The Legacy of Paul Berg

Paul Berg was a renowned biochemist who invented recombinant DNA technology, which led to countless advances in biotechnology and medicine. However, the potential risks of this technology prompted Berg to call a voluntary moratorium on research until guidelines for its safe use could be established. He convened two meetings, which led to the US National Institutes of Health publishing guidelines in 1976, allowing for the safe use of recombinant DNA technology. Berg’s contributions to the early days of molecular biology and molecular genetics have left a lasting impact, and his loss will be deeply felt by the world of academia. Berg was also a skilled advocate of common sense and brought it to bear on contentious public-policy issues, including the use of embryonic stem cells in biomedical research.

Paul Berg: The Pioneer Behind Recombinant DNA Technology

Paul Berg, a renowned biochemist, is credited with inventing one of the most powerful tools in modern biology – recombinant DNA technology. This technique involves incorporating DNA from one species into the genetic material of another and is the basis for a biotechnology industry worth hundreds of billions of dollars. In recognition of his groundbreaking work, Berg was awarded the Nobel Prize in Chemistry in 1980.

Early Life and Education

Berg was born in New York City in 1926 and attended Abraham Lincoln High School in Brooklyn, the same school that produced another Nobel laureate, biochemist Arthur Kornberg, who would later become Berg’s mentor. After a brief stint in the US Navy during World War II, Berg completed his undergraduate education in biochemistry at Pennsylvania State University. He then moved on to Case Western Reserve University in Cleveland, Ohio, where he studied biochemistry and earned his PhD in 1952.

Career and Achievements

Berg’s early work in biochemistry focused on the metabolism of fatty acids, and he gained international attention for reporting the role of a new intermediate molecule in this process. He went on to discover transfer RNA, which plays a crucial role in the assembly of proteins.

In 1959, Berg joined the faculty at Stanford University, where he worked with virologist and cancer biologist Renato Dulbecco. This collaboration led to Berg’s interest in exploring gene function further, and he retooled his laboratory to work with animal cells as hosts for polyoma viruses, including the potentially cancer-causing DNA virus SV40. He also pursued techniques that allowed him to study the expression of viral genes in prokaryotes such as E. coli, and the expression of prokaryotic genes in animal cells.

Recombinant DNA Technology and Berg’s Legacy

Berg’s most significant contribution to the field of molecular biology was the invention of recombinant DNA technology. This breakthrough allowed scientists to manipulate and clone DNA, leading to countless advances in biotechnology and medicine. Berg also addressed concerns about the potential risks of this research and played a leading role in developing a consensus on responsible use of the technology.

Paul Berg passed away on February 15, 2023, at the age of 96. His contributions to molecular biology and biotechnology continue to impact the field and have provided the foundation for much of the progress in these areas over the past several decades.

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Paul Berg: Pioneer of Recombinant DNA Technology and Responsible Research

Paul Berg, a biochemist, invented recombinant DNA technology, a breakthrough that allowed scientists to manipulate and clone DNA, leading to countless advances in biotechnology and medicine. However, the potential risks of this research led to concerns that it could raise the risk of human cancer. As a responsible scientist, Berg called a moratorium on all recombinant DNA work in his laboratory until the issue could be explored more thoroughly.

Creating Recombinant DNAs

Berg’s strategy for generating DNA molecules that contain DNA from more than one species involved using enzymes to snip open the circular genome of the SV40 virus and to snip out a fragment containing three genes from the DNA of the bacterium E. coli. He then tailored the free ends of both molecules so that they would rejoin as a single circle of DNA. The idea was to use the modified SV40 as a viral vector to carry ‘foreign’ genetic material into animal cells.

Concerns and Conferences

Soon after Berg initiated his experiments, concerns arose that introducing SV40 genes into E. coli and other common human intestinal bacteria could raise the risk of human cancer. This led Berg to call a moratorium on all recombinant DNA work in his laboratory until the issue could be explored more thoroughly. The concern about the potential risks of this research prompted Berg to convene two meetings at the Asilomar conference center just south of San Francisco, California. The first, held in 1973, prompted Berg to circulate what became known as the Berg Letter to several journals, including Nature, requesting that members of the scientific community temporarily cease experiments involving recombinant DNA. Conscious of the wide public interest, Berg and the other organizers made a point of inviting members of the press to the 1975 meeting and encouraged them to ask questions but requested they not file their reports until the conference had concluded.

A Voluntary Moratorium

The conference participants agreed to a voluntary moratorium on research until guidelines could be promulgated for the safe use of the new technology. The US National Institutes of Health first published its guidelines in 1976, and these have been regularly updated ever since. As a result, the very real threat of a total ban on recombinant DNA research was averted, opening the door to genome sequencing and editing, and making possible countless advances in basic research, clinical medicine, drug discovery, and other applications of biotechnology.

Legacy

Berg devoted a significant amount of time to promoting the safe use of recombinant DNA technology, which he went on to deploy towards clinical application. In 1980, with biochemist Arthur Kornberg and geneticist Charles Yanofsky, Berg founded the DNAX Research Institute of Cellular and Molecular Biology in Palo Alto, California. He also served as the first director of Stanford’s multidisciplinary Beckman Center for Molecular and Genetic Medicine, opened in 1985.

Berg’s responsible approach to his work and his contributions to the field of molecular biology have left a lasting legacy, making it possible for countless researchers to use recombinant DNA technology safely and responsibly for the betterment of society.

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Paul Berg: A Remarkable Scientist and Advocate of Common Sense

Paul Berg was not only an exceptional scientist, teacher, mentor, and administrator, but also a strong advocate of bringing good, old-fashioned common sense to bear on contentious public-policy issues, including the use of embryonic stem cells in biomedical research. Though he closed his research laboratory in the early 2000s, he continued to advise his department and university, as well as serve as a consultant to biotechnology companies. Berg’s contributions to the early days of molecular biology and molecular genetics have left a lasting impact, and his loss will be deeply felt by the world of academia.

dio: https://doi.org/10.1038/d41586-023-00792-w

The author declares no competing interests.

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