Medical research on the front line
The complex and destructive nature of war has been a catalyst for some of the MRC’s greatest medical discoveries over the past century. Sarah Harrop reports.
The great war: infections and ingenuity
When the First World War broke out in 1914, the MRC was barely a year old, but it reacted quickly to focus research on the national war effort. Gangrene, caused by bacteria which thrive in oxygen-free conditions such as soil, was a particular problem for men fighting in the muddy trenches of France and Belgium during WW1. This horrifying condition causes living tissue to decay and die and was responsible for many limb amputations and deaths in soldiers whose wounds had become infected. But by the eve of Armistice Day in 1918, MRC researchers had managed to develop the first serum for the prevention and cure of wound gangrene, which contained anti-toxins against all three bacteria involved.
Desperate times also fuelled ingenuity. Ships bringing home the wounded had poor sanitary conditions, but antiseptics were in short supply. With MRC funding, British chemist Dr Henry Drysdale Dakin managed to work out a cheap way to produce large quantities of an antiseptic from sea water. ‘Dakin’s Solution’ reduced secondary infections in repatriated soldiers to almost zero.
Development of penicillin
Penicillin – the first broad-spectrum antibiotic – was discovered by chance by Alexander Fleming in 1928 when Penicillum mould contaminated his culture dishes and killed the bacteria growing there. But it wasn’t until 1940 that MRC-funded scientists Lord Howard Florey and Sir Ernst Chain managed to work out a way to scale up production of the compound to make it a viable antibiotic drug.
Realising the urgent need for penicillin to treat infections in wounded soldiers during the Second World War (WW2), the pair turned their department at Oxford university into a penicillin factory and carried out clinical trials at the city’s Radcliffe infirmary. The results helped persuade drug manufacturers in the uS to mass-produce the drug. By the time of the Normandy landings in 1944, penicillin was readily available to all servicemen who needed it.
From penicillin to ‘iraqibacter’
Today, multi-drug resistant bacteria are one of the greatest challenges faced by the medical community. At the university of Birmingham, Professor Mark Pallen has been carrying out MRC-funded research on a type of multi-drug resistant Acinetobacter bacterial infection, which is usually found in hospitals. Military patients returning from the Middle East are particularly susceptible to the bacterium, so much so that it used to be nicknamed ‘iraqibacter.’
“Patients who are critically ill are given lots of antibiotics, which decimates their natural balance of bacteria in the body. Acinetobacter gets into wounds and takes up a vacant niche,” Mark explains.
In 2008, Mark and colleagues published a study which proved that a particularly virulent outbreak had jumped from a military patient returning from Afghanistan to a civilian patient in an adjacent bed.
The MRC has funded him to carry out more detailed work on whole genome sequencing of Acinetobacter samples to look for tiny genetic variations – known as single nucleotide polymorphisms – that distinguish different bacterial isolates, and then use this information to piece together how the infection was transmitted from person to person, providing new insights into how multi-drug resistant infections can spread in hospitals.
Insights into trauma
The use of explosive shells for the first time on the frontline meant that surgeons began to see cases of traumatic shock – the body’s reaction to severe injury involving loss of blood. MRC researchers discovered that shattered tissues produce substances which hamper blood circulation, so they devised a blood substitute, gum acacia (derived from acacia tree sap) to restore lost blood volume. Blood for transfusion was difficult to preserve and transport, so this invention helped save many lives.
Nearly a century later, Professor Janet Lord, a principal investigator at the MRC Centre for immune Regulation in Birmingham, is also working to save the lives of those injured in conflicts. She’s studying the inflammatory response in severely injured soldiers sent home from Afghanistan, and using the findings to advance treatment of burns and trauma in the civilian population.
“When you’re exposed to acute trauma – for example burns, blasts or multiple amputations – there’s an immediate inflammation response, but also an anti-inflammation response,” she explains. “Inflammation is useful because it protects against infections and stimulates woundhealing. But if it doesn’t get turned off at the right time by the anti-inflammatory response, you can’t heal properly. We’re trying to understand what controls that yin and yang balance, and what dictates whether or not a patient makes a good recovery.”
She adds: “How well you recover from a burn is age-related; the older you are the less likely you are to recover. We think that’s to do with immune system changes that occur with age, in particular having fewer cells which promote inflammation and reduced functioning of cells that fight infections such as neutrophils and natural killer (NK) cells.
So we’re taking measurements from young patients flown in from Afghanistan and comparing them with elderly burns and trauma patients. It may be that if we can restore the pro- and anti-inflammatory balance and improve function of these cells we can improve patient outcomes.”
Health and rationing
Maintaining the health both of soldiers and those supporting them with the war effort was of critical importance during WW2, and the MRC was called upon to make recommendations to the War Cabinet about nutrition that directly influenced the uK’s food policy.
In 1937, MRC scientists Dr Elsie Widdowson and Dr Robert McCance bravely experimented on themselves to test out the efficacy of proposed ration diets in the event of another world war. Over three months, they pushed their bodies to the limit, for example by climbing fells in the Lake District, to test the physical impact on their health of limited food supplies. Both were fit and well at the end of the experiment and the results were secretly passed to the War Cabinet, which was reassured that rationing in the general population would be safe.
The pair went on to make many lasting contributions to nutrition research; their book on the constituents of commonly eaten foods is now in its sixth edition and is still used by researchers today.
Futuristic findings: tissue regeneration and artificial vision
War continues to shape and inform medical research, particularly in the fields of surgery and regenerative medicine. Wing Commander Rob Scott, an ophthalmic surgeon at the Royal Centre for Defence Medicine in Birmingham, specialises in traumatic eye injuries sustained in war and has treated around 200 serious eye injuries over the past decade. Alongside US collaborators, he has developed the Brainport, an artificial vision device for people who have lost their sight. The device consists of a camera attached to a pair of spectacles which takes a pixellated picture of the outside world and translates the pixels into a tingling sensation via a ‘lollypop’ which sits on the user’s tongue. it allows a blind person to build up a picture of the world around them, and is so effective that users can distinguish between knives and forks on a table and even men’s and women’s toilet signs.
For those whose sight could still be saved by surgery, it is critical to intervene before the process of scarring begins, explains Rob: “Scarring is an absolute disaster for eye surgery because it changes the shape of the tissue. But if you can get something to regenerate instead, you don’t get scarring.”
Working with molecular neuroscientist Professor Ann Logan from the University of Birmingham, Rob and his research team are carrying out research on a substance derived from amniotic membranes expelled by women during childbirth which has anti-inflammatory and antiscarring properties. They’re using the substance to encourage damaged optic nerve and retina tissue to regenerate into new tissue rather than forming scar tissue.
“I now supervise an MRC-funded PhD student who has found some of the main pathways that will allow the regeneration of damaged optic nerves. We’ve discovered a very simple way of ‘tricking’ cells into re-growing by reprogramming how their DNA is expressed to make it promote certain pathways. So actually by stimulating the regeneration of the nerves it prevents scarring. If we can get it to work in people, that would be a holy grail – we could make blind people see again.”
War is, unfortunately, always likely be a part of human existence, but medicine will continue to learn lessons from it to benefit health, as it has throughout the bloody conflicts of the last 100 years.
Professor Lord, Professor Pallen and Wing Commander Scott are all part of the NIHR Surgical Reconstruction and Microbiology Research Centre in Birmingham.
This article was first published in the Spring edition of Network.