nature’s little helpers

Maggots and wound healing

They may look revolting but they do a great job: maggots can work miracles in human wounds. The hunt is on for the key biological agents.

The sight of maggots crawling in a festering human wound is naturally disturbing - but once the maggots are removed the wound is often clean, with no pus or purulent odour, and the healthy pink granulation tissue indicates the wound is actually healing. At the University of Nottingham, Professor David Pritchard is attempting to identify the biological factors behind this phenomenon.

The use of maggots to treat wounds is "way ahead of anything similar on the market, anywhere," asserts John Church, the leading advocate for larva therapy in the UK. Mr Church, a retired orthopaedic surgeon from the Oxford region, noticed the effect of maggots in human wounds in Africa in the 1960s. In early 1995 he was a key figure in the introduction of larva therapy in the UK. In May 1995 he met Stephen Thomas, Director of the Surgical Materials Testing Laboratory in Bridgend, South Wales, who went on to set up the Biosurgical Research Unit, within the Laboratory, to breed bacteria-free maggots for clinical and research purposes. This unit is the only dedicated fly-culture laboratory in the UK.

Greenbottle maggots, Lucilia sericata, feed on decomposing organic material. They eject salivary enzymes onto the rotting tissue to break it down and then suck it back in a piston-like action. "In a chronic human wound which has tissue that is dying and infected with large numbers of bacteria these little creatures have a heyday," says Mr Church. Moreover, maggots feeding hungrily in a wound obligingly devour not only the rotting tissue but also the contaminating bacteria. "So you've got two things happening for the price of one: you have the removal of the dead tissue, but you also have the lowering of the infection." Added to which, since maggots are photophobic they will naturally migrate into the depths of a wound. "They go into the nooks and crannies, which is exactly where I as a surgeon would want them to go. We don't have to train them: they are already pre-programmed by nature to behave this way. It's almost too good to be true."

Laboratory breeding ensures that an appropriate species of fly is selected (some larvae that infest human wounds can invade living tissue), and that the maggots used are free of bacteria and will not introduce other contaminants into the wound. The medical benefits of maggots don't stop at wound cleaning, however. "When you take the maggots out of the wound," says Mr Church, "not only does the wound base look good, but the actual healing tissue looks healthy and is obviously well on the mend. So there is evidence that they actually produce something within their secretions which 'kickstarts' the healing mechanism into action." It is this intriguing area that is the focus of Professor Pritchard's research.

Professor Pritchard's work on maggots grew out of earlier research on the interaction between the hookworm, Necator americanus, and its human host. Like the maggot, the hookworm secretes enzymes that interact with human skin; it can also have beneficial effects on the host (there is some evidence that hookworm infections can protect humans from cerebral malaria); and it does not appear to be susceptible to the host's immune system. It was a logical step for Professor Pritchard to transfer the knowledge and techniques from his hookworm investigations to the study of greenbottle larvae, and he initiated this new programme of research in 1998, supported by a Sir Henry Wellcome Commemorative Award for Innovative Research (a 'Showcase' grant).

Professor Pritchard and his team at Nottingham buy their research maggots from the Biosurgical Research Unit in Bridgend. These are sent out in bacteria-free containers as first or second instar (early stage) larvae, three to four millimetres long. In transit they try to feed by pumping out digestive enzymes, and other as yet unknown material. When they arrive, the Nottingham researchers begin work on the material they have secreted in the transit container. "What we're actually conducting is a biochemical survey of what's in the tube at that time," says Professor Pritchard.

In addition to proteolytic enzymes capable of digesting protein, the hypothesis is that the material produced by the maggots also contains (or stimulates the wound to make) growth factors or cytokines - molecules that promote the growth of healthy tissue. One of these is thought to promote the proliferation of fibroblasts - cells that provide the architecture for tissue healing by depositing extracellular matrix such as collagens in the wound - and to boost secretions by these cells.

It is also thought that maggots might be able to digest blood clots, allowing bloodflow and platelet access to the wound. Of considerable interest is a molecule known as platelet-derived growth factor, which is thought to promote wound healing. Catalyst BioMedica Ltd (the technology transfer arm of the Wellcome Trust which supports the translation of biomedical research into healthcare products) is engaged in discussions with the University of Nottingham and private investors, to promote continued investigation into the molecular basis of maggot secretions and develop a strategy to exploit significant findings.

Professor Pritchard's team is also assessing the ability of maggot proteins to modulate the immune response. Work so far indicates that greenbottle maggots do not incite a severe allergic response. "This bespeaks the fact that the parasite doesn't want the host to know it's there - and thus get rid of it," observes John Church. "It's rather like a stealth bomber." This of course is yet another advantage to the patient having his or her wound cleaned and healed. It also opens up the possibility of refining the compounds in the maggot secretions, and using them in pharmaceutical agents to treat parts of the body that the maggots cannot reach.

Larva therapy also has financial advantages. Three days of treatment costs only approximately £60 whilst amputation surgery, which maggots might have prevented, can cost £50 000 or more. In addition, patients treated with maggots can remain mobile, and thus can be treated at home. Hospital treatment can cost the NHS £250 a day, merely for accommodation. Maggots save limbs, lives and money, says Mr Church. He is adamant that they should be used not as a last ditch attempt, but as a 'first ditch' - to clean a wound thoroughly before other interventions are undertaken. "In my book they should be an integral part of modern wound care."

Wars, wounds and maggots:

A brief history of larval therapy
Maggots have been used to treat wounds throughout the centuries wherever people have lived cheek by jowl with nature. There is evidence that Australian Aborigines, Burmese hill people and the Maya Indians used maggots to clean suppurating or gangrenous wounds.

In the 1820s Napoleon’s outstanding battlefield surgeon, Baron Dominique-Jean Larrey (the man who invented the field ambulance), described how wounded soldiers with maggot-infested wounds would arrive on the carts already recovering. The phenomenon was noted again by surgeons during World War I, where conditions were so appalling that the main activity of battlefield surgeons was the amputation of gangrenous limbs. One surgeon,William Baer, saw two men who had lain on the battlefield with maggots in their wounds for seven days – yet had no fever or infection. Not only had the maggots protected the soldiers against tetanus, gangrene and septicaemia (the big killers of World War I ), but their wounds were actually healing.

In 1929, Baer decided to put his wartime observations to the test and conducted a trial treating wounds with blowfly maggots. The results were so good that Baer and his associates then began cultivating blowflies and sterilising their eggs for clinical use. By the 1930s, maggots were being used in more than 300 hospitals in Canada and the USA. By the end of World War II penicillin started to be mass-produced, and the birth of antibiotics (an undeniably more ‘aesthetic’ modality) led to the virtual disappearance of maggot therapy. Today, however, bacteria are becoming increasingly resistant to antibiotics and severe wounds or ulcerations are an ongoing problem. This is costly in both money and lives (it costs £30 000 or more to treat ulceration from a pressure sore, and 60 000 people die from the condition every year in the USA).

Ten years ago, Robert Sherman, an entomologist and physician in Los Angeles, noticed healthy infection-free tissue in a leg wound crawling with ‘worms’. He established an insectary in California to breed maggots for clinical use, and carried out the first controlled study showing that maggot therapy significantly increases the rate of healing of chronic pressure sores – at much lower cost than the usual regimen of repeated surgery and antibiotic treatments. “He reinvented the wheel. He was a latter-day pioneer,” says John Church, who visited Dr Sherman in 1994. Impressed with what he saw, he initiated clinical trials in the UK in early 1995 with colleagues in Oxford. If patients and medical practitioners can overcome a natural revulsion to introducing maggots into wounds, larval therapy may yet make a comeback.

External links

Catalyst Biomedica Ltd
Surgical Materials Testing Laboratory : breeds bacteria-free maggots for clinical and research purposes
World Wide Wounds : Electronic journal of wound management practice
School of Pharmaceutical Sciences at the University of Nottingham

nature’s little helpers

Maggots and wound healing

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