Tag Archives: Rosalind Franklin

Crystallography: From Chocolate to Drug Discovery

This post was contributed by Dr Clare Sansom, senior associate lecturer in the Department of Biological Sciences. Dr Sansom attended inaugural Rosalind Franklin Lecture during Birkbeck Science Week 2016.

Rosalind Franklin - slide

Birkbeck has already established lecture series in honour of some of its most distinguished alumni. Until 2016, however, Rosalind Franklin – co-discoverer of the DNA structure and perhaps the most widely recognisable of its ‘famous names’ – was missing from the list of honourees. This gap has now been filled; the annual Rosalind Franklin lecture forms part of the college’s Athena SWAN programme and will always be given by a distinguished woman scientist.

And fittingly, the inaugural lecture, which was part of Science Week 2016, was devoted to Rosalind Franklin’s own discipline, crystallography. Elspeth Garman, Professor of Molecular Biophysics at Oxford University, gave an entertaining and illuminating lecture to a large audience that included Rosalind’s sister, the author Jenifer Glynn.

Exploring crystals

Garman began her lecture by showing a short video that she had produced for OxfordSparks.net that used a ‘little green man’ to illustrate the method of X-ray crystallography that is used to obtain molecular structures from crystals. The rest of the lecture, she said, would simply go through that process more slowly. She started by showing some beautiful examples of crystals. All crystals are formed from ordered arrays of molecules. They can be enormous, such as crystals of the mineral selenite in a cave in Mexico that measure over 30’ long or too small to be visible with the naked eye.

In the early decades of crystallography, structures could only be obtained from crystals of the smallest, simplest molecules: the first structure of all, published in 1913 by the father-and-son team of W.H. and W.L. Bragg, was of table salt. When they were jointly awarded the Nobel Prize for Physics in 1915, the younger Bragg was a 25-year-old officer in the trenches on the Western Front. His record as the youngest Nobel Laureate was unbroken until Malala Yousafzai’s Peace Prize in 2014.

The Braggs’ discoveries paved the way for studies of the structures of many, many substances: including the chocolate of the lecture title. Few of the audience can have known that chocolate exists in six different crystal forms, or that only one of these (Form V) is good to eat. The process of ‘tempering’ – a series of heating and cooling steps – is used to ensure that it solidifies in the correct form.

Professor Nick Keep and Professor Elspeth Garman at the inaugural Rosalind Franklin lecture

Professor Nick Keep and Professor Elspeth Garman at the inaugural Rosalind Franklin lecture

Protein crystallography

Garman then moved on to talk about her own field of protein crystallography. Proteins are the ‘active’ molecules in physiology, and they are formed from long, linear strings of 20 different ‘beads’ (actually, small organic molecules known as amino acids). Chemists can quite easily find out the sequence of these beads in a protein, but it is impossible to work out from this the way that the string will fold up into a definite structure ‘like a piece of wet spaghetti’. And it is this structure that places different units with different chemical properties on the surface or in the interior of the protein, or near each other, and that therefore determines what the protein will do.

Protein crystallography only became technically possible in the mid-twentieth century, and even then it was a painfully slow and complex process that could only be used to study the smallest, simplest proteins. Dorothy Hodgkin, also a professor at Oxford, won her Nobel Prize in Chemistry in 1964 for the structures of two biologically important but fairly small molecules: penicillin, with 25 non-hydrogen atoms and vitamin B12, with 80. She is perhaps better known for solving the structure of insulin, the protein that is missing or malfunctioning in diabetics. This has 829 non-hydrogen atoms; in contrast, the 2009 Chemistry Nobel Prize was awarded for the structure of the ribosome, the large (by molecular standards) ‘molecular machine’ that synthesises proteins from a nucleic acid template. The bacterial ribosome used for the Nobel-winning structural studies is well over 300 times larger than insulin, with over a quarter of a million atoms.

Real world applications

Dr Rosalind Franklin

Dr Rosalind Franklin

Protein structures are not only beautiful to look at and fascinating to study, but they can be useful, particularly for drug discovery. Many useful drugs have already been designed at least partly by looking at a protein structure and working out the kinds of molecule that would bind tightly to it, perhaps blocking its activity. Some viral proteins have been particularly amenable to this approach.

Rosalind Franklin did some of the first research into virus structure when she was based at Birkbeck, towards the end of her tragically short life, and her student Aaron Klug cited her inspiration in his own Nobel lecture in 1982. X-ray crystal structures were used in the design of the anti-flu drugs Relenza™ and Tamiflu™ and of HIV protease inhibitors, and more recently still structures of the foot and mouth virus are helping scientists develop new vaccines for tackling this potentially devastating animal disease. The foot-and-mouth virus structure even made the front page of the Daily Express.

The equipment that Dorothy Hodgkin and her contemporaries used to solve protein structures in the 1960s and 1970s looks primitive today. Now, almost every step of protein crystallography has been automated. Powerful beams of X-rays generated by synchrotron radiation sources, such as the UK’s Diamond Light Source in Oxfordshire, allow structures to be determined quickly from the smallest crystals. It is even possible to control some of these machines remotely; Garman has operated the one at Grenoble from her sitting room. Yet there is one step that has changed remarkably little. It is still almost as difficult to get proteins to crystallise as it was in the early decades. Researchers have to select which of a large number of combinations of conditions (temperature, pH and many others) will persuade a protein to form viable crystals. Guesswork still plays a large part and some researchers seem to be ‘better’ at this than others: Garman adds the acronym ‘GMN’ or ‘Grandmother’s maiden name’ to her list of conditions to reflect this.

Yet, with every step other than crystallisation speeded up and automated beyond recognition, the trickle of new structures in the 70s and even 80s has become a torrent. Publicly available structures are stored online in the Protein Data Bank, which started in 1976 with about a dozen structures: it now (May 2016) holds over 118,000. Protein crystallography as a discipline is thriving, but there are many challenges ahead. We are only now beginning to tackle the 70% or so of human proteins that are only stable when embedded in fatty cell membranes and are therefore insoluble in water. It is possible to imagine a time when it is possible to solve the structure of a single molecule, with no more need for time-consuming crystallisation. And, hopefully, women scientists will play at least as important a role in the second century of crystallography as they – from Quaker Kathleen Lonsdale, who developed important equations while jailed for conscientious objection during World War II, through Franklin and Hodgkin to Garman and her contemporaries – have in the first.

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Life Story: The Race for the Double Helix

This post was contributed by Professor Nick Keep, Executive Dean of the School of Science. Professor Keep attended the Birkbeck Science Week 2016 film screening of “Life Story: The Race for the Double Helix” on Monday April 11 at the Birkbeck Cinema.


“Life Story: the race for the Double Helix”is a 1987 BAFTA award winning film length TV dramatisation of the story of the discovery of the structure of DNA. The film screening was co-introduced by Dr Richard Hamblyn from the Dept of English and Humanities, who works at the interface of science and literature, and Dr Tracey Barrett from the Dept Biological Sciences, a female protein crystallographer in a Birkbeck tradition that goes back to Rosalind Franklin.

Richard described the film as having two classic odd couples; Crick and Watson in a glossy tourist Cambridge, and Wilkins and Franklin in a rainy London, contrasting with Franklin’s former sunny life in Paris and the easy going relationship with her previous collaborator Vittorio Luzzati, the inventor of the Luzzati plot.

The search for truth in science

Tracey outlined the importance of the science and the changes for women in Science. There are no longer men-only common rooms, such as Franklin encountered at Kings, but there are still problems. They also discussed the interplay between the search for truth in science and competition to be first and famous. Birkbeck is mentioned in the film as the place of refuge Franklin can relocate to escape the oppressive atmosphere at Kings. Richard quoted Rosalind Franklin as writing that she “will be moving from a palace” (Kings) “to a slum” (Birkbeck)” but I’m sure I will find Birkbeck pleasanter all the same”.

The film itself was excellent with Juliet Stevenson as Franklin, Alan Howard as Wilkins, Tim Piggot-Smith as Crick and Jeff Goldblum as the ambitious Watson. I found Clive Panto very convincing (if a little overweight) as Max Perutz, the only character that I knew in person, albeit later in his life. The widespread smoking was an authentic period touch that stood out for me. Whether a 2017 production would do that I am not sure.

Discussing the injustice

The Race for the Double Helix.jpg

By Source, Fair use, https://en.wikipedia.org/w/index.php?curid=46189683

After the showing, the audience discussed the injustice of Rosalind Franklin not winning the Nobel Prize. Firstly the prize is never awarded to more than three people so a decision had to be made and by this time Rosalind Franklin had tragically died. Interestingly, checking afterwards, the ban on posthumous prizes was only formalised in 1974, well after the 1962 award for DNA (See section on Posthumous Nobel Prizes), although observed in practice for Science awards until it was discovered that one of the 2011 winners for Physiology and Medicine had died three days before the announcement, but this was not known to the Swedish Academy when they released the names.

The 1961 Peace prize, just a year before the Medicine and Physiology award to Crick, Watson and Wilkins, was knowingly awarded to the UN Secretary General, Dag Hammarskjöld, who had recently died in an air crash, as was the 1931 Literature Prize to a Swedish Poet. Whether Rosalind Franklin is better known now for not having been awarded the Nobel Prize, than she would have been if she had received it is a matter for debate. Birkbeck, where she worked at the end of her life, remembers her via the Rosalind Franklin Laboratory built in 1996 and, from this year, the annual Rosalind Franklin lecture by a leading woman scientist in a field Birkbeck researches in.

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