For thousands of years, Komodo dragons have thrived on an isolated chain of rocky Indonesian islands despite competing with other venomous reptiles, hunting deer and buffalo capable of crushing bone with a single kick and dealing with annual monsoons, tsunamis and drought.
The reason for their success may be that the bite of these giant lizards – they sometimes weigh 300 pounds and grow seven or more feet long – is so poisonous that even a nip can kill. They have more than 50 varieties of bacteria in their mouths yet rarely fall ill.
They’re also immune to the bites of other dragons. Scientists say that’s because the blood of Komodo dragons is filled with proteins called antimicrobial peptides, AMPs, an all-purpose infection defense produced by all living creatures, that one day may be used in drugs to protect humans. That would be a welcome development because some antibiotics are losing their effectiveness as bacteria develop resistance to the drugs.
“Komodo peptides are unlike any others. The animals have bacteria in their mouth in the wild and they live in a challenging environment and they survive,” says Barney Bishop, a George Mason University chemist who co-discovered the unusual characteristics of the peptides in the dragons’ blood in 2013. “If we can find out why they’re able to fight bacteria and what makes them so successful, we can use that knowledge to develop antibiotics.”
Bishop and his team have identified more than 200 peptides in Komodo blood that hadn’t been seen before, using a process he calls bioprospecting.
There has been at least one major find. One of the dragon peptides was used to design a synthetic substance, called DRGN-1, that breaks down the layer of bacteria that attaches to the surface of a wound and can impede healing. When DRGN-1 was tested on living bacteria and on wounds infected with bacteria, the results were startling: The wounds healed significantly faster than if left untreated.
Microbiologist Monique van Hoek, who worked with Bishop on the project, described DRGN-1 in a George Mason news release last spring as “a new approach to potentially defeat bacteria that have grown resistant to conventional antibiotics. The antimicrobial peptides we’re tapping into represent millions of years of evolution in protecting immune systems from dangerous infections.”
Finding these peptides and testing them isn’t simple. DRGN-1 was developed after a mass spectrometer identified dragon-blood peptides with the potential to attack antibiotic-resistant bacteria.
“If a peptide shows strong microbial activity” in lab testing, Bishop says, “we can look at it for other applications. If we’re lucky, it’s a new candidate right there. Odds are, we’ll have to tweak the sequence and structure.”
The researchers hope to find other potential drugs based on Komodo blood – as well as in the blood of crocodiles and alligators – and then persuade a drug company to help bring their discoveries to market. So far, they’ve identified 48 potential AMPs in Komodo blood that have never been seen before. He says these discoveries might lead to applications to curb everyday problems such as acne and pneumonia and to counteract biological weapons such as anthrax.
Infections of antibiotic-resistant bacteria kill as many as 700,000 people a year, according to the World Health Organization, a number that it projects could rise to 10 million a year by 2050. The WHO says that resistant bacteria are rising to “dangerous levels in some parts of the world . . . threatening our ability to treat common infectious diseases including pneumonia, tuberculosis, blood poisoning and gonorrhea.”
“The startling truth,” researchers wrote last year, “is that for large populations, the era of effective antibiotics has already, or will very soon, come to an end.” Governmental health agencies, including the Centers of Disease Control and Prevention, have been pushing for research into new drugs and methods to combat antibiotic resistance.
Bishop and van Hoek are testing dragon blood AMPs against a panel of bacteria that includes those related to highly resistant bacteria labeled priority pathogens by the WHO.
Even after four years focused on Komodos, Bishop remains unsure as to why their peptides are unlike any others. Is it their environment, he wonders, or does it have something to do with their evolution? “Are these peptides unique to Komodos?” he wonders.
It’s tough to study an animal that is difficult to capture, both because of its remoteness and because of its poisonous bite. Bishop has been using samples from Tujah, a Komodo at the St. Augustine Alligator Farm Zoological Park in Florida.
For those worrying about the animal’s welfare: Bishop’s collaborators take only about a pencil-tip’s worth of blood from the dragon, obtained by a quick needle poke in Tujah’s tail. They’ve taken only a handful of collections since 2012.
“Every microliter of that blood is precious,” Bishop said. But “if it’s not going to work because he’s not up for it, we don’t get the blood. We’re aware of his health and well-being.”
Samples are then analyzed in a process that identifies substances with the potential to be developed into drugs. “We’re not going to have Komodo farms; we identify peptides, sequence them, then synthesize,” he said.
Bishop’s Komodo dragon project began in 2012, with a $7.6 million Defense Department grant to analyze species that thrive despite major environmental challenges and interaction with pathogenic bacteria. In addition to the dragons, Bishop has been studying Chinese alligators and saltwater crocodiles, which have shown strong immunity against disease despite eating bacteria-infested animals and living in bacteria-rich environments and even surviving loss of limbs without getting infections.
The grant’s research was initially aimed at helping soldiers heal faster and finding ways of protecting them from bacterial bioweapons. The research could eventually lead to consumer products that might heal cuts or reduce skin infections.
Human health benefits have also been found in chemicals extracted from other deadly animals, including one of the world’s most venomous snakes, Australia’s taipan. In 2006, researchers said that chemicals that might someday be used to rapidly curb excessive bleeding in surgery had been identified in taipan venom. In 2015, Mexican researchers showed that scorpion venom could kill cancer cells.
“The most unlikely of animals are where the wonder drugs of tomorrow will be found,” says Bryan Fry, a University of Queensland herpetologist who discovered in 2009 that Komodos use venom to kill prey. Until then, Fry says, the assumption was that a dragon’s bite caused a deadly infection produced by the Komodo’s putrid saliva. That idea was so ingrained in researchers’ minds that no one bothered to test if the lizards were, in fact, venomous.
Fry agrees with Bishop’s take that Komodos could be the next frontier for medicine, comparing the lizard’s potential “to drugs such as captopril, which was developed from South American lancehead viper venom 40 years ago to treat high blood pressure. It remains a $10 billion-a-year market.”
The drug taken from the lancehead is now an ACE inhibitor used widely in cardiovascular treatment.
Bishop knows that if he’s going to turn Komodo blood into a wonder drug, he needs more blood. “Much more blood,” he laments. “We need a larger number of animals to study.”
Tujah is Bishop’s lone sample, and he thinks wild dragons probably have more curative peptides flowing through their veins than his 13-year-old captive source, because living in the wild forces immune systems to function at their highest.
Bishop has never seen a Komodo in the wild, and he knows it’s unlikely that he’ll get out into the field. It’s costly to travel to the small island chain where Komodos live. Luckily, the giants have a long life span in captivity, about 25 years.
Drug discovery is a long haul, yet he’s confident. “I’ve got a 7-year-old daughter who sleeps on a stuffed Komodo,” he says. “I’d like her to grow up in a world with effective antibiotics.”
