Part 2: The history of structural biology
Michael Glazer is Emeritus Professor of Physics, University of Oxford and Vice President of the International Union of Crystallography. His field of research is in crystallography, with a particular focus on the relationship between crystal structures and physical properties. Georgina Ferry is a science writer and wrote the first biography of Dorothy Hodgkin.
Jonathan Webb: Understanding the function of a protein is an important step in figuring out why the bodies succumbs to disease, But how do scientists, find these proteins and discover how they work? I'm in Oxford's Museum of the history of science. It's filled with historical artefacts that have been part of some of the biggest scientific discoveries of our time from penicillin to Einstein's theory of relativity. One of the most important breakthroughs in structural biology over the last century has been the development of X ray crystallography, which is a technique that lets scientists look at the 3d structure of a protein. Tiny proteins are too small to be seen under a normal light microscope, and even a hospital X ray would be too weak to image, a single protein molecule. So, scientists have to line them up in rows to form crystals.
Michael Glazer: It was discovered just over a hundred years ago in 1912, that if you shone x rays at a crystal, the X ray beam, was scattered in different directions and this is called diffraction. And if you then put a photographic plate behind the crystal, you get spots on the plate.
Jonathan Webb: 2014 marks the centenary of the first Nobel prize that was awarded for this crystallography technique. It went to German scientists Max Von Laue who proved for the first time that crystals could diffract x rays. Then the first scientists to analyse a crystal structure, using x rays, with a father and son team, William and Lawrence Bragg.
Michael Glazer: In the end of 1912, the young Lawrence Bragg, aged 22 realised how you could interpret these photographs from these spots work back to the structure of the crystal Laue's bride once said, it's a bit like watching a film running backwards of a man eating a chicken, you see that the chicken comes out of the mouth, and it reforms itself on the plate that's a bit like what crystallographers have to do with trying to solve crystal structures from diffraction patterns.
Jonathan Webb: The Bragg's were awarded the Nobel Prize in Physics in 1915. While Lawrence, who was just 25, years old, was in the fields of France, fighting in the First World War.
Michael Glazer: They remain the only father and son team to share a Nobel Prize and young Lawrence at the age of 25. He's still the youngest Nobel Prize winner.
Lawrence Bragg: In this course, 24 lectures on physical optics. I'm going to talk about the interference and diffraction of light waves.
Jonathan Webb: 20 years later, Oxford structural biologists Professor Dorothy Hodgkin was the first person to use x ray crystallography to study the structure of pepsin, Dorothy went on to determine the structures of a whole series of molecules.
Georgina Ferry: And it was for her work on penicillin and vitamin B 12 that she was awarded the Nobel Prize in 1964. As part of one of the speeches she made after she won her Nobel Prize. She said I wouldn't like you to think that X ray problems are easy to solve. I seem to have spent much more of my life, not solving structures than solving them. And I think it's very important really because I think when we read in the press about scientific breakthroughs. You always get the impression that that's what the scientists life is you go into the lab, you have a breakthrough you go into the lab you have another breakthrough. Whereas in truth, an awful lot of work is done before you get these incredible insights. So in fact, her solution of the structure of insulin didn't come out until 1969, and she started working on it in 1934. There aren't many research projects that would be allowed to continue that long these days.
Jonathan Webb: A century after its discovery, X ray crystallography is still one of the most popular and successful techniques for finding the 3d structure of a protein.
Michael Glazer: Crystallography is an underpinning subject, sort of sat back there and hidden away, working behind the scenes. And on the other hand, if we look at Nobel Prizes as a guide, what we see is that at least 28, owe their award's to some aspect of crystallography.
Jonathan Webb: Advancements in X ray technology are continuing to improve the way that we do structural biology. Today's synchrotron X ray sources are housed in buildings that are several times bigger than St Paul's Cathedral. And because of their size, these huge sources can produce beams of light that are 100 times smaller than a human hair. And that means that scientists can zoom down even further into the minute details about proteins, and a world of new possibilities.