cap0011.pngIt is customary to think about fashions in things like clothes or music as spreading in a social network. But it turns out that all kinds of things, many of them quite unexpected, can flow through social networks, and this process obeys certain rules we are seeking to discover.  We’ve been investigating the spread of obesity through a network, the spread of smoking cessation through a network, the spread of happiness through a network, the spread of loneliness through a network, the spread of altruism through a network.  And we have been thinking about these kinds of things while also keeping an eye on the fact that networks do not just arise from nothing or for nothing.  Very interesting rules determine their structure.

SOCIAL NETWORKS ARE LIKE THE EYE

A Talk with Nicholas A. Christakis

christakis185.jpgNicholas A. Christakis, MD, PhD, MPH, is an internist and social scientist who conducts research on social factors that affect health, health care, and longevity. He is a professor of medical sociology in the Department of Health Care Policy at Harvard Medical School; professor of sociology in the Department of Sociology in the Harvard Faculty of Arts and Sciences; and an attending physician in the Department of Medicine at the Harvard-affiliated Mt. Auburn Hospital. He is on the executive committee of the Robert Wood Johnson Scholars in Health Policy program at Harvard.

Dr. Christakis’s past work has examined the accuracy and role of prognosis in medicine, ways of improving end-of-life care, and the determinants and outcomes of hospice use. His book on prognosis, Death Foretold: Prophecy and Prognosis in Medical Care, was published by the University of Chicago Press in 1999; it has been widely reviewed and was translated into Japanese in 2006.

Currently, he is principally concerned with health and social networks, and specifically with how ill health, disability, health behavior, health care, and death in one person can influence the same phenomena in others in a person’s social network. Some current work focuses on the health benefits of marriage and on how ill health in one spouse can have cascading effects on the other spouse. It seems likely that improving the health of one partner in a marriage can have meaningful effects on the health of the other, and that both parties would value this—in a way that influences health policy. Other work examines a very large social network (12,000 people, including family, friends, and neighbors) followed for over 30 years to look broadly at the role of networks in health and health care. This work involves the application of network science and mathematical models to understand the dynamics of health in longitudinally evolving networks. To the extent that health behaviors such as smoking, drinking, or unhealthy eating spread within networks in intelligible ways, there are substantial implications for our understanding of health behavior and health policy.

Further lines of research include exploring the conceptual foundations of the phenomenon of iatrogenesis and examining physicians’ responses to the problem of medical harm; evaluating effect of neighborhoods on health; and considering various topics in biodemography (such as the demographic determinants of human longevity).

Dr. Christakis’s research has implications for understanding why people become sick and how they use medical care to become well again. It also has implications for clinical and policy actions to enhance the quality of care given to seriously ill patients.

Dr. Christakis received his BS degree from Yale University, his MD from Harvard Medical School, his MPH from the Harvard School of Public Health, and his PhD from the University of Pennsylvania. He has served on several editorial boards (including the British Medical Journal, Journal of Palliative Medicine, Palliative Medicine [UK], and American Journal of Sociology) and review committees (including in the United States, Australia, and Korea). He was elected to the Institute of Medicine in 2006. Over the past several years, he has given invited talks in Australia, Canada, China, Germany, Greece, Italy, Portugal, South Korea, South Africa, and the United Kingdom. He teaches quantitative and qualitative research design, epidemiology, medical sociology (including Sociology 190 at Harvard College), health services research, and palliative medicine.

For more information about Dr. Christakis, his research group, and his research and teaching (including copies of papers), click here.

http://content.nejm.org/cgi/content/full/357/4/370
Article: New England Journal of Medicine

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Charles F. Baer

Citation: Baer CF (2008) Does Mutation Rate Depend on Itself. PLoS Biol 6(2): e52 doi:10.1371/journal.pbio.0060052

Published: February 26, 2008

Copyright: © 2008 Charles F. Baer. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Charles F. Baer is in the Department of Zoology at the University of Florida, Gainesville, Florida, United States of America. E-mail: cbaer@zoo.ufl.edu
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Many a research paper, textbook chapter, and grant proposal has begun with the phrase “Mutation is the ultimate source of genetic variation.” Implicit in this phrase is the assumption that genetic variation is required for evolution. Without mutation, evolution would not be possible, and life itself could never have arisen in the first place. However, there is overwhelming evidence that the great majority of mutations with detectable effects are harmful [1–3]. Deleterious mutations are the price we living organisms pay for the ability to evolve.

Deleterious mutations are known or thought to influence a wide variety of biological phenomena (see the special issue of Genetica (1998) for a comprehensive account), the most notable of which is sexual reproduction. To make a very long story short, there are several reasons that asexually reproducing taxa are expected to have a short-term evolutionary advantage over sexually reproducing taxa. Specifically, the fact that a gene is passed to all the offspring of an asexual individual and to only half the offspring of a sexually reproducing individual provides a 2-fold fitness advantage to a new mutation that confers asexual reproduction when it arises in a population of sexual organisms. This 2-fold difference in fitness is known as the “2-fold cost of meiosis” [4]. However, a wealth of empirical evidence suggests that asexual reproduction is an evolutionary dead end, at least for eukaryotic taxa [5].

Understanding why and how sexual taxa have managed to consistently overcome the 2-fold cost has probably absorbed more intellectual energy than any other single problem in evolutionary biology. Many arguments have been advanced to explain the prevalence of sexual reproduction [4, 6], but the most widely accepted arguments invoke deleterious mutations as a primary cause [7–9]. The sine qua non of sex is genetic recombination, and deleterious mutations are more readily removed from a population in the presence of recombination than in its absence. A large body of theory predicts that, all else equal, the greater the mutation rate, the greater the probability that sexual reproduction will be favored. However, recent research by Aneil Agrawal [10,11] calls that conclusion into question.

A key property shared by all of the underlying models is the assumption that the mutation rate is constant, although it has long been recognized that mutation rates vary between and even within taxa [1, 12]. However, there is intriguing evidence not only that the mutation rate is variable within groups but that the variation in mutation rate is correlated with fitness, such that low-fitness individuals have higher mutation rates. A correlation between fitness and mutation rate could have two (not mutually exclusive) underlying causes, one adaptive and one not adaptive. The “adaptive mutation” scenario has been influential in the world of microbial genetics, following the observation of Cairns and Foster [13] that Escherichia coli have higher mutation rates when starved (reviewed in [14]). The basic idea of adaptive mutation is that under normal conditions, low mutation rate is favored by selection because most mutations are deleterious. However, in a very poor environment, death is certain in the absence of a beneficial mutation that confers high fitness in that environment. Individuals with high mutation rates are more likely to “find” that beneficial mutation. Thus, natural selection will favor inducible mutation rates, which are low under normal conditions but greatly increased under stressful (i.e., low-fitness) conditions. Adaptive mutation remains controversial, but there is evidence from E. coli that the stress-induced mutation rate differs consistently with certain ecological circumstances [15].

Importantly, the adaptive mutation scenario is only plausible in taxa that reproduce primarily asexually, because recombination breaks up the association between the alleles that influence mutation rate and alleles that influence fitness [16,17]. Another, perhaps more important possibility is that individuals in poor physiological condition have higher mutation rates for reasons having nothing to do with the possibility of generating a lucky beneficial mutation. Assuring the fidelity of DNA replication is metabolically costly and involves the products of many dozens or hundreds of genes [18]. Individuals in poor condition will have fewer resources to devote to genomic surveillance, leading to the possibility that individuals in poor condition will suffer an increased mutation rate.

Poor physiological condition may occur for two fundamental reasons, environment and/or genes. A simple example of the former is genetically identical plants raised under variable conditions of moisture: plants that are watered will be in better condition than those that are not. An example of the latter is harder to contrive, but it has been shown that under identical environmental conditions, there is genetic variation for fitness. Variation in fitness could be due either to variation in the number of deleterious alleles an individual carries in its genome or variation in the effects on fitness, or both. If individuals carrying more deleterious alleles tend to be in poor condition and if individuals in poor condition tend to have higher mutation rates, the existence of a positive-feedback process is suggested, which leads to an upwardly spiraling mutation rate and downwardly spiraling fitness.

Fitness-Dependent Mutation Rate: Theoretical Predictions

A useful way of quantifying population-genetic phenomena is in terms of the “genetic load,” the reduction in fitness of a population of interest relative to a population composed solely of the most-fit genotype. Of particular interest is the genetic load at mutation-selection balance (MSB), the point at which the input of genetic variation from mutation is exactly balanced by the removal of deleterious mutant alleles by natural selection. A classic, perhaps surprising result is that the genetic load at equilibrium in an infinitely large population is determined solely by the genomic deleterious mutation rate (U), which is assumed to be constant, and is independent of the strength of selection [19]. At MSB, mean fitness Ŵ is approximately e−U and the genetic load is 1 − e−U; this result holds for both sexual and asexual populations, in the absence of nonadditive effects [20].

A functional relationship between fitness and mutation rate complicates the situation. The first theoretical treatment of fitness-dependent mutation rates was given by Agrawal [10] for the infinite-population case. His model allowed mutation rate to vary over some range of possible values (UMIN to UMAX), with individuals in the best-possible condition mutating at rate UMIN and those in the worst-possible condition (other than dead) at UMAX. The functional relationship between fitness and U is assumed monotonic but not necessarily linear, and the fitness effects of mutations are assumed multiplicative across loci.

Two important proximate results emerge from Agrawal's analysis. First, for an asexual population, mean fitness at equilibrium is a function of the mutation rate of the genotype with the fewest deleterious alleles (i.e., the smallest genetic load). If the most-fit genotype has zero deleterious mutations, Ŵasex ≈eUMIN, even though most genotypes in the population may have many more than zero mutations. Second, the equilibrium fitness of a sexual population depends critically on the nature of the functional relationship between mutation rate and fitness (Figure 1). If the mutation rate is a concave downward (decelerating) function of genetic load, then Ŵsex will approach that expected at the maximum mutation rate (UMAX). Conversely, if the mutation rate is a concave upward (accelerating) function of genetic load, Ŵsex will be much closer to that expected at the minimum possible mutation rate (UMIN).

10.1371_journal.pbio.0060052.g001-M.jpg

Figure 1. Graph of Mutation Rate (U) against Mutation Load

Plot of U as a function of mutation load, scaled relative to that of the least-loaded genotype (UMIN = 0). Ui = UMAX− (UMAXUMIN) Wik. Load = 1 − wi where wi is relative fitness of a genotype with i deleterious mutations; wmax = w0 = 1. Note: this figure is slightly different from the analogous figure in [10] in which mutation rate is plotted against fitness rather than load.

This analysis points to a key difference in the equilibrium genetic load in sexual and asexual populations under constant and fitness-dependent mutation rates. If the mutation rate is constant, then sexual and asexual populations are expected to have the same genetic load at equilibrium. In contrast, if the mutation rate is fitness-dependent, the expected fitness in an asexual population at equilibrium will be that of the most-fit genotype, while in a sexual population, the equilibrium fitness will be less than that of the most-fit genotype, perhaps much less. Thus, surprisingly, the “cost of sex” may in fact be much greater than 2-fold.

Fitness-Dependent Mutation Rate: Empirical Evidence

Although condition-dependent, inducible increases in mutation rate are well-documented in microbes, including yeast [21] and the unicellular alga Chlamydomonas [22], there is scant evidence from multicellular eukaryotes. A recent study by Ávila et al. [23] showed that the rate of decay of viability and the rate of increase of genetic variance in a stock of Drosophila melanogaster that had been allowed to accumulate mutations for 160 generations increased 2.5-fold over the ancestral stock. That result is consistent with an increase in the mutation rate with genetic load (as claimed by the authors in the title of the article), but it is also consistent with an increase in the average deleterious effect of a new mutation with increasing genetic load, i.e., “synergistic” epistasis [20].

In this issue of PLoS Biology, Agrawal and Wang report a study designed to determine if the mutation rate is condition-dependent in D. melanogaster without the ambiguity associated with classical mutation accumulation studies [11]. Their experiment takes advantage of the fact that DNA repair does not occur post-meiotically in male D. melanogaster, but DNA damage carried in sperm can be repaired post-fertilization in D. melanogaster embryos via maternal repair enzymes. Manipulating female condition could alter maternal repair processes. There are multiple maternal repair pathways, some of which are error prone and some of which are not. The error-prone pathways are believed to be less metabolically costly. Agrawal and Wang hypothesized that females in poor condition would preferentially use the less-costly error-prone mechanisms, whereas females in good condition would preferentially use the more-costly high-fidelity mechanisms. Condition was manipulated by diet; genetically identical females were fed high- or low-quality diets and fertilized with sperm that had been subject to mutagenesis. The relative frequency of recessive lethal alleles was 30% greater on paternally derived X chromosomes that had passed through low-condition females rather than high-condition females.

Do these results prove that the mutation rate is condition-dependent? Not quite. It remains to be shown that the spontaneous mutation rate is condition-dependent. However, if the efficacy of DNA repair is in general condition-dependent, a lack of condition-dependence of the spontaneous mutation rate would require there be a compensatory reduction in the probability that DNA damage occurs. Nevertheless, this study provides the strongest evidence yet for condition-dependent mutation rate in a multicellular eukaryote.

Broader Implications

Condition- (i.e., fitness) dependent mutation leads to some interesting possibilities for the long-term genetic health of populations, including our own species. For example, it has been argued that modern technology (e.g., sewage treatment, eyeglasses, etc.) has led to the relaxation of selection against mildly deleterious mutations in the developed world, leading to a build-up of genetic load [24,25]. If the mutation rate is self-dependent, future generations may be burdened with an ever-growing genetic load. If the somatic and germ-line mutation rates are correlated, such a build-up of genetic load could be expected to lead to an increase in cancer and other diseases resulting from somatic mutation. (Less often invoked is the possibility that the improved physiological condition of modern humans will act to reduce the mutation load).

A second interesting possibility is that condition-dependent mutation could, in effect, render temporary increases in mutagenesis due to environmental causes permanent. Many anthropogenic factors are known to be mutagenic, not only to humans but to many other organisms. If the mutation rate is condition-dependent, a short-term increase in the input of mutation due to (say) a mutagenic pollutant could lead to a long-term increase in the mutation rate, and thus in the genetic load. Similarly, genetic drift allows the fixation of slightly deleterious alleles in small populations. With condition-dependent mutation rate, a temporary bottleneck in population size that results in the increase in frequency of deleterious alleles could lead to an effectively permanent increase in the mutation rate.

Source: The U.S. Chamber of Commerce

By Thomas J. Donohue, President and CEO, U.S. Chamber of Commerce
February 26, 2008

For too long, America’s education system has failed to equip students with the knowledge they need to make good financial decisions. An alarming number of adults are unable to balance a checkbook, understand the terms of a basic mortgage, realize the benefits of compound interest, and properly manage credit card debt.

Today we are suffering the consequences. We can see it in the subprime mortgage meltdown, skyrocketing credit card debt, personal bankruptcies, and a low savings rate. Beyond individuals broken dreams, this lack of financial and economic education is threatening the competiveness and wellbeing of our country. So what can–and should–be done about it?

Ideally, an understanding and appreciation of economics and finances would be taught at school levels from kindergarten to the 12th grade and beyond. It should be taught as part of a robust curriculum as determined by the states, in the same way that music and art are taught. Unfortunately, local school boards decline to include financial and economic literacy as part of the core curriculum. Many college students can earn a degree without having taken any courses in basic economics.

That means the private sector, nonprofits, parents, and religious groups must step in to fill the void. Many companies in the financial services industry have robust and effective programs to teach kids how to handle their personal finances. They have partnered with groups like Junior Achievement, the Boys and Girls Club, Operation Hope, and Jump$tart, among many others.

We must also clearly recognize that our citizens will not be financially literate without first learning basic math. Without the ability to do fractions and percentages, students will not be able to calculate compound interest, amortize loans and mortgages, or figure out other financial products like annuities and 401(k)s. It’s all tied together, and it’s why the Chamber has a major initiative underway to renew and strengthen No Child Left Behind.

But there’s something more … The lack of financial and economic education is at the core of the growing and dangerous trends against international trade and immigration. Many of our citizens do not understand how the worldwide economy works. They do not understand how trade and direct investment create good-paying jobs, lower prices, and increase choice. They do not understand the reality of why some jobs go overseas even as many more are created here at home. They do not understand the looming worker shortages in both high- and low-skill jobs.

This puts our economy in peril. It leaves citizens easily susceptible to fear mongering by politicians who are eager to confirm people’s belief that whatever is wrong in their life is somebody else’s fault.

If America is to compete and win in the 21st century economy, we need citizens who can not only make smart financial decisions in their personal lives, but in the economic life of the nation.

Take a look at the extraordinary talent, of the three founders of PLoS, Harold E. Varmus MD [Nobel prize winner] and Patrick O. Brown MD, PhD. And Michael B. Eisen PhD. Also, look at the impressive credentials of the Board of Directors of PLoS. An article, published by PLoS is at the end of this list.

Harold E. Varmus

varmus_200x273.jpgHarold Varmus, former director of the National Institutes of Health (NIH) and co-recipient of a Nobel prize for studies of the genetic basis of cancer, currently serves as the president and chief executive officer of the Memorial Sloan-Kettering Cancer Center in New York City. A native of Freeport, Long Island, Varmus majored in English literature at Amherst College and earned a master’s degree in English at Harvard University. A graduate of Columbia University’s College of Physicians and Surgeons, he worked as a medical student in a hospital in India and served on the medical house staff at Columbia-Presbyterian Hospital. His scientific training occurred first as a Public Health Service officer at the NIH, where he studied bacterial gene expression with Ira Pastan, and then as a post-doctoral fellow with J. Michael Bishop at the University of California, San Francisco (UCSF). Much of his scientific work was conducted during 23 years as a faculty member at UCSF, where he, Bishop, and their co-workers demonstrated the cellular origins of the oncogene of a chicken retrovirus. For this work, Bishop and Varmus received the 1989 Nobel Prize in Physiology or Medicine. In 1993, Varmus was named by President Bill Clinton to serve as the director of the NIH, a position he held until his appointment as CEO of the Memorial Sloan-Kettering Cancer Center. Varmus is married to Constance Casey, a journalist and horticulturist; their two sons, Jacob and Christopher, also live in New York City.

Patrick O. Brown

brown_100x137.jpgPatrick O. Brown was born in Washington, D.C., in 1954, and grew up in Northern Virginia; Paris, France; and Taipei, Taiwan. In 1972, he entered the University of Chicago, finally emerging nearly a decade later with a B.A., M.D., and Ph.D. His thesis work, with Nick Cozzarelli, investigated the basic molecular mechanisms of DNA topoisomerases. Brown completed residency training in pediatrics in 1985, at Chicago’s Children’s Memorial Hospital. In a post-doctoral fellowship at the University of California, San Francisco, with J. Michael Bishop and Harold Varmus, he characterized the mechanism by which retroviruses, such as HIV, incorporate their genes into the genomes of their hosts. In 1988, he joined the Howard Hughes Medical Institute and Stanford University School of Medicine, where he is currently a professor in the department of biochemistry. His current research activities include systematic studies of global gene expression programs and their regulation; the use of DNA microarrays and other “genomic” approaches to explore fundamental questions in cell biology, physiology, and development; and the development and application of new high-dimensional molecular profiling methods for detection and diagnosis of disease. Brown is married to Sue Klapholz, M.D., Ph.D., with three children: Zach, Ariel, and Isaac.

Michael B. Eisen

eisen_100x137.jpgMichael B. Eisen is a computational and evolutionary biologist at the University of California at Berkeley and the Ernest Orlando Lawrence Berkeley National Laboratory, and an ardent advocate for the free flow of scientific methods, data, and knowledge. He received his undergraduate degree in mathematics (with extensive side studies in ecology and evolutionary biology) from Harvard College in 1989. He received a Ph.D. in biophysics from Harvard University in 1996 for his doctoral research on influenza virus proteins structure and function. After a summer working as a play-by-play announcer for the Columbia Mules (a minor league baseball team in Columbia, Tennessee), he joined the laboratories of Patrick O. Brown and David Botstein at Stanford as a postdoctoral fellow. While at Stanford, Eisen developed methods and software for the analysis of data from genome-wide expression studies. In 2000, he moved to Berkeley, where he runs his own lab studying how regulatory information is encoded in genome sequences and the role that variation in regulatory sequences has played in evolution. He is a 2001 Pew Biomedical Scholar and received a 2004 Presidential Early Career Award for Scientists and Engineers.

PLoS Board of Directors

Harold E. Varmus, PLoS Co-founder and Chairman of the Board
President & Chief Executive,
Memorial Sloan-Kettering Cancer Center

Patrick O. Brown, PLoS Co-founder
Stanford University School of Medicine
Howard Hughes Medical Institute

Michael B. Eisen, PLoS Co-founder
Assistant Professor of Genetics, Genomics and Development, Department of Molecular and Cell Biology
University of California, Berkeley

Brian Druker
Investigator, Howard Hughes Medical Institute
JELD-WEN Chair of Leukemia Research & Professor of Medicine
Oregon Health & Science University Cancer Institute

Paul Ginsparg
Professor of Physics and Computing and Information Science
Cornell University, Ithaca, NY

Allan C. Golston
President, U.S. Program
Bill & Melinda Gates Foundation, Seattle, WA

Lawrence Lessig
Professor, Stanford Law School, Palo Alto, CA
CEO, Creative Commons
Fellow, Academy of Arts and Sciences

Don Listwin
Founder, Canary Foundation

Elizabeth Marincola
President, Science Service
Publisher, Science News

Richard Smith
Chief Executive European arm of UnitedHealth Group
Visiting Professor, London School of Hygiene & Tropical Medicine
Former Chief Executive & Editor of BMJ

Rosalind L. Smyth
Brough Professor of Paediatric Medicine and Head of the Division of Child Health at University of Liverpool

Marty Tenenbaum
Chairman and Founder of CommerceNet

Tom Unterman
Managing Partner, Rustic Canyon Partners

Beth Weil
Head of the Marian Koshland Bioscience and Natural Resources Library
University of California at Berkeley

Here’s the link to the article published in PLoS Medicine.

Michael B. Eisen, Patrick O. Brown, Harold E. Varmus
Citation: Eisen MB, Brown PO, Varmus HE (2004) PLoS Medicine—A Medical Journal for the Internet Age. PLoS Med 1(1): e31 doi:10.1371/journal.pmed.0010031

Published: October 19, 2004

Copyright: © 2004 Eisen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Michael B. Eisen, Patrick O. Brown, and Harold E. Varmus are the co-founders of the Public Library of Science. Michael B. Eisen is at the Lawrence Berkeley National Laboratory and the University of California, Berkeley, California, United States of America; Patrick O. Brown is at the Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California, United States of America; Harold E. Varmus is president and chief executive of Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. E-mail: plos@plos.org

The Internet is awash with medical information. Eight hundred million people have direct access to the Internet [1], and in the United States over 60% have searched for health or medical information on the Web [2]. Go to any search engine and type in the name of a disease or drug, and you will be directed to hundreds of sites, ranging from the sound and useful to the quackish and dangerous. Google “medical” and you get 85 million pages, “drug,” 40 million, and “health,” 230 million.

But something is conspicuously missing. The most reliable medical information on the Internet—the contents of peer-reviewed medical journals—is hidden from the public and most of the world’s physicians. Although most medical journals are available online, their publishers limit access to those who choose, and can afford, to pay for access. This should not, and need not, be so.

In the 19th and early 20th centuries independent physicians and small medical societies, interested in making the best new medical knowledge available to doctors, students, and the public, began to publish general medical journals containing case reports, ideas for new treatments, and the results of medical experiments. These pioneers took advantage of the best available technology for disseminating information, printing titles like The Lancet, The New England Journal of Medicine, and The Journal of the American Medical Association on cheap paper and selling them to subscribers at a few pennies a copy. For more than a century, printed journals like these were the dominant means of conveying medical knowledge around the world.

But technology has changed. The Internet is now the most economical and efficient conduit for the delivery of information to most places. Publishers of medical journals realize this—when the Internet took off, they took their journals online. But while they adapted their means of distribution to the 21st century, they left their business model in the 19th century, continuing to charge readers for access just as they had done for their printed journals. This has been good for business—medical publishing has never been more profitable—but it comes at a huge cost. The established medical publishers have turned their back on the opportunity to make the latest and best medical information available to anyone with an Internet connection. With the launch of PLoS Medicine, we are embracing this opportunity.

Everything we publish is immediately, freely available online throughout the world, with no restrictions on distribution, copying, printing, or legitimate use.

Everything published in PLoS Medicine is immediately freely available online throughout the world, with no restrictions on distribution, copying, printing, or legitimate use. Of course, it costs us money to publish this journal, and we must cover our expenses. But the fee-for-access business model that made perfect sense for the printed journal is no longer consistent with the mission of medical publishing because it needlessly limits the reach of the medical literature. And so we have adopted a new model. Instead of charging readers for access to our journal, we ask the authors of accepted research articles to pay a publication fee to cover the costs of peer review, editorial oversight, and production. This “open access” business model ensures our financial health as a publisher while allowing us to convey everything we publish to the widest possible audience.

Of course, we do not expect authors to cover publication costs personally—rather, we expect the government agencies, companies, foundations, research institutions, hospitals, or universities that sponsor the research to pay the fee. These organizations have always considered the wide dissemination of the results of the research they support to be an integral part of their mission. Virtually every leading sponsor of medical research has announced its willingness to pay for open-access publication, the costs of which average less than one percent of the cost of the research itself—a small price to pay to ensure that everyone who could benefit from their research can benefit from it.

We realize that not everyone with something important to convey in a medical journal has access to such funds. To ensure that we don’t replace a barrier to access with barriers to publication, we’ve raised money to cover the publication costs of articles whose authors are unable to pay them. And, for every PLoS journal, an author’s ability to pay will never be a consideration in our decision to publish an article.

Despite its obvious benefits, open-access publication has met with fierce opposition. Established medical publishers—now businesses more than forces for change—see open-access not as an opportunity to fulfill a mission of public service but as a threat to their lucrative businesses. They contend that their journals still serve the community well, and object that open access threatens their very existence. This is nonsense!

It is our responsibility as publishers and members of the medical community not only to give patients access to the medical literature, but to provide them with tools to use it wisely.

The Wellcome Trust, the world’s largest charitable sponsor of biomedical research, seeking to ensure that the results of the science it funds are “disseminated widely and freely available to all,” recently commissioned a thorough analysis of the scientific and medical publishing industry [3]. It concluded that the current market “does not operate in the long-term interest of the research community,” and issued a strong statement in support of open access [4]. Responding to concerns about journal finances, the trust commissioned a detailed economic analysis of open-access publishing [5], based on which it concluded that “the open access model of scientific publishing—where the author of a research paper pays for peer reviewed research to be made available on the web free to all who wish to use it—is economically viable, guarantees high quality research and is a sustainable option which could revolutionise the world of traditional scientific publishing” [6]. (This report, freely available online, is an excellent resource for anyone with questions about the economics of open-access publishing).

We know firsthand that the Wellcome Trust is right. In October 2003, we launched our first journal, PLoS Biology, and it is thriving—not only as a destination for the best research in all areas of biology, but also as a resource for students, teachers, and members of the public who have never before had direct access to the product of scientific inquiry (see for yourself at www.plosbiology.org). We are now bringing this success and this spirit to medicine.

The world of medical journals needs a fresh infusion of idealism. All of today’s leading medical journals are more than 70 years old, and PLoS Medicine is here to challenge the status quo. We are first and foremost an open-access publisher working to ensure that everyone has access to the latest medical research and expertise. But we aim to be more than just an open-access alternative to established general medical journals. We are determined to make PLoS Medicine the best medical journal in the world by providing outstanding original research and new ideas; thought-provoking, educational, and imaginative features for readers; and the fastest, fairest, and most rigorous peer review for authors.

As an open-access journal, we see our audience differently than do the conventional medical journals: our audience is composed of medical researchers, physicians, and other health-care providers, patients and their advocates, students, and the public around the world. It will be a great challenge to create a journal that will serve such a diverse audience—we welcome this challenge. We will make it possible for the results of advanced research on infectious diseases to guide treatment in remote clinics thousands of miles away. We will make the results of a clinical trial of a new drug accessible and understandable both to doctors who might prescribe it and to people who might start taking it. We will make research on rare diseases accessible to general practitioners and patients so that they can work together to recognize and treat them.

Whereas some would argue that medical journals should not be accessible to patients because patients are unable to use the information effectively, we believe it is our responsibility as publishers and members of the medical community not only to give patients access, but to provide them with tools to use the medical literature wisely. Medical research is a partnership between medical scientists and millions of voluntary human participants, conducted largely with public funds. What better way to acknowledge the public’s contribution and ensure their willingness to sponsor and participate in future research than to openly share the product of this research with them?

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Many fish, amphibians and reptiles — have lots of reproductive tricks. 1) ___ can store sperm for a long time, tiding them over when conditions may be poor for reproduction. Another trick is the natural ability to clone. DNA analysis of seeming “miracle embryos” show that every bit of their 2) ___ simply came from the female. Virgin birth, known to biologists as 3) ___ (from the Greek, “parthen” meaning virgin or maiden and “genesis,” beginning), has been seen in species over the years. Some lizards, like the Komodo Dragon, occasionally produce offspring by 4) ___. So do several species of fish, including a female hammerhead shark at the Henry Doorly Zoo in Omaha, Nebraska that produced offspring without a male in 2007. The shark example is particularly striking because sharks are very primitive living fish, having shared a common ancestor with us over 400 million years ago. Biological cloning is not a recent invention of scientists; it is an ancient ability, from nature. Sharks, fish and lizards are probably only the tip of the iceberg. We know of this 5) ___ cloning, only in those rare instances when we’ve been lucky enough to see it. Nobody knows how common it is because there has been no systematic search for the phenomenon. The big question that parthenogenesis raises is, if some females can get along without males, why does any species have males? The reason is that naturally cloned hatchlings are simply genetic duplicates of the mother. In a world of clones, there would not be enough variation for populations to adapt. Biological cloning is a great stopgap measure to ensure the survival of a species, but works against it in the long haul. Cloning is one of many mechanisms species use to 6) ___ in a dangerous world. Some reptiles do not determine gender genetically, but rely on different incubation temperatures to determine the development of males and females. Other creatures can actually switch gender during their lifetimes, being born male and developing as females. Still others can switch gender based on behavioral cues in the social group. However, without 7) ___, the world would be static and unchangeable, and species would gradually disappear as they failed to meet challenges like changing climates and environments.

ANSWERS: 1) Females; 2) DNA; 3) parthenogenesis; 4) cloning; 5) natural; 6) survive; 7) variation

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cap001.pngOne of the first Afro-American Female Physicians in the United States, Dr. Johnson was the first female doctor to pass the Alabama state medical examination and was the first woman physician at Tuskegee Institute. 

She was the eldest of nine children born to African Methodist Episcopal bishop Benjamin Tucker Tanner and Sarah Elizabeth Miller in Pittsburgh, Pennsylvania in 1864. Her brother, Henry Ossawa Tanner, became a noted artist. Shortly after Halle was born the Tanners moved to Philadelphia where the children were educated.

In the middle 1880s Halle Tanner worked with her father on the AME Church Review. In 1886 she married Charles E. Dillon and the two moved to Trenton, New Jersey where they had a daughter, Sadie. Charles Dillon died of an unknown cause and Halle Tanner Dillon moved back to Philadelphia to live with her parents. Tanner decided to become a physician and enrolled at the Woman’s Medical College of Pennsylvania. The only African American woman in her class, Tanner graduated with an M.D. and high honors after three years of study in 1891. While at the college, she learned of a job opportunity as resident physician at Tuskegee Institute. She contacted Booker T. Washington, the Principal of Tuskegee. Washington appointed her and helped her prepare for the Alabama state medical examination.

Dr. Tanner Dillon sat for the ten day examination and passed. She served at Tuskegee University as a physician, pharmacist, teacher, and ran a private practice for 3 years. While at Tuskegee she founded a training school for nurses and a dispensary (pharmacy). In 1894 she married her second husband, Reverend John Quincy Johnson, an aspiring theologian and mathematics professor at Tuskegee Institute. The couple moved to Nashville where Reverend Johnson pursued a graduate degree in divinity while serving as pastor of Saint Paul’s AME Church. Dr. Tanner Dillon Johnson, meanwhile, resumed her medical practice. The couple had three more children but in 1901 Dr. Halle Tanner Dillon Johnson died of complications resulting from childbirth.

Matthew Oliver Ricketts MD (1858-1917) 

Ricketts was born to enslaved parents in Henry County, Kentucky in 1858. His parents moved to Booneville, Missouri when he was a child, and he completed school there. In 1876 he received a degree from the Lincoln Institute in Jefferson City, Missouri, and moved to Omaha, Nebraska in 1880. Ricketts was admitted to the Omaha Medical College and worked as a janitor to pay his tuition. In March 1884 he graduated with honors, and soon after opened an office in Omaha. Ricketts quickly earned a reputation for “being a very careful physician, as well as an exceedingly likable young man.”A charismatic and controversial speaker, Ricketts quickly became the acknowledged leader of Omaha’s African American community. After being elected in 1892, Rickets served the Nebraska Legislature twice as a Republican in whole-county elections, from 1893 to 1897. He was the first African American to serve in the Nebraska Legislature. Dr. Ricketts was regarded as one of the best orators there, and was frequently called upon for his opinions. He is credited for creating Omaha’s Negro Fire Department Company, and for securing appointments for blacks in city and state government positions. Ricketts was elected Worshipful Master of Omaha Excelsior Lodge No. 110 of the Prince Hall Masons. Ricketts addressed the 1906 Grand Convocation of the Freemasons in Kansas City, Missouri. Ricketts was married to Alice Nelson in 1884; they had three children. After leaving the Legislature Ricketts was an unsuccessful candidate for a federal position, largely because his appointment was opposed by a Nebraska congressman. Ricketts subsequently moved to St. Joseph, Missouri to continue his medical career in 1903. He died in St. Joseph, Missouri in 1917, at the age of 64.

 

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