‘Jimmy’. Mass Live 2023
• The Story of Jimmy. Dana-Faber Cancer Fund