Photo by Todd McNaught
Unlike scientific discoveries in the movies, no one shouted, "Aha!" Instead, the detection of a new fungal species began with Molly Weaver's furrowed brow and a sense that something was amiss. Weaver, a technician in Dr. Kieren Marr's lab in the Clinical Sciences Division, had noticed some odd properties in mold samples she was studying. The specimen was supposed to be a species called Aspergillus fumigatus, a fungus that can cause life-threatening infections in transplant patients. She called over Dr. Arunmozhi "Arun" Balajee, a staff scientist in the lab, and thus began a four-year quest to determine what exactly was in that petri dish.
A new species
Balajee, a mycologist — a scientist who works with fungi — agreed the mold was "weird" and examined samples under the microscope. "I looked at them in many classical mycology ways and it looked very much like A. fumigatus except there were subtle differences. In a regular microbiology lab, they wouldn't have noticed this," she said. "So we decided to do a molecular analysis."
A long and exhaustive investigation of the mold's genes by Balajee and Marr, with technical support from Jennifer Gribskov and University of Washington computational biologist Dr. David Nickle, proved the lab had uncovered a new species — Aspergillus lentulus. While novel fungi are frequently found in crops and soil worldwide, this discovery is important since all of the A. lentulus samples were recovered from clinical specimens. Balajee and colleagues published their findings in the March edition of the journal, Eukaryotic Cell.
This marriage of classical mycology — a very defined field of observation that hasn't changed much since its beginnings in the 1860s — and molecular phylogenetics — looking at species and their relationships on a genetic level — yielded irrefutable evidence of a distinct species. Good thing, said Balajee, since you "can get kicked around" for making such bold pronouncements.
The Fred Hutchinson scientists were so nervous about announcing a new species that they played it safe until the evidence was rock-solid. They published their first paper on the findings in 2003, but cautiously called the mold a variant of A. fumigatus.
"It's difficult to define a new species," Balajee said. "You have to be careful because there can be small variations in growth and structure because fungus grows differently in different conditions. Everything has to be very consistent before you compare."
"Two fungi can be physically alike but genetically different," she said. "By using robust phylogenetic tools, we proved that our fungi deserved a species status of their own. Even the most authoritative fungal laboratories thought this was A. fumigatus. It took us to say it."
"A reviewer of the paper said, in effect, 'Mycologists usually don't go to such lengths to define a species, and these people have done everything.' I'm really proud of it."
Praise and predictions
Thoroughness has its rewards. In March, a peer-evaluated scientific literature Web site — Facultyof1000.com — selected Balajee's work as the best new biology paper. The reviewers praised the multi-gene approach used by Balajee and her infectious-disease colleagues, predicting that the method will lead to a sharp increase in the identification of new fungi in the future.
A particularly satisfying moment for Balajee occurred when Dr. Rob Samson, a renowned European mycologist with the world's largest collection of fungus, requested a sample of A. lentulus — the professional equivalent of Michael Jordan asking for pointers on his shot. She agreed, of course.
While some skeptics initially argued that the species was likely a mutation of A. fumigatus specific to the center — perhaps due to a unique combination of drug therapies — Balajee and colleagues have now identified A. lentulus at several different clinical centers in the United States, Japan and Australia. "There's not an argument anymore," Balajee said.
Aspergillus is a group of molds, only a few of which can cause illness in humans and animals. The diseases caused by the molds are called aspergillosis; not all are severe, but some can have lethal consequences for people with weakened immune systems. Mold infections have increased steadily in this population over the last decade. Almost 10 percent of transplant patients get invasive aspergillosis, leading to a significant number of deaths.
In the lab, A. lentulus is resistant to multiple antifungal medications, which may mean it could be difficult to treat in patients. Balajee and Marr are working with animal models now to test new therapies.
Balajee tempers her excitement over the fungal discovery with the pragmatic concerns of patient-care providers.
"Clinicians don't care what you name a specimen. It's just a fungus for them, and they need to get their patient well," she said. "This is clinically relevant only if you have discovered a new species that cannot be treated optimally with available medications."
"But this is an exciting time. Combining mycology with molecular identification will definitely change things. Fortunately for our patients and for my colleagues, this is the era of thrilling new discoveries in mycology."
More than anything, Balajee said, this discovery is "all about great team work, with each of us adding to the success of the project."