Thursday, January 29, 2015

For those convinced that science [in this case medical science] is making steady porgress, two good articles from the New York Times Oped pages.

The Opinion Pages | OP-ED CONTRIBUTOR
‘Moonshot’ Medicine Will Let Us Down
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ROCHESTER, Minn. — PRESIDENT OBAMA’S new budget is expected to include hundreds of millions of dollars for so-called precision medicine. The initiative, which he introduced last week in his State of the Union address, has bipartisan support and is a bright spot in the otherwise tight funding environment for medical research. Unfortunately, precision medicine is unlikely to make most of us healthier.
The basic idea behind it is that we each have genetic variants that put us at increased or decreased risk of getting various diseases, or that make us more or less responsive to specific treatments. If we can read someone’s genetic code, then we should be able to provide him or her with more effective therapeutic and preventive strategies.
But for most common diseases, hundreds of genetic risk variants with small effects have been identified, and it is hard to develop a clear picture of who is really at risk for what. This was actually one of the major and unexpected findings of the Human Genome Project. In the 1990s and early 2000s, it was thought that a few genetic variants would be found to account for a lot of disease risk. But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases.
Age, sex, body weight and a few simple blood tests are much better predictors of Type 2 diabetes, for example, than a genetic score based on how many snippets of “risky” DNA you have. And the advice for those at risk to exercise more and eat more healthfully remains the same.
When higher-risk genetic variants are found, their predictive power is frequently dependent on environment, culture and behavior. The main genetic variant associated with obesity, for instance, is associated with obesity only in people born after the early 1940s — most likely because of the low-physical-activity, high-calorie world that emerged after World War II.
A second unexpected finding of the Human Genome Project was the problem of “missing heritability.” While the statistics suggest that there is a genetic explanation for common conditions and diseases running in families or populations, it turns out that the information on genetic variants doesn’t explain that increased risk.
Several high-profile attempts to use genetic variants to target patients with commonly used drug therapies have also failed in clinical trials. Perhaps the most notable example is the anticoagulant warfarin, which is used by millions of patients to prevent blood clots and strokes. Researchers have found that genetic information on how patients metabolize drugs does not improve on the standard way of adjusting the dose up or down, based on factors like age, weight and blood test results.
For relatively rare diseases like cystic fibrosis, exciting new drugs have been developed using genetic information, but they have not been able to fix defective genes via gene therapy, as originally hoped. There have also been positive reports about precision therapies for specific genetic defects in cancer, but it’s difficult to design clinical trials to test this strategy in a large number of patients. Many tumors are also notorious for their ability to mutate and ultimately circumvent the best therapies.
The push toward precision medicine could also lead to unintended consequences based on how humans respond to perceptions of risk. There is evidence that if people believe they are less at risk for a given disease, they feel excessively protected and their behavior gets worse, putting them at increased risk. Likewise, those who feel they are at greater risk, even if the increased risk is small, might become fatalistic, making their behavior worse as well. Then there are the worriers, who might embark on a course of excessive tests and biopsies “just in case.” In a medical system already marked by the overuse of diagnostic tests and procedures, this could lead to even more wasteful spending.
We have been down this road before. The idea behind the “war on cancer” was that a deep understanding of the basic biology of cancer would let us develop targeted therapies and cure the disease. Unfortunately, although we know far more today than we did 40-plus years ago, the statistics on cancer deaths have remained incredibly stubborn. The one bright spot has been tobacco control — again highlighting the dominant role of culture, environment and behavior versus biological destiny in what ails most of us.
Given the general omertà about researchers’ criticizing funding initiatives, you probably won’t hear too many objections from the research community about President Obama’s plan for precision medicine. But I am deeply skeptical. Like most “moonshot” medical research initiatives, precision medicine is likely to fall short of expectations. Medical problems and their underlying biology are not linear engineering exercises, and solving them is more than a matter of vision, money and will.
We would be better off directing more resources to understanding what it takes to solve messy problems about how humans behave as individuals and in groups. Ultimately, we almost certainly have more control over how much we exercise, eat, drink and smoke than we do over our genomes.
Michael J. Joyner is an anesthesiologist and physiologist at the Mayo Clinic.

Redefining Mental Illness
JAN. 17, 2015
CreditRoman Muradov
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TWO months ago, the British Psychological Society released a remarkable document entitled “Understanding Psychosis and Schizophrenia.” Its authors say that hearing voices and feeling paranoid are common experiences, and are often a reaction to trauma, abuse or deprivation: “Calling them symptoms of mental illness, psychosis or schizophrenia is only one way of thinking about them, with advantages and disadvantages.”
The report says that there is no strict dividing line between psychosis and normal experience: “Some people find it useful to think of themselves as having an illness. Others prefer to think of their problems as, for example, an aspect of their personality which sometimes gets them into trouble but which they would not want to be without.”
The report adds that antipsychotic medications are sometimes helpful, but that “there is no evidence that it corrects an underlying biological abnormality.” It then warns about the risk of taking these drugs for years.
And the report says that it is “vital” that those who suffer with distressing symptoms be given an opportunity to “talk in detail about their experiences and to make sense of what has happened to them” — and points out that mental health services rarely make such opportunities available.
This is a radically different vision of severe mental illness from the one held by most Americans, and indeed many American psychiatrists. Americans think of schizophrenia as a brain disorder that can be treated only with medication. Yet there is plenty of scientific evidence for the report’s claims.
Moreover, the perspective is surprisingly consonant — in some ways — with the new approach by our own National Institute of Mental Health, which funds much of the research on mental illness in this country. For decades, American psychiatric science took diagnosis to be fundamental. These categories — depression, schizophrenia, post-traumatic stress disorder — were assumed to represent biologically distinct diseases, and the goal of the research was to figure out the biology of the disease.
That didn’t pan out. In 2013, the institute’s director, Thomas R. Insel,announced that psychiatric science had failed to find unique biological mechanisms associated with specific diagnoses. What genetic underpinnings or neural circuits they had identified were mostly common across diagnostic groups. Diagnoses were neither particularly useful nor accurate for understanding the brain, and would no longer be used to guide research.
And so the institute has begun one of the most interesting and radical experiments in scientific research in years. It jettisoned a decades-long tradition of diagnosis-driven research, in which a scientist became, for example, a schizophrenia researcher. Under a program called Research Domain Criteria, all research must begin from a matrix of neuroscientific structures (genes, cells, circuits) that cut across behavioral, cognitive and social domains (acute fear, loss, arousal). To use an example from the program’s website, psychiatric researchers will no longer study people with anxiety; they will study fear circuitry.
Our current diagnostic system — the main achievement of the biomedical revolution in psychiatry — drew a sharp , clear line between those who were sick and those who were well, and that line was determined by science. The system started with the behavior of persons, and sorted them into types. That approach sank deep roots into our culture, possibly because sorting ourselves into different kinds of people comes naturally to us.
The institute is rejecting this system because it does not lead to useful research. It is starting afresh, with a focus on how the brain and its trillions of synaptic connections work. The British Psychological Society rejects the centrality of diagnosis for seemingly quite different reasons — among them, because defining people by a devastating label may not help them.
Both approaches recognize that mental illnesses are complex individual responses — less like hypothyroidism, in which you fall ill because your body does not secrete enough thyroid hormone, and more like metabolic syndrome, in which a collection of unrelated risk factors (high blood pressure, body fat around the waist) increases your chance of heart disease.
The implications are that social experience plays a significant role in who becomes mentally ill, when they fall ill and how their illness unfolds. We should view illness as caused not only by brain deficits but also by abuse, deprivation and inequality, which alter the way brains behave. Illness thus requires social interventions, not just pharmacological ones.
ONE outcome of this rethinking could be that talk therapy will regain some of the importance it lost when the new diagnostic system was young. And we know how to do talk therapy. That doesn’t rule out medication: while there may be problems with the long-term use of antipsychotics, many people find them useful when their symptoms are severe.
The rethinking comes at a time of disconcerting awareness that mental health problems are far more pervasive than we might have imagined. The World Health Organization estimates that one in four people will have an episode of mental illness in their lifetime. Mental and behavioral problems are the biggest single cause of disability on the planet. But in low- and middle-income countries, about four of five of those disabled by the illnesses do not receive treatment for them.
When the United Nations sets its new Sustainable Development Goals this spring, it should include mental illness, along with diseases like AIDS and malaria, as scourges to be combated. There is much we still do not know about mental illness, and much we can do to improve its care. But we know enough to do something, and to accept that knowing more and doing more should be a fundamental commitment.
Correction: January 25, 2015 

An opinion article about mental illness last Sunday incorrectly referred to a group that recently issued a report on schizophrenia. It is the British Psychological Society, not the British Psychological Association.
T. M. Luhrmann is a contributing opinion writer and a professor of anthropology at Stanford.

Thursday, January 16, 2014

Hands Off! This May Be Love

I am excited to announce the publication of Hands Off! This May Be Love, my first book written for a general audience.

Comprising exciting new material along with parts of my previous books, Hands Off! This May Be Love presents a Jewish, down-to-earth perspective on the hows and whys of refraining from physical contact before marriage, a practice that resonates with many religious Christians and others troubled by today’s societal norms. We are hoping that it will find its way into the hands not only of young adults, but also parents, youth pastors and other leaders. This book can make a real difference in people's lives and will also, God willing, achieve tremendous kiddush Hashem.

If you know anyone who may be open to the message of Hands Off! This May Be Love, please pass this email along to them. And if you have any ideas or connections for getting this book out there, please let me know!

And here's a link for the ebook:

Thanks so much!

With blessings,

Gila Manolson

Wednesday, January 15, 2014

Salty surprise - ordinary table salt turns into "forbidden" forms

[Suggested reading for a student who recently told me about what has been proved by peer-reviewed science.] 

High-pressure X-ray experiments violate textbook rules of chemistry

High-pressure experiments with ordinary table salt have produced new chemical compounds that should not exist according to the textbook rules of chemistry. The study at DESY's X-ray source PETRA III and at other research centres could pave the way to a more universal understanding of chemistry and to novel applications, as the international research team, led by Prof. Artem Oganov of Stony Brook University (State University of New York) and Prof. Alexander Goncharov of Carnegie Institution, reports in the scientific journal Science.
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The electron localization function in the cubic NaCl3 structure. Credit: Artem Oganov/Stony Brook University 
Table salt, also known as sodium chloride or NaCl, is one of the best-known and most studied chemical compounds. It crystalises in a cubic unit cell and is very stable. Its chemical composition is simple - one sodium atom (Na) and one chlorine atom (Cl). Or at least that's true under ambient conditions. Other compounds of the two elements are forbidden by the classical rules of chemistry. For instance, according to the octet rule all chemical elements strive to fill their outermost shell with eight electrons, which is the most stable configuration, found in noble gases. Sodium has one extra electron and chlorine is missing one, so sodium donates one electron to chlorine, leaving both atoms with an outer shell containing eight electrons and forming a strong ionic bond.
But when the scientists put table salt under high pressure of 200,000 atmospheres and more at PETRA III and added an extra dash of either sodium or chlorine, "forbidden" compounds like Na3Cl und NaCl3 turned up. "Following the theoretical prediction, we heated the samples under pressure with lasers for a while," explains co-author Dr. Zuzana Konôpková of DESY, who supported the experiments at DESY's Extreme Conditions Beamline P02 (ECB). "We found other stable compounds of Na and Cl which came as a surprise." This is not supposed to happen, as these compounds require a completely different form of chemical bonding with higher energy, and nature always favours the lowest state of energy.
But Oganov's team had calculated before that exotic compounds might form under extreme conditions and remain stable under these conditions. “We have predicted and made crazy compounds that violate textbook rules: NaCl3, NaCl7, Na3Cl2, Na2Cl, and Na3Cl,” says Dr. Weiwei Zhang, the lead author of the paper and a visiting scholar at Oganov's lab at Stony Brook. At PETRA III and at Carnegie Institution the scientists tested the predictions in what they call "cook and look" experiments, targeting Na3Cl and NaCl3, the two compounds that were predicted to be more easily made than others, and indeed found them. “These compounds are thermodynamically stable and once made, remain so indefinitely," says Zhang. "Classical chemistry forbids their very existence. Classical chemistry also says atoms try to fulfil the octet rule - elements gain or lose electrons to attain an electron configuration of the nearest noble gas, with complete outer electron shells that make them very stable. Well, here that rule is not satisfied.”
The experiments help to explore a broader view of chemistry. “I think this work is the beginning of a revolution in chemistry,” Oganov says. “We found, at low pressures achievable in the lab, perfectly stable compounds that contradict the classical rules of chemistry. If you apply rather modest pressure, 200,000 atmospheres – for comparison purposes, the pressure at the centre of the Earth is 3.6 million atmospheres – much of what we know from chemistry textbooks falls apart.”
One reason for the surprising discovery is that textbook chemistry usually applies to what we call ambient conditions. "Here on the surface of the earth, these conditions might be default, but they are rather special if you look at the universe as a whole," Konôpková explains. What may be "forbidden" under ambient conditions on earth, can become possible under more extreme conditions. "'Impossible' really means that the energy is going to be high," Oganov says. "The rules of chemistry are not like mathematical theorems, which cannot be broken. The rules of chemistry can be broken, because impossible means softly impossible. You just need to find the conditions where the energy balance shifts and the rules hold no more."
Apart from its fundamental meaning, the discovery can also produce new practical applications. “When you change the theoretical underpinnings of chemistry, that’s a big deal,” Goncharov says. “But what it also means is that we can make new materials with exotic properties.” Among the compounds Oganov and his team created are two-dimensional metals, where electricity is conducted along the layers of the structure. “One of these materials – Na3Cl – has a fascinating structure,” Oganov says. “It is comprised of layers of NaCl and layers of pure sodium. The NaCl layers act as insulators; the pure sodium layers conduct electricity. Systems with two-dimensional electrical conductivity have attracted a lot interest.”
The experiments with table salt might only be the beginning of the discovery of completely new compounds. “If this simple system is capable of turning into such a diverse array of compounds under high-pressure conditions, then others likely are, too,” Goncharov explains. “This could help answer outstanding questions about early planetary cores, as well as to create new materials with practical uses.”

“Unexpected stable stoichometries of sodium chloride”; Weiwei Zhang, Artem R. Oganov, Alexander F. Goncharov, Qiang Zhu, Salah Eddine Boulfelfel, Andriy O. Lyakhov, Elissaios Stavrou, Maddury Somayazulu, Vitali B. Prakapenka, Zuzana Konôpková; Science, 2013; DOI:10.1126/science.1244989

Monday, January 6, 2014

Scientists discover double meaning in genetic code

A team of researchers have made the discovery that the genetic code used by DNA to store information actually contains a double meaning, with the second set of coded information having major implications for how scientists read and interpret the instructions within it.  According to the authors of this study, this fascinating find could help them to better understand both disease and health.
DNA, or deoxyribonucleic acid, is present in the cells of all humans, as well as almost every other living organism.  It contains the information for building and maintaining an organism in the form of a chemical code.  Four basic chemical bases – adenine, guanine, cytosine and thymine – are strung together in various sequences; and, the sequencing of these bases is what determines what information is coded within them, much like letters of the alphabet can be put together to create many different words and sentences.
The overall structure of DNA is what is known as a double helix.  The bases of DNA pair up with each other, with adenine pairing with thymine and cytosine pairing with guanine.  Each base pair then attaches to a sugar molecule as well as a phosphate molecule and this complete package is called a nucleotide.  Sequences of nucleotides arrange themselves in two long strands, somewhat like a ladder joined by base pair rungs, and the DNA molecule takes on a spiraling, helical shape.
DNA is able to make copies of itself by “unzipping” its two strands, allowing each strand to serve as a template for new DNA to be formed.  This process is how new DNA is created whenever cells divide and multiply.
Since 1962, when James Watson and Francis Crick received the Nobel Prize in Physiology or Medicine for discovering DNA, it has been thought that this was all there was to know about how DNA worked.  However, a research team lead by Dr. John Stamatoyannopoulos of the University of Washington, has made a startling new discovery.  DNA is actually used to write in two different languages, giving a double meaning to the genetic code.
One of these languages, the one that was discovered by Watson and Crick, is used to code information about proteins.   The second one, which was just discovered, codes information which tells the cell how to control genes.  Genes are sections of DNA molecules which, when taken by themselves, code for specific proteins.  Humans have thousands of genes, all of them controlling different traits, such as eye color or height.
It took scientists a long time to locate this second language because one language is superimposed over the other one.
Speaking about this new find,  Stamatoyannopoulos note that “[t]hese new findings highlight that DNA is an incredibly powerful information storage device, which nature has fully exploited in unexpected ways.”
According to the UW team, the genetic code uses a 64-letter “alphabet” called codons.  What they discovered in their work was that some of these codons actually had two different meanings, one which affected protein sequencing and one which affected gene control.  These codons, which they call duons, seem to have evolved these double meanings in order to help stabilize certain beneficial features of proteins and their manufacture.
Their findings have important implications for how scientists interpret a person’s genome, they say, opening up new ways to diagnose and treat disease.  Because the genetic code is communicating two different types of information at the same time, diseases which appear to be the result of alterations in protein sequencing might actually be caused by changes in gene control programs, or even both factors.
The findings from the study were published in the December 13, 2013 issue of Science.
By Nancy Schimelpfening

If Chemistry Can Be Wrong, How Much More Evolutionary Theory?

salt-320-use-this-one.jpgAlong with astronomy, chemistry is one of the ancient sciences. Progressing from alchemy to rational chemistry, physical chemistry and quantum mechanics of our day, its status as "hard science" seems secure. Its theories have been refined for centuries. Moreover, its experiments (unlike macroevolution) are observable and repeatable. How, then, could researchers at Stony Brook University (academic home, by the way, of ENV contributor Dr. Michael Egnor, Vice-Chairman, Department of Neurological Surgery) say that a discovery has challenged the foundation of chemistry?
Experiments at the lab are causing a stir -- if not a revolution -- in this hallowed science:
All good research breaks new ground, but rarely does the research unearth truths that challenge the foundation of a science. That's what Artem R. Oganov has done, and the professor of theoretical crystallography in the Department of Geosciences will have his work published in the Dec. 20 issue of the journal Science....
"I think this work is the beginning of a revolution in chemistry," Oganov says. "We found, at low pressures achievable in the lab, perfectly stable compounds that contradict the classical rules of chemistry. If you apply the rather modest pressure of 200,000 atmospheres -- for comparison purposes, the pressure at the center of the earth is 3.6 million atmospheres -- everything we know from chemistry textbooks falls apart." [Emphasis added.]
We all know NaCl, table salt. Ever heard of NaCl3? How about Na3Cl? Those are some of the novel compounds Oganov's lab has produced. They were stunned to find them to be stable, real compounds.
"We found crazy compounds that violate textbook rules -- NaCl3, NaCl7, Na3Cl2, Na2Cl, and Na3Cl," says Weiwei Zhang, the lead author and visiting scholar at the Oganov lab and Stony Brook's Center for Materials by Design, directed by Oganov. "These compounds are thermodynamically stable and, once made, remain indefinitely; nothing will make them fall apart. Classical chemistry forbids their very existence. Classical chemistry also says atoms try to fulfill the octet rule -- elements gain or lose electrons to attain an electron configuration of the nearest noble gas, with complete outer electron shells that make them very stable. Well, here that rule is not satisfied."
The discoveries open up new possibilities for the supposedly mature science. "When you change the theoretical underpinnings of chemistry, that's a big deal," one team member says. "But what it also means is that we can make new materials with exotic properties."
How could this happen in a "hard" science? For one, Oganov, described as curious and obstinate, was driven by the word "impossible" to explore its limits.
To Oganov, impossible didn't mean something absolute. "The rules of chemistry are not like mathematical theorems, which cannot be broken," he says. "The rules of chemistry can be broken, because impossible only means 'softly' impossible! You just need to find conditions where these rules no longer hold."
Oganov compares the team's findings to discovering a new continent. Understanding and predicting high-pressure compounds can lead to new theories. And he envisions applications for astrophysics and planetary sciences, where high pressures abound.
If an unexpected foundation-shaking paradigm shift can occur in a "hard" science like chemistry, where findings can be checked by observation and experiment, how confident can evolutionists be that their theories about the unobservable past?
In recent years, major problems have surfaced in evolutionary theory: the overthrow of "junk DNA," the discovery of codes within codes, the intransigence of the Cambrian enigma to name a few. Yet its advocates continue to bully anyone who doesn't toe the line. Darwinism acts like a religion, not science. If Darwinists were proper scientists, they would embrace the new discoveries that break their rules. They would gladly follow the mounting evidence that points in a new direction for the biology of the 21st century -- intelligent design.
Image credit: Electron localization function in the cubic NaCl3 structure/Stony Brook University.
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Wednesday, December 11, 2013

Randy Wayne Schekman (born December 30, 1948) is an American cell biologist at the University of California, Berkeley,[6] and former editor-in-chief of Proceedings of the National Academy of Sciences.[2][7][8] In 2011 he was announced as the editor of eLife, a new high profile open access journal published by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust launching in 2012.[9] He was elected to the National Academy of Sciences in 1992.[10] Schekman shared the 2013 Nobel Prize for Physiology or Medicine with James Rothman and Thomas C. Südhof.[5][11]

How journals like Nature, Cell and Science are damaging science | Randy Schekman

I am a scientist. Mine is a professional world that achieves great things for humanity. But it is disfigured by inappropriate incentives. The prevailing structures of personal reputation and career advancement mean the biggest rewards often follow the flashiest work, not the best. Those of us who follow these incentives are being entirely rational – I have followed them myself – but we do not always best serve our profession's interests, let alone those of humanity and society.
We all know what distorting incentives have done to finance and banking. The incentives my colleagues face are not huge bonuses, but the professional rewards that accompany publication in prestigious journals – chiefly NatureCell and Science.
These luxury journals are supposed to be the epitome of quality, publishing only the best research. Because funding and appointment panels often use place of publication as a proxy for quality of science, appearing in these titles often leads to grants and professorships. But the big journals' reputations are only partly warranted. While they publish many outstanding papers, they do not publish only outstanding papers. Neither are they the only publishers of outstanding research.
These journals aggressively curate their brands, in ways more conducive to selling subscriptions than to stimulating the most important research. Like fashion designers who create limited-edition handbags or suits, they know scarcity stokes demand, so they artificially restrict the number of papers they accept. The exclusive brands are then marketed with a gimmick called "impact factor" – a score for each journal, measuring the number of times its papers are cited by subsequent research. Better papers, the theory goes, are cited more often, so better journals boast higher scores. Yet it is a deeply flawed measure, pursuing which has become an end in itself – and is as damaging to science as the bonus culture is to banking.
It is common, and encouraged by many journals, for research to be judged by the impact factor of the journal that publishes it. But as a journal's score is an average, it says little about the quality of any individual piece of research. What is more, citation is sometimes, but not always, linked to quality. A paper can become highly cited because it is good science – or because it is eye-catching, provocative or wrong. Luxury-journal editors know this, so they accept papers that will make waves because they explore sexy subjects or make challenging claims. This influences the science that scientists do. It builds bubbles in fashionable fields where researchers can make the bold claims these journals want, while discouraging other important work, such as replication studies.
In extreme cases, the lure of the luxury journal can encourage the cutting of corners, and contribute to the escalating number of papers that are retracted as flawed or fraudulent. Science alone has recently retracted high-profile papers reporting cloned human embryos, links between littering and violence, and the genetic profiles of centenarians. Perhaps worse, it has not retracted claims that a microbe is able to use arsenic in its DNA instead of phosphorus, despite overwhelming scientific criticism.
There is a better way, through the new breed of open-access journals that are free for anybody to read, and have no expensive subscriptions to promote. Born on the web, they can accept all papers that meet quality standards, with no artificial caps. Many are edited by working scientists, who can assess the worth of papers without regard for citations. As I know from my editorship of eLife, an open access journal funded by the Wellcome Trust, the Howard Hughes Medical Institute and the Max Planck Society, they are publishing world-class science every week.
Funders and universities, too, have a role to play. They must tell the committees that decide on grants and positions not to judge papers by where they are published. It is the quality of the science, not the journal's brand, that matters. Most importantly of all, we scientists need to take action. Like many successful researchers, I have published in the big brands, including the papers that won me the Nobel prize for medicine, which I will be honoured to collect tomorrow.. But no longer. I have now committed my lab to avoiding luxury journals, and I encourage others to do likewise.
Just as Wall Street needs to break the hold of the bonus culture, which drives risk-taking that is rational for individuals but damaging to the financial system, so science must break the tyranny of the luxury journals. The result will be better research that better serves science and society.