Meet the Unilever Colworth Prize Winner, Professor Paul Griffiths

06 April 2022

Each year, the Microbiology Society awards the Unilever Colworth Prize to an individual who has made a significant contribution to translational microbiology.
Ahead of the Unilever Colworth Prize Lecture, PhD candidate Onalenna Neo interviewed Professor Paul Griffiths to learn more about his career and how it feels to win a Microbiology Society prize.

When did you discover your passion for science?

I have always been interested in how things work and the illumination that you get from scientific discoveries. I was interested in medicine, but I wanted to pursue the scientific evidence-based parts of medicine rather than pure clinical practice where you apply current knowledge. I wanted to discover new knowledge and improve things. The science-based part of medicine is pathology. I went into pathology and one of the subjects within pathology is virology.

Why virology?

I started off on the undergraduate medical course, which was five years. In the two years preclinical, there was an option to do an extra year for an intercalated BSc. I chose to do biochemistry as I find it interesting and wanted to learn some of the laboratory methods and approaches which would help me in future research. Immediately after that, a professor of virology (Raymond Heath) gave a talk on viruses in the introductory part of the clinical course and said anyone interested in hearing more should come and see the lab. So, I took up the invitation, got chatting to him and ended up with a lab project to work on as something to begin with.

What were the main challenges that you faced in your career?

I think the main one was getting funding; the problem with trying to work with Cytomegalovirus (CMV) is persuading grant reviewers that CMV is worthy of investigation. There are so many other pathogens out there and much of the funding tends to go to big things like HIV, malaria and tuberculosis because of the major burden of disease. People don’t realise that there are other things that you could work on and that some of the principles that you learn can be applied to other infectious agents. I had tremendous help from the Wellcome Trust. They supported my research when I was a student, then with a series of three-year project grants, then eventually several five-year programme grants.

How do you think we can address vaccine hesitancy, especially considering Covid-19?

I think this is a very important question. There isn't one simple answer to it. The term vaccine hesitancy covers a wide range of things. I think I'd look at it from the point of view of the public to begin with; people are entitled to accurate information and explanations for what's going on, but this doesn't always work. We need to recognise that people need information presented in different ways.

For example, when the first COVID vaccines came through, there was a statement on the Department of Health website saying the vaccines aren't indicated for women who are pregnant. This is a true statement that’s derived from the legal process that gets you a product licence to be able to get market authorisation to sell your vaccine in the country. You can only get a vaccine for the age groups of people that you studied. So, if your trials excluded women who might be pregnant, as they did, you can't then make any claim about its efficacy or safety for pregnant women. Just making that correct statement led to lots of people wondering what was going on.

We need really strong evidence before you can give a vaccine to a pregnant woman, but we don't have any concerns with COVID vaccines. There's no plausible way in which current RNA or adenovirus vectors could damage the fetus; so, although they’re not licenced for that indication, women who are exposed to this virus should go and have a conversation with a doctor they trust and discuss their options. It would be wrong to deny women who are pregnant the protection that comes from those vaccines.

Another thing is that citizens deserve to be treated as individuals and, if they have concerns, they need access to a health professional who can listen to those concerns and answer their questions in a style that doesn't patronise them. One of the issues I've had to deal with from people and the local community is that they are concerned about COVID vaccines and think they must have cut corners because they have come through so quickly. I explain that all the regulatory requirements have been met, it's just that they cut out the bureaucracy, the paperwork. This is a great story, and so we should tell that to people; we should explain to them what’s happened.

Another factor that contributes to vaccine hesitancy is the convenience of vaccine administration. The people for whom it is particularly difficult to get to a vaccine centre may be the people who are in low paid jobs, facing the public and getting exposed to the virus all the time and these are exactly the people we want to give protection to. We should be more innovative about how we do it.

With regards to that, do you have comments on how we can tackle misinformation about vaccines and science

This is a personal view and not that of the Joint committee on Vaccination and Immunisation (JCVI) (I was on the JVCI for two four-year terms, but that ended more than a decade ago). I'm very concerned about the lies on the Internet. I think the malicious spreading of lies should be dealt with legally. Maybe if social media companies were turned into publishers, they would become legally liable for everything that appears on their sites. Citizens are entitled to their own opinions, but they're not entitled to their own facts. I think the BBC does quite well in fact checking on their website. Sometimes some of our prominent politicians say things that turn out not to be true and they call them out, through these fact checks.

As the Unilever Colworth Prize is awarded to someone ‘who has demonstrated an outstanding contribution to translational microbiology’, tell us more about the translational aspects of your work?

We started to look at the natural history of CMV and asked where it is coming from in the immunocompromised host, and why some people get sick while the majority don’t get sick, even though they have the virus. It turned out to be the quantity of virus that you have: the viral load. Once I understood the natural history the next step was to do randomised trials. The main issue was if we found the virus in the bloodstream of patients, we did not know exactly when to jump in. Should we be giving the drug early and risk giving them more side effects, or should we wait until later which risked them going on and becoming sick because we've done it too late? We informed the patients that we didn’t know what the best time was and that’s why we needed to randomise. So, I designed interventions that included pre-emptive therapy in transplant patients. We informed patients that when you start taking the medications that stop your immune system rejecting your graft, your immune system also can't respond very well to infections, one of them being Cytomegalovirus infection. We did randomised trials for pre-emptive therapy. We did some trials of when to start and when to stop at different cut-off levels of viral load.

In a different patient population, we did a randomised trial in neonates born with congenital CMV infection. We didn’t know whether the drug that inhibits the virus works in those kids, so we randomised them. Another trial I did was a randomised controlled trial of a vaccine given pre-transplant to people who are hoping to have a transplant in the future. We then monitored their viral load after transplant to ask: does the presence or receipt of vaccine compared to placebo reduce their quantity of virus afterwards? The first trial we did, we observed that it reduced viral load a bit, but not enough to have a licensed vaccine, and we've been chasing thereafter to find what the protective immune response is. All those studies required close collaboration with my clinical colleagues, the people responsible for the care of different patient groups. I don’t look after patients directly, so had to make sure that our clinical colleagues were happy with those studies.

When doing clinical trials as the principal investigator, you must present results regularly to a committee called the Data Safety Monitoring Board (DSMB). The investigators of the trial and the doctors must be blind to the treatments, but the DSMB look at the data when a third of the patients have been through, followed by when two thirds have been through and then finally at the end. If a drug turned out to be more efficacious early on, it means someone can find out sooner rather than two or three years down the line. This also means that the trial can be stopped if it’s found that a drug is very toxic early in the study or if it’s found to be really good.

So, having presented my results to the DSMB, one of the people who gave us the grant for doing the vaccine, which was National Institutes of Health in the States, said “Okay, now that you know the system, we're going to rope you in to become a member of our future DSMBs”. So, I've been a member of several DSMBs, and I've chaired others for people doing these studies around the world. All you do is log in and look at the results and use your experience to advise whether the study should continue as planned. This all goes on in the background and usually there is a line in the final publication that thanks members of the DSMB. It’s quite a bit of work, but it adds to the quality of the trial and gives patients assurance that they're not out there alone.

How easy is it to get people to sign up for randomised trials?

We were straightforward with patients. For the trials we did with determining the best time to administer the drug in immunocompromised hosts, we informed patients that there were two options, and we didn’t know which one was better to take in terms of when to administer treatment. We told them that it was not something that was going to help them as an individual, but it would help the next patients coming through for the same infection.

For the trial with neonates, it involved discussions with parents because they're signing up not just for themselves but for their child, and they want to do the best for their child. The way I put it to them was that all kids like yours are currently getting placebo, because no-one's getting any intervention. We have a hope that this drug might be better, but we can't guarantee that to you; in fact, it may turn out to have more side effects and we just don't know. We informed them that before we can make a recommendation to parents, we need to know that it is both safe and efficacious, and the way to generate evidence is to do randomised controlled trials.

Are you still working on this in any capacity?

My colleague (Matt Reeves) is carrying on with aspects of the work. He's doing much more laboratory-based work rather than clinical application. I’m still involved on the vaccine side. We are continuing to understand how the prototype vaccines provide protection. It was quite clear that they provide partial protection, but it wasn't clear what the mechanism was, and we are working on it to try to understand it until, ultimately, we can improve it, leading to a vaccine formulation good enough for licensure.

So, what has been the most defining moment of your career?

I think looking back it is going to be the understanding that measuring viral load is key to understanding natural history, epidemiology, treatment design and in pharmacodynamic study design to identify effective vaccines. The pharmacodynamic approach is broad; it tells the whole story and helps you admit what you don’t know. You can deploy a vaccine and check whether it brings down the viral load or not, and then look back to investigate what the immune correlate of protection is.

How do you feel about having won this prize?

I am very honoured to have won this prize and I'm going to accept it on behalf of the whole team. Many people have been through my lab for many years working on CMV projects and many of them were quite long term. I'm really delighted that the prize will bring attention to what is a neglected pathogen.

What advice would you give to early career researchers?

To someone wanting to focus on the scientific aspects of medicine I would tell them to go to a lab that has a track record in training medical people, because one must understand that medical people are pulled in a different direction; they need to keep their hand in with the emerging technologies in medicine as they are going through their research. It’s important to do good science, but it can be too detailed and too abstract. It's nice for it to be relevant to a clinical subject, otherwise you lose the motivation of some of the medical people.

In terms of career advice, I think people should consider advice from senior people like me carefully but shouldn’t feel obliged to accept it when it’s offered. It is okay to ignore it sometimes. I remember people telling me not to get interested in CMV because it would never turn out to be important. I did not take this advice because I found CMV interesting and so I persisted with it. I’ve now spent my professional life being paid to work with my favourite virus; so what’s not to like? Find something that interests you and work on it.