A Blog Around The Clock

PLoS Biology at 5: The Future Is Open Access:

On the 13th of October in 2003, with the first issue of PLoS Biology, the Public Library of Science realized its transformation from a grassroots organization of scientists to a publisher. Our fledgling website received over a million hits within its first hour, and major international newspapers and news outlets ran stories about the journal, about science communication in general, and about our founders--working scientists who had the temerity to take on the traditional publishing world and who pledged to lead a revolution in scholarly communication (see, for example, [1,2]). It was not only scientists and publishers who wanted to see what this upstart start-up was doing; we had somehow captured the imagination of all sections of society. Not all of the reactions were positive, of course, especially from those in the scientific publishing sector with a vested interest in maintaining the subscription-based system of journal publishing. But thanks in no small part to the efforts of the founders--Pat Brown, Mike Eisen, and Harold Varmus--and an editorial team that included a former editor of Cell and several from Nature, our call for scientists to join the open-access revolution [3,4] did not go unheeded. Five years on, the publishing landscape has changed radically. How much have PLoS Biology and PLoS contributed to that change and what might the future hold for us and for publishing?

PLoS Biology is the flagship journal that gave PLoS its initial credibility as a publisher, paving the way for the equally successful launch of the flagship medical journal PLoS Medicine, four leading subject-specific journals (PLoS Computational Biology, PLoS Genetics, PLoS Pathogens and PLoS Neglected Tropical Disease), and its most radical, interdisciplinary peer-reviewed upstart, PLoS ONE

Rethinking Dams: Pacific Salmon Recovery May Rest on Other Factors:

Approaching the confluence of the Snake and Columbia Rivers in 1805, Lewis and Clark marveled at the "almost inconceivable multitudes" of salmon hurling themselves through the roiling waters, but worried at the "emence numbers" of bruised, battered, and dead fish farther upriver. The American explorers, unaware that Pacific salmon die after an orgy of spawning, were mystified at the frenzied spectacle of life and death before them.

An estimated 16 million salmon once swam the ancient migration route from river to ocean and back again, sustaining then-abundant bear, eagle, mink, and river otters along the way and releasing nutrient-rich compounds to replenish Columbia Basin streams and forests as their spent bodies decayed. By 1930, decades of overfishing, unchecked mining, logging, and engineering projects pushed wild stocks into serious decline--just as the US government resolved to fully exploit the hydroelectric and irrigation potential of the Columbia with a massive system of dams.

Brain Growth Receptors Control Lifespan:

When resources are short, growing organisms face an existential choice: should you ignore the shortage and hope for better times soon, or scale back and live within your limited means? And if you do scale back, will there be any payoff later in life? For animals, these choices are played out hormonally, with environmental fluctuations leading to internal rearrangements in endocrine signal and response throughout the growing body.

In mammals, two principal hormones--growth hormone (GH) and insulin-like growth factor 1 (IGF-1)--promote growth. Remarkably, inhibiting one or both of these two not only retards growth, but also extends lifespan, not just in lab animals, but possibly also in people: mutations that reduce the function of the IGF-1 receptor have recently been discovered in centenarians (who are also short). Growth occurs throughout the body, and receptors for IGF-1 are found in every organ on virtually every cell. But Laurent Kappeler et al. now show that it is the IGF-1 receptors in the brain that set the pattern for growth and lifespan.

Is Bayh-Dole Good for Developing Countries? Lessons from the US Experience:

Recently, countries from China and Brazil to Malaysia and South Africa have passed laws promoting the patenting of publicly funded research [1,2], and a similar proposal is under legislative consideration in India [3]. These initiatives are modeled in part on the United States Bayh-Dole Act of 1980 [4]. Bayh-Dole (BD) encouraged American universities to acquire patents on inventions resulting from government-funded research and to issue exclusive licenses to private firms [5,6], on the assumption that exclusive licensing creates incentives to commercialize these inventions. A broader hope of BD, and the initiatives emulating it, was that patenting and licensing of public sector research would spur science-based economic growth as well as national competitiveness [6,7]. And while it was not an explicit goal of BD, some of the emulation initiatives also aim to generate revenues for public sector research institutions [8].

We believe government-supported research should be managed in the public interest. We also believe that some of the claims favoring BD-type initiatives overstate the Act's contributions to growth in US innovation. Important concerns and safeguards--learned from nearly 30 years of experience in the US--have been largely overlooked. Furthermore, both patent law and science have changed considerably since BD was adopted in 1980 [9,10]. Other countries seeking to emulate that legislation need to consider this new context.

Using Both Sides of Your Brain: The Case for Rapid Interhemispheric Switching:

The vertebrate brain is symmetrically organized, with two identical-looking cerebral hemispheres and a brainstem that contains identically named nuclei on both sides of the midline. However tempting it is to think of each brain half as a mirror image of its contralateral counterpart, this is an incorrect oversimplification. Careful anatomical comparison of select anatomical structures and their connections reveals asymmetries across sides [1]. These asymmetries are not limited to anatomical features but also include extensive functional differences between cerebral hemispheres [2]. The existence of asymmetries implies that the two hemispheres are not just two massively redundant networks, but rather functionally specialized entities that work synergistically to coordinate the behavior of the organism.

Off-Label Promotion, On-Target Sales:

For prescription drugs, demonstrated benefits define the parameters of acceptable risks. For example, liver toxicity may be acceptable in a drug approved for cancer, but unacceptable in a drug approved for acne. Government regulatory bodies review laboratory, animal, and human data to confirm that a drug has the claimed efficacy and safety prior to approving its release in the market for specific approved ("labeled") uses.

Once a drug is approved for at least one indication, it may be prescribed off-label for a different condition, a different population, or in a different dose than what the drug is approved for. However, off-label uses have not been subject to the testing and review that is a precondition for marketing approval. The scientific review of evidence of effectiveness and safety that regulators weigh prior to approval for a labeled indication protects the patient. With off-label use, this protection often does not exist.

Off-label prescription of a drug is generally legal, but promotion of off-label uses by a drug manufacturer is usually illegal. This paper addresses public health issues associated with off-label use, and describes techniques by which pharmaceutical companies covertly promote off-label use even where such promotion is illegal.

Health Benefits of Universal Influenza Vaccination Strategy:

Most countries in Europe and North America target influenza immunization to persons at highest risk for complications, including seniors 65 years and older, those with certain chronic illnesses, and young children. Despite increases in vaccination rates in these high-risk groups over the last few decades, morbidity and mortality from influenza remain high.