“Drug-resistant bacteria represent one of the greatest threats to our species,” says ethnobotanist Mark Plotkin, president of the Amazon Conservation Team, which works with people in the Amazon region to conserve forests and culture. Coauthor Michael Shnayerson, a contributing editor at Vanity Fair, agrees. “People have no idea what bacterial dangers await them when they go to a hospital,” he says. In a new book Killers Within: The Deadly Rise of Drug-Resistant Bacteria, Shnayerson and Plotkin report medical researchers’ evidence that the number of disease-causing bacteria able to fend off the most commonly prescribed antibiotics has grown significantly. We live in a “grim new era” of superbugs, say the authors, who cite scientific studies suggesting that we have only ourselves to blame. Physicians who prescribe antibiotics when the medications are not necessary, patients who don’t complete antibiotic treatments, and ranchers who overuse antibiotics to spur livestock growth have all contributed to the development of extra-hardy bacteria strains—a microbial world acting out the old saying that what doesn’t kill you makes you stronger. The toll is huge. Public health experts estimate that infections from antibiotic-resistant bacteria kill some 40,000 Americans annually. Killers Within highlights efforts by experts to curb the problem and to develop new antimicrobial medications. In the excerpt that follows, scientists research powerful natural substances that some animals secrete to fight off infection—substances that may lead to the antibiotics of the future.
The first time he stalked a dragon, in November 1995, Terry Fredeking was scared. Bad enough to have flown all the way to Indonesia, deal with notoriously difficult Indonesian bureaucrats, brave the stifling heat, and find a local boat owner willing to whisk the biologist and two colleagues over to the sparsely inhabited island of Komodo. Worse, much worse, to lie in wait, awash with sweat, for the world’s largest lizard to emerge from the forest in a hungry mood. That first time, Fredeking watched a Komodo dragon attack a goat. The Komodo was at least eight feet long and weighed well over 200 pounds. It looked like a dinosaur, Fredeking thought, it really did. It was almost all scales, with a huge mouth of large, curved teeth. One second it was lying in wait, all but invisible. The next, it was ripping out the terrified goat’s stomach with a single bite. As it did, thick saliva dripped from the dragon’s mouth, mixing with the blood and guts of the goat. Ah, yes, the saliva, thought Fredeking as he and his colleagues advanced from the bushes, tremulously holding long forked sticks. The saliva was why they were here.
With luck, the dragon’s viscous, revolting drool would contain a natural antibiotic that in some synthesized form could fight multidrug-resistant Staphylococcus aureus, which causes sometimes fatal blood poisoning, and other bacterial pathogens. At the least, Fredeking, a genial, stocky, self-styled Indiana Jones from Hurst, Texas, would have the adventure of his life and possibly contribute to the fascinating new field of animal peptides. It sure beat collecting bat spit in Mexico and harvesting giant Amazonian leeches in French Guiana.
This latest approach to antibiotic discovery traced in large part to a well-ordered lab at the National Institutes of Health. On a fragrant, early summer day in June 1986, a mild-mannered M.D. and research scientist named Michael Zasloff had noticed something decidedly odd about his African clawed frogs. As chief of human genetics at a branch of the NIH, Zasloff was studying the frogs’ eggs to see what they could teach him about the flow of genetic information from the nucleus of a cell to the cytoplasm. He would inject genes into the eggs, then see what happened. The frogs just happened to have large, good eggs for this purpose; their own biology was irrelevant to his work.
Some lab scientists killed the frogs after cutting them open to remove their eggs. Not Zasloff. He would stitch them up crudely—he was a pediatrician, not a surgeon—and when enough of them accumulated in a murky tank in his lab, he would secretly take them to a nearby stream and let them go. On this particular day, Zasloff noticed that the tank appeared to have “something bad” in it, because several frogs had died overnight and were putrefying. But some of the frogs he’d operated on, sutured and thrown back into the tank appeared fine. Why was that? Certainly the frogs’ stitches were not tight enough to prevent bacteria and other microbes from infiltrating their bloodstreams. Yet no infection occurred. No inflammation, either.
This was, as Zasloff put it later, his “eureka” moment, for even as he asked himself the question, he intuited the answer: the surviving frogs must have generated some substance that afforded them natural antibiotic protection. (Zasloff never did figure out why the dead frogs hadn’t done the same, but he suspected that their immune systems had been too compromised to help save them.) No likely suspects appeared under a microscope, so Zasloff began grinding samples of frog skin and isolating its elements. After two months, he still couldn’t see what he was after. He could identify it, however, by its activity. He was dealing with two kinds of short amino acid chains called peptides—like proteins, but smaller. Scientists knew that peptides participated in many metabolic functions of living organisms, either as hormones or other compounds. They didn’t know what Zasloff had just realized: that some peptides in frogs worked as antibiotics. Zasloff named them magainins—the Hebrew word for “shields”—and theorized that they might lead to a whole new class of human-use antibiotics. So promising was Zasloff’s finding that when it was published a year later, the New York Times devoted an editorial to it, comparing Zasloff to Alexander Fleming, the British discoverer of the antibiotic properties of a fungus called Pencillium. “If only part of their laboratory promise is fulfilled,” the Times opined of his peptides, “Dr. Zasloff will have produced a fine successor to penicillin.”
Like Fleming, Zasloff had made his discovery through serendipity. It was a means about to become quaint. Soon genomics would begin to transform drug discovery into a high-speed, systematic search with state-of-the-art tools that analyzed bacterial DNA—the very antithesis of serendipity. But targeting individual genes, by definition, would yield narrow-spectrum drugs. No doctor wanted to rely exclusively on narrow-spectrum drugs, especially in the hours before a patient’s culture was analyzed at the lab. Besides, a drug designed to hit one bacterial gene might soon provoke a target-changing mutation. Whole new kinds of broad-spectrum antibiotics were needed, too, and the best of those seemed less likely to be found by genomics than by eureka moments like Fleming’s and Zasloff’s, when a different approach presented itself as suddenly and clearly as a door opening into a new room. To date, virtually all antibiotics with any basis in nature had been found in soil bacteria or fungi. The prospect of human antibiotics from an animal substance suggested a very large room indeed.
The world had changed a lot since Fleming had published his observation about a Penicillium fungus, then basically forgot about it for more than a decade. Now biotech venture capitalists scanned the medical journals for finds that might be the next billion-dollar molecule. Zasloff would find himself swept from his NIH lab into the chairmanship of a new public company with Wall Street money and Wall Street expectations, his magainins hyped as the Next New Thing. Nearly $100 million later, he would also be the tragic hero of a cautionary tale about the challenges a maverick faced in bringing new antibiotics to market.
As he monitored their action, Zasloff discovered that the peptides he called magainins act not by targeting a bacterial protein, as nearly all modern antibiotics do, but by punching their way through the bacterial cell’s membrane and forming ion channels that let water and other substances flow in. These, in turn, burst the bacterium. This bursting or lysing occurred because the magainins were positively charged and the bacteria had negatively charged elements called phospholipids on their membrane walls. The positively charged peptides homed in on the negatively charged cell membrane as if piercing an armored shell.
The wall-punching mechanism suggested that peptides might be especially useful against resistant bacteria. The proteins targeted by nearly all existing antibiotics could be changed or replaced. For a bacterium to change its whole membrane would be orders of magnitude more difficult. It seemed impossible. And as far as Zasloff could see, peptides were drawn only to bacterial cell walls—never, in vitro at least, to the membranes of normal human cells. Which made them a perfect antibiotic.
Another NIH scientist might have published his findings, as Zasloff did, and gone back to tinkering in his lab with the next intellectual challenge. But as a pediatrician, remembering babies with cystic fibrosis, Zasloff wanted to see peptides turned into drugs right away. His first step was to call the Food and Drug Administration. “I’m from the NIH and I just made a discovery that’s about to be published,” he told the bureaucrat he reached. “Can I get someone from the FDA to help me do what I have to do to make this into a drug?” The FDA had no system, it turned out, to help government researchers develop drugs while keeping their government jobs. Nor did the NIH have any such guidelines. (Not long after, the agency would allow researchers to profit in modest ways from technology transfer, but the burgeoning biotech industry would be filled with NIH refugees wanting a larger share of the proceeds of their discoveries.) Zasloff risked being fired or sued, he discovered, simply for fielding the calls that began to pour in after his article was published. If he talked to Merck, he could be sued by Bristol-Myers, because he was a government official obligated to favor no company over another.
A call from venture capitalist Wally Steinberg decided his future. Steinberg offered Zasloff a deal that allowed him to help with the start-up—to be called Magainin—to teach, and to continue to practice as a pediatrician. In short order, Zasloff became a professor of genetics and pediatrics, in an endowed chair, at the University of Pennsylvania, and chief of human genetics at Philadelphia’s Children’s Hospital. For Magainin, set up outside Philadelphia in a corporate park of former farm town Plymouth Meeting, he worked as a part-time consultant.
It should have been an ideal setup, a dream life guaranteed to make any medical researcher sick with envy. But while Zasloff had thought he could work on peptides in his hospital lab and pass the results on to Magainin, the hospital’s directors thought not. Work funded by the hospital, they declared, ought to remain the hospital’s intellectual property. When the university, the third leg of Zasloff’s new career, began lobbying for its own share of the proceeds, Zasloff gave up. Heartsick, he resigned a directorship at the hospital, and gave back the endowed chair to the university. As of 1992, he would gamble his entire career on Magainin.
Since peptides seemed to work against almost anything, Zasloff and his colleagues scanned the market for a condition treated by only one drug: less competition, more opportunity. They settled on impetigo, the mild skin infection characterized by rashlike lesions, and caused by skin bacteria, usually certain streptococci or S. aureus. If the peptides worked as well or better than Bactroban, the existing treatment, they’d be approved. From there, Magainin could go on to test peptides against more serious topical infections, have a couple of profit-making products on the market, and so gird up for serious bloodstream infections.
The peptides sailed through phase one trials: applied to healthy human skin, they caused no harm. In phase two, they seemed to produce good results on 45 people who actually had impetigo. The Bactroban trials had involved a placebo: simple soap and water. Magainin followed suit. But when the results of the phase three trials were compiled in mid-1993, Zasloff was stunned. Though the peptides had done as well as Bactroban, neither product had done as well as soap and water! How, then, had Bactroban won approval in the first place? Zasloff never learned. The FDA merely announced that peptides had failed to do better than Bactroban. Overnight, Magainin’s stock plunged from $18 to $3 a share. As Magainin teetered on the verge of collapse, Zasloff pulled a rabbit out of his hat. Or rather, a dogfish shark.
By 1993, inspired by zasloff’s original paper, dozens of other scientists had gone in search of peptides in other animals. They’d found them just about everywhere they’d looked—70 different antibiotic peptides in all—in everything from insects to cows to Komodo dragons. Intriguingly, different creatures secreted peptides from different kinds of cells. Many insects made them in their white blood cells. In horseshoe crabs, they appeared in the blood elements called platelets. In the frog, as Zasloff had determined, they appeared in a part of the nervous system called the granular glands: the frog empties these glands, Zasloff found, when the animal is stressed, or when the skin is torn. As for humans, they turned out to harbor peptides of their own: in white blood cells, in the gut and, notably for cystic fibrosis babies, in certain cells of the airway called the ciliated epithelium. Perhaps, thought Zasloff, some other animal’s peptides would make a more potent antibiotic than those of the African clawed frog—potent enough to bring investors scurrying back to Magainin.
One day Zasloff gave his standard stump talk about peptides to a group of scientists at the Marine Biological Laboratory in Mount Desert, Maine. John Forrest, a professor at YaleUniversity’s medical school, raised his hand to say that he’d spent 19 summers studying the dogfish shark, and, by God, if the African clawed frog had peptides, so must the shark. The shark had long been Forrest’s experimental animal model, as the frog was Zasloff’s. Small and hardy, the shark had large, simple cells and organs that made it easy to study. Best of all, when Forrest operated on a dogfish shark, he could suture it up and toss it back in a tank of dirty water, as Zasloff did with his frogs. Inevitably, the shark healed without infection. Zasloff went home with a shark stomach expecting to find peptides. Instead, he found a new kind of steroid with even stronger antibacterial action—yet another element of the innate immune system. He called it squalamine. “Hey!” he told Forrest by phone. “Send me more of those shark stomachs!”
Eventually, Zasloff found a way to purify shark squalamine, and switched to livers, because a commercial fishery called Seatrade in New Hampshire could Federal Express him half a ton of them a week. Zasloff himself would wheel the heavy boxes of stinking shark organs in from the loading dock, then start slinging them into a giant meat grinder. The purification process involved heating the ground livers in garbage cans like great vats of soup, skimming the squalamine-rich scum from the top, then filtering the scum through a high-tech set of steps.
Along with squalamines, Zasloff found other steroids in the purified gunk. He figured there were more than 12 kinds in all. Each had broad antibiotic effects, but each also seemed to target a specific kind of cell in the shark’s body. Publication of the discovery of squalamines had brought calls from around the world, and these helped focus Zasloff’s study. Several of the steroids worked as anticancer agents both in dogfish sharks and in humans. One kind even prevented lymphocytes from carrying out the AIDS virus’ orders to make more virus.
Certain that he had found a way to save his company, Zasloff contacted Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at NIH and, as such, the top U.S. government official involved in fighting AIDS. Fauci established a Cooperative Research and Development Agreement, or CRADA, with Magainin, and Zasloff started injecting squalamines into AIDS-infected mice and dogs and monkeys. The squalamines worked brilliantly—up to a point. They stopped the growth of the lymphocytes, just as they had in laboratory experiments. Unfortunately, as soon as the treated animals were hit with the squalamines, they stopped eating and began to lose weight.
For months, Zasloff struggled to solve the dilemma. A lonely figure reeking of shark liver, he spent his days skimming scum and injecting steroids into AIDS-infected lab animals. No approach worked. The animals’ lymphocytes stopped growing, as did the AIDS virus, but the animals simply would not eat. Anthony Fauci gave up hope: the prospect of halting a patient’s AIDS infection while having him die of starvation was obviously unacceptable. Okay, Zasloff declared at last, Okay. All was not lost. “What nature has given us,” he announced to his devastated colleagues, “is anappetite suppressant.”
Zasloff had two strikes against him, and as far as his backers were concerned, it was the bottom of the ninth. But by the mid-1990s, the sharp rise in resistance around the globe had cast peptides, his other finding, in a more favorable light. Peptides still appeared utterly impervious to all the new mechanisms of resistance that bacteria had employed. Intrigued, the FDA offered to let Magainin try peptides once more, this time on a more serious topical condition than impetigo: infected diabetic ulcers. As the FDA knew, the existing antibiotics used against these painful foot lesions caused such debilitating side effects that patients usually stopped taking them—even though the lesions, when infected, tended to invade muscle and bone, and even led to amputation of the affected limb. Now, in addition, resistance to these antibiotics was rising. Worse, the most promising of them, Trovan, would soon be pulled from the market for causing liver toxicity. Here was a real need—and market niche—that peptides seemed perfect to fill.
Because patients could suffer irreversible harm from diabetic ulcers, the FDA ruled that no placebo would be needed. Zasloff’s peptides merely had to do as well or better than one of the comparators, a powerful antibiotic called ofloxacin, which came not as a topical ointment but in oral form. Magainin breezed through phase one trials: the peptides, as shown in the previous trials, caused no harm to the skin of healthy people. To speed the process, the FDA let Magainin combine the next two phases. Roughly 1,000 patients were recruited from more than 50 medical centers in the United States between 1995 and 1998. These were very sick patients, their lesions excruciatingly painful. When doctors swabbed the lesions with a peptide solution, most of the patients seemed to improve.
As Zasloff pored over the final results, he felt encouraged, if not wildly optimistic. The topical peptides had not quite outperformed oral ofloxacin, but they’d done nearly as well. Certainly the tests had shown that MSI-78, as Magainin’s latest peptide was known, had a broad and powerful spectrum, did not provoke resistance, and had no direct side effects. The results were strong enough for Smith-Kline Beecham to sign on as a partner. SKB would market the product as Locilex. Now all Magainin needed was formal approval by an FDA advisory panel.
The panel, comprised of seven experts from various fields, met on March 4, 1999, in Silver Spring, Maryland, to spend the whole day debating the merits of Locilex. Zasloff, looking on from the audience of 300, thought the morning session went well, but the afternoon was a different story.
Perhaps the panel members were served an inedible lunch. Perhaps the meeting room was too hot or cold. Whatever the reason, the members reconvened in a grumpy mood. One of the seven declared that in her opinion—founded not on clinical experience, only on the morning’s 30-minute tutorial—no antibiotics were needed for infected diabetic ulcers. “Just cut the infected tissue out and throw it in the garbage can,” she declared. One after another of the members agreed. The panel’s chairman, Dr. William Craig, pointedly disagreed. Nevertheless, the vote was 7-5 not to approve the drug, a decision upheld formally by the FDA some months later. Michael Zasloff’s 13-year crusade to use peptides against drug resistant bacteria was finished.
Over the next two years, Zasloff himself came to wonder if animal peptides would ever work in people. Perhaps the way to go was to focus on human peptides—plenty of those had been found—and to try to strengthen the barrier of innate immunity to fight human infections.
In a desperate bid to keep his company alive, Zasloff pushed squalamine into clinical trials as an appetite suppressant. He was serious. It was the Hail Mary play, as he put it, that might save the day. But no one else seemed to believe he could pull it off.
In the fall of 2000, Zasloff’s own directors lost faith. The scientist whose discovery had inspired the company was made a consultant—pushed out, as Zasloff later admitted—and the corporate direction changed. The clinical tests with squalamine as an appetite suppressant were carried on: the stuff did look promising, wacky as the route to its application may have been. Early results had shown squalamine to be effective, as well, against ovarian and non-small-cell lung cancer. But in corporate press releases, no further mention was made of antibiotics—or peptides. From now on, the company would use genomics to find new targets and new natural substances like hormones as drugs. To make that perfectly clear, the name Magainin was changed to Genaera.
In his more contemplative moments, Zasloff admitted he’d made mistakes. But he had no regrets about his role in establishing a burgeoning new field: some 3,000 articles on peptides had been written since his seminal paper of 1987, some 500 peptides discovered. The innate immune system was now part of science. And for Zasloff, the most promising aspect of peptides was still their potency against resistant bacteria. They’d persisted through most, if not all, of evolutionary history. In all that time, bacteria had never become resistant to them. Was it too much to suggest that they constituted the Achilles’ heel of pathogens? That bacteria never would become resistant to peptides? “They’ve had a billion years to fend these things off,” Zasloff said, “and this is what we’ve got.”
As the president of antibody systems, a small, Texasbased biotech company, Terry Fredeking had dedicated himself to the search for peptides and other natural substances in animals, the more exotic the better, that might lead to drugs for resistant pathogens. Michael Zasloff’s discovery had made his work possible; one of Zasloff’s former students was in his employ. Some of his samples—which included parasites from Tasmanian devils, among other odd things—showed promise in vitro, but Fredeking hungered for more. In truth, he was a bit of a showboater, eager to make his name, with the sort of chutzpah that made lab scientists shudder but sometimes got things done. “There’s got to be something bigger than this,” he said one day to one of his consultants, George Stewart, professor of parasitology and immunology at the University of Texas. “What can we do next that’s dangerous, exciting and will advance science?”
“How about Komodo dragons?” Stewart suggested.
“Komodo dragons?” Fredeking echoed. “What in the heck are they?”
Stewart explained that the world’s largest lizard, formally known as Varanus komodoensis, was justly famous for being one of a handful of predators big and fearless enough to prey on human beings on a somewhat regular basis. In fact, humans were by no means its largest prey: full-grown Komodos were known to bring down 2,000-pound water buffalo. Found only on the Indonesian islands of Komodo, Flores and Rinca, the dragons were descendants of mososaurs, massive aquatic reptiles that roamed the seas 100 million years ago. Though the Komodo dragon did often hunt down and devour its prey, it also had a craftier method of killing that hinted at the presence of antibiotic peptides. A stealth hunter, the dragon lay in wait for sambar deer, crab-eating macaque monkeys and other mammals of its habitat, then lunged for the abdomen of its passing prey with toothy jaws as strong as a crocodile’s. Almost always, its wounded victims escaped, because the dragons, many of them heavier than a fat, six-foot-tall man, could run only in short bursts. But because the dragons often feasted on rotting carcasses, their jaws teemed with virulent bacteria. Within 72 hours of being bitten by the great lizard, animals would die of bloodstream infections brought on by these bacteria. Eventually the dragon would come lumbering over to take his meal at last.
Both because of its lethal saliva, and because the dragon ate carrion teeming with more bacteria, zoologists had long wondered what made the dragons immune to all these pathogens. Whatever it was had to be really powerful, because of an evolutionary oddity about the dragon’s teeth. Razor-sharp as they were, and serrated like a shark’s, the dragon’s teeth were actually covered by its gums. When it snapped its jaws shut on its prey, the teeth cut through the gums. The dragon’s lethal saliva, then, had access to its bloodstream. Yet the Komodo remained uninfected. “In all likelihood,” Stewart finished, “the dragon’s bacteria has been battling with its immune system for millions of years, with both sides getting stronger and stronger over time to keep each other in balance.”
“That’s it!” Fredeking exclaimed. “Lead me to ’em!”
Nearly three years passed before Fredeking and two colleagues could secure permits to take samples of Komodo dragon saliva. Both the Indonesian and the U.S. governments had to be petitioned, because the dragon is an endangered species, and most of the 6,000 animals that remain are found within KomodoNational Park, which covers several islands and is now a World Heritage Site. Finally, on November 30, 1995, came the momentous day. Fredeking and Jon Arnett, curator of reptiles at the Cincinnati Zoo, flew to Bali, where they met up with Dr. Putra Sastruwan, a biology professor and Komodo dragon specialist at the University of Udayiana in Bali. They took two days to recover from jet lag, then flew to the Indonesian island of Flores in a small Fokker plane that made Fredeking more nervous than the prospect of facing Komodo dragons.
The next day they crossed over to Komodo by ferry—another unnerving experience for Fredeking, since the ferry had sunk on several occasions. From a distance, the island appeared shrouded in fog, with protruding volcanic cliffs. Close-up, Fredeking saw that its coastline was lined with rocky headlands and sandy bays. Much of its interior was dry, rolling savanna, with bamboo forests halfway up the larger peaks. The island supported a variety of large mammals, all imported by man: deer, water buffalo, boar, macaque monkey and wild horse. No one knew how the Komodo dragons had come to the island. Paleontologists believed their genus evolved in Asia 25 million to 50 million years ago as reptiles, then migrated to Australia when those two land masses collided. Because Indonesia lay closer to Australia at that time, the dragons may have swum to the islands and proliferated, growing larger over time, because the islands contained no predators for them.
Hot and sweaty, the biologists spent their first night on the island in a village that was nothing more than a cluster of bamboo huts. Over a local dinner of rice and fish, they heard stories of the dragons’ ferocity. Eight villagers, mostly children, had been attacked and killed by Komodos in the 15 years since the national park was established and records began to be kept. One old man had paused beside a trail to take a nap: his supine form looked vulnerable and inviting, and he, too, fell victim to a dragon’s steel-trap jaws. Other stories, unverifiable, had circulated ever since W. Douglas Burden came over in 1926 on behalf of the AmericanMuseum of Natural History and made a first formal study of the beasts, capturing 27 of them and naming them Komodo dragons. Burden also brought the first Komodo dragon back to New York City. He told the story of his adventure to Meriam C. Cooper, among many others, and fired the Hollywood producer’s imagination. Cooper changed the dragon to an ape, added Fay Wray, and in 1933 gave the world King Kong.
It was the next morning that Fredeking saw a Komodo dragon rip open the belly of a terrified goat. He had briefly considered bringing tranquilizer guns to bag his prey, but scotched the idea when he learned that a sedated dragon is likely to be eaten by his peers. Komodos are so cannibalistic that they will eat each other, including their own young. Newly hatched dragons know, by biological imperative, to scamper immediately up tall trees and spend their first two years as arboreal creatures, safe from the snapping jaws of their parents below.
Instead of using sedatives, Fredeking and his cohorts emerged from their hiding places with long forked sticks and one long pole designed for catching crocodiles: an extendable pole with a wide noose at the end. The noose was slipped over the dragon’s head and pulled tight. Before the befuddled creature could react, six men jumped on him. The Cincinnati Zoo’s Jon Arnett held the dragon’s head and began wrapping duct tape around it. Others wrapped tape around its extended claws. Equally important, a ranger grabbed the dragon’s powerful tail. Fredeking reached for the long Q-Tips he’d brought for swabbing at the dragon’s saliva. He looked at the dragon’s furious eyes and, then, startled at its third eye: a “parietal” eye in the roof of its cranium, which acts as a lightsensing organ. He dabbed at the saliva, shocked at how thick and viscous it was—like Vaseline. One sample was slipped into a vial, then another. Fredeking began to feel euphoric. That was when he heard one of the others say, in real terror, “Oh my God.”
Fredeking looked up and felt the paralyzing fear of the hunter who has gone from being predator to prey. More than a dozen Komodo dragons were advancing from all sides. Drawn by the noisy struggle of the dragon that had been captured, the lizards had converged with the quaintly Komodian hope of eating it—along with the men around it. Panting with adrenaline, the men pushed at the dragons with their forked sticks. With their length, body mass and sheer reptilian power, the dragons easily could have pushed right up to the men and started chomping away, either at the duct-taped dragon or at the hors d’oeuvres plate of tasty human legs. But the sight of tall men with sticks seemed to confuse them. One of the park guards—an old hand at dealing with the dragons—aggressively advanced on one of the larger lizards, and pushed him away with his forked stick. For a tense minute or so, the outcome remained uncertain. Then, one by one, the dragons turned and clumped away. Fredeking took a long breath. “Man, oh man,” he said. “What we do for science.”
On that first trip, both of Fredeking’s cohorts incurred deep scratches on the insides of their calves by sitting on the dragon’s back to help restrain him. They knew that the dragon’s scaly skin—as scaly as chain mail—was rife with bacteria too. Within hours, they were infected and running fevers. Fredeking was running a fever too. All three took Ciprofloxacin and soon felt better. Not surprisingly, the dragon’s bacteria were susceptible, given that the bugs had probably never encountered commercial antibiotics.
Along with saliva swabs, Fredeking came away with samples of blood from the dragon’s bleeding gums. Flash frozen in liquid nitrogen and stored in Thermos-like containers, the samples were flown back to Texas, where Fredeking’s researchers got to work. They counted 62 different kinds of bacteria in Komodo saliva. The most potent of the lot was Pasteurella multicida, common in many domestic animals, thoughin far less virulent strains. They found antibiotic peptides, too, along with a small molecule that did an even better job of killing bacteria. In vitro, the molecule knocked out three of the worst bacterial pathogens: methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and E. coli 0157:H7 or Escherichia coli. Don Gillespie, a veterinarian in touch with Fredeking because of his work with Komodos at the Nashville, Tennessee, zoo, worried that the peptides might not last long in the human body. But this new small molecule, he thought, might not be recognized by human antibodies, and so be a perfect candidate for a new class of antibiotic.
First, the researchers would have to try the peptides, and the molecules, in mice, then guinea pigs, then primates. And even the gung ho Fredeking knew better than to make any predictions. “If it makes mice grow long green tails and crave human flesh, we’ll know it’s not good,” he said. “Basically, anywhere along the trail here, this thing could fall apart.”