Junk in our genome?

Re: "Junk worth keeping,"1 just because functions have been identified for some regions of genomes thought to be non-functional does not mean that all regions thought to be junk are functional. This is particularly true for bloated genomes (like the human genome) which are loaded with parasitic elements.

A nearly neutral model for the evolution of eukaryotic genome structure, proposed by Michael Lynch2, suggests that mutational biases can overwhelm the costs associated with many deleterious changes if population sizes are small enough. If so, many features of eukaryotic genomes (introns, elaborate transcriptional regulatory systems, etc.) would be the result of semi-neutral processes, not adaptive evolution.

Richard Meisel
The Pennsylvania State University
University Park, PA
meisel@psu.edu

References

1. R. Gallagher, "Junk worth keeping," The Scientist, 21(7):15, July, 2007. 2. M. Lynch, "The origins of eukaryotic gene structure," Mol Biol...
"Our problems aren't because we got too much [money] too fast, our problem is that we changed our priorities."

When more funding isn't enough

As an assistant professor constantly thinking about tenure (thus, thinking about funding), I couldn't agree more with Adam Jaffe's assertion in "Double research funding? Be careful" 1 that the current funding situation is bad, frightening, terrifying, even demoralizing at times. We must, however, consider the following: more National Institutes of Health grants are being funded than ever before. Even if this means a smaller percentage of applications are being funded, it's difficult to argue that more grants equals bad.

I also argue that writing proposals can be helpful, even if they're not funded. The very act of creating the proposal causes us to think carefully about our experiments, and gain a sense of the direction our labs will follow over a period of several years.

The article suggests that we can avoid the pitfalls encountered by the NIH if we increase the National Science Foundation budget more gradually, but it's difficult to imagine how a slower increase will have the effect we all seek. Our problems aren't because we got too much too fast, our problem is that we changed our priorities. We decided to spend money elsewhere instead of staying true to our past priorities. Moreover, when calling for a slower, steadier increase in the NSF budget, how confident can we be that a plan to do anything over 10 years is possible in today's political environment? Even in times of peace and budget surpluses, it seems these days that the White House thinks on a four-year timeframe.

As tough as it is to be a young scientist these days, if I were forced to choose between a slim possibility of doubling the budget over ten years (which may or may not be better in the long run) or a far better chance of doubling it over five, I would take the sure bet any day, even with the problems it may bring.

Derek Daniels
University at Buffalo, SUNY
Buffalo, NY
danielsd@buffalo.edu

When the NIH budget doubled, universities and other institutions built new facilities and hired more people, reasoning that NIH grant money would cover all expenses for supporting and maintaining research in these facilities, and universities will not be financially responsible. When the NIH budget leveled off, that money wasn't available, which helped create the current crisis.

Expanding the NIH budget without changing the system will be counterproductive. Universities must be more responsible for their expansions. They have to know that NIH grant money under no circumstances will fully cover labs and facilities, and part of the financial responsibility is theirs. In order to achieve it, NIH needs to put a cap on the fraction of principal investigator (PI) salaries covered by grants. For example, if NIH regulations do not allow covering more than 40% of a PI's salary, then universities will know that they are responsible for the remaining 60%. This means that in fundraising campaigns they will have to consider future responsibilities for new PIs, will organize the fundraising accordingly, and expand responsibly.

Of course, such a transition will be painful for universities, and NIH needs to make it as smooth as possible. For example, it could be done gradually within several years. I believe at the end everybody will benefit, and future NIH expansions will not damage the system of scientific research.

Michael Sherman
Boston University Medical School
Boston, MA
sherma1@bu.edu

References

1. A.B. Jaffe, "Double research funding? Be careful," The Scientist, 21(7):31, July 2007.

Peer review: too much of a good thing?

Re: "Can journalists help improve peer review?" 1 Andrew Moore's idea to let journalists examine research about to be published for a media peer review sounds nice, but I think it is a very bad idea. My prime objection is that journalists who are enlisted for this review process - even though they will be paid by "philanthropic or scientific foundations" - will become part of the system. Thus, they jeopardize their objectivity. It will be only a matter of time before the big journals or the pharmaceutical industry will start organizing educational conferences for reviewing journalists at nice locations, enticing them to adopt a certain point of view.

Also, peer review by journalists will never stop all bad press releases. Therefore, it might be more helpful if newspapers and other media would be stimulated to enlist properly trained science journalists. It is strange that the sports pages are usually filled by highly specialized journalists, whereas too often science stories are left to whoever wants them.

Rene Fransen
Freelance science journalist
Roden, The Netherlands
r.fransen@rug.nl

References

1. A. Moore, "Can journalists help improve peer review?" The Scientist, 21(7):25, July 2007.

Lessons, limitations of animal models

Model organisms provide essential windows into normal development. But, it is strange that despite years of failure, the National Institutes of Health continues to pour dollars into research for therapeutics using rodent models.1 Obviously there are technical challenges involved in developing and refining human therapies, but mice appear to be a very, very poor model for human diseases. The most glaring I think is cancer research. How many times have cancer cures been observed in mice? The research money could be much better spent looking for better models that would be more appropriate for translational research.

Brian D. Ackley
University of Kansas
Lawrence, KS
bdackley@ku.edu

We, as scientists, must admit that models are simply models. Although statistical robustness is certainly needed in animal studies, it must be accepted that models do not, and often cannot, recapitulate sophisticated human physiology. These vast differences between humans and non-primates are not identified until one examines systems at a biochemical level, and this has become a very rare event. For too long, we have studied evolution in terms of investigating "similarities" between different species. These examples gave us clues as to the existence of evolution. But the evolutionary process, by definition, actually refers to the vast differences that exist between species, and even between cells within a given species.

I suspect that even if all the animal models faithfully mimicked the actual primary defects found in human diseases that they would still fall short of mimicking the human situation. For this reason, I sometimes wonder to what extent science actually advanced (in terms of understanding human disease) during the genomics era?

Richard N. Sifers
Baylor College of Medicine
Houston, TX
rsifers@bcm.tmc.edu

References

1. A Gawrylewski, "The trouble with animal models," The Scientist, 21(7):44-51, July 2007.

Seeing inside the sea anemone

While the findings presented in "Surprises in the sea anemone genome" 1 certainly indicate that this ancestral animal genome was quite complex, fly and worm genomes are unquestionably not without complexity of their own.

The study authors suggested that the sea anemone genome has some similarities to the human genome that the genomes of fruit flies and nematodes don't share, and that the fly and worm genomes perhaps lost some of their complexity as they evolved. Surely it is as reasonable to suppose that fly and worm evolution replaced some of the ancestral intricacy with more streamlined, efficient, and successful (in the Darwinian sense) genomic organization? Could it be that the "intricacy" of a genome is best assessed at the level of expression?

Simon Waters
Worcester, MA
simon@simonwdesign.com

References

1. ML Phillips, "Surprises in the sea anemone genome," The Scientist Daily News, July 5, 2007.

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