Wednesday 16 May 2012

Wellcome Digital Library Project featured on BBC Radio 4 "Today" programme

The Wellcome Digital Library project was today featured on BBC Radio 4's "Today" programme. The report by Fergus Walsh, medical correspondent of the BBC featured recordings from King's College London, Wellcome Trust and Churchill Archives, Cambridge. The report centered on the archives relating to the critical discovery of the structure of DNA and the contributions of Crick, Franklin, Watson and Wilkins respectively.


The report can be heard on the BBC iPlayer (for those based in the UK) for the next week and starts at the 02:50 mark until 02.55. (http://www.bbc.co.uk/iplayer/episode/b01hjs46/Today_16_05_2012/) or is available on the Today programme website (http://news.bbc.co.uk/today/hi/today/newsid_9721000/9721286.stm).


In the visit to King's, Fergus Walsh was given a tour of our principle vault and shown "Photo 51" alongside a number of other items in the joint Maurice Wilkins/Biophysics collection. Some of these images can be seem on his blog post (http://www.bbc.co.uk/news/health-18041884).


For our partner institutions, a photo gallery of Crick correspondence from the Wellcome Trust collection was put up on the BBC Today programme home page (http://news.bbc.co.uk/today/hi/default.stm).



Maurice Wilkins and the ultrasonic pursuit of the mechanisms of life



 The scientific career of Maurice Wilkins did not solely focus on the structure and refinement of DNA. Having begun reading Physics at Cambridge in 1936, Wilkins went on to work on luminosity and phosphorescence and made contributions to wartime radar research in Birmingham and later at the University of California, Berkeley, on the Manhattan Project to develop the first atomic bomb. After reading Erwin Schrödinger’s seminal What is Life?” (1944), which influenced a generation of scientists, and following a period of soul-searching following the atomic bombing of Hiroshima and Nagasaki, Wilkins decided to focus his research on biophysics – the use of physics to study biological structures. He began his work by investigating the effect of ultrasonics on chromosomes.

Wilkins’ began research on the biological implications of ultrasonic technology when he first moved back to the UK after his wartime experience in America. Whilst at St Andrews, he was talking to the Glasgow University-based geneticist, Charlotte Averback, about Hermann Muller’s work using x-rays to cause mutations within fruit flies and he wondered whether he could replicate it using another physical agent. As Wilkins states in the The Third Man of the Double Helix (2003):

No-one seemed to have tried strong high frequency sound (ultrasonics) on chromosomes...it was a way of starting [in biophysics]; I could do it on my own and it might help us to understand how genes worked” (p91)

The aim of his experiments was to explore the effects of ultrasonics on a living cell nucleus and especially its effect on the process of mitosis. The hope was that the ultrasonics ray would cause breakage of the chromosome and provide an interesting comparison with similar breaks engendered by other agents such as x-rays.

The initial experiments typified Wilkins’ approach to science, as he constructed by himself a high power ultrasonic generator for the experiments. A paper produced by G G Selman and Wilkins published in July 1949, states that their high intensity ultrasonic apparatus could “generate and measure higher unfocused ultrasonic intensities than any we have yet found recorded in the literature” (p229, G. G. Selman & M. H. F Wilkins, "The production of high intensity ultrasonics at megacycle frequencies” in Journal of Scientific Instruments, Volume 26).


KDBP/1/1/0031A Microscope images of the effect of ultrasonics on various cellular samples. Dated  May 1949. 

Yet results proved disappointing: no evidence of the cytogenetical effects of ultrasonics were found despite using an array of different samples including root tips, chick heart fibroblasts and Tradescantia pollen tubes.

Wilkins was soon keen to move onto other projects when he realised pursuing ultrasonics was not worthwhile and he was asked by John Randall to take over research into how DNA moved and grew in living cells. It was this shift into microscope studies of DNA that would lead Wilkins to recognise the potential of x-ray diffraction to elucidate the structure of the molecule.

Thursday 10 May 2012

Selecting Material for Digitisation: Glass Slides and X-ray acetates


Part of my role for the project is to select relevant material from the Biophysics collection for digitisation. The Biophysics collection of paper, glass plate and acetate photographic material produced by staff members and spans from the department's inception in 1947, to 1984. My brief was to select a subset of 4000 images from this collection relating to DNA research carried out by Maurice Wilkins and others.

The bulk of the images came from the quarter plate glass plate negative collection that comprises of 18300 individual items. While DNA research accounts for a significant proportion, other departmental work notably on muscle and the structure of collagen are also represented. The DNA related slides had to be handpicked from this larger total. Fortunately, the entire series had been indexed by the department. During the cataloguing project in 2011, these index books were digitised and transcribed into a spreadsheet, which made the task of selection much easier. 


Example of index entries for the quarter plate glass negatives: The entry referenced as "867" is of particular interest as this refers to "Photo 51", the best image of Structure B DNA produced by Rosalind Franklin.



The selection criteria used was based on my own understanding of the collection and the brief of the project. Having worked on the cataloguing project of the papers prior to this role, I felt confident in my ability to determine which material should be included. For the most part this was fairly academic as each slide indicated who created them and all material from well known DNA researchers was selected (e.g. Wilkins, Franklin, Gosling, Wilson etc.). When the creators’ relationship to DNA research was not so obvious, such as visiting academics or PhD students, then I consulted the catalogue to see whether they collaborated in DNA research. I decided to include all work (not just DNA research) in the early years of the department as often related project techniques and microscopy work helped shape the later DNA research. Supplementary material relating to microscopy studies, chemical analysis and model building and a smaller number of half plate glass plate negatives and photographic prints were also included.

An example of a quarter plate glass negative: This image was referenced in the index as "2747" and shows an x-ray diffraction exposure of lithium (Li) DNA in a B configuration created by Maurice Wilkins in April 1958.



The jewel in the crown so to speak was the third main source of material - the x-ray acetates. Remarkably, some of the original x-ray exposures have survived and capture the various samples, salts and techniques that the KCL Biophysics department used in their x-ray diffraction studies of DNA and later RNA and nuceleoproteins. It was decided early on that all the x-rays were to be digitised, due in part due to their intrinsic value but secondly because of their unstable physical condition. Acetate film has a tendency to deteriorate and undergo what is known as vinegar syndrome. This is when the acetate degrades and begins to oxidise creating a vinegar smell. The surface often begins to warp and crack and fades the original image. The condition is autocatalytic which means that once it has begun it cannot be stopped with the only stabilisation solution being to isolate and freeze the material. Many of the x-rays show the early signs of this condition (small pock marks) but the vast majority have retained clear x-ray patterns.
X-ray diffraction exposure showing clear warping and peeling of the emulsion layer but retaining the x-ray pattern of DNA.



X-ray diffraction exposure of DNA with typical pock marks associated with acetate deterioration

Digitisation is the best strategy for long term preservation of this material for several reasons. Firstly, by producing a digital copy we can retain valuable content before further deterioration ensues. Secondly, the digital copy will be more accessible than the original as a high quality scan can provide a greater degree of clarity than the physical copy and thirdly by producing a digital surrogate it reduces the risk of damage from physical handling and allows for the original material to be put into cold storage. 

Overall, the images selected from the Biophysics Department are representative of the biophysical approach to genetics taken between 1947-1969.The collection provides an unprecedented record of x-ray diffraction studies in genetics as well as fully documenting the experimental work of Maurice Wilkins and his colleagues carried out at King’s.