Science’s "big questions"

The July 1st, 2005, issue of Science included a list of 25 “hard questions” in celebration of the 125th anniversary of the journal, one of the most prestigious on the planet. (A more detailed discussion is currently underway at Sandwalk — I thought I would throw in my 2 cents).

Here is how they came up with the list, as described by Donald Kennedy and Colin Norman in the introductory article “What Don’t We Know?“:

We began by asking Science‘s Senior Editorial Board, our Board of Reviewing Editors, and our own editors and writers to suggest questions that point to critical knowledge gaps. The ground rules: Scientists should have a good shot at answering the questions over the next 25 years, or they should at least know how to go about answering them. We intended simply to choose 25 of these suggestions and turn them into a survey of the big questions facing science. But when a group of editors and writers sat down to select those big questions, we quickly realized that 25 simply wouldn’t convey the grand sweep of cutting-edge research that lies behind the responses we received. So we have ended up with 125 questions, a fitting number for Science‘s 125th anniversary.


We selected 25 of the 125 questions to highlight based on several criteria: how fundamental they are, how broad-ranging, and whether their solutions will impact other scientific disciplines. Some have few immediate practical implications–the composition of the universe, for example. Others we chose because the answers will have enormous societal impact–whether an effective HIV vaccine is feasible, or how much the carbon dioxide we are pumping into the atmosphere will warm our planet, for example. Some, such as the nature of dark energy, have come to prominence only recently; others, such as the mechanism behind limb regeneration in amphibians, have intrigued scientists for more than a century. We listed the 25 highlighted questions in no special order, but we did group the 100 additional questions roughly by discipline.

The questions are:

What Is the Universe Made Of?
Charles Seife

What Is the Biological Basis of Consciousness?
Greg Miller

Why Do Humans Have So Few Genes?
Elizabeth Pennisi

To What Extent Are Genetic Variation and Personal Health Linked?
Jennifer Couzin

Can the Laws of Physics Be Unified?

Charles Seife

How Much Can Human Life Span Be Extended?

Jennifer Couzin

What Controls Organ Regeneration?
R. John Davenport

How Can a Skin Cell Become a Nerve Cell?
Gretchen Vogel

How Does a Single Somatic Cell Become a Whole Plant?
Gretchen Vogel

How Does Earth’s Interior Work?
Richard A. Kerr

Are We Alone in the Universe?
Richard A. Kerr

How and Where Did Life on Earth Arise?

Carl Zimmer

What Determines Species Diversity?
Elizabeth Pennisi

What Genetic Changes Made Us Uniquely Human?
Elizabeth Culotta

How Are Memories Stored and Retrieved?
Greg Miller

How Did Cooperative Behavior Evolve?
Elizabeth Pennisi

How Will Big Pictures Emerge From a Sea of Biological Data?
Elizabeth Pennisi

How Far Can We Push Chemical Self-Assembly?
Robert F. Service

What Are the Limits of Conventional Computing?
Charles Seife

Can We Selectively Shut Off Immune Responses?
Jon Cohen

Do Deeper Principles Underlie Quantum Uncertainty and Nonlocality?
Charles Seife

Is an Effective HIV Vaccine Feasible?
Jon Cohen

How Hot Will the Greenhouse World Be?
Richard A. Kerr

What Can Replace Cheap Oil–and When?
Richard A. Kerr and Robert F. Service

Will Malthus Continue to Be Wrong?
Erik Stokstad

(The other 100 questions are listed here).

Overall, I think there are some good questions in there. I am also happy to see so many of them being about biology, given my interests. However, in some ways the list is rather disappointing. Many of the questions are simply about technology and not science as I understand the term. Others are simply “wait and see” types of questions that involve only continued measurements and no real innovations. Some are “wait and see” questions about technology, in fact.

A more significant point relates to the packaging. Several of the questions are indeed intriguing, but they are not big enough because they focus on one species. Here’s what I mean:

“Why Do Humans Have So Few Genes?”
Humans have what will have to be recognized as the standard amount of genes for a mammal. The real question is, how do those genes relate to proteomes (e.g., do most genes encode multiple proteins, for example via alternative splicing?), how do genes interact, how are genes regulated, and how did the regulatory systems evolve. All very important questions. The fact that humans have what was a somewhat surprisingly low gene number is very much secondary to all of this, and there is really nothing particularly relevant about humans having this number rather than, say, a cow.

“How Much Can Human Life Span Be Extended?”
The real issue is, what are the inherent limitations on longevity? This applies to all animals, not just humans, and can be studied from a variety of perspectives, including evolutionary theories of senescence, physiological work involving DNA damage (e.g., by oxygen radicals), links with diet, and genetic input. As phrased, it is a technology question, but viewed more broadly it is a very interesting and active area of research touching on multiple fields.

“How Can a Skin Cell Become a Nerve Cell?”
The real question is about how stem cells become specialized somatic cells in general, which is a fundamental question in developmental biology that happens to have major medical implications. The “biological alchemy” described in the article comes after the key processes are understood, and of course these insights extend well outside the boundaries of our own species and are relevant to the evolution of morphology in multicellular organisms as a whole.

In general, I think this is a useful exercise and it is always interesting to get people to think about the big picture in science. I just wish the picture were a little more scientific and a little bigger in this particular case.


Incidentally, I am glad to see that two questions that relate to my work made it on the secondary list of 100 questions. So glad, in fact, that I won’t even complain about anything they say, though readers can likely guess what my comments might be…

Why are some genomes really big and others quite compact?
The puffer fish genome is 400 million bases; one lungfish’s is 133 billion bases long. Repetitive and duplicated DNA don’t explain why this and other size differences exist.

What is all that “junk” doing in our genomes?
DNA between genes is proving important for genome function and the evolution of new species. Comparative sequencing, microarray studies, and lab work are helping genomicists find a multitude of genetic gems amid the junk.