Meet the team hoping to cracking the Covid-19 code. Photo / Getty Images
Meet the team hoping to cracking the Covid-19 code. Photo / Getty Images
Alan Turing was a brilliant mathematician, theoretical biologist and code breaker. He led the team that broke the German Enigma Code in 1943, a feat that probably shortened the war by two to four years and saved countless lives in the process. This was achieved at the now famous Bletchley Park, an 18th century mansion set in the rural environs of leafy Buckinghamshire.
Over the past two weeks, a new generation of code breakers has been assembling not at Bletchley Park but at Charterhouse Square, a secluded tree-lined pentagonal enclave in central London. This is the campus for Barts and the London School of Medicine and Dentistry, part of Queen Mary University of London, and here the task being undertaken is just as critical as Turing's was nearly 80 years ago; part of a national effort to help save the country from an assault that, once again, is threatening our very way of life. This new invader, a silent and merciless enemy, is the most virulent and deadly the country has faced in living memory — the Covid-19 virus.
Thus far, its attack strategy, the way it debilitates, then kills some of those who contract it, but barely touches others, remains a mystery. Why the impact of infection is so variable for different people is something still to be understood. A proportion will suffer no more than a sniffle or a cold whilst a significant minority will suffer rapid respiratory collapse, leading to general organ failure and death. We know the elderly are more susceptible than the young, men are more likely to suffer than women, and those with certain underlying medical conditions can be more vulnerable. But these predispositions are not hard and fast and the correlations are far from exact.
Charterhouse Square will be a key operational centre for a novel investigation into Covid's dark secrets. This will be done through a specialist team of volunteer researchers who will delve deeply into the pandemic's microbiology. Drawn from Barts Health, Queen Mary University of London and Genomics England, the team is headed by Sir Mark Caulfield.
The professor of clinical pharmacology, knighted for his work on cardiovascular and rare disease genomics has personal as well as professional reasons for wanting to suppress Covid-19. In 1920, his great grandparents were killed by the Spanish Flu pandemic. Between 1918 and 1920, that virus infected 500 million people worldwide (a quarter of the world population at the time) and by some estimates killed up to 100 million. Significantly, Sir Mark's great grandparents were not killed by the initial outbreak of infection, but by the second or even third wave that proved ever more virulent.
Described as "one of the most influential researchers in the world", Sir Mark Caulfield has a very particular view of Covid-19. "On the one hand this virus is a massive threat to us all, but it is also an unique opportunity," he explains. "It is only in the midst of a pandemic that you can really begin to understand it and how to combat this type of disease. We have to grab this chance with both hands now in case there are subsequent waves of the infection that could, through mutation, be even more lethal than what we are faced with now."
The first thing Sir Mark and his team of medical code breakers will need is data — and lots of it. To this end, a small army of outreach volunteer researchers is being recruited and trained to gather the information required across Britain.
The first tranche of volunteers reported for duty two weeks ago. Amongst them were medical professionals, including research trained nurses, clinical and academic doctors, clinical scientists, specialists in infectious diseases, administrators and disaster relief specialists. They were ushered into the Derek Willoughby Lecture Theatre, which has a capacity of more than 200, but the requirement for everyone to keep two metres apart meant that only 30 people were allowed in to the auditorium at a time. For this reason, registration, induction and training is being spread over some weeks.
Despite the inability to interact normally — these days even elbow bumps are considered a greeting too far — there was a genuine sense of excitement on that first day; a real buzz in the air. Sir Mark Caulfield welcomed everyone with genuine warmth and appreciation but was quick to follow up with an inspiring "call to arms". He added that understanding how to defeat this infection was their professional opportunity to help not only British patients but others worldwide.
"We have to get this right," he beseeched. "This might be our major chance to understand and defeat Covid-19 and get insights into how to prevent future pandemics."
So what is the battle plan? In short, it is to search for patterns in the way the infection invades a population at the viral level. The teams will test specific treatments in nationally prioritised trials, such as aids to recovery using, amongst other drugs, Hydroxychloroquine — so favoured by President Trump.
The volunteers, once trained, will enter and work alongside those in the red zones of intensive care units and already some have taken up residence at London's Nightingale Hospital, as well as the vastly expanded intensive care units of The Royal London, Barts, Whipps Cross & Newham. Their job will be to collect blood and detailed demographic details and offer trial opportunities to as many patients as possible. Those well enough can sign a consent form; others, less well, may nod their agreement. Some, ventilated, cannot, so consent has to come from the close family.
Much of the blood samples for analysis are to be taken from the "waste blood". Modern analysers only test microlitres of blood, so the bulk of a good quality sample is normally kept for a few days, then discarded. Now, routine samples taken from all Covid-19 patients every day can be intercepted before destruction, collated, separated and analysed. It is an enormous logistical challenge but one way or another sufficient data has to be collected for the code breaking, and the other trials, to proceed.
The key is to decrypt the biomarkers in the human cipher in order to understand the way Covid-19 invades human bodies, damages the host, who then multiplies its number and then transmits it within populations. The response to this virus depends on variations within humans, variations within the virus and variations in the way they combine.
By decrypting these features, it may be possible to avoid future similar pandemics, but it will involve some major number crunching of billions of data points derived from each patient's blood samples. The variations and combinations involved far exceed even the coding possibilities of the Enigma machine, which itself ran to about 10 to the power of 23. We are talking an unimaginable number of possible combinations.
On the face of it, the virus seems almost indestructible, but there will be underlying patterns to its behaviour, however, as well as weaknesses in its propensity to contaminate and infect. It is hoped that studies, such as the half million people in the UK Biobank study and the Covid-19 sufferers, will now pay rich dividends in terms of revealing the dynamics of Covid-19 infection and why it presents so differently between individuals.
Sir Mark Caulfield and his team are intent on what they call "rapid, action-orientated genomic research" and "surge preparedness". In normal "peace-time conditions", he recognises, "it would take months to mobilise a team this size and mount an initiative like this, but we have done this in days and weeks in a brand new hospital".
Dr David Collier, clinical director of the William Harvey Research Institute Clinical Research Centre and deputy director of Barts Clinical Trials Unit, is helping to train the volunteers for data collection. He has been engaged in research amongst high altitude mountaineers over many years and this highly-specialised research could itself start to pay unexpected returns in the fight against Covid-19.
"We are busy pooling and collating knowledge from every corner of medicine and physiology," he told the volunteers as he put up a slide of the British Mount Everest Medical Expedition climbers on Everest, where he carried out his own research. "Mountaineers are able to survive and thrive on very low oxygen levels — a condition called hypoxia — and this could also help in our efforts to understand the impact of Covid-19 because of the way the body responds to low oxygen levels". No stone is being left unturned in the search for clues to crack the virus code.
Collier emphasises to the volunteers that intensive care staff now, like his Everest climbers, carry significant personal risk. The real heroes, he emphasises, are the front-line nurses and doctors, and that intensive care and clinical research do not always make ideal bedfellows. He quotes the example of Rupert Pearse, professor of intensive care medicine and head of research and development for Barts Health, whose own research has been delayed by the imperative to care for the sick and to oversee the national priority trials that will be in the long run "most likely to save lives". It is a tricky balance, but on their nightly 6pm conference Zoom calls, Sir Mark and Rupert Pearse lead a large and hugely diverse team that is co-ordinating the ongoing effort to decipher a virus.
This initiative to crack the Covid-19 code is at least as important as the Bletchley code breakers' efforts to break the German Enigma code. The complexity of the Enigma — an electromagnetic machine that replaced plain text letters with random letters chosen according to the settings of a series of rotors — lay in the fact that its inner elements could be set in billions of different combinations, meaning it would be virtually impossible to decode text without knowing the original settings.
As the war progressed, the German military added more rotors to the machine, making it even more complex. The Enigma machine was, in effect, being forced to mutate just as Covid-19 will do. The code breakers now, as then, are trying to zone in on an ever moving target.
"The work at Barts Health," says Sir Mark Caulfield, "provides a key platform from which to launch a concerted attack on Covid-19 in a way that will alter strategic planning for secondary and tertiary waves of this pandemic. As a world, we have to be ready for that eventuality."
He then adds with undisguised pride, "Britain is uniquely placed to take a lead in this research. As a people, we have the character, altruism and inclination to pull together and this will serve us well as we attempt to collect and analyse the data we need. Not only are we world leaders in genome research but our centralised National Health Service means that we in the UK can act not only to protect our own population but gain insights that benefit mankind as a whole."
Covid-19, the muscular super-virus sweeping our planet, has all but closed down entire communities, countries and even continents, but it is hoped that the work being done at Barts Health and Queen Mary will play a significant part in the global effort to stop the virus in its tracks.
St Bartholomew's Hospital, Barts to its friends, has a long and proud history of looking after Londoners. Established almost 900 years ago it sustained the capital through the Plague, the Great Fire and the Blitz. Now the famous old hospital, and it's rebuilt and enlarged Trust, has been equipped with an en-suite field hospital, The Nightingale, dedicated to treating victims of Covid-19. In its new guise, Barts is rising to perhaps its greatest challenge to date.
