letter from the director
by Alan Saltiel
In the pursuit of the next discovery, the next publication and the next grant, we often become overly focused on uncovering the small truths that seem to confound us, while forgetting the impact our work can have on real people facing much more difficult challenges. I was recently reminded in a stark and indelible way of the potential significance of our efforts, and how important it is for us to persist in the face of uncertainty, frustration and failure.
Over the past two and a half years I've had the sad misfortune to watch as the son of very close friends struggled with and finally succumbed to neuroblastoma, a childhood cancer that strikes about 650 children a year and is rarely cured. Michael was diagnosed with stage 4 neuroblastoma at 4 1/2 and passed away two weeks after his seventh birthday, after having undergone 20 rounds of chemotherapy, over 50 radiation treatments, experimental treatments in clinical trials, a bone marrow transplant and many surgeries, often traveling to hospitals throughout the country, including U-M.
According to the American Cancer Society, more than 1.6 million new cases of invasive cancer will be diagnosed this year. Despite the significant progress in our understanding and treatment of the disease, many types of cancer remain incurable, especially those that strike children, and we still don't fully grasp what combinations of genetics and environment cause cancer to manifest and spread. The brutal mystery of cancer rivets scientists from a wide range of fields, and the urgency around cancer research has fueled much of our work.
As a result, many of the most important and interesting insights in biology have derived from cancer research, insights that have impacted therapies for cancer and other diseases in a profound way. At the same time, an understanding of cellular processes from work geared towards the desire to diagnose and treat these other diseases has led to unexpected knowledge of how cancer cells behave, and how their multiplication and spreading might be stopped.
For example, progress in two areas—the study of signal transduction (how cells communicate with each other) and cellular metabolism (how cells use or store energy)—has emerged mainly from investigations into metabolic syndrome, immune disorders, and heart disease. Insights from this work have yielded some of the most important and promising new therapeutic approaches to cancer. Likewise, studies performed under the aegis of cancer research, such as those investigating mechanisms of cell differentiation and death, have led to new discoveries in the biology of aging as well as immunity.
We have seen many examples of this cross-fertilization as we assembled the LSI faculty over the last nine years, seeking top scientists from diverse research areas who use different approaches and model systems, each pursuing their own path to knowledge. As the faculty has moved forward on those paths, a few points of convergence have emerged. Unsurprisingly and appropriately, one of those intersections is cancer biology.
Dan Klionsky uses yeast to examine the role of autophagy in cancer cells, learning that defects in this process play a crucial role in cancer cell survival. Yukiko Yamashita is looking at the mechanisms underlying stem cell division in fruit flies, which has provided hints to understanding why some cancer cells decide to divide when they shouldn’t. Jason Gestwicki is deciphering the chemical makeup of tumor cells that have lost the ability to deal with misfolded proteins. Ivan Maillard is exploring how dysregulated notch signaling is related to cancer, and how this pathway might impact the complications of stem cell transplants in cancer treatment. Steve Weiss seeks to understand how cancerous cells move from one place to another in the body, the most fatal attribute of cancer cells. And these are just a few examples.
It’s been more than 40 years since the National Cancer Act increased funding for cancer research in the U.S. Although the committee on Labor and Public Welfare declared war on the disease when it submitted the bill in 1971, the act struck a positive note: “There seems to be a consensus among cancer researchers that they are within striking distance of achieving the basic understanding of cancer cells which has eluded the most brilliant medical minds in the world,” the committee claimed.
Decades later, although much progress has been made, the war against cancer is still on, and a complete “basic understanding of cancer cells” still eludes us. Of course, we are frustrated that as acquisition of knowledge drives the expansion of our horizons, we become more aware of the vastness of what we don’t understand. The complexity of already-complex subjects like cancer seems to increase as we learn more about the basic mechanisms involved. At the LSI, we embrace the ambiguity and unpredictability inherent in scientific exploration, with the knowledge that all good science, whether it leads directly to new therapies, triggers new questions or even sometimes fails altogether, moves us closer to a transformative understanding of biology and disease. We are obligated to Michael and others like him—and to ourselves—to persevere in our pursuit of these most intractable questions.