MadSci Network: Science History
Query:

Re: What did Phebus A. Levene hypothesize about DNA and who corrected him?

Date: Tue Mar 30 13:01:34 1999
Posted By: Shirley Chan, Ph.D.
Area of science: Science History
ID: 921955848.Sh
Message:

Phoebus Aaron Theodor Levene (1869-1940)

Phoebus Levene was an organic chemist at the Rockefeller Institute in New York. He is perhaps best known for his incorrect tetranucleotide theory of DNA.

Levene was a well-known and well-respected scientist in the early 1900s. He worked with some of the most famous chemists of the day, and published numerous papers on the chemical structures of sugars, amino acids and also nucleic acids. In the early 1900s, quite a few scientists, Levene included, thought that proteins were the molecules of heredity. Proteins were long chain molecules that came in all different shapes and sizes. The basic building blocks of protein are amino acids. And although the exact number of amino acids (20) was not known then, there were definitely more than 10 and these amino acids could be combined in all sort of ways.

DNA, deoxyribonucleic acid, is different. The basic building block of the DNA moleucle is a nucleotide, which is made up of a phosphate group, a deoxyribose sugar and one of four nitrogenous bases: adenine, guanine, cytosine and thymine. Levene published the first accurate model of how these nucleotides can bind together to form a long chain molecule. He also figured out the sugar difference between DNA and RNA. DNA uses deoxyribose sugar in its backbone; RNA uses ribose sugar.

Levene's mistake was to assume that DNA had equal amounts of each of the four nitrogenous bases. He proposed a tetranucleotide model of DNA where the four nucleotides were arranged in an unchanging order. These blocks then hooked up to form long chains. By fixing the order of the nucleotides, Levene made DNA a "stupid" molecule, unable to carry any useful information.

In the '40s and '50s, a number of "classic" experiments were carried out that pointed to DNA, and not protein, as the hereditary molecule. (ref. Hershey/Chase blender experiment, and also Oswald Avery's work on Pneumococcus. Interesting fact: Oswald Avery was also a Rockefeller scientist and his group did their work mostly in the '30s while the tetranucleotide theory was in favor.) These experiments by default proved that DNA couldn't be made up of tetranucleotide blocks. If DNA carried hereditary information, then it couldn't have the simple repeated structure proposed by Levene. Scientists began to reexamined the chemical structure of the DNA molecule.

The biggest nail in the coffin to Levene's tetranucleotide theory came in 1949. Erwin Chargaff published a paper with accurate quantitative measurements of the nitrogenous bases. He found that within a species, the amount of adenine was similar to thymine and the amount of guanine was similar to cytosine. If DNA was truly made up of tetranucleotides, then not only should all the bases be equal, the base amounts should be similar in all species as well. This was not the case.

In 1953, James Watson and Francis Crick proposed the double helix model of DNA. This led to the deciphering of the genetic code and all the subsequent discoveries in molecular biology. DNA does have specific sequences of nucleotides that make up genes--an average human gene could be thousands of nucleotides long--but it certainly is not made up of repeating tetranucleotides.


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