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Monday, May 28, 2007

SCIENCE Questions: What Controls Organ Regeneration?

"What Controls Organ Regeneration?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Davenport, R. John (2005) What Controls Organ Regeneration 309: 84.
[Text] [PDF]
John Davenport is Science magazine's editor for the Science of Aging Knowledge Environment (SAGE KE).

He writes,
Unlike automobiles, humans get along pretty well for most of their lives with their original parts. But organs do sometimes fail, and we can't go to the mechanic for an engine rebuild or a new water pump--at least not yet. Medicine has battled back many of the acute threats, such as infection, that curtailed human life in past centuries. Now, chronic illnesses and deteriorating organs pose the biggest drain on human health in industrialized nations, and they will only increase in importance as the population ages. Regenerative medicine--rebuilding organs and tissues--could conceivably be the 21st century equivalent of antibiotics in the 20th. Before that can happen, researchers must understand the signals that control regeneration.
This is another example of a "fundamental" science question that's put in the context of technology development. I find this disappointing. Rather than simply expressing an interest in organ regeneration for the sake of understanding developmental biology, the writer assumes that the question has to be rationalized by making it relevant to medicine.
Animals such as salamanders and planaria regenerate tissues by rekindling genetic mechanisms that guide the patterning of body structures during embryonic development. We employ similar pathways to shape our parts as embryos, but over the course of evolution, humans may have lost the ability to tap into it as adults, perhaps because the cell division required for regeneration elevated the likelihood of cancer. And we may have evolved the capacity to heal wounds rapidly to repel infection, even though speeding the pace means more scarring. Regeneration pros such as salamanders heal wounds methodically and produce pristine tissue. Avoiding fibrotic tissue could mean the difference between regenerating and not: Mouse nerves grow vigorously if experimentally severed in a way that prevents scarring, but if a scar forms, nerves wither.

Unraveling the mysteries of regeneration will depend on understanding what separates our wound-healing process from that of animals that are able to regenerate. The difference might be subtle: Researchers have identified one strain of mice that seals up ear holes in weeks, whereas typical strains never do. A relatively modest number of genetic differences seems to underlie the effect. Perhaps altering a handful of genes would be enough to turn us into superhealers, too. But if scientists succeed in initiating the process in humans, new questions will emerge. What keeps regenerating cells from running amok? And what ensures that regenerated parts are the right size and shape, and in the right place and orientation? If researchers can solve these riddles--and it's a big "if"--people might be able to order up replacement parts for themselves, not just their '67 Mustangs.
These are interesting questions but they're hardly fundamental question on the frontiers of scientific knowledge. The article alludes to the answers—it's a question of regulating gene expression. There are no profound mysteries here. What controls organ regeneration is almost certainly the same thing that controls other aspects of development; namely, signals (such as hormones), and transcription factors.

We may not know the details but it sure looks to me like we already know the principles. Recall that the special issue was introduced by an essay on "In Praise of Hard Questions" [see: SCIENCE Questions: Asking the Right Question]. The type of questions were defined as,
Science's greatest advances occur on the frontiers, at the interface between ignorance and knowledge, where the most profound questions are posed. There's no better way to assess the current condition of science than listing the questions that science cannot answer.
So the question is whether understanding organ regeneration is really on the frontier or whether it's part of a mopping up exercise behind the front lines.

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