Embryo Project Encyclopedia Articles

Franklin William Stahl studied DNA replication, bacteriophages, and genetic recombination in the US during the mid-twentieth and early twenty-first centuries. With his colleague Matthew Meselson, Stahl performed an experiment called the Meselson-Stahl experiment, which provided evidence for a process called semi-conservative DNA replication. Semi-conservative replication is a process in which each strand of a parental DNA double helix serves as a template for newly replicated daughter strands, so that one parental strand is conserved in every daughter double helix. Those findings supported the Watson-Crick Model for DNA replication proposed in 1953 by James Watson and Francis Crick, convincing many biologists about DNA’s structure and replication in the 1950s. Stahl’s genetics research, especially that of DNA replication, showed researchers how genetic information is distributed within a cell and is passed down from cell to cell.

In May 1953, scientists James Watson and Francis Crick wrote the article “Genetical Implications of the Structure of Deoxyribonucleic Acid,” hereafter “Genetical Implications,” which was published in the journal Nature. In “Genetical Implications,” Watson and Crick suggest a possible explanation for deoxyribonucleic acid, or DNA, replication based on a structure of DNA they proposed prior to writing “Genetical Implications.” Watson and Crick proposed their theory about DNA replication at a time when scientists had recently reached the consensus that DNA contained genes, which scientists understood to carry information that determines an organism’s identity. Watson and Crick’s replication mechanism as presented in “Genetical Implications” contributed to the two scientists sharing a portion of the 1962 Nobel Prize in Physiology or Medicine. With their suggested DNA replication mechanism in “Genetical Implications,” Watson and Crick explained how genes are copied and passed along to new cells and organisms, thereby explaining how the information contained within genes is preserved through generations.

Telomerase is an enzyme that regulates the lengths of telomeres in the cells of many organisms, and in humans it begins to function int the early stages of embryonic development. Telomeres are repetitive sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling. In 1989, Gregg Morin found that telomerase was present in human cells. In 1996, Woodring Wright and his team examined human embryonic cells and found that telomerase was active in them. Scientists manipulate telomerase in cells to give cells the capacity to replicate infinitely. Telomerase is also necessary for stem cells to replicate themselves and to develop into more specialized cells in embryos and fetuses.

In 2001, Yale University Press published Frederic Lawrence Holmes' book, Meselson, Stahl, and the Replication of DNA: A History of "The Most Beautiful Experiment in Biology" (Replication of DNA), which chronicles the 1950s debate about how DNA replicates. That experiment verified that DNA replicates semi-conservatively as originally proposed by Watson and Crick. Rather than focusing solely on experiments and findings, Holmes's book presents the investigative processes of scientists studying DNA replication. Based on personal accounts, letter correspondence, and preserved research documents, Replication of DNA serves as a detailed account of the initial issues surrounding DNA replication and the Meselson-Stahl experiment from a scientist's perspective.

Max Ludwig Henning Delbrick applied his knowledge of theoretical physics to biological systems such as bacterial viruses called bacteriophages, or phages, and gene replication during the twentieth century in Germany and the US. Delbrück demonstrated that bacteria undergo random genetic mutations to resist phage infections. Those findings linked bacterial genetics to the genetics of higher organisms. In the mid-twentieth century, Delbrück helped start the Phage Group and Phage Course in the US, which further organized phage research. Delbrück also contributed to the DNA replication debate that culminated in the 1958 Meselson-Stahl experiment, which demonstrated how organisms replicate their genetic information. For his work with phages, Delbrück earned part of the 1969 Nobel Prize for Physiology or Medicine. Delbrück's work helped shape and establish new fields in molecular biology and genetics to investigate the laws of inheritance and development.

In 1954 Max Delbruck published On the Replication of Desoxyribonucleic Acid (DNA) to question the semi-conservative DNA replication mechanism proposed that James Watson and Francis Crick had proposed in 1953. In his article published in the Proceedings of the National Academy of Sciences, Delbrück offers an alternative DNA replication mechanism, later called dispersive replication. Unlike other articles before it, On the Replication presents ways to experimentally test different DNA replication theories. The article sparked a debate in the 1950s over how DNA replicated, which culminated in 1957 and 1958 with the Meselson-Stahl experiment supporting semi-conservative DNA replication as suggested by Watson and Crick. On the Replication played a major role in the study of DNA in the 1950s, a period of time during which scientists gained a better understanding of DNA as a whole and its role in genetic inheritance.

Matthew Stanley Meselson conducted DNA and RNA research in the US during the twentieth and twenty-first centuries. He also influenced US policy regarding the use of chemical and biological weapons. Meselson and his colleague Franklin Stahl demonstrated that DNA replication is semi-conservative. Semi-conservative replication means that every newly replicated DNA double helix, which consists of two individual DNA strands wound together, contains one strand that was conserved from a parent double helix and that served as a template for the other strand. Meselson's work enabled researchers to better explain and control cellular development by showing how DNA are copied when a cell divides and interpreted when a cell makes proteins.

Matthew Meselson, Franklin Stahl, and Jerome Vinograd, developed cesium chloride, or CsCl, density gradient centrifugation in the 1950s at the California Institute of Technology, or Caltech, in Pasadena, California. Density gradient centrifugation enables scientists to separate substances based on size, shape, and density. Meselson and Stahl invented a specific type of density gradient centrifugation, called isopycnic centrifugation that used a solution of cesium chloride to separate DNA molecules based on density alone. When Meselson and Stahl developed the technique in the mid-1950s, scientists had no other way to separate macromolecules that were of similar size but varied in density. Meselson and Stahl employed their method to determine how DNA replicates, became known as the Meselson-Stahl experiment. Density gradient centrifugation using cesium salts allowed scientists to isolate DNA and other macromolecules by density alone.

In an experiment later named for them, Matthew Stanley Meselson and Franklin William Stahl in the US demonstrated during the 1950s the semi-conservative replication of DNA, such that each daughter DNA molecule contains one new daughter subunit and one subunit conserved from the parental DNA molecule. The researchers conducted the experiment at California Institute of Technology (Caltech) in Pasadena, California, from October 1957 to January 1958. The experiment verified James Watson and Francis Crick’s model for the structure of DNA, which represented DNA as two helical strands wound together in a double helix that replicated semi-conservatively. The Watson-Crick Model for DNA later became the universally accepted DNA model. The Meselson-Stahl experiment enabled researchers to explain how DNA replicates, thereby providing a physical basis for the genetic phenomena of heredity and diseases.

In 1956, Gunther Stent, a scientist at the University of California Berkeley in Berkeley, California, coined the terms conservative, semi-conservative, and dispersive to categorize the prevailing theories about how DNA replicated. Stent presented a paper with Max Delbrück titled “On the Mechanism of DNA Replication” at the McCollum-Pratt Symposium at Johns Hopkins University in Baltimore, Maryland. In response to James Watson and Francis Crick’s proposed structure of DNA in 1953, scientists debated how DNA replicated. Throughout the debate, scientists hypothesized different theories about how DNA replicated, but none of the theories had sound experimental data. Stent introduced DNA replication classes that, if present in DNA, would yield distinct experimental results. Conservative, semi-conservative, and dispersive DNA replication categories shaped scientists' research into how DNA replicated, which led to the conclusion that DNA replicated semi-conservatively.