From Bench to Bedside- a conversation with Professor Benny Chain

In 2010, Professor Benny Chain contributed to the development of a PhD program “From Bench to Bedside”, which has since ceased  to operate. Curious about this initiative, and Benny’s thoughts on clinical awareness within the life sciences, we were lucky to have a conversation with him about it, and many other things!  

Laure Mourgue d’Algue: Could you introduce yourself briefly? 

Benny Chain: I went to Cambridge where I studied Natural Sciences. I stayed on to do a PhD in a completely different topic- electrophysiology. I then left for America and went on to work in comparative immunology, looking at insects and worms’  immune systems- sort of from a zoological point of view. I then came back to London where I went more mainstream (up the animal scale), partly because we could not get funding for invertebrate immunity though it is now a really hot topic. 

I’ve been at UCL ever since, since 1982! Most of my career I was a molecular/ cellular immunologist, and I was particularly interested in dendritic cells (DCs), the primary gatekeepers to the immune system, the first ones to light up when there is a new immune response. We were among the first groups to work on these cells in the UK. Discovered in the 70s, these are quite a rare population, but now there are thousands of people working on them. Ten years ago, I changed track. Partly because there were so many people working on DCs, I decided it would be more fun  to do something else- so I went back to Maths, which was something I enjoyed at university! I did a sabbatical at the Weizmann Institute and became interested in computational immunology. Since then, I have been somewhere between Data Science, Maths and Immunology, looking into modelling and data analysis. For the last few years, I’ve had a joint appointment in the department of Computer Science: I’m 80% in Infection & Immunity and 20% there. 

L.M.A: That’s very cool. So what drew you to science? 

B.C: It was slightly inevitable. Both my parents were biochemists, so I guess there was kind of a strong family influence. I can’t remember ever wanting to do anything other than science- it was sort of natural! In terms of Immunology, it was a bit of chance. I met Professor Avrion Mitchison (currently in his 90s) through my parents, who was sort of the father of UK Immunology. He said “why don’t you come and work with me?”. I then became hooked, so I stayed in that field! Turned out to be a good choice!

L.M.A:  Your research seems to be more on the “basic” rather than “translational” side. Why is awareness of the clinical context of a field, liked Immunology, nonetheless important? What has this awareness brought to your own practice?

B.C: Because I’ve been at UCL, I’ve been surrounded by clinicians and have had a lot of interactions with them. We train a lot of clinician scientists- PhDs which are on fellowship or MBPhDs who fall out of the main medical training and do a PhD before going back, so I’ve had a lot of interaction with these people. What’s striking is quite often the perspective from a clinical point of view is really quite different. The things that seem important to a clinician are not necessarily the ones which a basic scientist will think about.. 

I’ve always been a fundamental scientist and never really worked on very applied projects-  I’m more interested in the basic mechanisms at play. In fact, when projects get too applied, I feel that somebody else is probably best placed to take them forward. But I think the view from a clinician on how the body works, and particularly when it goes wrong, can be incredibly instructive. That’s sometimes missing for people who work entirely at the bench without any input from their clinical colleagues. 

But I have to say UCL is a bit unusual because we have such close interactions with clinicians, particularly in immunology which is part of the Faculty of Medical Sciences. I have had a lot of joint projects: for many years, I ran a lab with Professor David Katz, who was a histopathologist, clinician by training but an immunologist in practice. I now share an office and run a lab jointly with Professor Mahdad Noursadeghi, a consultant in Infectious Diseases. This makes me very aware of their way of thinking and has influenced the way I think about a problem. 

Also, my thinking is a bit influenced by my family. As I mentioned, my father was a Biochemist and he often discussed how to improve the interaction between Medicine and Biochemistry to the mutual advantage of both.

L.M.A: Yes, I work on Parkinsons’ in Dr Kerri Kinghorn’s lab right now, and what I’m doing makes more sense and has added value because I did a placement in a Neurology ward. That’s why I looked up what you were doing, because I thought it was a shame some sort of “clinical awareness” training didn’t officially exist. I think it’s useful both in contributing to your understanding of a disease, but also giving extra value to what you’re doing- it can be easy to forget why you’re going through a set of repetitive experiments, and I find it helpful to visualise some of the patients I’ve met to remember why I’m involved in a given project! 

B.C: Yes. There’s a lot of activity the other way round: a lot of programs are established to train medics in science, and UCL is at the avant-garde of that. But exposing life science students to a more clinical perspective is less common. As a graduate tutor back then, I felt that was something that was lacking- and that’s why we started the “Bench to Bedside” PhD program. Not everybody agreed- some thought that scientists that were driven just by the fundamental quest to learn were the ones most committed, and irrespective of their research being “good” or “bad” for mankind, they would keep going. I think there is room for both actually. I never suggested all PhD students should have a clinical perspective, but there’s a second band of students who are genuinely interested and would be motivated to do good research at that boundary. 

L.M.A: I know the program now closed, but what sort of projects did students on the project end up running? How did the scheme work?

B.C: We set the program up sometime around 2010. I set it up as a program which students could come on, with different sorts of funding. We had for example a MRC centre in virology which funded 1 or 2 studentship per year for many years in our department, and these studentships were part of the program. But of course, we also had students from other places. At the time, the MRC were very enthusiastic about the program, and when we applied for that centre’s funding, the fact that they liked “From Bench to Bedside” counted very strongly. 

Within the program, each student pursued a normal PhD (lab based) but also had to show evidence of some sort of engagement in clinical activity e.g. attending weekly meetings with clinics as an observer, going to interdisciplinary meetings when various clinicians get together to discuss a particular case, etc. Projects themselves were very varied. One student was working in Professor Mala Maini’s lab, who works on hepatology, the immune response in the liver and hepatitis B vaccines. The clinical engagement included participating in hepatology clinics. She’s still working in Mala Maini’s lab now! Some students came to our own group where they worked on the interaction between macrophages and tuberculosis or HIV. They were able to go to TB or HIV clinics, which are run at Mortimer Market, the Whittington and the Royal Free. Looking back at the list of students that went through the program over five years (around 20-25), many of them are still working in research, though I haven’t made a full audit. In that sense, the program was quite successful! 

L.M.A: Did some aspects of the clinical training/ awareness programme end up incorporated in the MRC-funded studentships?

B.C: I’m not sure, but not that I know of. It wasn’t always very easy to insure these clinical contacts took place because often the lab itself is really divorced from what is going on in the clinic- students really had to make an effort to make space for it in their everyday work, while getting caught up in experiments

L.M.A: I can imagine! Were medical staff open to welcoming students from the life sciences?

B.C: Yes! Actually that worked pretty well and wasn’t a barrier. The projects remained really fundamental, which is what I wanted- there are different schemes for very applied translational PhDs, and that’s not what I wanted to develop. The clinical perspective was really like a parallel experience, not a direct contribution to the lab project- sort of an “enrichment” activity as UCL would probably like to put it today.

L.M.A: That’s a great initiative- I was really disappointed the PhD no longer ran! Last year, I had my first Immunology modules, and I really enjoyed my lecturers mentioning patients/ relevant clinical cases. Coming from the Genetics, Evolution and Environment Department, I didn’t feel I had been put in contact with such material. I guess the risk with such a program is people accuse it of pushing research towards the translational side- though that’s not what you wanted to do, and where the nuance is important!

B.C: Yes. In general, I think the UK has gone too far towards focusing on translational research at the expense of fundamental research, and this does not always result in good translational research. That’s the case in part because the government needs to justify its spending to tax payers. A case in point is COVID related research: money has been thrown at anything with “COVID” in the title in the last year, and I suspect a large proportion of it is not very good research. Don’t get me wrong, there is some fantastic translational research, but it’s relatively easier to invent a project that is “sort” of translational. The key thing for good research is it must address a really good question- whether it’s fundamental or translational doesn’t matter. Today, when we write grants, the first thing we have to do is include some sort of impact statement, something that says “this will lead to this”. But actually I think the most important discoveries have come from basic research. When scientists see potential for use or translation, they’ll be the first to try it out. 

L.M.A: I agree. The problem probably lies in the public’s perception of science, and that’s why it’s so important that we as scientists highlight why fundamental research is nonetheless key. From personal experience, when I explain I’m investigating a subset of cells in the retina, most of my friends don’t see the point. But actually long term, this understanding enables genetic therapies to target the appropriate cell type to prevent onset of blindness.

B.C: I agree!

L.M.A: Do you think “clinical awareness” is a skill that could be introduced to students at earlier stages e.g. during their BS? Would you push for such PhD schemes to be reimplemented?

B.C: Yes I think it would be great to have schemes like that, or introduce relevant elements into existing schemes. At the moment, BBSRC students are introduced to computational tools and other transferable skills as part of their phd, even if theirs is not computational. The MRC should be developing some sort of “clinical awareness” (whatever you want to call it) component. 

At the Bachelor level, I’ve personally found it often engages students to teach concepts via a more clinical angle. You’re not presenting clinical research, but rather showing students what they can learn from a particular clinical situation- it enhances the lectures and makes them more memorable.  I often teach immunology like that, if there is a relevant example. Practically speaking, it’s not feasible for undergraduates in large numbers to engage with patients, but introducing clinical perspective within biomedical lectures is a good idea. 

L.M.A: Do you have examples where your research was influenced by your clinician colleagues?

B.C: Exposure to clinicians within my office has influenced me, so I definitely have examples. Currently we are looking at T-cell response to COVID. An interesting unanswered question to me, and may stay so if the vaccines are really efficient, is: what is the immunopathology of COVID? Why do we get sick? It’s been very instructive to talk to the clinicians. Strikingly, if you measure virus levels, you find viraemia peaks 5-6 days after infection and you get mild flu-like symptoms in the first few days. By day 7, the virus dies and disappears and it’s very hard to detect the virus from then on- it’s not clear if live virus is still present. But the actual disease, if you talk to people who care for these patients, occurs much later (two to three weeks post infection). Answering why that happens is a really interesting question and we’re trying to address it to some extent in our research. Whether we get an answer, my thinking has been enormously influenced by talking to clinicians. 

L.M.A: Yes, even at my student level I’ve been influenced by my conversations with clinicians. I used to find biomarker research in neurodegeneration a bit boring, but conversations with a neurologist changed my mind and shed light on its value in medical context. It’s interesting to get these conversations going to ameliorate cooperation between the Life Sciences and the medical community.  

Just one last question, why did the PhD program end? 

B.C: I stepped down as graduate tutor, and there was a feeling along a lot of the influential members of the department that it was a distraction- PhDs were short enough anyway (compared to PhDs in the rest of Europe or the US for example) and students were already under pressure to do more “transferrable skills” training via the Graduate School . Since I was no longer in charge, somebody else made the decision. Whether that was the right decision, I’m not sure!

You can find out about Benny Chain’s research on his website Innate2Adaptive, on Twitter @BennyChain or read the Blog Immunology with numbers. Also check out Benny’s most recent youtube video on “The Science of Vaccination”,  https://youtu.be/Ro2-anHdFgY

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