W. French Anderson Papers

Collection

Identifier: MS C 620

Abstract

Correspondence, reports, research data, meeting agendas and minutes, and protocols documenting Dr. W. French Anderson's pioneering application of gene therapy in a human subject.

Dates

Creation: 1977-1995

Extent

9.59 Linear Feet (10 boxes)

Creator

Anderson, W. French, 1936- (Person)

Physical Location

Materials stored onsite. History of Medicine Division. National Library of Medicine

Language of Materials

Collection materials primarily in English

Access Restrictions

Collection is restricted. Portions of the collection are restricted according to HMD's Access to Health Information of Individuals policy. Contact the Reference Staff for information regarding access. For access to the policy and application form, please visit https://www.nlm.nih.gov/hmd/manuscripts/phi.pdf.

Copyright and Re-use Information

Donor's copyrights were transferred to the public domain. Archival collections often contain mixed copyrights; while NLM is the owner of the physical items, permission to examine collection materials is not an authorization to publish. These materials are made available for use in research, teaching, and private study. It is the user's responsibility to research and understand any applicable copyright and re-publication rights not allowed by fair use. NLM does not grant permissions to publish.

Privacy Information

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Biographical/Historical Note

William French Anderson was born in Tulsa, Oklahoma on December 31, 1936. He received both his undergraduate and medical degrees from Harvard, the latter in 1963. After an internship at Children's Hospital Medical Center in Boston and a post-doctoral fellowship at Harvard, Anderson began his 27-year career at NIH with a 2-year position through the USPHS surgeon service in 1965. From 1965 into 1968 he worked for Dr. Marshall Nirenberg in the National Heart Institute's (NHI) Biochemical Genetics Laboratory, where he became an integral member of Nirenberg's DNA-coding team.

From the very start of his medical training, Anderson's primary interest was to develop a means of healing by replacing faulty genes that caused a disease with normally functioning genes. In 1968 he became chief of NHI's newly-created Section of Human Biochemistry and began researching gene therapy exclusively. During this same period he also taught molecular genetics at George Washington University School of Medicine and was a faculty member of the NIH Graduate Program's Department of Genetics.

From then until the early 1980s, Anderson pursued gene repair using microinjection techniques. The results, however, proved unsatisfactory. By 1980 he had reached an impasse in his research and began exploring other medical fields, notably sports medicine.

His interest in gene therapy was revived when experimentation with gene replacement, notably by Richard C. Mulligan, demonstrated the effective use of a retrovirus as a genetic vector. Seizing upon the possibilities, Anderson determined that the most likely initial candidate for genetic transplantation would be adenosine deaminase (ADA), due to its relative simplicity. When deficient, this enzyme causes a human body's immune system to fail leading to severe combined immunodeficiency (SCID). Persons suffering from this condition rarely survive childhood and are vulnerable to nearly every pathogen in the environment.

Though experimentation with ADA in primate bone marrow proved only marginally encouraging, Anderson felt confident that the tests should be conducted in humans. Throughout 1986 and 1987 he began the groundwork to obtain approval for human ADA gene therapy from NIH, NIH's Recombinant DNA Advisory Committee (RAC), and the Food and Drug Administration (FDA).

By early 1989 Anderson, and partners Dr. Steven A. Rosenberg and Dr. Robert M. Blaese from NCI, had secured approval from NIH, the FDA, and RAC's Human Gene Therapy Subcommittee to conduct a genetic transfer experiment on 10 terminal human subjects whose treatments by all known methods had failed. The technique involved re-inserting a malignant melanoma patient's own modified tumor-infiltrating lymphocytes (TIL), which had been imbued with a distinctive marker. On May 22, 1989, Maurice Kuntz received the marker injection which Rosenberg called "the first time ever that a new gene has been introduced into a human." This successful experiment demonstrated that gene transfer in humans was safe.

Encouraged by the experiment's outcome, Anderson and his team sought approval to take the procedure a step further and initiate human gene therapy trials with an ADA/SCID patient. Shortly after receiving FDA's approval, Anderson replaced the defective ADA gene in 4-year-old Ashanthi DeSilva on September 14, 1990. The procedure was recognized as the first time a healthy gene had been infused into a human. In January, 1991, 9-year-old Cindy Cutshall was also treated. The treatments did not bring about total correction of SCID in either patient, but were therapeutically substantial enough that suppported by a regular medication routine the patients were able to enjoy relatively normal lives.

Although scientific consensus about the trial's success was mixed, the groundbreaking work by Anderson and his team in developing and demonstrating the efficacy of genetic transplantation was hailed internationally as the first steps in a new field of medical treatment. Because of this work Anderson has been called "The Father of Gene Therapy."

Anderson left the NIH in 1992 to accept a position as director of the Norris Comprehensive Cancer Center's Gene Therapy Laboratories (GTL) at USC's Keck School of Medicine, and as professor of biochemistry and pediatrics.

Collection Summary

Correspondence, laboratory and patient research data, clinical trial proposal development and IRB review records, meetings and conferences files, presentations, and videotapes document French Anderson's groundbreaking work to develop procedures for and to perform the first therapeutic introduction of gene therapy in humans. The collection concentrates almost exclusively on Anderson's tenure at the Molecular Hematology Branch of the National Heart, Lung and Blood Institute and in collaboration with the National Cancer Institute. It covers only the period of his career from 1977 to 1995. It does not include his post-NIH career at the University of Southern California.

Series 1, Biographical Information (1988-1992) is a small and disparate set of folders devoted to high school and college class reunions and some documentation of the terms of Anderson's move from NIH to the University of Southern California in 1992.

Series 2, Human Gene Therapy (1977-1992) contains fairly comprehensive documentation of Anderson's efforts to develop an effective gene therapy protocol, particularly between 1984 and 1990 when he concentrated on the method of introducing genes with a retrovirus. It is divided into two main sections comprising information about his two major breakthroughs: demonstration of the efficacy of gene therapy protocols (Tumor-Infiltrating Lymphocytes) and introduction of a healthy gene into a human being to correct a malfunctioning gene (Adenosine Deaminase). Each section contains subsets of correspondence, meeting agendas and reports relating to the lengthy process of developing protocols and receiving approval, applications and descriptions of experimental drugs, and data produced.

Series 3, Activities Outside NHLBI (1979-1992) is comprised of Anderson's collected materials relating to teaching engagements, lectures given, and meetings and conferences attended that were not directly involved with his lab work. They range from meetings at other NIH institutes to international conferences.

Series 4, Writings (1984-1990) is a small set of articles co-authored by Anderson, some written by others. All are devoted to gene therapy theory and practice as seen in the results of animal testing, mostly concerned with use of the ADA enzyme.

Series 5, Audiovisual Materials (1985-1995) are exclusively videocassettes and are organized into subseries developed by Anderson. Tapes in the Gene Therapy-related Subjects subseries (1986-1995) are mostly segments of commercial broadcast programs which address the concept of gene therapy. The Anderson Lectures subseries (1986-1994) present a series of speeches given by Anderson himself describing the potential of gene therapy. Clips from News Programs subseries (1989-1990) documents reporting done by various national television programs and networks about Anderson's gene therapy experiments.

Additional Description

Abstract

Correspondence, reports, research data, meeting agendas and minutes, and protocols documenting Dr. W. French Anderson's pioneering application of gene therapy in a human subject.