Franklin Stahl, DNA Replication Pioneer, Dies at 95

2025-10-04 21:43:33

Franklin W. Stahl, an American molecular biologist whose landmark 1957-58 experiment with colleague Matthew Meselson revealed how DNA replicates, helping pave the way for a revolution in genetics research, died April 2 at his home in Eugene, Oregon. He was 95.

The cause was congestive heart failure, said his son Andy Stahl. The death was known among faculty at the University of Oregon in Eugene, where Dr. Stahl spent most of his career and became an emeritus professor of biology, but was not widely reported outside academic circles, said his son.

Dr. Stahl’s laboratory work had an indelible impact on science and medicine, from DNA repair and editing to the use of gene therapy to treat diseases.

His critical experiment with Meselson, performed between October 1957 and January 1958 when both were young scientists at the California Institute of Technology in Pasadena, answered a major question in the then-nascent field of molecular biology: How does DNA — the genetic material central to life — replicate?

Known today as the Meselson-Stahl Experiment, their work is regarded as an essential part of the biology and genetics canon. With its use of DNA labeling to create a simple and elegant visual presentation of DNA replication, it was famously described by British biochemist John Cairns as “the most beautiful experiment in biology.”

The period in which Dr. Stahl began his scientific career marked the beginning of a new era in biology.

Between 1951 and 1953, scientists
Maurice Wilkins
and Rosalind Franklin photographed how X-rays diffract when striking DNA, providing evidence for its structure. In 1953, their groundbreaking results allowed
Francis Crick
and James D. Watson to deduce and publish the structure of DNA, often called the blueprint of life.

The model that Crick and Watson proposed consisted of two strands of DNA that coiled around each other to form a double helix. And yet the scientific community was slow to accept this model for DNA, an attitude that Dr. Stahl’s experiment with Meselson helped change.

In Crick and Watson’s model, the DNA strands connected to each other like the two sides of a zipper, with interlocking molecules running along the inside of the double helix like a zipper’s teeth. These molecules — known as “bases” in the field of genetics — form the genetic code that allows all organisms to pass on hereditary information.

Wilkins, Crick and Watson won the 1962 Nobel Prize for Physiology or Medicine (Franklin died in 1958, and the prize is not awarded posthumously). Their discovery left the fundamental mystery of how DNA replicates.

When Watson and Crick published the structure of DNA in April 1953 in the journal Nature, they stated that the pairing of DNA bases “suggests a possible copying mechanism for the genetic material.”

Their hypothesis was that the two strands would separate, uncoiling the double helix and exposing their bases. These “parent” strands would then be replicated within the cell, resulting in two “daughter” strands. When the cell containing them divided, a set of strands would go to each new cell.

Because DNA is too small to be studied in detail under a microscope, scientists including Watson and Crick were left to speculate on the ways that DNA replication might occur. Dr. Stahl and Meselson confirmed Watson and Crick’s view of DNA replication by process of deduction.

Their experiment involved the element nitrogen, a major component of DNA. They used two types of nitrogen: “light” and “heavy.” The first (nitrogen 14) is the type commonly found in nature, while the second (nitrogen 15) is extremely rare.

Dr. Stahl and Meselson grew E. coli bacteria in a food source that contained heavy nitrogen and then moved them to light nitrogen. After each generation, they extracted the bacterial DNA and put it into a centrifuge. The machine rotates so rapidly that its liquid contents separate into distinct bands according to their density.

Just as centrifuges are used to separate milk from dense cream, they can — if run for a sufficiently long time — separate DNA suspended in a saline solution if the molecular density of the DNA varies.

Using this method, Dr. Stahl and Meselson measured the density of the DNA and showed that as it replicated, the heavy parent strands remained paired with light daughter strands after each generation. The results, published in 1958 in Proceedings of the National Academy of Sciences of the United States of America, proved Watson and Crick’s hypothesis.

Despite its reputation as a simple undertaking, “the experiment originated in complexity, was surrounded by complexity, and directed the way toward the discovery of future complexities,” Frederic L. Holmes wrote in his 2001 book “Meselson, Stahl, and the Replication of DNA: A History of ‘The Most Beautiful Experiment in Biology.’ ” “It was the product of a complex investigative pathway.”

Lauded by many prominent scientists, including Watson, the Meselson-Stahl experiment paved the way for broad acceptance of the Watson-Crick model for DNA.

A fortuitous meeting

Franklin William Stahl was born in Boston on Oct. 8, 1929, the youngest of three children, and grew up in the suburb of Needham. His father worked for New England Telephone as an equipment specialist, and his mother was a homemaker.

Dr. Stahl studied biology at Harvard with the goal of becoming a doctor, but to pay for his classes, he had to work part time and commute, resulting in grades that wouldn’t qualify for medical school.

Upon graduating in 1951, he considered teaching high school biology, but his mother encouraged him to continue his studies. He was accepted to three graduate programs in genetics and chose the University of Rochester because it was the only one that offered him financial support.

In the summer of 1952, Dr. Stahl’s doctoral adviser sent him to study at Cold Spring (N.Y.) Harbor Laboratory. A course that Dr. Stahl took there on bacteriophages — viruses that prey on bacteria by injecting their DNA into them — would shape his trajectory by convincing him that innovations in genetics would arise from work on the relatively simple genomes of viruses and bacteria.

Two years later, Dr. Stahl went to the Marine Biological Laboratory in Woods Hole, Mass., to enroll in a molecular biology course being taught by Watson and Crick. On the day he met Meselson — then a graduate student at Caltech — Dr. Stahl vividly recalled sitting under a tree drinking a gin and tonic as he worked on a math problem.

The two struck up a friendship, spending hours discussing ways to investigate the pressing questions about DNA, especially how it replicated. While Meselson had ideas for new experimental approaches, Dr. Stahl had the mathematical skills necessary. They planned for Dr. Stahl to join Meselson at Caltech to do postdoctoral research together after he completed his doctorate at Rochester in 1956.

In his personal life, he was also a young man in a hurry. In 1955, he married Mary Morgan, then an undergraduate student at Antioch College in Ohio, a week after their first date.

His wife, who became his research technician, co-wrote many of their papers and shared in their discovery of the first DNA recombination hotspot — a place where DNA strands frequently exchange pieces of genetic material. She died in 1996.

Dr. Stahl’s companion, Henriette “Jette” Foss, died in 2022. In addition to his son, survivors include a daughter, Emily Morgan, and eight grandchildren.

After completing his celebrated experiment, Dr. Stahl left Caltech in 1958 and settled at the University of Oregon. In 1964, he published “The Mechanics of Inheritance,” an overview of recent advances in genetics. Over the next decade, he focused on the study of viral genetics and in 1979 published his second book, “Genetic Recombination.”

Dr. Stahl’s honors included the MacArthur Foundation “genius grant,” two Guggenheim fellowships and the Genetics Society of America’s Thomas Hunt Morgan Medal for lifetime contributions.

Over the course of his career, Dr. Stahl steadfastly continued exploring the replication and recombination of genes, combining his efforts with other prominent biologists.

While Dr. Stahl’s 1957-58 experiment with Meselson exemplified the power of the investigative tools that were then being developed by molecular biologists, his laboratory work in the years that followed helped open the path for new generations of geneticists to make many discoveries that have since transformed our current understanding of genetics.

In correspondence with Holmes in 1988, Dr. Stahl wrote of his famous experiment, “It set a standard for me in science which I don’t know I can ever achieve again, but it’s worth shooting for. Anytime I write a paper I remember that one, and say … come as close as you can.”