2 May 2018

In the run up to NHS70, Professor Hugh Pennington CBE reflects on a long and fruitful career in pathology, exploring how time and technology have transformed public health and the management of infectious diseases

Pathology is natural history, in that pathologists identify naturally occurring things. But as naturalists, our aim is not about ‘saving’ the things we observe – we classify cancers to destroy them, and identify viruses and other harmful agents to eradicate them.

It’s the latter work – detecting and working to prevent the spread of infectious diseases – that has become my career of choice. Over the last 53 years of working in infections, I’ve seen some incredible advances in medicine, and also some old adversaries come to rear their ugly heads.

The past

At school, I was fascinated by natural history. I read about famous forensic pathologists like Sir Bernard Spilsbury and, aged 17, got work experience in a local pathology lab. Let’s just say it didn’t turn me off!

One of my tasks was to look for tuberculosis bacilli (TB) in sputum. At the time (the mid-1950s) memories of TB as a big killer were very fresh. My grandmother had been a nurse in a TB isolation block, established because the disease was the second most common cause of death in the psychiatric hospital she worked in. The top killer was ‘general paralysis of the insane’ – a delayed complication of syphilis that caused delusions of grandeur, then dementia, then lethal paralysis.

The spread of both TB and syphilis was eventually thwarted thanks to pathologists. One of the greatest pathologists of all time, the Nobel Prize-winning Robert Koch, laid the scientific foundations for attacking TB by discovering its cause in the 1880s. And by the 1950s syphilis had gone too, thanks to a discovery made by another pathologist, Alexander Fleming – also a Nobel Prize winner. Penicillin kills the syphilis spirochaete stone dead. It still does.

In 1963, I was recruited into bacteriology by Professor Ronald Hare. He had worked with Fleming, but was put out of a job in 1936 researching child bed fever due to the success of sulphonamides – the first generally applicable antibacterial drugs. These were discovered by another Nobel winning pathologist, Gerhard Domagk.

Hare moved onto pioneering work on influenza. Together with the formidable bacteriologist Mary Barber, his forte was now antibiotic resistant bacteria in hospitals – but he forbade me to work on the subject, as he felt all the important things about resistance had already been discovered. Instead, I was put to work on the classification of anaerobic streptococci, a bit daunting because they were very difficult to grow (oxygen kills them!).

The present

Ronald Hare was right. Subsequent problems have been caused by failures to implement what was already known about antibiotic resistance. Its onward march is a brilliant example of the challenges that face pathologists working on infection. The microbes evolve in real time. To keep up, our technologies have to evolve too.

And how they have. After a spell as a virologist, I returned to bacteriology in the 1980s, as new technologies were starting to transform the field. The fingerprinting methods used to track the spread of bacteria in communities were inadequate. But molecular biology methods – particularly techniques for identifying microbes on the basis of nucleic acid (DNA and RNA) sequences – were moving from research laboratories and becoming useful for public health purposes. Their application started a revolution in pathology that is still rolling fast, not only in the investigation of infectious diseases, but in all aspects of medicine, including cancer.

Although based on solid scientific foundations, the revolution started slowly. A project to sequence the E.coli genome started in 1991. It took six years and cost several million dollars. Technical developments in speed and cost then took off. A decade ago they outpaced Moore’s Law (the law that states computer power doubles every two years). An E.coli genome can now be sequenced in a few hours and at a fraction of the original cost. We are using these methods to track the origin and spread of old enemies like Salmonella, as well as new ones, like E.coli O157.

Thankfully, these advances haven’t removed the human element from the work of virologists and those specialising in infections. Rather than spending all day peering down microscopes and reading computer outputs, many of us operate in the public domain – getting our expert messages across, advising bodies like the World Health Organisation. We even appear on TV!

The future

Early in my career, I was told that specialising in infections was a mistake. Antibiotics and vaccines were close to finishing them off. But not only are bacteria fighting back and anti-vaccinators busy; new bad bugs are continually emerging. E.coli O157 was unheard of before 1982. HIV, of far greater importance, was first isolated in 1983.Ten years later MRSA took off (again) in UK hospitals. Like HIV, its origin goes back much further; both had been evolving for decades.

Old adversaries are still active too. HIV gave TB a new lease of life through immunosuppression. It’s almost inevitable that there will be a flu pandemic sometime soon. And this uncertainty – the possibly of new challenges, new threats – is why the work of virologists and bacteriologists is so vital.  The pathology of infection remains a dynamic natural history. Better than bird watching, it saves lives. It is hard to think of a more exciting or rewarding job.