Whitehead Fellows Roundup

We asked Whitehead Fellows to answer the same question and collected their responses below.

In your opinion, what is the most important unanswered question in biology today?

How does life originate? This is probably the oldest and most basic question that all of biology wants to answer at some level. To have an answer to what makes an organism tick would have tremendous implications for the entire field. That said, this question is probably more of a mission statement than a question that can be answered by a single experiment. Rather it has to be tackled from many different sides. Here at the Whitehead, we’re doing biomedical research, so we focus on what keeps an organism going. We try to get an understanding of diseases and human health. Clearly, our research will have a more immediate impact on human well-being, but it is to be expected that this research will also contribute pieces to the bigger puzzle of what is life.

—Whitehead Fellow Andreas Hochwagen

There are so many important questions in biology, but I personally would have to say: How do organs regenerate?

Researchers have been puzzled for centuries over how organs renew themselves. Organisms such as planaria, zebrafish and salamanders can regenerate whole new organs if the originals are lost or damaged. Although humans are not that flexible, millions and millions of unique types of blood, skin, and intestinal cells are produced each day. Additionally, for instance, after surgical removal of part of a liver, healing signals tell remaining liver cells to undergo division to expand the organ back to its original size. Given this remarkable renewal capacity, then why do our hearts fill with scar tissue, our bones degenerate, and our brain cells die? Could we learn from the renewing tissues in our bodies and teach heart or brain tissue to regenerate?

To a certain extent regeneration of adult tissues occurs by the re-activation of genetic programs that are used during early embryonic development. This is a double edged sword, as these pathways, which induce cell division and proliferation, might elevate the likelihood for cancer. What then prevents highly regenerating cells and tissues from running amok?

Understanding the mysteries of tissue regeneration will not only then be useful for making cell replacement therapies a reality, but understanding the basic biology behind it will also give us tremendous clues about the development of cancer.

—Whitehead Fellow Fernando Camargo

There are so many important questions in biology today that it is hard to pick a single one as "the most." In my opinion, one of the most important questions is one that has been studied for many years—how a fertilized egg develops into a human being. Scientists have been probing this question from various angles , but there are still a lot of gaps in our knowledge. It is also a challenge to synthesize all the knowledge into an integrated view and use this to engineer a cell so that it changes its current status. For example, can we turn a skin cell into a nerve cell? Whitehead scientists have contributed a lot to solving these problems. My lab develops new approaches to integrate high-throughput biological data into system-level views of embryonic development.

—Whitehead Fellow Hui Ge

There are a lot of important questions to be answered in biology. And we may even not know the existence of the most important questions yet and still get the answers through research. That’s the beauty of doing science; experiments will bring us to areas where nobody has ever looked around before. I guess this is why doing science is so much more interesting and exciting than climbing the Mount Everest or sailing the ocean.

—Whitehead Fellow Thijn Brummelkamp

I dislike mega-thought questions. For me, it’s the wrong way to approach things. Most of the time, when people make a lot of progress, it’s by asking small, well-defined questions. In some ways, I think it’s dangerous to think too big. You lose focus on all the small details you need to get right if you get too caught up in trying to make waves.

I'm not sure that the big questions have changed that much. It is our standard for what constitutes an answer that continues to evolve and grow. The most important questions are still (and always will be) where do we come from and how does life work? Are these questions unanswered? Every time we approach an answer to these questions, everyone moves the goal posts and the processes starts all over again. To some, this might sound frustrating but to scientists it means that we never come to the end of this great adventure.

I think what is perhaps most surprising to non-scientists is that big questions are almost always answered by carefully and systematically answering well defined, simple questions, that to an outsider might seem like minutia. I mean to say that the likes of Darwin and Einstein didn't sit around waiting for mega-thoughts. They didn't have a checklist on the whiteboard with a list of the ten most important unanswered questions with check marks next to the ones they already answered. They pulled on small loose ends and as the story unraveled, they had the insight to interpret their results and assemble the big picture.

Each generation of scientists develops a new set of tools with which to study nature. Often discovery is the result of using new tools (often adapted from other fields) or using existing tools to study problems from a new perspective. The last few years have seen the development of single-molecule techniques that allow biological questions to be answered one molecule at a time. At other times discovery is the result of improved technology. For example in biology, the last few years have witnessed the sequencing of genomes and the birth of practical, high-throughput, genome-wide assays. We have become quite proficient in generating massive amounts of data--or "loose ends"--but the magic of science is--as ever--in their interpretation. Unfortunately (or fortunately) this still needs to be done one little mystery at a time.

—Whitehead Fellow Paul Wiggins (from an interview)