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Wednesday, June 5, 2019

The History of the Development of Genealogical DNA: Part Eight: Discovering DNA

Many of the important scientific discoveries of the 19th and 20th Centuries were inexorably dependent on technological advances. The first "discovery" of what we now call DNA was made in 1869, by the Swiss physiological chemist Friedrich Miescher. first isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of white blood cells. However, it took more than 50 years for the technology to develop to the point where a further discovery the importance of what he had found was possible. Miescher isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of white blood cells.

During the period 1885 to 1901, Ludwig Karl Martin Leonhard Albrecht Kossel, a German biochemist was able to isolate and name its five constituent organic compounds: adenine, cytosine, guanine, thymine, and uracil. These compounds are now known collectively as nucleobases, and they provide the molecular structure necessary in the formation of stable DNA and RNA molecules. See Wikipedia: Albrecht Kossel.

The term "deoxyribonucleic acid (DNA)" began to evolve when Richard Altmann, who was a German pathologist and histologist from Deutsch Eylau in the Province of Prussia, coined the term, "nucleic acid" in 1889. See Wikipedia: Richard Altmann.

The missing link was making a connection between identifying the presence of the organic compounds and determining their function in the reproductive and inheritance process. One more step towards acquiring this understanding came in 1902 when Sir Archibald Edward Garrod, an English physician, was the first to associate a disease with inheritance. For a detailed history of the discovery, see Wikipedia: Archibald Garrod.

What is remarkable is that so much of the technology necessary for the identification and utilization DNA for forensic, genealogical, and medical purposes has been developed only in the last 100 years with major developments only in the last 75 years or so.

DNA finally came center stage in 1944 with the discoveries of Oswald Avery, an immunochemist at the Hospital of the Rockefeller Institute for Medical Research. He is best known for the experiment, published in 1944 in conjunction with his co-workers Colin MacLeod and Maclyn McCarty, that isolated DNA as the material of which genes and chromosomes are made. See Wikipedia: Avery-MacLeod-McCarty experiment. Here is a citation to the original published article.


The next step in the process occurred in 1950 when Erwin Chargaff, an Austro-Hungarian biochemist who immigrated to the United States during the German Nazi era and was a professor of biochemistry at Columbia University medical school, discovered two rules that helped lead to the discovery of the double helix structure of DNA. See Wikipedia: Erwin Chargaff. Here is a quote from that Wikipedia article that explains how that occurred.
Erwin Chargaff proposed two main rules in his lifetime which were appropriately named Chargaff's rules. The first and best known achievement was to show that in natural DNA the number of guanine units equals the number of cytosine units and the number of adenine units equals the number of thymine units. In human DNA, for example, the four bases are present in these percentages: A=30.9% and T=29.4%; G=19.9% and C=19.8%. This strongly hinted towards the base pair makeup of the DNA, although Chargaff did not explicitly state this connection himself. For this research, Chargaff is credited with disproving the tetranucleotide hypothesis (Phoebus Levene's widely accepted hypothesis that DNA was composed of a large number of repeats of GACT). Most researchers had previously assumed that deviations from equimolar base ratios (G = A = C = T) were due to experimental error, but Chargaff documented that the variation was real, with [C + G] typically being slightly less abundant. He was able to do this with the newly developed paper chromatography and ultraviolet spectrophotometer. Chargaff met Francis Crick and James D. Watson at Cambridge in 1952, and, despite not getting along with them personally, he explained his findings to them. Chargaff's research would later help the Watson and Crick laboratory team to deduce the double helical structure of DNA.
The second of Chargaff's rules is that the composition of DNA varies from one species to another, in particular in the relative amounts of A, G, T, and C bases. Such evidence of molecular diversity, which had been presumed absent from DNA, made DNA a more credible candidate for the genetic material than protein.
The formulation of the structure of DNA in the now ubiquitous double-helix is often so completely condensed into a single discovery that the contributions of many scientists working on different aspects of the problem are almost completely ignored. A key factor in the discovery is attributed to Rosalind Franklin, an English chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, coal, and graphite. See Wikipedia: Rosalind Franklin.  Although all the recognition for the discovery went to James Watson and Francis Crick, the actual discovery was based on a crucial X-ray diffraction image of DNA labeled as "Photo 51", from Rosalind Franklin in 1952. See Wikipedia: Nucleic acid double helix. While Watson and Crick went on to receive the Nobel Prize in Physiology or Medicine in 1962 with Maurice Hugh Frederick Wilkins, Rosalind Franklin's crucial part in the discovery process was ignored because she died in 1958 of bronchopneumonia, secondary carcinomatosis, and ovarian cancer. Exposure to X-ray radiation is sometimes considered to be a possible factor in her illness. See Wikipedia: Rosalind Franklin.

Who was Maurice Hough Frederick Wilkins? Here is a short summary of him and his work from Wikipedia: Maurice Wilkins.
Maurice Hugh Frederick Wilkins CBE FRS (15 December 1916 – 5 October 2004) was a New Zealand-born British physicist and molecular biologist, and Nobel laureate whose research contributed to the scientific understanding of phosphorescence, isotope separation, optical microscopy and X-ray diffraction, and to the development of radar. He is best known for his work at King's College London on the structure of DNA. 
Wilkins' work on DNA falls into two distinct phases. The first was in 1948–50, when his initial studies produced the first clear X-ray images of DNA, which he presented at a conference in Naples in 1951 attended by James Watson. During the second phase, 1951–52, Wilkins produced clear "B form" "X" shaped images from squid sperm, images he sent to James Watson and Francis Crick, causing Watson to write "Wilkins... has obtained extremely excellent X-ray diffraction photographs" [of DNA]. 
In 1953 Wilkins' colleague Rosalind Franklin instructed Raymond Gosling to hand over to Wilkins a high quality image of "B" form DNA (Photo 51), which she had made in 1952 but had “put it aside” as she was leaving King's College London. Wilkins showed it to Watson. This image, along with the knowledge that Linus Pauling had proposed an incorrect structure of DNA, “mobilised” Watson and Crick to restart model building. With additional information from research reports of Wilkins and Franklin, obtained via Max Perutz, Watson and Crick correctly described the double-helix structure of DNA in 1953.
What did Crick and Wason do to become famous? It is somewhat difficult to find an accurate description of the work done because most accounts leave out the contributions of Wilkins and Franklin. At least Wilkins got recognition in the award of 1/3 of the Nobel Prize. Scientific advancement is the accumulation of the contributions of many small advancements. That we choose to recognize and award some is sometimes tragic and patently unfair. Here is the citation to the 1953 article:

Watson, James D., and Francis Crick. 1953. "Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid". Nature. 171 (4356): 737-738.

It is surprisingly difficult to find an online copy of the original article. Here is a link to a copy.

Notwithstanding the emphasis on Crick and Watson, the entire contribution was monumental in beginning an understanding of the processes involved in genetic inheritance.

Stay tuned.

See these previous posts:

Part One:
Part Two:
Part Three:
Part Four:
Part Five:
Part Six:
Part Seven:


  1. I highly recommend to anyone interested in these stories to get the book: "The Gene: An Intimate History" by Siddhartha Mukherjee, 2017. It includes many pages on the work of Watson, Crick, Wilkins and Franklin.

    1. That is one of the books I have read recently.

  2. I found the book, The Double Helix, by James D. Watson, very interesting. It could shed light on some of the questions you raised about what Watson & Crick actually did, but obviously from Watson's point of view.