Brilliance in the genes: inside Britain's 'Nobel prize factory'
FT science editor Clive Cookson on the latest R&D at the UK Medical Research Council's Laboratory of Molecular Biology. The maverick institution has produced 16 Nobel laureates in the past 60 years.
Directed and filmed by James Sandy, edited by Oliver McGuirk
Transcript
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The FT has been given access to one of the most sophisticated research facilities in the world, a laboratory so successful that it's been called a Nobel Prize factory.
This is the MRC's Laboratory of Molecular Biology.
The LMB, as it's known for short, has won 12 Nobels in total, more than any other institution of its size. So what's the secret of the lab's success? We're here to ask some of its leading scientists first-hand.
If I knew what the secret sauce of this place is, I would be very rich and very famous. Unfortunately, I don't. But one of the properties of this lab that makes it a bit maverick is the trust and engagement with risky science and long-term science that we believe delivers the goods, in the end.
One of the most audacious projects that the LMB is led by Madeline Lancaster. Her team are encouraging stem cells to grow into clusters of human brain tissue, sometimes referred to as mini-brains.
These are basically 3D neural tissues that model the the developing...
May I have a look?
...human brain. Yes, of course. The really special aspect is that they are self-organising. So we're not coming in and forcing the cells to make specific cell types. We're allowing these tissues to develop on their own. Also, of course, in a three dimensional conformation, which is the way the brain develops naturally.
Using this technique, Madeline can study the way in which healthy cells arrange themselves within the embryonic brain. She can even look at how neurons fire interactivity.
I think, generally, if you understand how something is built, then you'll also understand more about how that works. And so that's kind of the goal here, is to try to let these things build themselves, and we can watch that process and learn something about human brain development, and also what goes wrong in neurological conditions.
Madeline's method may be unusual, but bold approaches like hers have led to revolutionary work at the LMB. Take her colleague, Richard Henderson. He received the 2017 Nobel Prize for chemistry for his work on cryo-electron microscopy, or cryo-EM.
It's a technique that quickly freezes tiny biological molecules in a very thin layer of ice, preserving their natural structure without the need for unnatural staining.
The images you get are actually images of the molecules themselves in their normal environment, amorphous ice instead of water. And so by recording a stack of images like that, which would be images of the part of the molecule at different angles, in the computer you can process it into a high resolution near-atomic structure.
And so instead of finding the subunit structure - the outline of the molecule in a rough detail - you can actually see right into it and see all the atoms, the amino acids, the DNA, the nucleic acids. It can be used to understand how drugs bind to molecules in biology.
And this is terribly important in drug design, and it will be going to the heart of a number of human physiologies that we need better drugs for.
After more than 20 years of research, cryo-EM has the potential to revolutionise so-called structure-based drug design, making medicines that are more effective with fewer side effects. It's a fantastic example of how long-term investment by the UK's Medical Research Council can translate directly to healthcare. .
And the process is accelerated even further when labs like the LMB work with pharmaceuticals companies, such as AstraZeneca.
To be able to push the boundaries of science, to work at the frontier of science means that we have to employ the best scientists within our laboratories. We have to collaborate and partner with the best scientists globally.
And these partnerships are either to develop new approaches by which we can develop medicines, which we can then take forward to the clinic, or to understand the basic mechanisms of disease.
You're looking at one of the great hopes for understanding how the brain works. It's called a connectome, a map of some of the pathways that information can take as it passes from neuron to neuron.
It's enriching our understanding of behaviour and memory, and it could one day help us find a treatment for Alzheimer's disease.
Greg, we're looking at a spectacular rotating fly's brain. What's it's showing us?
The big challenge at the moment in trying to understand how brains actually control behaviour is to understand the network of connections within the brain, and how information flows through those networks while the animal is producing a particular behaviour.
And that's true whether you're talking about a fly - which is what we study - a worm, a mouse, or a human.
Even in a fly brain, which is just a millimetre across, Greg's team have a huge task on their hands, tracing the path of individual neurons through stacks of electron microscope images, and then painstakingly recreating all the connections in a computer model.
Greg, what did it take to produce this beautiful picture?
So it took the combined efforts of many different scientists with many expertise, there are contributions for over 150 people in this image. And there's about 30m clicks tracing neurons through this electron microscopy image data, that have turned into this image that we see here.
Good science takes a village. Fortunately, Cambridge is building such a village, the Cambridge Biomedical Campus. It's already home to some 17,000 health professionals and research scientists, and there's space on campus for another 14 Wembley pitches of new developments.
The impetus behind the whole project - collaboration.
Having proximity to other collaborators in the Cambridge cluster is really important. We've got the Royal Papworth, we've got UK buildings, lots of great clinical researchers.
The key is really understanding how we take some of the discoveries that we're building here and really bring them in to general practise. And I think a lot of that is understanding how best to make the right kind of connections, how best to put the right infrastructure and informal networks in place to encourage dialogue.
Thanks to institutes like the LMB, the UK is already a world leader in biomedical research and development. And if the country takes lessons learned from this lab's history, it has the potential to achieve even more success.