Editorial | Published:

A timely reminder

Nature Structural & Molecular Biology volume 14, page 569 (2007) | Download Citation

An interesting and diverse meeting last month reminds us of the importance of supporting basic science research.

A rather peculiar meeting took place at the Cold Spring Harbor Laboratory last month. For starters, many presentations began with an image of the Earth seen from space, half shrouded in nocturnal shadow (no, this wasn't a sci-fi convention). Another unusual feature was the curious mix of scientists—biochemists, microbiologists, fly and mouse geneticists, plant biologists, neurobiologists, clinical researchers—all mingling and discussing their work. Even for a seasoned conference-attending editor, this was quite a remarkable gathering.

The topic of the 72nd Symposium on Quantitative Biology was 'Clocks and Rhythms'. Most researchers in the field, also called chronobiology, investigate circadian rhythms, endogenously generated rhythms of about 24 h that allow organisms to adjust to the environmental changes caused by the Earth's rotation. This internal clock determines sleep and wakefulness cycles, when to forage or when to photosynthesize. The clock is reset by environmental cues such as light and temperature, but the controlled processes remain rhythmic even when the organisms are kept under constant conditions in the lab, demonstrating the endogenous nature of the clock. There are other instances of temporal organization in biological systems, such as developmental processes and aging, and these were also discussed at the meeting.

Because all organisms live in four dimensions, keeping track of time is an important ability that should influence several aspects of physiology and ecology. Nevertheless, chronobiology has a relatively small community, albeit an active one. The field has advanced to the point where the molecular mechanisms are now being revealed. Integration of knowledge from molecular events to cellular activities to behavior, the final output of the clock, still looms in the future, and will require the interdisciplinary approach that is already an essential trait of chronobiological research.

In addition to the notable progress within the field, chronobiology is also attracting attention from researchers in other areas. Scientists investigating cancer, aging, immunology and metabolism are uncovering interesting connections between these processes and clock components. This knowledge will have a direct impact on issues such as timing of drug delivery. Learning how the biological clock works—and how it can be tinkered with—may also lead to pharmaceutical and biotechnological applications. For instance, clock-modulating drugs could help patients with sleep disorders (not to mention millions of jet-lagged travelers). The manipulation of biological rhythms in plants might lead to higher biomass yields, making biofuels a more attractive alternative to nonrenewable fossil fuels.

It is not really unexpected that so many biomedical areas are linked to biological clocks, given their pervasive influence. However, the bounty of potential applications was not what drove the field to where it stands today. According to Rae Silver, senior advisor at the National Science Foundation, the main force pushing research in the core of the field is pure curiosity. Several researchers actually stumbled into clock studies by chance, after finding that the transcription of a particular gene oscillated in a circadian way. The main questions being asked are basic: How does a biological oscillator work? How does it receive input from the environment? How does it control the output?

Yet it might be hard to get funding for exploration of such basic questions. To Michael Menaker of the University of Virginia, the field is indeed undersupported, even considering the overall grim funding situation at the moment. This is even more critical for systems that lack obvious applications. However, as Menaker points out, a longstanding feature in the clocks field, and one of its strengths, is the use of myriad model organisms. In fact, more organisms should be studied, as a diurnal mammalian model is still sorely needed, and insects other than flies would offer new insights. For instance, Steven Reppert of the University of Massachusetts Medical School, who has worked on mammalian and fly clocks, is now investigating the migratory monarch butterfly. This organism uses the sun to orient itself during migration, and as the sun changes its position relative to the horizon throughout the day, the butterfly is able to time-compensate its compass, using its biological clock. Reppert has found that the clock in the butterfly resembles that of Drosophila, but also contains a factor similar to one found in vertebrates. Understanding how these two systems coexist and cross-talk in the butterfly and other insects could shed light on the integration of multiple oscillators in other species. Another example is the work of J. Woodland (Woody) Hastings at Harvard University on dinoflagellates — work that suffered from lack of support in the 1990s, even as it revealed that the clock in these organisms is regulated by post-transcriptional events, in contrast to the transcriptional loops thought at the time to govern the eukaryotic clock. Similar mechanisms were later found to operate in flies and mammals as well.

These examples raise two important points. The first is that concentrating research efforts in just one or two systems because of their potential applications will necessarily limit our appreciation of nature's ability to find different solutions to the same problem. Moreover, general principles can emerge only through comparison of many different systems. A second point is serendipity, illustrated by well-known studies with no apparent applications that later turned out to be of great utility or general importance. During Hastings' career studying bioluminescence of marine organisms, two examples stand out: the identification of green fluorescent protein from a coelenterate (which, along with several engineered versions, is one of the most widely used tools in biology) and the discovery of quorum sensing in bacteria (which turned out to be widespread among bacteria and to play a major role in pathogenesis).

As Hastings puts it, basic research provides a wider understanding of biology in all its ramifications and contributes to the body of knowledge on which practical and medical applications depend. This is certainly true in the clocks field, which has been drawing scientists from other areas, in a clear example of 'if you build it, they will come'. We just have to provide the builders with the necessary support.

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