Doctor Fungus

Mike McGinnis is his name; medical mycology is his game

By Jim Kelly

The Japanese pathologists were stumped. After a routine chest X-ray had detected what looked like a quarter-sized tumor on a thirty-one-year-old woman’s left lung, they had performed a biopsy and discovered not cancer, but an area of dead tissue containing the spores of a fungus. Lab tests identified it as Coccidioides immitis, a species that could cause dangerous, even fatal, respiratory infections, particularly in patients with weak immune systems.

The woman had no symptoms of disease, but that wasn’t what was puzzling the doctors; otherwise healthy patients often fight off fungal infections on their own. What the pathologists couldn’t understand was how a resident of a village in the mountains of Nagano prefecture could have been infected by Coccidioides immitis—a fungus found only in the Western Hemisphere. Was it possible that the organism had somehow been introduced into Japan and was now in the process of infecting a population that had never been exposed to it and might be especially vulnerable to its effects?

To solve their mystery, they called Michael McGinnis, a UTMB pathology professor and world-renowned authority on medical mycology, the study of infections and diseases caused by fungi. McGinnis considered the puzzle briefly, and then began “playing detective” as he puts it, zeroing in on the solution with a series of simple questions.

Had the woman ever been to the United States?

No, she had never left Japan.

“That eliminated her coming to the fungus,” McGinnis says. “Now we had to find out how the fungus came to her.”

Had she ever worked in a textile mill?

Yes, she had—for a year, six years before.

“I knew what had happened then,” McGinnis recalls, “but I thought it’d be better to help them see what the answer was for themselves instead of just telling them.”

He asked one last question.

Had she ever worked with cotton?

When the Japanese doctors replied that she had— that in fact her job had involved opening bales of raw cotton nearly every day—they saw what McGinnis was getting at.

Cotton hadn’t been the only thing in those bales. Every time one had been opened, it had released a cloud of dust from the fields where the cotton had been grown, on farms located in Arizona and California. And mixed with that dust had been spores of Coccidioides immitis, which is common in the American Southwest.

“In general, fungi aren’t looking for a person to grow on or in—they just end up there,” McGinnis says. “And then, if our defenses aren’t working properly, we wind up with an infection.”

Talk to people who know Mike McGinnis and you’ll hear plenty of stories like that one. Anecdotes about the medical mycologist’s mastery of fungal arcana and uncanny ability to see patterns and connections that others miss are matched with others illustrating his quirky Socratic style, friendliness, and generosity with his time and knowledge. “Mike is one of the mycologists who have set standards for years,” says John Rex, vice president and medical director for infections at Britain’s AstraZeneca Pharmaceuticals
and a former professor at UT Health Science Center at Houston. “He’s one of the reference points in the fungal
universe. I knew of him long before I actually met him, and my initial impression was that he was an awfully nice fellow for somebody so famous.”

McGinnis’ demeanor seems at odds with such eminent status. Despite his imposing, bear-like build (he was an All-American hammer-thrower for the Cal State Polytechnic track team), this mycologist comes off as anything but intimidating—perhaps because of the expression most often on his broad face, an odd blend of earnest curiosity and amiable mischief. He got his start in science at age twelve, collecting fossils from riverbanks and quarries, and fifty years later still displays a childlike joy in sharing his discoveries with others.
Today, instead of digging out pieces of shale to uncover long-extinct sea creatures, McGinnis focuses on a group of organisms that are just as strange and mysterious, in spite of being found everywhere from the rain forest to the refrigerator. Defined as yeasts or molds depending on whether they form colonies of round single cells (yeasts) or grow as tangled masses of multicellular filaments (molds), fungi have been placed in a taxonomic kingdom all by themselves in recognition of the profound differences between them and other living things.

Unlike plants, with which they are often confused (although, McGinnis says, fungi are actually genetically closer to animals, which complicates efforts to develop anti-fungal drugs), yeasts and molds are incapable of using sunlight to produce energy. Instead, they must rely on the organic material on which they grow for nutrition. Dead or living, plant or animal (including human), everything organic gets the same treatment: a bath of powerful fungus-made chemicals known as “exo-enzymes,” which break down whatever they touch into a broth of simpler molecules the fungus can absorb and use. Fungi, McGinnis points out, don’t care that the organic material they’re eating might happen to be a piece of a living person.

“In general, fungi aren’t looking for a person to grow on or in—they just end up there,” McGinnis says. “And then, if our defenses aren’t working properly, we wind up with an infection.” Such infections can occur virtually anywhere—on skin, hair and nails, in the sinus cavities, the lungs, and even the deep internal organs. And in a population made more vulnerable by the immune system-weakening effects of AIDS, anti-rejection drugs for organ transplants, and chemotherapy, they threaten many more people today than they did when McGinnis started out in the early 1970s.

Medical mycology remains a small field, though, one in which a single outstanding researcher can have a major impact. McGinnis has made his mark with his work on taxonomy, the biological discipline that aims to understand living things better by classifying them into related groups. “You have to understand that when an odd fungus comes along, it is what is in large part ‘because McGinnis says so,’” Rex says, describing McGinnis’ influence on fungal taxonomy, which has been promulgated through hundreds of papers, a half-dozen books, and doctorfungus.org, a web site he co-founded.

McGinnis’ fascination with the complex jigsaw puzzle of fungal taxonomy has a utilitarian aspect—improvements in the ability to identify and classify species of fungi to help physicians make more accurate diagnoses and drug makers devise more effective anti-fungal agents. But there’s a deeper impulse at work as well, an urge to figure out how the natural world is really organized and pass on that knowledge to others in the most effective and elegant way possible.

“We want to put living things together in such a way that we can clearly see the relationships between similar and even dissimilar organisms, and classify them in a way which is truly related to their evolutionary relationship,” he says. “To me, the scientific name of an organism is part of a classification scheme like the one in a library. It exists so that we can communicate with each other in shorthand, and bring large amounts of information together that pertain to that particular living thing.”

His passion for identification and classification of species may seem old-fashioned—more appropriate to a nineteenth-century naturalist than a twenty-first-century biomedical researcher—but McGinnis also was one of the first to apply the techniques of modern molecular biology to fungal taxonomy. According to David Walker, chair of pathology at UTMB, that kind of enthusiasm for the new world of genomics and molecular biology is rare in such a “morphologically oriented” researcher. “Most structurally oriented people hate numbers, they hate different ways of looking at things,” Walker says. “But Mike saw molecular taxonomy as an opportunity and found a way to excel at it.”

Walker first met McGinnis nearly three decades ago, when both men were young researchers at the University of North Carolina at Chapel Hill. Even then, McGinnis was famous for his ability to dumbfound physicians with correct identifications of obscure fungi. Walker recruited McGinnis to UTMB in 1988, not long after Walker came to head the pathology department. As vice-chair of pathology, McGinnis helped create the World Health Organization Collaborating Center for Tropical Diseases at UTMB, helping lay the groundwork for today’s thriving UTMB infectious diseases program.

“Mike’s a very intelligent and creative guy—he’s an amazing person when it comes to looking at things differently from everybody else and coming up with original solutions to problems,” Walker says. “He also has this ability to see the big picture in a way that an awful lot of people can’t.”

“I think it would be a nice thing to do, to be able to complete this,” he says. “The question of gene expression in microgravity is an important one, and it’s related to something even more intriguing: How has gravity influenced the evolution of life here on Earth?”

In a world where scientists often get locked into narrow specialties, McGinnis has made a point of building connections with all sorts of other researchers. “For me, interacting with different people is really where the enjoyment is,” he says. His colleagues have recognized his efforts repeatedly, most recently by electing him president of the International Association for Human and Animal Mycology in 2003. (In addition, he holds the distinction of having a newly discovered fungus named in his honor—Exserohilum mcginnisii, a species first isolated when it caused a sinus infection in an Arizona man.)

McGinnis has also branched out in a number of less conventional directions. In the mid-1990s, he and Lester Pasarell, who then supervised his lab, created a pioneering web site that has evolved into doctorfungus.org, one of the world’s most comprehensive resources for information on fungi and their relationship to human health. For more than a decade he’s served as an expert witness in litigation involving fungus infestations in buildings, a legal field that mushroomed after high-dollar judgments generated a media frenzy about “killer toxic mold.” And in collaboration with NASA, he’s launched an investigation of the biology of fungi in microgravity, carrying out a series of studies that culminated with an experiment lost on the tragic final flight of the space shuttle Columbia.

The NASA work has dominated McGinnis’ basic research agenda for the last six years. Conducted in the apparatus destroyed with Columbia and ground-based “bioreactors” that simulate weightlessness in constantly turning cylindrical vessels, it aims to determine how the lack of gravity affects the growth, metabolism, and response to anti-fungal agents of baker’s yeast. The experiments also draw on McGinnis’ skill with molecular techniques, measuring changes that show alterations at the most basic level of cellular activity.
NASA wants to know how fungi behave in space because it’s concerned about the health of astronauts on long-duration missions. The ability of fungi to thrive inside spacecraft has long been known; the Russian Mir outpost, the longest-occupied human orbital habitat, suffered a particularly heavy infestation, with fungi filling nooks and crannies all over the station, clouding portholes, and creating worries about fungi-generated chemicals damaging wiring behind control panels. Moreover, potentially “there’s a direct impact on crew health,” McGinnis says. “We have evidence that bacteria become more virulent in microgravity. Yeast infections may do the same thing. And if you’re going to Mars, there aren’t any drug stores around.”

Characteristically, McGinnis also sees additional dimensions to his NASA investigation. Understanding what genes are turned on and turned off in microgravity, he points out, may provide a way to compare and understand how fungal genes function on Earth. And since yeasts have long been studied in basic genetic research, it makes sense to employ them as model organisms to study the effect of microgravity on gene function in general—generating insights not only about how the process works in fungi, but also in animals, including humans.

If Columbia had returned safely, McGinnis would be pondering these questions in light of data generated by the yeast-growth studies carried out on board the shuttle. As far as he knows, the experiments went well. Instead of being transmitted from orbit, though, these results were intended to be analyzed after the flight by a lab on Earth. And whatever the results were, they were obliterated when Columbia broke apart high over Texas. “We spent five years putting that together, and it was all lost on that one flight,” he says.
Despite the trauma of Columbia’s loss and the uncertainty of future launch schedules, McGinnis is pushing forward with a proposal for experiments to grow yeast that could be performed at the International Space Station after shuttle flights resume. “I think it would be a nice thing to do, to be able to complete this,” he says. “The question of gene expression in microgravity is an important one, and it’s related to something even more intriguing: How has gravity influenced the evolution of life here on Earth?”

That’s a big question, and not one likely to be answered by a few simple yeast-growth experiments. But for McGinnis, the chance to add a few pieces to the puzzle and pass it along to others offers its own rewards. “In a way, I guess I am a naturalist,” he says. “You know, I always wanted to do something that would give me the chance to tell people what they were seeing in the world—to stand on a mountainside with my children and say, this is why those rocks are together over there, and this is how those lichens fit in, and those flowers. And in a way, I guess that’s what I do."