IRR People: Stephen Gordon

Now, both my wife [Melita Gordon] and I are in Edinburgh—she's a Professor at the Usher Institute, and I'm based here at the IRR. We wanted to try something new after a decade away from UK clinical research, and look forward to seeing what the next chapter holds.

Tell us about your research and its relevance to global health

I have long been committed to global health, with my research rooted in experimental medicine. I introduced research bronchoscopy to Malawi to study lungs cells of people living with HIV, back before antiretroviral therapy was widespread. One surprising observation during those studies was how blackened the lung macrophages were—caused by household smoke exposure. That led to further research on indoor air pollution and its link to pneumonia.

Over time, I got involved in controlled human infection models (CHIM)—intentionally introducing pathogens into volunteers to study immune responses. For the past 15 years, I’ve focused on pneumococcal challenge models, including work in the UK with elderly people and individuals with asthma, and more recently in Malawi with healthy adults and people living with HIV. We’ve studied existing and novel vaccines, demonstrating efficacy very efficiently with small numbers of carefully observed participant volunteers.

We’re just about to publish the first ever paper on a human challenge study in people living with HIV, which feels like a major milestone.

How safe are these challenge models?

It depends on the strain and the population. There are over 100 pneumococcal types. In healthy young adults, the procedure is relatively low-risk, and that's where we started. Gradually, we've expanded into more clinically relevant but vulnerable groups like older adults and people with asthma in the UK—and now people living with HIV in Malawi.

The key is starting safely and then building up evidence step by step. It’s a careful, ethical approach, and we’ve shown it can be done both in the UK and in Malawi. CHIM studies have a very much safer record than Phase 1 drug studies and can be very carefully planned and monitored.  They are an ideal tool to compare different populations response to vaccine and ensure that vaccines developed for one part of the world are optimally effective in other regions.

What kind of work do you hope to do in Edinburgh?

Investigators at the University of Edinburgh, and CMVM in particular, seem keen to expand Experimental Medicine and human challenge studies. Prof David Dockrell is exploring whether we could instil pneumococci directly into the lungs in order to understand the early prevention of pneumonia. No one's done that yet—but it’s possible.

I’ve recently collaborated in writing a grant with Prof Debby Bogaert looking at the microbiome of children in Malawi. She’s particularly interested in defining what constitutes a “healthy” microbial environment in the nose and gut, and then testing how it affects resistance to infection using human challenge models. If that research progresses, additional Edinburgh researchers could be involved directly or through collaborative analysis of samples.

Why are human challenge studies important?

We can study how people from different regions respond to vaccines or pathogens. 

There are consistent differences in vaccine effectiveness between Malawi and the UK. Vaccines developed for Europe or North America tend to underperform in African or Asian populations because they weren't designed with those environments in mind.

Human challenge studies are an essential step toward making vaccines more relevant to endemic populations. 

What’s the next big challenge in your research?

I think that the current holy grail of CHIM studies is a controlled human challenge model for tuberculosis (TB). The first new TB vaccine in years is being trialled in 54 sites across 5 countries and will cost about £500 million. That’s because TB takes so long to develop—from infection to disease—so trials are slow and expensive.

We’re working with BCG [the current TB vaccine] to create a model that can accelerate future vaccine testing. The idea is to move from BCG to a more TB-like mycobacterium, cutting trial time down to a year or two, with just a few hundred participants instead of tens of thousands.

We’re doing this in Liverpool first and then Malawi, and I’d love to see whether Edinburgh-based scientists would be interested in joining in with that effort.

Why have you chosen the IRR?

I’m excited about the opportunity to link IRR’s strengths in basic science with the clinical and translational challenges we see in Malawi. Take macrophages, for example—lots of IRR researchers work on them. And macrophages could be central to how the BCG vaccine works.

Comparing macrophage responses between people in Scotland and Malawi could offer invaluable insights.

How did you get interested in this field?

I trained at Cambridge and went to Zambia as a junior doctor with my wife, Melita. At that time, AIDS was tearing through southern Africa. We were working in a Salvation Army hospital, getting out of bed multiple times a night to certify deaths of children with congenitally acquired HIV. We knew we couldn’t just treat patients one by one—we had to get upstream, into teaching and research.

We returned to Malawi in 1997, before widespread access to HIV testing or treatment. We started basic studies like blood cultures to understand causes of illness—Melita focused on Salmonella, and I on pneumococcus.

Since then, we've seen real transformation. Antiretrovirals arrived, the pneumococcal vaccine arrived, and the medical school in Malawi started producing its own graduates. Just 18 months ago, I did a ward round in Malawi where none of the first 10 patients I saw had HIV. That’s never happened before in all the years I’ve worked there.

Can you tell us more about the Malawi Liverpool Wellcome Programme?

When I arrived, it was a small programme with just four fellows. By the time I left, it had grown to almost 1,000 people. I lead a group of 30 there, called MARVELS (Malawi Accelerated Research in Vaccines, Experimental and Laboratory Systems). We’re focusing on human challenge models, vaccine trials, and respiratory immunity.

We also just finished the CREATOR project—a £10M research and training facility, opened last year by the President of Malawi. It supports specialist training for medical doctors in the training grades, integrated with research and is a great opportunity for partnerships with Edinburgh.

I believe strongly in research equity. If an Edinburgh researcher comes to Malawi, a Malawian researcher should be able to come to Edinburgh. That’s how we ensure mutual benefit and career growth.

How can IRR researchers get involved with work in Malawi?

There are many ways: travel to Malawi or collaborate on a globally-relevant research project. For example, macrophage biologists could contribute to TB vaccine development through joint projects, hybrid workshops, or mentoring postgraduate students and lab scientists. 

Malawi Liverpool Wellcome Programme

Gordon research group