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10 November 2017Big Pharma

LSIPR 50 2017: Richard Henderson—Meet the hands-on scientist

In May 2016, British scientist Richard Henderson was awarded the prestigious Copley Medal from the Royal Society, the independent scientific academy of the UK.

The Copley Medal was first awarded in 1731, following donations from Godfrey Copley, a wealthy English landowner and public figure. The society’s oldest and most prestigious award, it is handed out annually for outstanding achievements in any branch of science. Henderson is a group leader in structural biology at the Medical Research Council Laboratory of Molecular Biology (MRC LMB) at the University of Cambridge, and is a self-confessed “hands-on scientist”.

He was awarded the Copley Medal because of “his fundamental and revolutionary contributions to the development of electron microscopy of biological materials”, according to the society’s website.

Electron microscopy is a process that enables the materials’ atomic structures to be deduced.

Previous winners include Albert Einstein, Charles Darwin and Benjamin Franklin.

“They’ve been giving the Copley Medal for about 350 years so it marks some particular achievement; it is nice to be acknowledged,” says Henderson.

“It’s unlikely to make a lot of difference to my career, but having a Copley Medal, particularly for people who might know about its history and impact, might give me a little bit more influence.

“When I suggest something or give advice on a topic, the people listening might pay slightly more attention than they might do otherwise. The Copley Medal and having some grey hair might also affect my influence,” he explains.

Henderson was the first to solve the structure of bacteriorhodopsin, a light-harvesting protein found in the membrane of single cell Archaea microorganisms, and analysis revealed it was composed of helices.

According to his Royal Society profile: “In collaboration with neuroscientist Nigel Urwin, he uncovered the three-dimensional arrangement of the helices within a bacterial membrane protein by electron microscopy (EM)—pioneering the powerful technique’s use to study biological molecules.” His research allowed scientists to see their structure.

Bacteriorhodopsin, Henderson explains, is a protein which absorbs light and pumps protons across the membrane of a bacterial cell and thereby powers the organism to do all sorts of other tasks.

It is a “protein in the membrane of a bacterium that interfaces from inside the bacterium to the outside world”.

“That was one of the earliest membrane protein structures to be determined,” he says.

To determine the structure, the scientists used a “novel method”—EM—rather than X-ray crystallography, which was the method previously used.

“We’re working to make cryo-EM meet its theoretical maximum potential."

An electron microscope uses a beam of electrons to create an image of a specimen and is capable of much higher magnifications than a light microscope.

“Having revealed that one structure using that method, I realised that this was a very powerful method with a lot more potential than we’d been using it for,” Henderson says.

Nowadays, he is focused on the same issue as 30 years ago, and uses cryo-EM, a form of transmission EM, where the sample is studied at very low temperatures to determine the structure of biological molecules. As a result of his breakthrough work alongside the work of others, researchers are now using the technique to determine the structures of hundreds of molecules, which was not possible previously by any other method.

“We’re working to make cryo-EM meet its theoretical maximum potential,” he says.

“The goal is to make it much quicker, much simpler and much cheaper and turn it from an already very valuable method that people are piling in to use, into the top method in biological structure determination.”

However, to make this possible, Henderson and his team at the MRC LMB have to overcome “various hurdles” and “barriers”.

A physicist’s path

Henderson recalls that he was interested in physics from a young age and spent his teenage years trying to find out what direction physics was going in.

“There’s plasma physics, particle physics, solid-state physics, astrophysics. There are lots of different sectors in the field, and many of them are extremely productive,” he says.

However, he focused on biophysics and the structure of biological molecules.

Henderson studied at the University of Edinburgh, where he achieved a first class honours degree in physics. He completed his PhD at the MRC LMB at the University of Cambridge in 1969.

Since 1973 he has worked at MRC LMB and was joint-head of the Division of Structural Studies from 1986 to 1999. He was director of the laboratory from 1996 to 2006.

In 2006, with the MRC LMB now under the direction of cell biologist Hugh Pelham, Henderson “got back to the bench to do my own experiments”.

His advice for anyone wanting to break into his field is clear.

“First, make sure that you are interested in the field. You definitely want to go in the direction that you are internally self-motivated towards and not just go into it for some pragmatic reason,” he says.

Once you have decided the direction you want to focus on, Henderson explains, you need to “join a productive lab and get some basic experience because a lot of people come into it and don’t really know enough about it when they start”.

After you have gained some basic experience, worked out what the current bottlenecks are and found your feet, some important decisions must be made, says Henderson.

“You should decide whether you’re going to contribute to improving the whole methodology of the field, by focusing on improving the methods.

“Or, are you basically happy with it and simply want to become a user and possibly try to make it easier for everybody else?” Henderson asks.

His final words of wisdom cover the impact an individual can make on their given field.

“You have to decide when you enter any field—are you going to focus on the frontier and try and make the frontier better? Or are you going to consolidate it and help to establish it in a wider sense?” he says.

With a Copley Medal already in hand, this award-winning scientist hopes to continue discovering new and important methods in his field.