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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, according to his son, Andy Stahl. The passing was recognized by the faculty at the University of Oregon in Eugene, where Dr. Stahl spent the majority of his professional life and later became an emeritus professor of biology, though it did not receive significant attention beyond academic communities, as noted by his son.
The research conducted in Dr. Stahl's lab left a lasting mark on the fields of science and medicine, spanning from advancements in DNA repair and modification to the application of gene therapy in combating illnesses.
His groundbreaking experiment with Meselson, conducted from October 1957 to January 1958 when both were early-career scientists at the California Institute of Technology in Pasadena, addressed a key issue in the emerging field of molecular biology: How does DNA — the fundamental genetic material of life — copy itself?
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 time when Dr. Stahl started his scientific career signified the start of a new age in the field of biology.
From 1951 to 1953, researchersMaurice Wilkins and Rosalind Franklin photographed how X-rays diffract when striking DNA, providing evidence for its structure. In 1953, their groundbreaking results allowed Francis Crickand James D. Watson to determine and release the configuration of DNA, frequently referred to as the blueprint of life.
The model introduced by Crick and Watson involved two DNA strands that twisted around one another, creating a double helix structure. However, the scientific community was initially hesitant to embrace this DNA model, a perspective that Dr. Stahl's experiment, conducted with Meselson, eventually altered.
In the model proposed by Crick and Watson, DNA strands are linked together similar to the two sides of a zipper, with interlocking components running along the inner part of the double helix like the teeth of a zipper. These components — referred to as "bases" in the field of genetics — create the genetic code that enables all living organisms to transmit hereditary information.
Wilkins, Crick, and Watson were awarded the 1962 Nobel Prize in Physiology or Medicine (Franklin passed away in 1958, and the prize is not given after death). Their findings raised the central question of how DNA reproduces.
When Watson and Crick released the DNA structure in April 1953 in the journal Nature, they noted that the base pairing "implies a potential method for copying the genetic material."
Their theory suggested that the two strands would split apart, unwinding the double helix and revealing their bases. These "parent" strands would then be copied inside the cell, producing two "daughter" strands. As the cell containing them divided, a pair of strands would move to each new cell.
Since DNA is too minute to be examined closely using a microscope, scientists such as Watson and Crick had to theorize about the mechanisms involved in DNA replication. Dr. Stahl and Meselson validated Watson and Crick's theory on DNA replication through deductive reasoning.
Their study focused on the element nitrogen, which is a key part of DNA. They employed two forms of nitrogen: "light" and "heavy." The first type (nitrogen 14) is the one typically found in nature, whereas the second type (nitrogen 15) is very uncommon.
Dr. Stahl and Meselson cultivated E. coli bacteria in a medium with heavy nitrogen and then transferred them to a light nitrogen environment. Following each generation, they extracted the bacterial DNA and placed it in a centrifuge. The device spins at such high speed that the liquid components separate into distinct layers based on their density.
Just as centrifuges are utilized to separate milk from thick cream, they can — when operated for a prolonged period — isolate DNA that is suspended in a salt solution, provided the DNA's molecular density differs.
By employing this technique, Dr. Stahl and Meselson analyzed the density of DNA and demonstrated that the heavy parent strands stayed connected to the light daughter strands following each generation. The findings, released in 1958 in the Proceedings of the National Academy of Sciences of the United States of America, confirmed Watson and Crick's theory.
Although it is often seen as a straightforward task, "the experiment began in complexity, was enveloped by complexity, and pointed the way toward uncovering future complexities," wrote Frederic L. Holmes in his 2001 book "Meselson, Stahl, and the Replication of DNA: A History of 'The Most Beautiful Experiment in Biology.'" "It emerged from a complex process of investigation."
Recognized by numerous influential scientists, such as Watson, the Meselson-Stahl experiment contributed to the widespread approval of the Watson-Crick model of DNA.
A fortuitous meeting
Franklin William Stahl was born in Boston on October 8, 1929, as the youngest of three children, and spent his childhood in the suburb of Needham. His father was employed by New England Telephone as an equipment specialist, while his mother managed the household.
Dr. Stahl pursued biology at Harvard with the intention of becoming a physician, yet he needed to work evenings and travel back and forth, leading to academic performance that was insufficient for medical school admission.
After graduating in 1951, he thought about teaching high school biology, but his mother advised him to keep pursuing his education. He was admitted to three graduate programs in genetics and selected the University of Rochester since it was the only one that provided him with financial assistance.
During the summer of 1952, Dr. Stahl's doctoral mentor sent him to study at Cold Spring Harbor Laboratory in New York. A class that Dr. Stahl attended there about bacteriophages—viruses that attack bacteria by inserting their DNA into them—would influence his path by making him believe that advances in genetics would come from studying the simple genomes of viruses and bacteria.
Two years later, Dr. Stahl traveled to the Marine Biological Laboratory in Woods Hole, Massachusetts, to attend a molecular biology course led by Watson and Crick. On the day he encountered Meselson—then a graduate student at Caltech—Dr. Stahl clearly remembered sitting under a tree sipping a gin and tonic while tackling a math problem.
The two became friends, spending many hours exploring methods to study the critical questions regarding DNA, particularly its replication process. Although Meselson had ideas for new experimental techniques, Dr. Stahl possessed the mathematical expertise required. They arranged for Dr. Stahl to join Meselson at Caltech for postdoctoral research after completing his doctorate at Rochester in 1956.
In his private life, he was also a young man eager to move forward. In 1955, he married Mary Morgan, who was an undergraduate student at Antioch College in Ohio, just a week after they met for the first time.
His wife, who later became his research technician, collaborated on numerous papers and was involved in their discovery of the first DNA recombination hotspot — a location where DNA strands often swap segments of genetic information. She passed away in 1996.
Dr. Stahl's companion, Henriette "Jette" Foss, passed away in 2022. Along with his son, family members who remain include a daughter, Emily Morgan, and eight grandchildren.
After finishing his renowned experiment, Dr. Stahl departed from Caltech in 1958 and moved to the University of Oregon. In 1964, he released "The Mechanics of Inheritance," a summary of recent developments in genetics. During the following ten years, he concentrated on researching viral genetics and in 1979 authored his second book, "Genetic Recombination."
Dr. Stahl's accolades featured the MacArthur Foundation "genius grant," two Guggenheim fellowships, and the Genetics Society of America's Thomas Hunt Morgan Medal recognizing his lifetime achievements.
Throughout his professional journey, Dr. Stahl consistently pursued the study of gene replication and recombination, working alongside other leading biologists.
Although Dr. Stahl's 1957-58 experiment with Meselson demonstrated the effectiveness of the research methods being created by molecular biologists at the time, his subsequent laboratory work paved the way for future generations of geneticists to achieve numerous discoveries that have greatly advanced our present knowledge of genetics.
In a 1988 letter to Holmes, Dr. Stahl spoke about his renowned experiment, "It established a benchmark for me in science that I don't believe I can ever match again, but it's worth striving for. Every time I write a paper, I recall that one and think... try to get as close as possible."
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