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The real lysophospholipid story?

I feel that the article "How the lysophospholipid got its receptor" ¹ focuses too exclusively on cloning of the receptor as the crucial step in defining lysophosphatidic acid (LPA) as a G protein-coupled receptor (GPCR) agonist. Whereas the cloning of the receptor was an important step forward indeed, by that time we (the Moolenaar lab, Gabor Tigyi in Miledis lab, and isolated publications such as Tokumura, Murayama, and others that even preceded that) had clearly shown that there had to be an LPA GPCR. ^2,3 Beyond reasonable doubt: The US death rows are filled with people convicted on less convincing evidence.

We also had made good progress in showing how [the receptor] signaled, and identified a range of different biologic effects downstream of it. In fact, evidence for multiple isotypes had already been put forward before 1996. Cloning of the receptor was not the start of an era, but just the logical next step.

Kees Jalink k.jalink@nki.nl The Netherlands Cancer Institute
Amsterdam

Dr. Jalink was undoubtedly convinced, and correct, that a GPCR existed for LPA, yet this view ignored other ideas at the time, including those of the S1P field that were dominated by second messenger hypotheses. His 1989 publication that influenced us⁴ provided prima facie evidence for GPCRs, yet the data were based on G protein activation, which does not necessarily require a GPCR.⁵ It is fact that a cloned receptor eluded the labs that Jalink cited, and thus other possible mechanisms had to be at least considered in the seven-year hiatus before our report.

The first receptor identity provided clarity and focus, leading rapidly to more LPA receptors, S1P receptors, and molecular genetics approaches, which continue to drive this exciting and growing field forward. The expanding receptor literature of today would not exist in the absence of a first receptor; we feel privileged to collaborate with Dr. Moolenaar towards adding new insights to it. We'd be pleased to have Jalink's help in this endeavor.

Jerold Chun
Scripps Research Institute
La Jolla, CA

Parity over passion

Re: " The Scientist 2007 Life Sciences Salary Report,"¹ I think we need to move past the silly notion that "passion" should drive the scientist forward. Passion doesn't pay the bills. Letting passion lead every decision that you make could well lead the scientist to the wrong side of the poverty line. These are lines of reasoning offered by principle investigators and the higher-ups at the National Institutes of Health that contributed to the glut of postdocs. They have benefited handsomely from the logjam of postdocs that has resulted by creating high-tech sweat shops.

This situation has ruined many a promising career, when financial reality bumped up against passion. It's past time to start talking about parity; if we don't start, we will find that our brain trust has done what I was forced to do: abandon science for business and a decent income.

Ruthmarie Hicks
Pace University
White Plains, NY RGHicks02@aol.com

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NIH: More money, less research?

Editor's Note: In September, to spark a discussion, we published online the opinion included in this month's issue. We asked our readers to provide their hypotheses for why the doubling of the NIH budget doesn't seem to have doubled productivity. We include samples of the responses we received below.

Re: "Is the NIH budget saturated?" Frederick Sachs asks why the Unites States has not experienced a corresponding spike in publications following the recent doubling of the budget. ¹ I suggest part of the problem may be the rising cost of equipment. Particularly in the biosciences, it is hard to do anything now without use of quite expensive equipment such as flow cytometers. Complicating this is the fact that much of this equipment is sold to people with little understanding of it.

So, when a lab tries to duplicate results and they can't, what does that mean? Something? Or nothing? The list goes on and on. That's one reason that today's science is more expensive. Everything is more expensive, and fewer of us understand even whether what we are being sold as kits is actually doing what it claims.

Ellen Hunt
Davis, CA grey-seal@att.net

My guess is that the increased budget allowed and promoted a widened scope, which will produce fewer papers. For example, studying expression of one gene may not be interesting enough; one must study the expression of 20,000 genes to place it into perspective. The higher ambition level is more costly but also more scientifically healthy. In this respect, NIH and the United States may be leading global biomedical science towards more definite and relevant knowledge.

Jonas Blomberg
University of Uppsala
Sweden jonas.blomberg@medsci.uu.se

Surely in the last decade we have seen an increase in the number of publications from large multinational projects, with extensive author lists. If the number of published NIH-funded authors (on all publications) was plotted over the same period, would this increase with the rising budget? The rise in quality means that larger projects are tackled, with more authors, and hence fewer publications.

Andrew Currie
University of Western Australia ajcurrie@cyllene.uwa.edu.au

One factor that could explain, at least partly, why publications have not kept pace with total funding is that, under increasing pressure, researchers have been spending more of their time writing grant proposals and less time writing journal articles. Also, as the best journals have become more competitive, increasingly, articles have to be submitted serially to multiple journals, slowing down the publication process. And finally, as research pushes technology to its limits, larger research teams have to use increasingly expensive equipment in order to learn new things. What all this means is that research funding will have to increase further in order to yield an increase in journal articles.

John Kounios
Drexel University
Philadelphia,PA john.kounios@gmail.com

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Meat, in vitro?

Developing an in vitro system to support long-term space exploration with steak, turkey, or fish in a tissue culture flask isn't a very promising venture - especially in a confined space. ¹ So why not just consume the raw material?

Plants are probably the most efficient food-production factories in the universe, converting ultraviolet radiation, water, minerals, N2 and CO2 into legions of biologic products, both edible and not. So one might consider a plant-based in vitro system. All you would need is a UV light and a way to recycle by-products - perhaps including some nitrogen-fixing bacteria that could be genetically engineered for multiple recycling services.

Lewis Kelly
University of Kentucky, Lexington lakell2@email.uky.edu

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