Wound Treatment with Larvae: “How Are You Girls Doing Today?”

The breeders manage the entire life cycle of these two-winged insects, from fly to egg to larvae. And they find these insects very likable. The basic requirements for maggot therapy include the special culture media from Merck KGaA, Darmstadt, Germany that are needed to breed the larvae.

If larvae are swarming in a wound, the process of debridement — the removal of dead, damaged, or infected tissue to promote healing — is accelerated. This kind of wound treatment by larvae increases the patient’s chances of survival. That’s why the French surgeon Dominique-Jean Larrey (1766–1842) was delighted when he saw larvae swarming in the wounds of injured soldiers in a battlefield hospital in Syria. The soldiers themselves, however, wanted these apparent messengers of doom to be removed at any price. But Larrey had observed that these larvae accelerated the healing of wounds, thus helping nature to do its work. He had also observed that these larvae only attacked dead tissue and “always spared living flesh.”    

Every species of fly prefers a different kind of taste. One species can digest healthy as well as necrotic tissue. Other species, which include the larvae of the common green bottle fly, only feed on dead flesh. The U.S. surgeon William S. Baer (1872−1931) was the first doctor to systematically apply his experiences on the battlefields of World War I to the challenges of treating civilian patients. He was a specialist for bone infections, and in 1929 he deliberately put larvae of the common green bottle fly into the opened wounds of his patients. After two months, all 21 patients were completely healed and could be sent home.

Starting in 1940, sulfonamides and penicillin gradually replaced this seemingly archaic therapy. But ever since the 1990s, wound treatment with larvae has been experiencing a revival. Doctors in the United States have found that using this method for bedsores (decubitus) promotes wound treatment and wound healing faster than any other nonsurgical measures. Natural wound treatment has also produced good results in patients with diabetes. Their chronically open wounds heal either slowly or not at all, and as a result the amputation of the affected limbs would be in many cases the last resort. A renaissance of larva therapy began, and today even the breeding of the larvae has reached a very high level of quality.

At a laboratory in Barsbüttel, a small town near Hamburg, about 22,000 common green bottle flies (Lucilia sericata) are buzzing in 40 cabinets. “We even breed the fly colonies ourselves,” says Judith van Leeuwen, the biology lab technician who monitors the production process in this two-story building. Like all the other approximately 30 lab employees, she is fascinated by the flies, the larvae, and the effects they achieve. “Sometimes we knock on the cabinets and ask, ‘How are you girls doing today?’” she says. That’s because the females are crucial.

If they are fed protein-rich food, they lay their first clutch of eggs when they are almost two weeks old. Their nests are small containers with an attractant at the bottom. The lab technicians harvest 45,000 fly eggs, weighing as much as three grams in total, when they empty a cabinet. The temperature in the lab is tropical, but the zoo smell is very faint. The laboratory, with its cleanrooms, personnel airlocks, lab coats, hairnets, and disinfectant dispensers, has the appearance of a clinical production line for highly integrated electronic chips.

“After all, we are manufacturing a medical product here,” says Judith van Leeuwen. Highly demanding hygiene standards and its painstaking quality management are the company’s backbone. That also applies to the room for breeding cabinets, in which the fly eggs, which have previously been disinfected, are hatched in Petri dishes within one day. “Merck KGaA, Darmstadt, Germany provides us with the Petri dishes containing the culture media, which it produces according to our own recipe,” says van Leeuwen. She explains that the composition of the culture medium was perfected by means of lengthy experiments to ensure optimal growth of the larvae. Without specific culture media, the production of larvae to be used as medical products would not be possible. “We are one of the few companies that manufacture customized products of this kind for microbiology in line with pharmaceutical requirements,” says Sheriff Aziz.

“That’s because we regard ourselves as a partner of our customers. We want to provide them with customized solutions that meet their needs.” Aziz, who has doctorates in biology and virology, is the Head of Sales for products for microbiological applications at the Merck KGaA, Darmstadt, Germany site in Eppelheim, Germany, which also provides the larvae producer with control strips for the room air and contact plates for the work surfaces. These devices are used to continuously monitor the microbiological status of the production rooms. “If nothing is growing, everything is all right,” says Aziz. Otherwise, bacteria colonies form on these control media, and the appropriate measures are then taken.    
“That’s because we regard ourselves as a partner of our customers. We want to provide them with customized solutions that meet their needs.” Aziz, who has doctorates in biology and virology, is the Head of Sales for products for microbiological applications at the Merck KGaA, Darmstadt, Germany, site in Eppelheim, Germany, which also provides the larvae producer with control strips for the room air and contact plates for the work surfaces. These devices are used to continuously monitor the microbiological status of the production rooms. “If nothing is growing, everything is all right,” says Aziz. Otherwise, bacteria colonies form on these control media, and the appropriate measures are then taken.    

After sterile tests are conducted in a large pressurized cleanroom, the larvae are collected from the plates under aseptic conditions and transferred to special packaging with the help of a dosing machine that was developed in-house. They are transferred either to patented polyester mesh bags of different sizes containing between 50 and 300 larvae or to ampoules for “free-range” larvae. These containers have to arrive at the customer’s premises — that is, a clinic — within 48 hours. In many cases, they are even fresher than fresh fish. At the clinic, the doctor places the mesh bag full of larvae directly on the wound or applies free-range larvae to wounds where the necrotic tissue is difficult to access.    

For as long as four days, the maggots then secrete their saliva, which contains enzymes that break down the dead tissue and is thus an extremely effective agent for the treatment of wounds. The larvae feed on this solution and grow from the size of a tiny grain of rice to a length of about twelve millimeters. Clinical studies have shown that their saliva and their digestion products contain compounds that can further support the healing process. Because of the damp environment of the wound, the maggots do not develop into flies. And if people know the background of this process, they don’t feel any disgust.