In memoriam Paul Berg, Nobel-winning pioneer of genetic engineering

Paul Berg, a Nobel Prize-winning biochemist who ushered in the era of genetic engineering in 1971 by successfully combining DNA from two different organisms, died on Wednesday at his home on the Stanford University campus in California. He was 96. After his breakthrough with DNA, Dr. Berg led a momentous convocation of scientists to establish safeguards against the misuse of genetic research.

In 1971, he was already a well-known researcher at Stanford University when he oversaw the artificial introduction of DNA from one virus into another, creating the first recombinant DNA, or rDNA. The achievement was the first link in the chain of advances that has led to the genetic engineering of new therapeutic treatments for diseases and of vaccines, like the messenger RNA versions used to counter the virus that causes Covid-19.

Dr. Berg’s work earned him the 1980 Nobel Prize in Chemistry, which he shared with Walter Gilbert and Frederick Sanger, who were cited for their work on genetic sequencing. In remarks at a Nobel banquet, Dr. Berg said that through his research he had “experienced the indescribable exhilaration, the ultimate high, that accompanies discovery, the breaking of new ground, the entering into areas where man had not been before.”

Often described as the blueprint for every cell, DNA, or deoxyribonucleic acid, is the spiral-staircase-shaped strand of molecules that carry the code by which cells duplicate themselves. Dr. Berg showed that the blueprint could be altered and cells made to produce new offspring that could ultimately do — or not do — very different things from the original cells.

As David A. Jackson, a postdoctoral fellow who was one of Dr. Berg’s trainees, later recalled to Dr. Berg’s biographer, Errol C. Friedberg: “One morning Paul and I got together and he suggested that we attempt to put new genes into SV40 DNA and use the recombinant molecules to introduce foreign DNA into animal cells.”

The researchers used the DNA part of a virus (a circular DNA), which can be propagated in the E. coli bacteria, and incorporated it into a simian virus (a circular SV40 DNA genome). Each of the circular DNAs was converted into linear DNAs with an enzyme. Using an existing technique, these linear DNAs were modified so that the modified ends attracted each other. Mixed together, the two DNAs recombined and created a loop of rDNA, which contained the genes from the two different organisms. Dr. Berg and his team began preparing for the next step: introducing the rDNA into E. coli and animal cells. But as word about his work spread among researchers, Dr. Berg was challenged to guarantee that this newly created DNA — which, after all, consisted partly of material from a virus that lived in one of the world’s most common bacteria, E. coli — could not escape the laboratory and cause incalculable harm.

Dr. Berg recognized that such an absolute certainty was not then possible, and he halted further experiments, although other researchers quickly moved forward.