Developmental Biology 278 (2005) 274 – 288 www.elsevier.com/locate/ydbio
Friedrich Miescher and the discovery of DNA
Max Planck Institute for Developmental Biology, Department 3 – Genetics, Spemannstr. 35/III, D-72076 Tubingen, Germany ¨ Received for publication 5 October 2004, revised 17 November 2004, accepted 20 November 2004 Available online 21 December 2004
Abstract Over the past 60 years, DNA has risen from being an obscure molecule with presumed accessory or structural functions inside the nucleus to the icon of modern bioscience. The story of DNA often seems to begin in 1944 with Avery, MacLeod, and McCarty showing that DNA is the hereditary material. Within 10 years of their experiments, Watson and Crick deciphered its structure and yet another decade on the genetic code was cracked. However, the DNA story has already begun in 1869, with the young Swiss physician Friedrich Miescher. Having just completed his education as a physician, Miescher moved to Tqbingen to work in the laboratory of biochemist Hoppe-Seyler, his aim being to elucidate the building blocks of life. Choosing leucocytes as his source material, he first investigated the proteins in these cells. However, during these experiments, he noticed a substance with unexpected properties that did not match those of proteins. Miescher had obtained the first crude purification of DNA. He further examined the properties and composition of this enigmatic substance and showed that it fundamentally differed from proteins. Due to its occurrence in the cells’ nuclei, he termed the novel substance bnucleinQ—a term still preserved in today’s name deoxyribonucleic acid. D 2004 Elsevier Inc. All rights reserved. Keywords: Friedrich Miescher; DNA; Nuclein; Discovery; History; Tqbingen; Felix Hoppe-Seyler; Leucocytes; Spermatozoa; Heredity
Introduction The year 2003 marked the 50th anniversary of the historic characterization of DNA by James Watson and Francis Crick with an article in the journal Nature on April 25, 1953, that revealed the structure of DNA (Watson and Crick, 1953). Their discovery was the culmination of a decade of intense research following Oswald T. Avery, Colin MacLeod, and Maclyn McCarty’s demonstration that DNA, not protein as previously thought, is the hereditary molecule (Avery et al., 1944). Today, the history of DNA is often told as though it started with these fundamental discoveries. However, the description of DNA actually began 135 years ago with its discovery by Friedrich Miescher, a much less known man who isolated the hereditary material in 1869. The second half of the 19th century was a period in which many key concepts in biology were established. For * Fax: +49 7071 601 448. E-mail address: firstname.lastname@example.org. 0012-1606/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ydbio.2004.11.028
one, the focus of biologists was shifting from studying organisms, organs, or tissues to their component cells. Matthias J. Schleiden and Theodor Schwann had just shown that all tissues have a cellular origin and that both animals and plants consist of the same fundamental units of organization, cells, which interact to give rise to complex organisms (reviewed in Mayr, 1982). Experiments by, among others, Louis Pasteur and Rudolph Virchow demonstrated that new cells can only arise from other cells (Virchow, 1855)—rebutting the notion of spontaneous generation of new cells from lifeless matter, which had prevailed for a long time. In parallel to these breakthroughs in cytology, the basic concepts of heredity and evolution were being worked out. The publication of Charles R. Darwin and Alfred R. Wallace’s theories of evolution by natural selection occurred in 1858 (Darwin and Wallace, 1858), and 1 year later, Darwin’s famous book On the Origin of the Species by Means of Natural Selection appeared (Darwin, 1859). In 1865, Gregor Mendel discovered the laws of heredity through his breeding...
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