Basic Sciences Division

Harold M. Weintraub, Ph.D.

Harold Weintraub was a Member of the Basic Sciences Division of Fred Hutchinson from 1978 until his death from cancer in 1995 at the age of 49. A creative intellect, Hal contributed profoundly to our understanding of the molecular biology of development.

From his early work on the structure of the eukaryotic chromosome to the recent identification of genes capable of eliciting an entire program of cellular differentiation, Hal repeatedly identified important problems in biology and solved them in an elegant fashion. For those fortunate enough to have shared Hal's enthusiasm for science or to have been touched by his humanity, his premature death was an immeasurable loss.

Hal Weintraub grew up playing baseball and basketball on the streets of Newark. He began his training in science as an undergraduate at Harvard College and received M.D. and Ph.D. degrees from the University of Pennsylvania, working in the laboratory of Howard Holtzer.

As a Ph.D. student in the early 1970s Hal became intrigued by the problem of how the regulation of gene expression during development leads to the differentiation of specific cell types. Insight into the molecular mechanisms of gene control had only recently emerged for a few phage and bacterial genes. Despite the complexity of mammalian development, Hal initiated a bold effort to understand the relationship between the structure of eukaryotic genes in the chromosome and the regulation of their expression during development.

In experiments initiated at the Medical Research Council in Cambridge, and continued at Princeton University and at Fred Hutchinson Cancer Research Center, Hal used the globin gene clusters as a model system to discern the structure of a transcriptionally active chromosomal domain. This work established an important relationship between gene activity and chromosome structure.

In the early 1980s Hal began to think about the problem of identifying genes central to embryonic development in vertebrates. Recognizing the difficulty in obtaining useful developmental mutants in vertebrates, Hal introduced the idea of using anti-sense RNA to elicit specific mutant phenotypes. This approach, in which a complementary strand of mRNA is expressed in cells or embryos to inhibit the expression of specific mRNAs, allows the generation of lack-of-function phenotypes and permits the assessment of the role of specific genes in development in the absence of classical developmental genetics.

More recently, in a remarkable series of experiments, Hal identified a single gene, myoD, which can elicit the entire program of muscle differentiation when introduced into non-muscle cell types.

Hal Weintraub and his colleagues pioneered virtually every stage in the discovery and elucidation of the function of MyoD, from its structure to the mechanism of how it activates the myogenic program, and how MyoD itself is transcriptionally and post- transcriptionally regulated during development. These experiments led to the notion of MyoD and its homologs as regulatory genes which together play central roles in the flow of myogenic information from the early embryo to the mature myofibril, a concept of general importance in cellular differentiation.

This brief summary of Hal's accomplishments, however, does not adequately portray his unique approach to biology. His efforts were driven by a creative intuition coupled with a courage to experimentally explore his ideas. One of his greatest strengths was his ability to conceive of simple experimental approaches that led to major advances in our understanding of complex biological phenomena. His scientific persona was characterized by an odd mix of naivete and confidence that led him in directions where others feared to venture.

The breadth and intensity of Hal's interest in science was strongly felt, not only by his students and fellows, but by an entire community of biologists. He listened to the efforts of others with excitement and contributed his thoughts and ideas generously. … adapted from an obituary for Hal Weintraub written by Richard Axel and Tom Maniatis (Cell, 81: 317-318, 1995)

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