The Role of Chance

By Danielle LaVaque-Manty

It's only by chance that Daniel Klionsky ended up studying autophagy, a process of cellular degradation—literally, "self-eating"—that could, if brought under human control, lead to advances in the treatment of not only cancer but also neurodegenerative diseases such as Huntington's and Parkinson's. He certainly didn't plan to. "It's not like I said, hey, autophagy, that's going to be a great field, I think I'll study that."

In fact, when he enrolled in college at UCLA, he thought he would major in history. But pragmatic concerns soon troubled him. "At some point, I thought, what am I going to do with this, in terms of a career?"

He discovered, too, that his college courses in history just weren't that interesting. "I think part of me started to say, what is the point of this? This is all known information, I'm trying to memorize this, and it's in these books...yes, I can do it, but why?" He had also been taking biology courses all along, so he decided to switch.

After spending a quarter taking an intensive course on Catalina Island, he thought he might want to focus on marine biology, a plan he now finds "bizarre." For one thing, "I'm prone to motion sickness, so being a marine biology major was not really that sensible." For another, "if one is getting out of history because of concerns about a future career, marine biology is not necessarily a whole lot better."

A very different biology course taught by an electron microscopist also excited him, so when he applied to graduate schools, he applied about equally to marine biology and basic science programs, ultimately deciding to pursue cell biology at Stanford. This, too, was partly due to chance: when he went to interview there, one of the people he talked to, who later became his adviser, was working on the ATPase in bacteria, which Klionsky had enjoyed learning about in the electron microscopy course. That hooked him. "It's almost scary when you think back," he says, "how many of these things are by chance."

When he finished graduate school, he decided to switch to protein targeting and wanted to work on a eukaryotic system, though he wasn't sure which one. He applied for several postdocs, and chose to go to Caltech, where he could work with yeast, which has a simpler eukaryotic system than that found in mammalian cells.

Caltech held another attraction as well: Scott Emr. "Here's a guy who was so excited he almost couldn't sit still in his chair—'Let me tell you about this project, this is great, you're going to love this'...I thought, wow, if in my postdoc I'm feeling a little bit tired, I'll just go talk to this guy, and I'll be energized."

Last but not least, going to Caltech would let him stay in California. "At that time, I thought California was the place to be. I didn't think you really could live outside of California."

His first faculty position was also in California, at UC Davis. There, while studying an unusual protein pathway through a cell, he conducted a canvas of similar research. "Just to be thorough," he talked to a couple of labs working on autophagy. He was shocked to discover a major overlap in findings from those labs and his own, and depressed by the implications. "Oh, no!" he says. "Who wants to work on autophagy?"

Soon enough, however, someone discovered that autophagy played a role in tumor suppression, and the field began to take off.

Soon, too, he decided it was possible to live outside of California after all, and he chose to move to Ann Arbor. He accepted a position in the Department of Molecular, Cellular, and Developmental Biology in 2000, and became a charter member of the Life Sciences Institute in 2003. The Institute, he says, offers a wonderfully collaborative environment. "The degree to which people are willing to help, to interact, is amazing...it's just an accelerated level of interaction."

Klionsky, a dedicated teacher, was named a Distinguished Teaching Scholar by the National Science Foundation in 2003. In 2006, he not only received a 1.5 million dollar grant from the Howard Hughes Medical Institute to promote innovative teaching of introductory science at research universities, but was also named an Education Mentor in the Life Sciences by the National Academies.

In 2005, with the encouragement of an editor at Landes Bioscience, he started a new journal, Autophagy, and became its editor-in-chief. He wasn't sure the world was ready for an entire journal dedicated to the subject, but the editor at Landes said, "By the time it's obvious that it's time for a journal, it's going to be too late. Someone else will do it."

So he decided to take the plunge, "not fully knowing what I was getting myself into, I have to say." For example, he didn't know that journals aren't automatically listed in PubMed. They have to publish four issues before they can even apply, and then they are evaluated by a committee at the National Library of Medicine.

"In the meantime," he says, "there's this Catch-22," because not being listed in PubMed makes it hard for fledgling publications to attract the high quality submissions they need in order to demonstrate that they are worthy of being listed by PubMed in the first place. Autophagy was accepted last year.

Looking back on the path his career has taken, Klionsky says, "We really stumbled into this, I can't deny it. Sometimes I'll be thinking about it and I'll go, oh my goodness, what if I hadn't done this? What would I be working on or doing now, where would I be? Who knows?"