Rosalind Franklin: How her legacy lives on

The X-shaped pattern in the photo showed clearly for the first time that DNA molecules had a helical structure, and was key for Cambridge scientists James Watson and Francis Crick to build their famous double-helix model of DNA. This scientific breakthrough was published in 1953 and later gained them a Nobel Prize in 1962, together with Maurice Wilkins at King’s; Rosalind Franklin by this time, sadly, had died at the age of only 37.

While Franklin’s achievements were ground-breaking at the time, her discovery has also led to remarkable breakthroughs in science since. Many of King’s research projects would not exist if it were not for Franklin’s discovery.

Predicting age

King’s Forensics is aptly located in the Franklin-Wilkins Building. The role of DNA in forensic evidence-gathering has become increasingly essential. Without the discovery of DNA, we would not be able to identify individuals from just a handful of cells today.

A more recent study led by Prof. Denise Syndercombe Court developed a genetic tool which uses a form of artificial intelligence to analyse a specific set of biomarkers in blood samples. Researchers were able to accurately predict the age of sample donors to within four years of age.

Co-author of the paper, Dr David Ballard, said: “Forensic science has been fundamentally changed by the discoveries that Franklin and co-workers found. The ability to use DNA in a legal setting has revolutionised the way that we can detect and prosecute crime. The intelligence tools that we are developing can take this area even further.”

Structural Biology

When Rosalind Franklin joined King’s she was concerned that, in her own words, “I am, of course, most ignorant of all things biological”. She had trained in physical chemistry and X-ray crystallography, whereas John Randall’s vision for his Biophysics Research Group, which he founded in the Physics Department, was for a multi-disciplinary research environment, bringing physicists, chemists, biologists and mathematicians together to solve important biological problems.

That ethos continues to drive research today in the Randall Centre for Cell and Molecular Biophysics, which traces its history back to that Biophysics Research Group, via the Randall Institute and before that the Biophysics Department, in laboratories in Drury Lane.

Rosalind was a superb experimentalist, and it was her attention to sample preparation, and in particular the hydration state of the DNA, that led to the famous Photograph 51. Attention paid to sample preparation is still critical for both X-ray crystallography and the new cryo-EM techniques, despite the technical advances since Rosalind’s time that have, for example, reduced the time taken to collect an X-ray diffraction image from the 62 hours required for Photograph 51, to fractions of a second.

Professor Brian Sutton, from the School of Basic & Medical Biosciences, said: “All of us in “The Randall” are proud of the key role played by Rosalind Franklin, together with Maurice Wilkins and others, in the determination of the structure of DNA, not least those of us “structural biologists”, a term coined by one of Rosalind’s later collaborators at Birkbeck College, Don Caspar, almost all of whom still employ X-ray crystallography in our work. Indeed, one of us, Mark Sanderson, and his group, are engaged in X-ray studies of the topoisomerase enzymes that “un-wind” DNA, an essential requirement of the twisted double-helical structure that was apparent the moment the structure was unveiled.”

The remarkable life of twins

TwinsUK is the UK’s largest twin registry with 15,000 identical and non-identical twins from across the UK. The research aims to investigate the genetic and environmental basis of complex diseases and conditions, such as cardiovascular disease, the genetics of metabolic syndrome and most recently Covid-19.

Professor Tim Spector, from the School of Life Course Sciences, said: "DNA - and subsequently genetics - is at the very heart of a twin study like TwinsUK. Identical twins have identical DNA, whereas non-identical twins share only 50%. This difference in the proportion of DNA shared helps us to work out to what extent certain conditions are caused by genes or by the environment.

“This allowed us and researchers around the world to discover the different genetic variants for hundreds of common diseases as well as the genetic sequences of all our gut microbes. In addition, a number of twins that come to us don't know whether they are identical or non-identical. A key method for determining this is of course a DNA test.

“We have a lot to thank Rosalind Franklin for, whose contributions to the discovery of DNA made health research as we know it today possible."

The Human Genome Project

Rosalind Franklin’s contribution to the three-dimensional structure of DNA set in motion the journey to deciphering our entire genome – the complete set of instructions that specify a human. The Human Genome Project, announced in June 2000, had put together the first genetic blueprint of a human being. Thousands of scientists from across the world succeeded in the publication of a full human genome.

Professor Tim Hubbard, Head of Department of Medical & Molecular Genetics was a part of that extraordinary project.

He said: “Twenty years later, much of the genome is still a mystery, but technological advances in sequencing are stunning. We can determine the complete genome sequence of an individual cost effectively, rapidly and accurately enough to be analysed to inform their clinical care. Following the 100,000 genomes project, successfully delivered by Genomics England and NHS England, the NHS leads the world by commissioning whole genome sequencing as part of standard care. King’s and Guy's and St Thomas' NHS Foundation Trust have a long history of early research and application of clinical genetics. The Guy’s campus continues this as home to one of the seven new Genome Laboratory Hubs which will deliver the new NHS Genome Medicine Service. This is just the start of genome medicine, helping to transform and personalise clinical care.”

The heart of Franklin’s legacy

Franklin’s technique to record Photo 51, small angle X-ray diffraction, is being used to study the structure of the myofilaments in cardiac muscle cells. A better understanding of the dynamic structural changes of the motor proteins that drive the contraction of cardiac muscle may lead to the development of better treatments for heart failure.

Dr Elisabetta Brunello, a British Heart Foundation Research Fellow working at the Randall Centre, studies the regulatory mechanisms that control the contractility of the heart and their modification in heart diseases.

She said: “Dr. Franklin and her co-workers were pioneers in the use of small-angle X-ray diffraction for the study of biological macromolecules. The proteins inside the functional unit of muscle are highly ordered in a quasi-crystalline structural assembly. This allows the use of the same biophysical technique used by Dr. Franklin, small angle X-ray diffraction, to study the structural changes in the molecular motors of muscle and in the myofilaments.

“Her work is inspirational because she is a charismatic example of a determined woman, an excellent experimentalist and a self-standing scientist in the biophysics field.”