One day last summer, Dr. Michael Zasloff was watching an African clawed frog swim in its tank in his laboratory at the National Institutes of Health when he suddenly noticed something that stunned him.

It was the wound on the frog's belly, a surgical cut made by Zasloff a few days earlier to remove the ovaries -- a procedure he had done hundreds of times on frogs in the preceding five years. The wound was clean, closed and healing perfectly, just as all the others had done. But for the first time, Zasloff wondered: Why should that be? The murky brown water in the tank teemed with bacteria that should have caused a serious infection.

"It struck me at that moment that we were seeing a medical miracle," said the 41-year-old scientist, who is chief of the genetics branch at the National Institute of Child Health and Human Development. That miracle -- the African clawed frog's astonishing ability to heal itself, even when surrounded by microscopic enemies -- launched Zasloff on a determined search for the explanation.

Within a few months, he found it: a previously unknown family of powerful natural antibiotics, dubbed "magainins" (pronounced ma-GAY-nins) from the Hebrew word for "shield," whose discovery holds the hope of both new treatments for many human infections and a deeper understanding of animals' defenses against disease. An announcement of the discovery will be made Friday, and Zasloff's paper describing it will appear in the August 15 issue of the journal Proceedings of the National Academy of Science.

Apparently acting in a way different from any known antibiotic, the magainins can kill a wide range of invaders -- including bacteria of many kinds, fungi, and parasites such as those that cause malaria -- and there is a possibility that they will also work against some viruses and cancers. Zasloff believes magainins may help explain the evolutionary success of amphibians and other water animals and may even underlie the traditional use of frogs as remedies in folk medicine.

The story of Zasloff's discovery of magainins is the kind of scientific detective tale seldom found in modern research. It is the story of how a single, elegantly simple observation led, with a speed rare in science, to the unfolding of a brand new area of animal biology. It vividly illustrates Louis Pasteur's dictum that in science, "chance favors only the prepared mind."

Like thousands of scientists who have used the African clawed frog, Xenopus laevis, for experiments, Zasloff had taken the animal's hardiness for granted until that day last July, when years of wondering about biological defense mechanisms suddenly made him see a wound on a frog's belly through new eyes.

Dr. DeWitt Stetten, a former deputy director for science at NIH, compared Zasloff's moment of illumination to that of Alexander Fleming, who discovered penicillin because he noticed that bacteria did not grow on culture dishes contaminated with a certain mold.

"It takes more than just seeing," Stetten said. "You've got to be aware of what you're looking at."

The chance observation led Zasloff, a pediatrician with a doctoral degree in biochemistry, away from his principal area of research, exploring how genetic messages travel out of a cell's nucleus to its cytoplasm, the region where proteins are made. "My political statement is going to be that you never know the ways of research," he said. "Let science be free. . . . We are not so smart as to know if what we do today is going to be important tomorrow."

The first thing Zasloff did after his insight was examine tissue from a healing frog wound under the microscope, looking for congregating white blood cells and other signs of the normal infection-fighting process seen in a healing wound in humans. They were absent. That persuaded him that his intuition was right: there must be some other, previously undiscovered biological defense system at work.

Zasloff's mind was ripe for such an idea because it had long been preoccupied with two related subjects. Zasloff, who came to NIH as a research associate in 1975 after completing his medical and doctoral degrees at New York University and his pediatric residency at Children's Hospital in Boston, had wondered for a decade why children born with cystic fibrosis, an inherited disease, develope frequent, severe lung infections from bacteria not found in the lungs of healthy individuals. Like others, Zasloff believed there must be some important defect in their natural defenses.

He was also intrigued by the implications of the discovery several years ago of cecropins, substances found in some insects, which appear to confer powerful, natural protection against bacteria. Cecropins are peptides, small bits of protein, and they apparently disrupt bacterial membranes -- the organism's "skin" -- without harming the membranes of insect cells. "That, to me, was too beautiful," Zasloff said. "I realized that nature wouldn't throw that away." But no one had yet discovered a similar defense system in higher animals. Perhaps the skin of his frogs would yield a clue.

He shared his hunch with a close friend and colleague, Dr. James Sidbury, a pediatric geneticist and former scientific director at the institutes. Sidbury, who has worked with Zasloff since coming to NIH in the late 1970s, described him as a brilliant and original scientist who often comes up with new approaches to problems and whose restless mind quickly sees connections that others miss.

"I was absolutely fascinated" with Zasloff's idea about the frog skin, Sidbury recalled. "Something that simple is usually going to be right. This was so simple and so direct that you had to think this was really going to be very big. I didn't realize how big."

Zasloff tested some mucus from the surface of a frog's skin to see if it inhibited the growth of bacteria. On the contrary, the mucus itself was loaded with bacteria, which made the skin's ability to heal all the more surprising.

Next, Zasloff ground up some skin from an African clawed frog and treated it chemically to extract its components, then purified the crude extract into its constituent parts and tested each to see if it prevented bacterial growth. At first, he got a whiff of antibacterial activity, just enough to encourage him -- and then, for almost a month, nothing.

Every time he felt like giving up, he said, he looked at another healing wound on one of his frogs and said, "It's there. It's got to be there."

Zasloff tried testing a small amount of clear fluid from one of the wounds and a sample of fluid found inside the belly. Each time, he was rewarded with faint but clear evidence of antibacterial activity.

It then occurred to him that the extraction process might be releasing cellular enzymes that destroyed the antibacterial substance he was trying to find. So he modified the procedure to reduce the activity of such enzymes during the extraction.

The next time he tested portions of the skin extract, the results were striking. When fluid from one of the samples was applied to a Petri dish coated with bacteria, it left a clear signature: a conspicuous spot where no bacteria grew.

Sidbury watched Zasloff's progress with growing excitement. "Each morning it was something different," he recalled. "It was incredible how fast" the project proceeded. "His mind goes a mile a minute, anyway. . . . I've been around a long time and I've never seen any really solid project go anywhere close to that fast."

"The other thing that boggled my mind {was that} he was the only one working on it," Sidbury added. "All this was with his own hands."

Most projects at NIH are undertaken by large groups of researchers. But at first, Zasloff said, he was unable to persuade even one other scientist that studying the frogs' skin was worthwhile. Later, as his results grew more intriguing, he had another concern endemic to the highly competitive world of science: If too many others heard about his work, someone else might beat him to the answer before his findings were published.

Sidbury said such reticence, though prudent, went against Zasloff's grain. "Mike is just completely open," he said. "It kills him to have secrets. His natural, knee-jerk reaction is to tell what's on his mind and communicate the excitement."

Naturally energetic, Zasloff was so elated by his findings that he couldn't sleep at night. Working in a narrow, cluttered laboratory on the 10th floor of NIH's Clinical Center, he set about purifying the promising fraction. "He works very fast with his hands," Sidbury noted. "He knows exactly the question he's asking."

The active ingredients turned out to be peptides, small bits of protein made of linked amino acids. Using a process called high-pressure liquid chromatography, Zasloff isolated two peptides highly active against bacteria. Two coworkers, Harry C. Chen and Brian Martin, then analyzed the peptides to identify the precise sequence of amino acids present in each.

The sequences bolstered Zasloff's theory that the new peptides represented a defense system similar to insects' cecropins. Like the cecropins, the makeup of the two new peptides gave them a special chemical property. They could twist into long, spiral-shaped molecules with two sides, one side soluble in fat and the other side soluble in water. This property lent them unique potential for interacting with the membranes of bacteria, viruses and animal cells. Such membranes, which are made mostly of fat, are crucial to the survival of all living things, and a number of antibiotics and other drugs work by altering their function in various ways.

Equally intriguing, the length of the peptide chain -- 23 amino acids -- was close to that of the cecropins, and was just the length needed to span such a membrane.

He decided to call them Magainin I and Magainin II, coining the name from the Hebrew word for shield. "I used it because it came from the skin and it was shielding, in my opinion," he said, adding, "What the hell, I hadn't heard a Hebrew name" in science before.

Zasloff had so far tested his peptides against only one kind of bacteria, Escherichia coli. The next step was to see whether they could stop the growth of other organisms, including several that frequently infect children with cystic fibrosis and other patients with decreased immunity to infections.

Magainin II proved more potent, but both were active against many kinds of bacteria. Next, Zasloff tested them against Candida albicans, a common yeast that produces difficult-to-treat infections in patients with AIDS and other diseases that suppress immunity.

"Much to both of our amazement, that was wiped out like it was a bacteria," Sidbury recalled.

When Zasloff tried the magainins against protozoa -- the group of single-celled organisms that includes amoebae, paramecia and malaria-causing parasites -- what he found was astonishing. The organisms were killed within a minute or two, so quickly that he could watch their demise through a microscope.

During a recent interview, Zasloff demonstrated by focusing a microscope on paramecia swimming in a drop of water. The transparent, barrel-shaped creatures could be seen moving rapidly across the field. Then he added a drop of magainin solution. Within a few seconds, the single-celled animals slowed down and went into a graceful spin, visibly swelling as water crossed their cellular membranes and could no longer be pumped back out. When the pressure of fluid inside grew too great, the membranes ruptured.

Watching what happened to the paramecia suggested to Zasloff that magainins kill some microscopic invaders by damaging their ability to maintain fluid balance, a critical function of all living cells. He speculated that a defect in a related human defense system might explain the vulnerability of cystic fibrosis victims to infection.

Zasloff explained that in cystic fibrosis, a little-understood defect in the cells of mucus-secreting glands seems to affect how such cells handle fluid, leading individuals with the disease to produce abnormally thick mucus and to suffer frequent infections. The magainins, which come from special glands in the frogs' skin, have the dual properties of killing dangerous microorganisms and affecting cells' fluid transport. He speculated that a deficiency of related peptides in humans might explain both the thick secretions and the vulnerability to infection found in cystic fibrosis.

To verify that the peptides he had isolated were truly natural products of the frogs' cells, and not the result of an experimental fluke, Zasloff used techniques common in modern molecular biology to isolate the genetic message coding for the two magainins. He showed that the cell manufactured them as part of a larger protein called a precursor, which was later chemically snipped apart to release the peptides.

Finally, he had a biochemical firm manufacture synthetic versions of the two magainins to see if they would be as effective as the natural ones. "I was praying that the damn activity was still there," he said. "You know, it's very scary. You work like this in isolation, there's no other report of anything like this -- you think maybe you're making a terrible mistake."

There was no mistake. The synthetic magainins worked just as well, and were easy to manufacture. They have been patented by the government, and Zasloff said a drug company will be licensed to develop and test them as drugs. He predicted that one of their first uses will be to treat burns, in which damage to the skin destroys the body's protective barrier against infection.

"I'm going to make certain I see this to the bedside," he said.

Coworkers at NIH are now testing the magainins against viruses and various types of cancer cells. Zasloff said that because magainins apparently can chemically distinguish between the membranes of normal animal cells and those of microscopic predators, they may also prove able to kill cancer cells selectively.

Zasloff has since found evidence that his two magainins are part of a larger family of substances that protect amphibians against infection, and he has clues to the existence of related compounds in birds and mammals. But he speculated that the skin of African clawed frogs may be uniquely rich in magainins that evolved as a natural defense against microorganisms living in stagnant pond water.

"I think that we've evolved to a different ecology," he said. "We don't need that degree of defense. They {frogs} are surrounded by microbes."

Zasloff said the frog's granular glands, skin glands that produce magainin, also manufacture a number of other substances similar to important chemical messengers in humans, such as the neurotransmitter serotonin and the stomach hormone gastrin.

He said scientists have often noted that if a frog escapes from a tank and dies in a laboratory, it does not decompose like other animals. He suggested that because of magainins, frogs "sterilize themselves as they die," a property that may explain the use of dried frogs as folk remedies.

He said that if a frog receives an injection of adrenalin, the glands release their contents, including magainins, into the water, killing all protozoa and bacteria nearby. Releasing magainins may allow the animal to kill germs in its immediate environment or to protect its eggs from microscopic predators.

"When you think of the food chain," he said, "it's always the big animals eating the little animals. Nobody's concerned about the little animals {the microbes} eating everybody else."

As news of his discovery hits the scientific press this week, Zasloff is already busily mapping out experiments to look for more magainins. The other day he bounced around his cramped laboratory, quaffing a soda and excitedly describing his strategy for isolating related compounds in mammals.

He paused to gaze admiringly at a tankful of Xenopus swimming vigorously in muddy water.

"Isn't it amazing?" he said. "I've never felt closer to nature."