The following is an adapted excerpt from The Evolution of the Genome, © 2005 Elsevier Academic Press.
In the mid- to late 1800s (and to an extent, well into the 20th century), proteins were considered the most significant components of cells. Their very name reflects this fact, being derived from the Greek proteios, meaning “of the first importanceâ€. In 1869, while de
veloping techniques to isolate nuclei from white blood cells (which he obtained from pus-filled bandages, a plentiful source of cellular material in the days before antiseptic surgical techniques), 25 year-old Swiss biologist Friedrich Miescher stumbled across a phosphorous-rich substance which, he stated, “cannot belong among any of the protein substances known hitherto†(quoted in Portugal and Cohen 1977 [1]). To this substance he gave the name nuclein, and published his results in 1871 after confirmation of the remarkable finding by his advisor, Felix Hoppe-Seyler (for reviews, see Mirsky 1968;
Miescher continued his work on nuclein for many years, in part refuting claims that it was merely a mixture of inorganic phosphate salts and proteins. Yet Miescher never departed from the common proteinocentric wisdom, and instead suggested that the nuclein molecule served as little more than a storehouse of cellular phosphorus. In 1879, Walther Flemming coined the term chromatin (Gr. “colourâ€) in reference to the coloured components of cell nuclei observed after treatment with various chemical stains, and in 1888 Wilhelm Waldeyer used the term chromosome (Gr. “colour bodyâ€) to describe the threads of stainable material found within the nucleus. For some time, debate existed over whether or not chromatin and nuclein were one and the same. The argument was largely settled when Richard Altman obtained protein-free samples of nuclein in 1889. As part of this work, Altman proposed a more appropriate (and familiar) term for the substance, nucleic acid. Over time, the components of the nucleic acid molecules were deduced, and by the 1930s, nuclein had become desoxyribose nucleic acid, and later, deoxyribonucleic acid (DNA).
The important developments that took place over the ensuing decades are well documented (e.g., Portugal and Cohen 1977; Judson 1996), including early hypotheses of DNA’s structure (such as Phoebus Levene’s failed tetranucleotide hypothesis, or the incorrect helical model of Linus Pauling), Erwin Chargaff’s discovery of the constant ratio of the two purines with their respective pyrimidines, Rosalind Franklin’s x-ray crystallography of the DNA molecule, and other key developments leading up to Watson and Crick’s monumental synthesis in 1953 and the subsequent deciphering of the genetic code.
Miescher died of tuberculosis in 1895 at the age of 51. His was a major contribution to biology, as were the discoveries of countless other individuals up to and beyond the elucidation of DNA’s physical structure and the dawn of molecular genetics.
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Notes
[1] I stumbled across this book at a used bookstore in Madison, Wisconsin at the 1999 SSE meeting. That was in the days before searches on Amazon.com, Google, and Wikipedia were easy and routine, and I was unaware that the book existed so I considered it quite a lucky find.
[2] Hoppe-Seyler also had his own journal, in which Miescher’s results were published, but was not a co-author on the paper. My, how things have changed!
[3] For more information about Miescher, see the following:
References
Judson, H.F. 1996. The Eighth Day of Creation. CSHL Press, Plainview, NY.
Lagerkvist, U. 1998. DNA Pioneers and Their Legacy. Yale University Press, New Haven, CT.
Miescher, F. 1871. Ãœber die chemische Zusammensetzung der Eiterzellen. Hoppe-Seyler’s medizinish-chemischen Untersuchungen 4: 441-460.
Mirsky, A.E. 1968. The discovery of DNA. Scientific American 218 (June): 78-88.
Portugal, F.H. and J.S. Cohen. 1977. A Century of DNA. MIT Press, Cambridge, MA.
Tracy, K. 2005. Friedrich Miescher and the Story of Nuclei Acid. Mitchell Lane Publishers.
Wolf, G. 2003. Friedrich Miescher, the man who discovered DNA.