Archive for the ‘Johns Hopkins University’ Category


Marta Orellana was experimented on when she was nine. Photograph: Rory Carroll/Guardian

Lawsuit with 800 plaintiffs seeks damages for individuals, spouses and children of people deliberately infected with STDs through US government program.

Nearly 800 plaintiffs have launched a billion-dollar lawsuit against Johns Hopkins University over its alleged role in the deliberate infection of hundreds of vulnerable Guatemalans with sexually transmitted diseases, including syphilis and gonorrhea, during a medical experiment program in the 1940s and 1950s.

The lawsuit, which also names the philanthropic Rockefeller Foundation, alleges that both institutions helped “design, support, encourage and finance” the experiments by employing scientists and physicians involved in the tests, which were designed to ascertain if penicillin could prevent the diseases.

Researchers at Johns Hopkins School of Medicine held “substantial influence” over the commissioning of the research program by dominating panels that approved federal funding for the research, the suit claims.

The lawsuit asserts that a researcher paid by the Rockefeller Foundation was assigned to the experiments, which he travelled to inspect on at least six occasions.

The suit also claims that predecessor companies of the pharmaceutical giant Bristol-Myers Squibb supplied penicillin for use in the experiments, which they knew to be both secretive and non-consensual.

The experiments, which occurred between 1945 and 1956, were kept secret until they were discovered in 2010 by a college professor, Susan Reverby. The program published no findings and did not inform Guatemalans who were infected of the consequences of their participation, nor did it provide them with follow up medical care or inform them of ways to prevent the infections spreading, the lawsuit states.

Orphans, prisoners and mental health patients were deliberately infected in the experiments.

The plaintiffs’ case quotes the correspondence from one of the program’s lead researchers who tells another doctor that if it were discovered by “some goody organization” that the program was testing people who were mentally ill it would “raise a lot of smoke”. The manager continues: “I see no reason to say where the work was done and the type of volunteer.”

Baltimore-based attorney for the plaintiffs Paul Bekman told the Guardian that of the 774 claimants, about 60 were direct survivors of the program. Many have died as a result of deliberate infection and others had passed on disease to family members and partners.

“The people who are responsible [for carrying out the research] now are long dead,” said Bekman “But the records are there, and we have detailed documentation that supports the allegations in our complaint.”

Marta Orellana was a nine-year-old orphan when she was included in the experiments. In an interview with the Guardian in 2011 she recalled being forcibly examined by light-complexioned foreigners and a Guatemalan doctor in the orphanage infirmary.

“They never told me what they were doing, never gave me a chance to say no,” Orellana said. “I’ve lived almost my whole life without knowing the truth. May God forgive them.”

Included within the legal claim are graphic descriptions of some of the methods used by the researchers to infect their subjects:

During the experiments, the following occurred:
1.Prostitutes were infected with venereal disease and then provided for sex to subjects for intentional transmission of the disease;
2.Subjects were inoculated by injection of syphilis spirochaetes into the spinal fluid that bathes the brain and spinal cord, under the skin, and on mucous membranes;
3.An emulsion containing syphilis or gonorrhoea was spread under the foreskin of the penis in male subjects;
4.The penis of male subjects was scraped and scarified and then coated with the emulsion containing syphilis or gonorrhea;
5.A woman from the psychiatric hospital was injected with syphilis, developed skin lesions and wasting, and then had gonorrhoeal pus from a male subject injected into both of her eyes and;
6.Children were subjected to blood studies to check for the presence of venereal disease.

The then secretary of state Hillary Clinton apologised for the programme in 2010 after a presidential bioethics commission investigation found the experiments “involved unconscionable basic violations of ethics”.

A federal lawsuit for damages under the Federal Tort Claims Act failed in 2012 after a judge determined the US government cannot be held liable for actions outside the US. Bekman told the Guardian he believed the new lawsuit stood a greater chance of success as it was lodged in the state court of Maryland and against private entities.

Both Johns Hopkins University and the Rockefeller Foundation have vigorously denied any involvement in the experiments.

A spokeswoman for Johns Hopkins School of Medicine said the institute expressed “profound sympathy” for the victims of the experiments and their families, but added: “Johns Hopkins did not initiate, pay for, direct of conduct the study in Guatemala. No nonprofit university or hospital has ever been held liable for a study conducted by the US government.”

The university stated it would “vigorously defend” the lawsuit.

The Rockefeller Foundation issued a detailed response to the claim online, which it described as seeking to “improperly to assign ‘guilt by association’ in the absence of compensation from the United States federal government”.

The statement continued: “In the absence of a connection to the Rockefeller Foundation, the lawsuit attempts to connect the Foundation to the experiments through misleading characterizations of relationships between the Foundation and individuals who were in some way associated with the experiments.”

A spokeswoman for Bristol-Myers Squibb declined to comment.

http://www.theguardian.com/us-news/2015/apr/02/johns-hopkins-lawsuit-deliberate-std-infections-guatemala

Thank to Kebmodee.


Sol Snyder, Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry, School of Medicine

Growing up, I never had any strong interest in science. I did well in lots of things in high school. I liked reading philosophy and things like that, but being a philosopher is not a fit job for a nice Jewish boy.

This was in the mid-1950s, and many of my friends were going into engineering, preparatory to joining the then prominent military industrial complex. Others were going to be doctors, so I got the idea that maybe I’d be a psychiatrist. I didn’t have any special affinity for medicine or desire to cast out the lepers or heal mankind.

I was always reading things. My father valued education. He wasn’t a big advice giver, but he … had a lot of integrity. What was important to him was doing the right thing. And he had great respect for the intellectual life and science.

My father’s professional life commenced in 1935 as the 10th employee of what became the NSA. He led a team that broke one of the principal Japanese codes. At the end of World War II, computers were invented, and, if you think about it, what could be the best entity to take advantage of computers than NSA, with its mission of sorting gibberish and looking for patterns. So my father was assigned to look at these new machines and see if they would be helpful. He led the computer installations at NSA.

Summers in college I worked in the NSA. My father taught me to program computers in machine language. Computers were a big influence on me.

I learned at the NSA about keeping secrets. What is top secret, what is need-to-know—that is one of the things you learn in the business. You don’t talk to the guy at the next desk even if you’re working on the same project. If that person doesn’t need to know, you just shut up.

In medical school, I started working at the NIH in Bethesda during the summers and elective periods, largely because the only thing I really did well up to that time was play the classical guitar and one of my guitar students was an NIH researcher. In high school I thought I might go the conservatory route, but that’s even less fitting for a nice Jewish boy than being a philosopher.

It was through my contacts at NIH that I was able to get a position working with future Nobel Prize winner Julius Axelrod. Julie was a wonderful mentor who did research on drugs and neurotransmitters. Working with him was inspirational. I just adored it.

What was notable about Julie was his great creativity, always coming up with original ideas. Even though he was an eminent scientist, he didn’t have a regular office. He just had a desk in a lab. He did experiments with his own two hands every day.

Philosophically, Julie emphasized you go where the data takes you. Don’t worry that you’re an expert in enzyme X and so should focus on that. If the data point to enzyme Y, go for it. Do what’s exciting.

My very first project with Julie was studying the disposition of histamine. I thought I had found that histamine had been converted into a novel product that looked really interesting, and I was wrong. I missed the true product because we separated the chemicals on paper and discarded the radioactivity at the bottom, throwing away the real McCoy. Another lab at Yale found it, led, remarkably, by a close friend since kindergarten. My humiliation didn’t last very long. I learned not to be so sloppy, to take greater care, and, most important, to explore peculiar results.

How does one pick research directions? You can go where it’s “hot,” but there you’re competing with 300 other people, and everyone can make only incremental changes. But if you follow Julie Axelrod’s rules and you don’t worry about what’s hot, or what other people are doing—just go where your data are taking you—then you have a better chance of finding something that nobody else had found before.

With the discovery of the opiate receptor, I was fortunate to launch a new field: molecular identification of neurotransmitter receptors. Later we discovered that the gas nitrous oxide is a neurotransmitter.

I’m a klutz. I can’t hammer a nail. So for the technical side, like dissecting brains to look at different regions, I enlisted friends. I learned to collaborate, a key element in so many discoveries.

Johns Hopkins has always been a collegial place. People are just friendly and interact with each other. This tradition goes back to the founding of the medical school, permeating the school’s governance as well as research. We tend to be more productive than faculty at other schools, where one gets ahead by sticking an ice pick in the backs of colleagues.

One of my heroes was my guitar teacher, Sophocles Papas, Andrés Segovia’s best friend. Sophocles was an important influence in my life, and we stayed close until he died in his 90s. In a couple of years after commencing lessons, I was giving recitals, all thanks to him. Like Julie, Sophocles emphasized innovative short cuts to creativity.

I’ve remained involved with music. I’m the longest-serving trustee on the Baltimore Symphony Orchestra, chairing for many years its music committee. Trustees of arts organizations are typically businesspeople selected for their fundraising acumen. But the person who nominated me reportedly commented, I’d like to propose something radical: I’d like to propose a trustee who cares about music.

Most notable about psychiatry is that the major drugs—antipsychotics for schizophrenia, antidepressants, and anti-anxiety drugs—were all discovered in the mid-1950s. Subsequent tweaking has enhanced potency and diminished side effects, but there have been no major breakthroughs. No new class of drugs since 1958—rather frustrating.

As biomedical science advances, especially with the dawn of molecular biology, our power to innovate is just dazzling. Today’s students take all of this for granted, but those of us who have been doing research for several decades are daily amazed by our abilities to probe the mysteries of life.

The logic of nature is elegant and straightforward. The more we learn about how the body works, the more we are amazed by its beauty and inherent simplicity.

One of my pet peeves is that the very power of modern science leads journal and grant reviewers to expect every “i” dotted and every “t” crossed. Because of this, four years or more of work go into each scientific manuscript. Then, editors and reviewers of journals are so picayune that revising a paper consumes another year.

Now let’s consider the poor post­doctoral fellow or graduate student. To move forward in his or her career requires at least one major publication—a five-year enterprise. If you only have one shot on goal, one paper in five years, your chances of success shrivel. The duration of PhD training and postdoctoral training is getting so long that from the entry point at graduate school to the time you’re out looking for a job as an assistant professor is easily 12, 15 years. Well, that is ridiculous. If you got paid $10 million at the end of this road, that would be one thing, but scientists earn less than most other professionals. We’re deterring the young smart people from going into science.

Biomedical researchers don’t work in a vacuum. They work with grad students and postdoctoral fellows, so being a good mentor is key to being a good scientist. Keep your students well motivated and happy. Have them feel that they are good human beings, and they will do better science.

The most important thing is that you value the integrity of each person. I ask my students all the time, What do you think? And this discussion turns into minor league psychotherapy. Ah, you think that? Tell me more. Tell me more.

The “stupidest” of the students here are smarter than me. It’s a pleasure to watch them emerge.

I see my life as taking care of other people. Although I didn’t go to medical school with any intelligent motivation, once I did, I loved being a doctor and trying to help people. And I love being a psychiatrist and trying to understand people, and I try to carry that into everything I do.

In medical research, all of us want to find the causes and cures for diseases. I haven’t found the cause of any disease, although with Huntington’s disease, we are making inroads. And, of course, being a pharmacologist, my métier is discovering drugs and better treatments.

My secret? I come to work every day, and I keep my own calendar. That way I have free time to just wander around the lab and talk to the boys and girls and ask them how it’s going. That’s what makes me happy.

Sol Snyder joined Johns Hopkins in 1965 as an assistant resident in Psychiatry and would later become the youngest full professor in JHU history. In 1978, he received the Albert Lasker Basic Medical Research Award for his role in discovering the brain’s opiate receptors. In 1980, he founded the School of Medicine’s Department of Neuroscience, which in 2006 was renamed the Solomon H. Snyder Department of Neuroscience.

http://hub.jhu.edu/gazette/2014/january-february/what-ive-learned-sol-snyder

http://en.wikipedia.org/wiki/Solomon_H._Snyder

drugs

dr nutt
Nutt says politicians often have a “primitive, childish” way of thinking about drugs.

David Nutt is trying to develop a new recreational drug that he hopes will be taken up by millions of people around the world. No, the 62-year-old scientist isn’t “breaking bad.” In fact, he hopes to do good. His drug would be a substitute for alcohol, to create drinks that are just as intoxicating as beer or whiskey but less toxic. And it would come with an antidote to reverse its effects, allowing people to sober up instantly and drive home safely.

Nutt, a neuropsychopharmacologist at Imperial College London and a former top adviser to the British government on drug policy, says he has already identified a couple of candidates, which he is eager to develop further. “We know people like alcohol, they like the relaxation, they like the sense of inebriation,” Nutt says. “Why don’t we just allow them to do it with a drug that isn’t going to rot their liver or their heart?”

But when he presented the idea on a BBC radio program late last year and made an appeal for funding, many were appalled. A charity working on alcohol issues criticized him for “swapping potentially one addictive substance for another”; a commentator called the broadcast “outrageous.” News-papers likened his synthetic drug to soma, the intoxicating compound in Aldous Huxley’s dystopian novel Brave New World. Some of his colleagues dismissed the idea as scientifically unfeasible.

Nutt wasn’t surprised. As a fierce advocate of what he says are more enlightened, rational drug policies, he has been a lightning rod for a long time. Politicians, in Nutt’s view, make irrational decisions about drugs that help them win votes but cost society dearly. Drug policy is often based on the moral judgment that people should not use drugs, he says. Instead, it should reflect what science knows about the harms of different drugs—notably that many are far less harmful than legal substances such as alcohol, he says. The plan for a synthetic alcohol alternative is his own attempt to reduce the damage that drug use can wreak; he believes it could save millions of lives and billions of dollars.

Such views—and the combative way in which he espouses them—frequently land Nutt in fierce disputes. Newspaper commentators have called him “Professor Nutty” or “the dangerous professor.” In 2009, he was sacked from his position as chair of the United Kingdom’s Advisory Council on the Misuse of Drugs, tasked with giving scientific advice to the home secretary, after he criticized a government decision on cannabis.

But in November 2013, he received the John Maddox Prize for standing up for science. “In circumstances that would have humiliated and silenced most people,” wrote neurobiologist Colin Blakemore, one of the judges, “David Nutt continued to affirm the importance of evidence in understanding the harms of drugs and in developing drug policy.”

Controversial comparisons
David Nutt does not look like a dangerous professor. Short and heavyset, he has a jovial, round face and an old-fashioned mustache; one could mistake him for a London taxi driver. He limps slightly, has a down-to-earth way of speaking, and laughs a lot when he talks. “He is a real personality,” says psychopharmacologist Rainer Spanagel of Heidelberg University in Germany. “You can be in a meeting and almost have a result, then he will come in an hour late, stir everything up, and in the end convince everyone of his position.”

Nutt says he realized at an early age that “understanding how the brain works is the most interesting and challenging question in the universe.” When he was a teenager, his father told him a story of how Albert Hofmann, the discoverer of LSD, took a dose of that drug and felt that the bike ride home took hours instead of minutes. “Isn’t that incredible, that a drug can change time?” he asks. On his first night as an undergraduate in Cambridge, he witnessed the powers of drugs again when he went drinking with fellow students. Two of them couldn’t stop. “I just watched them transform themselves. One of them started wailing and crying and the other became incredibly hostile.”

During his clinical training, Nutt says he treated many alcoholics but failed “to get anyone interested in how to reduce their addiction to the drug that was harming them.” He set out to answer that question, first in the United Kingdom, later as the chief of the Section of Clinical Science at the U.S. National Institute on Alcohol Abuse and Alcoholism, a job he held for 2 years. Today, he runs the department of neuropsychopharmacology at Imperial College, using modern imaging techniques to see what happens in the brain when people take drugs or develop an addiction.

But his biggest contribution to science, he says, was a discovery he made quite early in his career: that some molecules don’t just block receptors in the brain, but actually have the opposite effect of the molecules that normally stimulate them—and in doing so shut down a brain pathway. Nutt called these molecules contragonists, and he has made a second career out of being a bit of a contragonist himself, trying to calm society’s overexcited responses to the steady stream of alarming news about drugs.

Fictional affliction
In 2009, Nutt published an article in the Journal of Psychopharmacology comparing the harms from ecstasy with those caused by horse riding. Every 10,000th ecstasy pill is likely to hurt someone, he calculated, while an average horse enthusiast can expect a serious accident every 350 hours of riding. The sport, he concluded, was more dangerous than the notorious party drug. That “raises the critical question of why society tolerates—indeed encourages—certain forms of potentially harmful behaviour but not others such as drug use,” he added.

Politicians were not amused, and Nutt’s whimsical reference to a fictional affliction he called equine addiction syndrome, or “equasy,” did not help. In his book Drugs – Without the Hot Air, Nutt provided his account of a phone conversation he had with U.K. Home Secretary Jacqui Smith after the paper was published. (Smith calls it an “embroidered version” of their talk.)

Smith: “You can’t compare harms from a legal activity with an illegal one.”

Nutt: “Why not?”

“Because one’s illegal.”

“Why is it illegal?”

“Because it’s harmful.”

“Don’t we need to compare harms to determine if it should be illegal?”

“You can’t compare harms from a legal activity with an illegal one.”

Nutt says this kind of circular logic crops up again and again when he discusses recreational drugs with politicians. “It’s what we would call ‘splitting’ in psychiatric terms: this primitive, childish way of thinking things are either good or bad,” he says.

He’s often that outspoken. He likens the way drug laws are hampering legitimate scientific research, for instance into medical applications for psychedelic compounds, to the church’s actions against Galileo and Copernicus. When the United Kingdom recently banned khat, a plant containing a stimulant that’s popular among people from the Horn of Africa and the Arabian Peninsula, he compared the decision with banning cats. And he accuses the Russian government of deliberately using alcohol to weaken the opposition. “However miserable they are, however much they hate their government and their country, they will just drink until they kill themselves, so they won’t protest,” he says.

But it’s his stance on cannabis that got him sacked. In early 2009, ignoring advice from Nutt’s advisory council, Smith upgraded cannabis from class C to class B, increasing the maximum penalty for possession from 2 to 5 years in prison. A few months later, Nutt criticized the decision in a public lecture, arguing that “overall, cannabis use does not lead to major health problems” and that tobacco and alcohol were more harmful. When media reported the remarks, Alan Johnson, who succeeded Smith as home secretary in mid-2009, asked him to resign. “He was asked to go because he cannot be both a government adviser and a campaigner against government policy,” Johnson wrote in a letter in The Guardian.

Nutt did not go quietly. With financial help from a young hedge fund manager, Toby Jackson, he set up a rival body, the Independent Scientific Committee on Drugs, “to ensure that the public can access clear, evidence based information on drugs without interference from political or commercial interest.” Politics have skewed not just drug laws but research itself, he argues. “If you want to get money from the U.S. government to work on a drug, you have to prove it damages the brain,” he says.

One of his favorite examples is a paper that Science published in September 2002. The study, led by George Ricaurte at Johns Hopkins University, seemed to show that monkeys given just two or three doses of ecstasy, chemically known as MDMA, developed severe brain damage. The finding suggested that “even individuals who use MDMA on one occasion may be at risk for substantial brain injury,” the authors wrote. The paper received massive media attention, but it was retracted a year later after the authors discovered that they had accidentally injected the animals not with MDMA but with methamphetamine, also known as crystal meth, which was already known to have the effects seen in the monkeys. Nutt says the mistake should have been obvious from the start because the data were “clearly wrong” and “scientifically implausible.” “If that result was true, then kids would have been dropping dead from Parkinson’s,” he says.

Some resent this combative style. “He is a polarizing figure and the drug policy area is polarized enough,” says Jonathan Caulkins, a professor of public policy at Carnegie Mellon University in Pittsburgh, Pennsylvania. But Jürgen Rehm, an epidemiologist at the Centre for Addiction and Mental Health in Toronto, Canada, says Nutt has helped stimulate debates that were long overdue. “You don’t get to be on the front page of The Lancet and The New York Times unless you sharpen your arguments a little bit,” Rehm says. “I can live with that.”

Ranking the drugs
In 2010, Nutt sparked a new firestorm when he published another comparison: a Lancet paper ranking drugs according to the harm they cause. Nutt and other experts scored a long list of drugs on 16 criteria, nine related to the user, such as death from an overdose or wrecked relationships, and seven related to society, such as drug-fueled violence and economic costs. In the end, every drug was given a score between 0 and 100 to indicate its overall harm. Alcohol came out on top, ahead of heroin; mushrooms and ecstasy were at the low end.

Critics said the study’s methodology was flawed because it didn’t address drug interactions and the social context of drug use. “For instance, the number of fatalities caused by excessive alcohol use is going to depend in part on gun control laws,” says Caulkins, who calls the whole idea of expressing drug harm as a single number “embarrassing.”

Caulkins adds that even if a perfect ranking of drug harms were possible, it wouldn’t mean that politicians should put the tightest control measures on the most harmful drugs. Suppose drug A is more harmful to the individual and society than drug B, he says, but impurities in drug A, when illegally produced, can lead to potentially fatal organ failure while they just taste bad in drug B. If you were going to prohibit only one of the two drugs, it should be drug B, he says, even though it causes less harm per se, because criminalizing drug A would lead to a more dangerous product and more deaths. Nutt’s ranking of drugs, he says, is “a pseudoscientific exercise which is trying to take control of the policy process from a technocratic perspective in a way that isn’t even sound.”

Other scientists defended the paper. Using Nutt’s harm scales, “flawed and limited as they may be, would constitute a quantum leap of progress towards evidence-based and more rational drug policy in Canada and elsewhere,” two Canadian drug scientists wrote in Addiction. Regardless of its quality, the paper has been hugely influential, Rehm says. “Everyone in the E.U. knows that paper, whether they like it or not. There is a time before that paper and a time after it appeared.”

Nutt says his comparisons are an essential first step on the way to more evidence-based drug policies that seek to reduce harm rather than to moralize. The best option would be a regulated market for alcohol and all substances less harmful to the user than alcohol, he argues.

That scenario, under which only heroin, crack cocaine, and methamphetamine would remain illegal, seems unlikely to become a reality. But Nutt says he can already see more rational policies taking hold. Recently, Uruguay and the U.S. states of Colorado and Washington legalized the sale of recreational cannabis, going a step further than the Netherlands, which stopped enforcing laws on the sale and possession of small amounts of soft drugs decades ago. Nutt was also happy to read President Barack Obama’s recent comment that cannabis is less harmful than alcohol. “At last, a politician telling the truth,” he says. “I’ll warn him though—I was sacked for saying that.”

New Zealand, meanwhile, passed a law in 2013 that paves the way for newly invented recreational drugs to be sold legally if they have a “low risk” of harming the user. Nutt, who has advised the New Zealand government, is delighted by what he calls a “rational revolution in dealing with recreational drugs.” The main problem now, he says, is establishing new drugs’ risks—which is difficult because New Zealand does not allow them to be tested on animals—and deciding what “low risk” actually means. “I told them the threshold should be if it is safer than alcohol,” he says. “They said: ‘Oh my god, that is going to be far too dangerous.'”

Safer substitute
Nutt agrees that alcohol is now one of the most dangerous drugs on the market—which is why he’s trying to invent a safer substitute. The World Health Organization estimates that alcohol—whose harms range from liver cirrhosis, cancer, and fetal alcohol syndrome to drunk driving and domestic violence—kills about 2.5 million people annually. “When I scan the brains of people with chronic alcohol dependence, many have brains which are more damaged than those of people with Alzheimer’s,” Nutt says.

In a paper published this month in the Journal of Psychopharmacology, Nutt and Rehm summarize the top six interventions that governments should consider to reduce the harms of alcohol, such as minimum prices and restrictions on the places that can sell hard liquor. They also argue that governments should support the development of alternatives. Nutt points to e-cigarettes—devices that heat and vaporize a nicotine solution—as a model. “In theory, electronic cigarettes could save 5 million lives a year. That is more than [the death toll from] AIDS, malaria, tuberculosis, and meningitis put together,” he says. “I would argue that the e-cigarette is going to be the greatest health invention since vaccination.”

Can an alcohol alternative do the same? “I think that idea is utopian,” says Spanagel, the German psychopharmacologist. One reason is that researchers have recently developed a much more complex picture of what ethanol, as chemists call it, actually does. Twenty years ago, they thought that once it reached the brain, alcohol elicited its many effects by infiltrating the membranes of neurons there and changing their properties. “Now we know that’s nonsense. You would have to drink 5 liters of schnapps for that to happen,” Spanagel says.

In fact, scientists have learned that alcohol, like other drugs, interacts with the receptors for certain neurotransmitters. But unlike other drugs, it acts on a wide range of them, including receptors for GABA, NMDA, serotonin, and acetylcholine. That will make it hard to find a substance to emulate most of alcohol’s wanted effects while avoiding the unwanted ones, Spanagel predicts.

Nutt is concentrating on the GABA system—the most important inhibitory system in mammalian brains. Alcohol activates GABA receptors, effectively quieting the brain and leading to the state of relaxation many people seek. Nutt has sampled some compounds that target GABA receptors and was pleasantly surprised. “After exploring one possible compound I was quite relaxed and sleepily inebriated for an hour or so, then within minutes of taking the antidote I was up giving a lecture with no impairment whatsoever,” he wrote in a recent article.

But he wants to go one step further. “We know that different subtypes of GABA mimic different effects of alcohol,” he says. Nutt combed the scientific literature and patents for compounds targeting specific GABA receptors, and, in an as-yet unpublished report that he shared with Science, he identifies several molecules that he says fit the bill. Compounds targeting subtypes of the GABAA receptor called alpha2 and alpha3 are particularly promising, he says. Some of these molecules were dropped as therapeutic drug candidates precisely because they had side effects similar to alcohol intoxication.

Gregg Homanics, an alcohol researcher at the University of Pittsburgh, is skeptical that another substance could mimic all the positive effects of alcohol. “You could come up with a drug that might make you feel good. But is it going to be the same good feeling as alcohol? I doubt that.” Such a drug might have downsides of its own, warns Andreas Heinz, an addiction researcher at Charité University Medicine Berlin. It could still turn out to be addictive or to harm a small proportion of the population. “There is an advantage when you have known drugs for hundreds of years and you know exactly what they do,” he says.

Still, Nutt’s appearance on the BBC radio program attracted new investors, ranging “from Ukrainian brewers to American hedge funds,” he says, and Imperial Innovations, a company that provides technology transfer services, is working with him “to consider a range of options for taking the research forward,” a spokesperson says. “We think we have enough funding now to take a substance all the way to the market,” Nutt says—in fact, he hopes to be able to offer the first cocktails for sale in as little as a year from now.

Even a very good alcohol substitute would face obstacles. Many people won’t forsake drinks they have long known and loved—such as beer, wine, and whiskey—for a new chemical, Spanagel says. The idea will also trigger all kinds of political and regulatory debates, Rehm says. “How will such a new drug be seen? Will you be able to buy it in the supermarket? In the pharmacy? Will society accept it?”

Whatever the outcome, Nutt’s quest for a safer drink has already made people think about alcohol in a new way, Rehm adds. “It’s provocative in the best sense of the word.” Much the same could be said of the scientist who thought it up.

http://www.sciencemag.org/content/343/6170/478.full

lsd

Psychedelic drugs could help to keep ex-offenders out of prison, new research suggests.

U.S. scientists have found that drugs such as LSD and magic mushrooms could be used to help reform criminals under community correction supervision.

It has previously been thought that LSD could be used to treat alcohol addiction, but the new research is the first in 40 years to suggest it could be used to stop criminals from re-offending.

Researchers from the University of Alabama at Birmingham and Johns Hopkins University School of Medicine, Baltimore, collected data about 25,622 people under community supervision between 2002 and 2007.

All study participants were in the Treatment Accountability for Safer Communities (TASC) program, for people with a history of drug abuse, including alcohol addiction.

The researchers found that criminals diagnosed with a hallucinogen use disorder were less likely to fail the TASC programme, appear in court and be arrested and imprisoned, compared to those who did not have a history of taking the drugs.

Just one per cent of people on the programme were diagnosed with a hallucinogen disorder, while heavy users of cocaine, cannabis and alcohol were the most common.

‘Our results provide a notable exception to the robust positive link between substance use and criminal behaviour,’ the researchers wrote in their study, which was published in the Journal of Psychopharmacology.

‘They add to both the older and emerging body of data indicating beneficial effects of hallucinogen interventions and run counter to the legal classification as well as popular perception of hallucinogens as categorically harmful substances with no therapeutic potential,’ they added.

The scientists believe that offenders may be especially likely to benefit from LSD treatment as many people become criminals as a result of drug-seeking behaviour and impulsive conduct, often caused by compulsive drug use.

The study took factors such as race, employment, age, history of drug abuse and crimes, as well as gender and education into account.

However, the researchers warned that the findings of the study should not be seen to advocate recreational use of psychedelic drugs.

‘Nevertheless, they demonstrate that, in a real-world, substance-related intervention setting, hallucinogen use is associated with a lower probability of poor outcome,’ they wrote.

They believe the research should be the start of a continued investigation into the use of psychedelic drugs to treat criminals.

Read more: http://www.dailymail.co.uk/sciencetech/article-2537137/Could-LSD-cut-crime-Psychedelic-drug-help-prevent-criminals-offending.html#ixzz2qK1CX9Vz
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mindfulness-meditation

By Andrew M. Seaman

Mindfulness meditation may be useful in battles against anxiety, depression and pain, according to a fresh look at past research.

Using data from 47 earlier studies, researchers found moderate evidence to support the use of mindfulness meditation to treat those conditions. Meditation didn’t seem to affect mood, sleep or substance use.

“Many people have the idea that meditation means just sitting quietly and doing nothing,” wrote Dr. Madhav Goyal in an email to Reuters Health. “That is not true. It is an active training of the mind to increase awareness, and different meditation programs approach this in different ways.”

Goyal led the study at The Johns Hopkins University in Baltimore.

He and his colleagues write in JAMA Internal Medicine that meditation techniques emphasize mindfulness and concentration.

So-called mindfulness meditation is aimed at allowing the mind to pay attention to whatever thoughts enter it, such as sounds in the environment, without becoming too focused. Mantra meditation, on the other hand, involves focusing concentration on a particular word or sound.

Approximately 9 percent of people in the U.S. reported meditating in 2007, according to the National Institutes of Health. About 1 percent said they use meditation as some sort of treatment or medicine.

For the new report, the researchers searched several electronic databases that catalog medical research for trials that randomly assigned people with a certain condition – such as anxiety, pain or depression – to do meditation or another activity. These randomized controlled trials are considered the gold standard of medical research.

The researchers found 47 studies with over 3,500 participants that met their criteria.

After combining the data, Goyal said his team found between a 5 and 10 percent improvement in anxiety symptoms among people who took part in mindfulness meditation, compared to those who did another activity.

There was also about a 10 to 20 percent improvement in symptoms of depression among those who practiced mindfulness meditation, compared to the other group.

“This is similar to the effects that other studies have found for the use of antidepressants in similar populations,” Goyal said.

Mindfulness meditation was also tied to reduced pain. But Goyal said it’s hard to know what kind of pain may be most affected by meditation.

The benefits of meditation didn’t surpass what is typically associated with other treatments, such as drugs and exercise, for those conditions.

“As with many therapies, we try to get a moderate level of confidence that the therapy works before we prescribe it,” Goyal said. “If we have a high level of confidence, it is much better.”

But he noted that the researchers didn’t find anything more than moderate evidence of benefit from meditation for anxiety, depression and pain.

There was some suggestion that meditation may help improve stress and overall mental health, but the evidence supporting those findings was of low quality.

There was no clear evidence that meditation could influence positive mood, attention, substance use, eating habits, sleep or weight.

“Clinicians should be prepared to talk with their patients about the role that meditation programs could have in addressing psychological stress, particularly when symptoms are mild,” Goyal said.

Dr. Allan Goroll, who wrote an editorial accompanying the new study, told Reuters Health the analysis is an example of an area of much-needed scientific study, because many people make treatment decisions based on beliefs – not data.

“That is particularly the case with alternative and complimentary approaches to treating medical problems,” he said. “It ranges from taking vitamins to undergoing particular procedures for which the scientific evidence is very slim but people’s beliefs are very great.”

Goroll is professor at Harvard Medical School and Massachusetts General Hospital in Boston.

Goyal said people should remember that meditation was not conceived to treat any particular health problem.

“Rather, it is a path we travel on to increase our awareness and gain insight into our lives,” he wrote. “The best reason to meditate is to gain this insight. Improvements in health conditions are really a side benefit, and it’s best to think of them that way.”

SOURCE: bit.ly/WiwDtv JAMA Internal Medicine, online January 6, 2014.

Insomnia-Electronic-Cigarettes

An insomnia therapy that scientists just reported could double the effectiveness of depression treatment is not widely available nor particularly well understood by psychiatrists or the public. The American Board of Sleep Medicine has certified just 400 practitioners in the United States to administer it, and they are sparse, even in big cities.

That may change soon, however. Four rigorous studies of the treatment are nearing completion and due to be reported in coming months. In the past year, the American Psychological Association recognized sleep psychology as a specialty, and the Department of Veterans Affairs began a program to train about 600 sleep specialists. So-called insomnia disorder is defined as at least three months of poor sleep that causes problems at work, at home or in relationships.

The need is great: Depression is the most common mood disorder, affecting some 18 million Americans in any given year, and most have insomnia.

“I think it’s increasingly likely that this kind of sleep therapy will be used as a possible complement to standard care,” said Dr. John M. Oldham, chief of staff at the Menninger Clinic in Houston. “We are the court of last resort for the most difficult-to-treat patients, and I think sleep problems have been extremely underrecognized as a critical factor.”

The treatment, known as cognitive behavioral therapy for insomnia, or CBT-I, is not widely available. Most insurers cover it, and the rates for private practitioners are roughly the same as for any psychotherapy, ranging from $100 to $250 an hour, depending on the therapist.

“There aren’t many of us doing this therapy,” said Shelby Harris, the director of the behavioral sleep medicine program at Montefiore Medical Center in the Bronx, who also has a private practice in Tarrytown, N.Y. “I feel like we all know each other.”

According to preliminary results, one of the four studies has found that when CBT-I cures insomnia — it does so 40 percent to 50 percent of the time, previous work suggests — it powerfully complements the effect of antidepressant drugs.

“There’s been a huge recognition that insomnia cuts across a wide variety of medical disorders, and there’s a need to address it,” said Michael T. Smith, a professor at the Johns Hopkins School of Medicine and president of the Society of Behavioral Sleep Medicine.

The therapy is easy to teach, said Colleen Carney, director of the sleep and depression lab at Ryerson University in Toronto, whose presentation at a conference of the Association for Behavioral and Cognitive Therapies in Nashville on Saturday raised hopes for depression treatment. “In the study we did, I trained students to administer the therapy,” she said in an interview, “and the patients in the study got just four sessions.”

CBT-I is not a single technique but a collection of complementary ideas. Some date to the 1970s, others are more recent. One is called stimulus control, which involves breaking the association between being in bed and activities like watching television or eating. Another is sleep restriction: setting a regular “sleep window” and working to stick to it. The therapist typically has patients track their efforts on a standardized form called a sleep diary. Patients record bedtimes and when they wake up each day, as well as their perceptions about quality of sleep and number of awakenings. To this the therapist might add common-sense advice like reducing caffeine and alcohol intake, and making sure the bedroom is dark and quiet.

Those three elements — stimulus control, restriction and common sense — can do the trick for many patients. For those who need more, the therapist applies cognitive therapy — a means of challenging self-defeating assumptions. Patients fill out a standard questionnaire that asks how strongly they agree with statements like: “Without an adequate night’s sleep, I can hardly function the next day”; “I believe insomnia is the result of a chemical imbalance”; and “Medication is probably the only solution to sleeplessness.” In sessions, people learn to challenge those beliefs, using evidence from their own experiences.

“If someone has the belief that if they don’t sleep, they’ll somehow fail the next day, I’ll ask, ‘What does failure mean? You’ll be slower at work, not get everything done, not make dinner?’ ” Dr. Harris said. “Then we’ll look at the 300 nights they didn’t sleep well over the past few years and find out they managed; it might not have been as pleasant as they liked, but they did not fail. That’s how we challenge those kinds of thoughts.”

Dr. Aaron T. Beck, an emeritus professor of psychiatry at the University of Pennsylvania who is recognized as the father of cognitive therapy for mental disorders, said the techniques were just as applicable to sleep problems. “In fact, I have used it myself when I occasionally have insomnia,” he said by email.

In short-term studies of a month or two, CBT-I has been about as effective as prescription sleeping pills. But it appears to have more staying power. “There’s no data to show that if you take a sleeping pill — and then stop taking it — that you’ll still be good six months later,” said Jack Edinger, a professor at National Jewish Health in Denver and an author, with Dr. Carney, of “Overcoming Insomnia: A Cognitive-Behavioral Therapy Approach.”

“It might happen, but those certainly aren’t the people who come through my door,” he said.

Dr. Edinger and others say that those who respond well to CBT-I usually do so quickly — in an average of four sessions, and rarely more than eight. “You’re not going to break the bank doing this stuff; it’s not a marriage,” he said. “You do it for a fixed amount of time, and then you’re done. Once you’ve got the skills, they don’t go away.”

http://www.nytimes.com/2013/11/24/health/sleep-therapy-is-expected-to-gain-a-wider-role-in-depression-treatment.html?partner=rss&emc=rss&_r=0

universe

Is our universe merely one of billions? Evidence of the existence of ‘multiverse’ revealed for the first time by a cosmic map of background radiation data gathered by Planck telescope. The first ‘hard evidence’ that other universes exist has been claimed to have been found by cosmologists studying new Planck data released this past June. They have concluded that it shows anomalies that can only have been caused by the gravitational pull of other universes.

“Such ideas may sound wacky now, just like the Big Bang theory did three generations ago,” says George Efstathiou, professor of astrophysics at Cambridge University.”But then we got evidence and now it has changed the whole way we think about the universe.”

Scientists had predicted that it should be evenly distributed, but the map shows a stronger concentration in the south half of the sky and a ‘cold spot’ that cannot be explained by current understanding of physics. Laura Mersini-Houghton, theoretical physicist at the University of North Carolina at Chapel Hill, and Richard Holman, professor at Carnegie Mellon University, predicted that anomalies in radiation existed and were caused by the pull from other universes in 2005. Mersini-Houghton will be in Britain soon promoting this theory and, we expect, the hard evidence at the Hay Festival on May 31 and at Oxford on June 11.

Dr Mersini-Houghton believes her hypothesis has been proven from the Planck data that data has been used to create a map of light from when the universe was just 380,000 years old. “These anomalies were caused by other universes pulling on our universe as it formed during the Big Bang,” she says. “They are the first hard evidence for the existence of other universes that we have seen.”

Columbia University mathematician Peter Woit writes in his blog, Not Even Wrong, that in recent years there have been many claims made for “evidence” of a multiverse, supposedly found in the CMB data. “Such claims often came with the remark that the Planck CMB data would convincingly decide the matter. When the Planck data was released two months ago, I looked through the press coverage and through the Planck papers for any sign of news about what the new data said about these multiverse evidence claims. There was very little there; possibly the Planck scientists found these claims to be so outlandish that it wasn’t worth the time to look into what the new data had to say about them.

“One exception,” Woit adds, “was this paper, where Planck looked for evidence of ‘dark flow’. They found nothing, and a New Scientist article summarized the situation: ‘The Planck team’s paper appears to rule out the claims of Kashlinsky and collaborators,’ says David Spergel of Princeton University, who was not involved in the work. If there is no dark flow, there is no need for exotic explanations for it, such as other universes, says Planck team member Elena Pierpaoli at the University of Southern California, Los Angeles. “You don’t have to think of alternatives.'”

“Dark Flow” sounds like a new SciFi Channel series. It’s not! The dark flow is controversial because the distribution of matter in the observed universe cannot account for it. Its existence suggests that some structure beyond the visible universe — outside our “horizon” — is pulling on matter in our vicinity.

Back in the Middle Ages, maps showed terrifying images of sea dragons at the boundaries of the known world. Today, scientists have observed strange new motion at the very limits of the known universe – kind of where you’d expect to find new things, but they still didn’t expect this. A huge swath of galactic clusters seem to be heading to a cosmic hotspot and nobody knows why.

Cosmologists regard the microwave background — a flash of light emitted 380,000 years after the universe formed — as the ultimate cosmic reference frame. Relative to it, all large-scale motion should show no preferred direction. A 2010 study tracked the mysterious cosmic ‘dark flow’ to twice the distance originally reported. The study was led by Alexander Kashlinsky at NASA’s Goddard Space Flight Center in Greenbelt, Maryland.

“This is not something we set out to find, but we cannot make it go away,” Kashlinsky said. “Now we see that it persists to much greater distances – as far as 2.5 billion light-years away,” he added.

Dark flow describes a possible non-random component of the peculiar velocity of galaxy clusters. The actual measured velocity is the sum of the velocity predicted by Hubble’s Law plus a small and unexplained (or dark) velocity flowing in a common direction. According to standard cosmological models, the motion of galaxy clusters with respect to the cosmic microwave background should be randomly distributed in all directions. However, analyzing the three-year WMAP data using the kinematic Sunyaev-Zel’dovich effect, the authors of the study found evidence of a “surprisingly coherent” 600–1000 km/s flow of clusters toward a 20-degree patch of sky between the constellations of Centaurus and Vela.

The clusters appear to be moving along a line extending from our solar system toward Centaurus/Hydra, but the direction of this motion is less certain. Evidence indicates that the clusters are headed outward along this path, away from Earth, but the team cannot yet rule out the opposite flow.

“We detect motion along this axis, but right now our data cannot state as strongly as we’d like whether the clusters are coming or going,” Kashlinsky said.

The unexplained motion has hundreds of millions of stars dashing towards a certain part of the sky at over eight hundred kilometers per second. Not much speed in cosmic terms, but the preferred direction certainly is: most cosmological models have things moving in all directions equally at the extreme edges of the universe. Something that could make things aim for a specific spot on such a massive scale hasn’t been imagined before. The scientists are keeping to the proven astrophysical strategy of calling anything they don’t understand “dark”, terming the odd motion a “dark flow”.

A black hole can’t explain the observations – objects would accelerate into the hole, while the NASA scientists see constant motion over a vast expanse of a billion light-years. You have no idea how big that is. This is giant on a scale where it’s not just that we can’t see what’s doing it; it’s that the entire makeup of the universe as we understand it can’t be right if this is happening.

The hot X-ray-emitting gas within a galaxy cluster scatters photons from the cosmic microwave background (CMB). Because galaxy clusters don’t precisely follow the expansion of space, the wavelengths of scattered photons change in a way that reflects each cluster’s individual motion.

This results in a minute shift of the microwave background’s temperature in the cluster’s direction. The change, which astronomers call the kinematic Sunyaev-Zel’dovich (KSZ) effect, is so small that it has never been observed in a single galaxy cluster.

But in 2000, Kashlinsky, working with Fernando Atrio-Barandela at the University of Salamanca, Spain, demonstrated that it was possible to tease the subtle signal out of the measurement noise by studying large numbers of clusters.

In 2008, armed with a catalog of 700 clusters assembled by Harald Ebeling at the University of Hawaii and Dale Kocevski, now at the University of California, Santa Cruz, the researchers applied the technique to the three-year WMAP data release. That’s when the mystery motion first came to light.

The new study builds on the previous one by using the five-year results from WMAP and by doubling the number of galaxy clusters.

“It takes, on average, about an hour of telescope time to measure the distance to each cluster we work with, not to mention the years required to find these systems in the first place,” Ebeling said. “This is a project requiring considerable followthrough.”

According to Atrio-Barandela, who has focused on understanding the possible errors in the team’s analysis, the new study provides much stronger evidence that the dark flow is real. For example, the brightest clusters at X-ray wavelengths hold the greatest amount of hot gas to distort CMB photons. “When processed, these same clusters also display the strongest KSZ signature — unlikely if the dark flow were merely a statistical fluke,” he said.

In addition, the team, which now also includes Alastair Edge at the University of Durham, England, sorted the cluster catalog into four “slices” representing different distance ranges. They then examined the preferred flow direction for the clusters within each slice. While the size and exact position of this direction display some variation, the overall trends among the slices exhibit remarkable agreement.

The researchers are currently working to expand their cluster catalog in order to track the dark flow to about twice the current distance. Improved modeling of hot gas within the galaxy clusters will help refine the speed, axis, and direction of motion.

Future plans call for testing the findings against newer data released from the WMAP project and the European Space Agency’s Planck mission, which is also currently mapping the microwave background.

Which is fantastic! Such discoveries force a whole new set of ideas onto the table which, even if they turn out to be wrong, are the greatest ways to advance science and our understanding of everything. One explanation that’s already been offered is that our universe underwent a period of hyper-inflation early in its existence, and everything we think of as the vast and infinite universe is actually a small corner under the sofa of the real expanse of reality. Which would be an amazing, if humbling, discovery.

The image at the top of the page shows the most distant object we have ever observed with high confidence, according to Wei Zheng, the leading astronomer of the team at Johns Hopkins University who that noticed the galaxy on multiple images from both the Hubble and Spitzer space telescopes. At 13.2-billion years old, we are technically seeing this galaxy when it was very young, but its light is only reaching Earth now.

http://www.dailygalaxy.com/my_weblog/2013/10/is-our-universe-one-of-billions-new-planck-data-has-anomalies-caused-by-unknown-gravitational-pull-t.html

JN2_2846a1360362374

Daniel Yuan, pictured at his home in Laurel, raised doubts for years about the work of his colleagues in a Johns Hopkins medical research lab. “The denial that I am hearing from almost everyone in the group as a consensus is troubling to me,” he wrote in one e-mail. In December 2011, after 10 years at the lab, he was fired.

By Peter Whoriskey
The Washington Post Published: March 11
The numbers didn’t add up.

Over and over, Daniel Yuan, a medical doctor and statistician, couldn’t understand the results coming out of the lab, a prestigious facility at Johns Hopkins Medical School funded by millions from the National Institutes of Health.

He raised questions with the lab’s director. He reran the calculations on his own. He looked askance at the articles arising from the research, which were published in distinguished journals. He told his colleagues: This doesn’t make sense.

“At first, it was like, ‘Okay — but I don’t really see it,’ ” Yuan recalled. “Then it started to smell bad.”

His suspicions arose as reports of scientific misconduct have become more frequent and critics have questioned the willingness of universities, academic journals and the federal government, which pays for much of the work, to confront the problem.

Eventually, the Hopkins research, which focused on detecting interactions between genes, would win wide acclaim and, in a coup for the researchers, space in the pages of Nature, arguably the field’s most prestigious journal. The medical school even issued a news release when the article appeared last year: “Studies Linked To Better Understanding of Cancer Drugs.”

What very few readers of the Nature paper could know, however, was that behind the scenes, Yuan’s doubts seemed to be having profound effects.

In August, Yu-yi Lin, the lead author of the paper, was found dead in his new lab in Taiwan, a puncture mark in his left arm and empty vials of sedatives and muscle relaxants around him, according to local news accounts — an apparent suicide.

And within hours of this discovery, a note was sent from Lin’s e-mail account to Yuan. The e-mail, which Yuan saved, essentially blamed him for driving Lin to suicide. Yuan had written to Nature’s editors, saying that the paper’s results were overstated and that he found no evidence that the analyses described had actually been conducted. On the day of his death, Lin, 38, the father of three young daughters, was supposed to have finished writing a response to Yuan’s criticisms.

The subject line of the e-mail to Yuan, sent by an unknown person, said “your happy ending.”

“Yu-yi passed away this morning. Now you must be very satisfied with your success,” the e-mail said.

Yuan said he was shocked by the note, so much so that he began to shake.

But in the seven months since, he has wondered why no one — not the other investigators on the project, not the esteemed journal, not the federal government — has responded publicly to the problems he raised about the research.

The passions of scientific debate are probably not much different from those that drive achievement in other fields, so a tragic, even deadly dispute might not be surprising.

But science, creeping ahead experiment by experiment, paper by paper, depends also on institutions investigating errors and correcting them if need be, especially if they are made in its most respected journals.

If the apparent suicide and Yuan’s detailed complaints provoked second thoughts about the Nature paper, though, there were scant signs of it.

The journal initially showed interest in publishing Yuan’s criticism and told him that a correction was “probably” going to be written, according to e-mail rec­ords. That was almost six months ago. The paper has not been corrected.

The university had already fired Yuan in December 2011, after 10 years at the lab. He had been raising questions about the research for years. He was escorted from his desk by two security guards.

More recently, a few weeks after a Washington Post reporter began asking questions, a university spokeswoman said that a correction had been submitted to Nature and that it was under review.

“Your questions will be addressed with that publication,” a spokeswoman for the Hopkins medical school, Kim Hoppe, wrote in an e-mail.

Neither the journal nor the university would disclose the nature of the correction.

Hoppe declined an opportunity to have university personnel sit for interviews.

In the meantime, the paper has been cited 11 times by other published papers building on the findings.

It may be impossible for anyone from outside to know the extent of the problems in the Nature paper. But the incident comes amid a phenomenon that some call a “retraction epidemic.”

Last year, research published in the Proceedings of the National Academy of Sciences found that the percentage of scientific articles retracted because of fraud had increased tenfold since 1975.

The same analysis reviewed more than 2,000 retracted biomedical papers and found that 67 percent of the retractions were attributable to misconduct, mainly fraud or suspected fraud.

“You have a lot of people who want to do the right thing, but they get in a position where their job is on the line or their funding will get cut, and they need to get a paper published,” said Ferric C. Fang, one of the authors of the analysis and a medical professor at the University of Washington. “Then they have this tempting thought: If only the data points would line up . . . ”

Fang said retractions may be rising because it is simply easier to cheat in an era of digital images, which can be easily manipulated. But he said the increase is caused at least in part by the growing competition for publication and for NIH grant money.

He noted that in the 1960s, about two out of three NIH grant requests were funded; today, the success rate for applicants for research funding is about one in five. At the same time, getting work published in the most esteemed journals, such as Nature, has become a “fetish” for some scientists, Fang said.

In one sense, the rise in retractions may mean that the scientific enterprise is working — bad work is being discovered and tossed out. But many observers note that universities and journals, while sometimes agreeable to admitting small mistakes, are at times loath to reveal that the essence of published work was simply wrong.

“The reader of scientific information is at the mercy of the scientific institution to investigate or not,” said Adam Marcus, who with Ivan Oransky founded the blog Retraction Watch in 2010. In this case, Marcus said, “if Hopkins doesn’t want to move, we may not find out what is happening for two or three years.”

The trouble is that a delayed response — or none at all — leaves other scientists to build upon shaky work. Fang said he has talked to researchers who have lost months by relying on results that proved impossible to reproduce.

Moreover, as Marcus and Oransky have noted, much of the research is funded by taxpayers. Yet when retractions are done, they are done quietly and “live in obscurity,” meaning taxpayers are unlikely to find out that their money may have been wasted.

Johns Hopkins University typically receives more than $600 million a year from NIH, according to NIH figures.

For someone who has taken on a battle with Johns Hopkins and Nature, Yuan is strikingly soft-spoken.

He grew up in Gainesville, Fla., and attended MIT and then medical school at Johns Hopkins. He worked briefly as a pediatrician and an assistant professor of pediatrics before deciding that he preferred pure research. He has a wife and two kids and is an accomplished violinist.

In 2001, he joined the lab of Jef Boeke, a Hopkins professor of molecular biology and genetics. Boeke’s work on the yeast genome is, as academics put it, “highly cited” — that is, other papers have used some of his articles numerous times for support. Last year, he was named a member of the prestigious American Academy of Arts and Sci­ences.

The lab’s research focused on developing a methodology for finding evidence of genes interacting, primarily in the yeast genome and then in the human genome. Genetic interactions are prized because they yield insights into the traits of the genes involved.

During Yuan’s time there, the lab received millions in NIH funding, and according to internal e-mails, the people in the lab were under pressure to show results. Yuan felt the pressure, too, he says, but as the point person for analyzing the statistical data emerging from the experiments, he felt compelled to raise his concerns.

As far back as 2007, as the group was developing the methodology that would eventually form the basis of the Nature paper, Yuan wrote an anguished e-mail to another senior member of the lab, Pamela Meluh.

“I continue to be in a state of chronic alarm,” he wrote in August 2007. “The denial that I am hearing from almost everyone in the group as a consensus is troubling to me.”

Meluh quickly wrote back: “I have the same level of concern as you in terms of data quality, but I have less basis to think it can be better. . . . I’m always torn between addressing your and my own concerns and being ‘productive.’ ”

Then Boeke weighed in, telling Yuan that if he could improve the data analysis, he should, but that “the clock is ticking.”

“NIH has already given us way more time than we thought we needed and at some point we’ve got to suck it up and run with what we have,” Boeke wrote to Meluh and Yuan.

A few years later, another deadline was looming, and Elise Feingold, an NIH administrator, wanted to know what the lab had accomplished.

“I do need some kind of progress report on what you have been doing the past two years . . . and what you think you can accomplish with these funds,” she wrote to Boeke.

Citing Feingold’s message, ­Meluh wrote to Yuan, asking for help in explaining what the lab had produced. Its members had worked diligently, Yuan says, but hadn’t arrived at the kind of significant findings that generally produce scientific papers.

“I want to make it look like we’ve been busy despite lack of publications,” Meluh wrote.

Meluh did not respond to a request for an interview. Boeke referred questions to the university’s public relations team, which declined to comment further. An NIH official declined to comment.

While Yuan was growing increasingly skeptical of the lab’s methodology, Yu-yi Lin, who was also working at the lab, was trying to extend it. In the past, it had been applied to the yeast genome; Lin would extend it to the human genome — and this would become the basis of the Nature paper.

Lin, who was from Taiwan, was an up-and-comer. As a graduate student at Johns Hopkins just a few years before, he’d won an award for his work in cell metabolism and aging. He was also arranging for a prestigious spot at National Taiwan University.

At one point, when he was still at the Boeke lab at Hopkins, Lin asked Yuan to help analyze the data that would become the basis for the Nature paper, Yuan says. Yuan said he declined to get involved because he thought the methodology still had deep flaws.

Interactions between Lin and Yuan at the lab were few, Yuan said, and at any rate, Yuan had other things to worry about. He was slowly being forced out. He was demoted in 2011 from research associate to an entry-level position. A disagreement over whether Yuan should have asked Boeke if he wanted a byline on a paper erupted into further trouble, e-mail and other records show.

The Johns Hopkins spokeswoman, Hoppe, declined to discuss Yuan’s job termination.

On Dec. 15, 2011, Yuan was forced to leave the lab. He wasn’t allowed to make copies of his cell collection. He spent the next month trying to keep his mind busy. He read books about JavaScript and Photoshop, which he thought would enrich his research abilities. As he looked for other research jobs, he sensed that he had been blackballed.

Then, in February 2012, the Nature paper was published.

The research was a “profound achievement” that would “definitely be a great help to solve and to treat many severe diseases,” according to a news release from National Taiwan University, where Lin was now working.

Upon reading it, Yuan said, he was astonished that Lin had used what he considered a flawed method for finding genetic interactions. It had proved troublesome in the yeast genome, he thought. Could it have possibly been more reliable as it was extended to the human genome?

Lin, Boeke and their co-authors reported discovering 878 genetic interactions, or “hits.”

But Yuan, who was familiar with the data and the statistics, reanalyzed the data in the paper and concluded that there was essentially no evidence for any more than a handful of the 878 genetic interactions.

One of the key problems, Yuan wrote to the Nature editors, was that the numerical threshold the investigators used for determining when a hit had arisen was too low. This meant they would report far more hits than there actually were.

Yuan also calculated that, given the wide variability in the data and the relative precision required to find a true hit, it would have been impossible to arrive at any conclusions at all. By analogy, it would be like a pollster declaring a winner in an election when the margin of error was larger than the difference in the polling results.

“The overwhelming noise in the . . . data and the overstated strength of the genetic interactions together make it difficult to reconstruct any scientific process by which the authors could have inferred valid results from these data,” Yuan wrote to the editors of Nature in July.

His analysis attacks only the first portion of the paper; even if he is correct, the second part of the paper could be true.

Nevertheless, Yuan wanted Nature to publish his criticism, and following instructions from the journal, he forwarded his letter to Boeke and Lin, giving them two weeks to respond.

Just as the two weeks were to elapse, Boeke wrote to Nature asking for an extension of time — “a couple weeks or more” — to address Yuan’s criticism. Boeke explained that end-of-summer schedules and the multiple co-authors made it difficult to respond on time.

A day later, Lin was discovered dead in his office at National Taiwan University.

“Renowned scientist found dead, next to drug bottles,” the headline in the Taipei Times said.

Even in his death, the Nature paper was a kind of shorthand for Lin’s scientific success.

“A research team [Lin] led was featured in the scientific journal Nature in February for their discovery of the key mechanism for maintaining cell energy balance — believed to be linked to cellular aging and cancer,” the newspaper said.

If there was a suicide note, it has not been made public, and it is difficult to know what went through Lin’s mind at the end of his life. The apparent suicide and the e-mail to Yuan suggest only that Lin may have been distraught over the dispute; they do not prove that he acted improperly.

Shortly after the Nature paper appeared, Yuan hired lawyer Lynne Bernabei to challenge the way he was terminated at Hopkins.

In late August, Yuan asked the Nature editors again whether they would publish his criticism. Lin was dead, but Boeke and the others had had a month to respond, and Yuan hadn’t heard a thing.

On Sept. 28, a Nature editor informed Yuan by e-mail that the journal was still waiting on a fuller response from Boeke and that “experiments are being done and probably a Correction written.”

Such a correction has not appeared.

So as a last attempt, he figured he’d try the federal government, which paid for much of the research. But the government suggested that the threat to the federal research, if there was any, ended with Lin’s death.

“It is our understanding that these allegations are being investigated by Johns Hopkins University,” said the letter from the Office of Research Integrity.

Besides, it noted, the person responsible for the paper was Lin.

“Deceased respondents no longer pose a risk,” the letter said.

http://www.washingtonpost.com/business/economy/doubts-about-johns-hopkins-research-have-gone-unanswered-scientist-says/2013/03/11/52822cba-7c84-11e2-82e8-61a46c2cde3d_story_4.html

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

 

How far should doctors go in attempting to cure addiction? In China, some physicians are taking the most extreme measures. By destroying parts of the brain’s “pleasure centers” in heroin addicts and alcoholics, these neurosurgeons hope to stop drug cravings. But damaging the brain region involved in addictive desires risks permanently ending the entire spectrum of natural longings and emotions, including the ability to feel joy.

In 2004, the Ministry of Health in China banned this procedure due to lack of data on long term outcomes and growing outrage in Western media over ethical issues about whether the patients were fully aware of the risks.

However, some doctors were allowed to continue to perform it for research purposes—and recently, a Western medical journal even published a new study of the results. In 2007, The Wall Street Journal detailed the practice of a physician who claimed he performed 1000 such procedures to treat mental illnesses such as depression, schizophrenia and epilepsy, after the ban in 2004; the surgery for addiction has also since been done on at least that many people.

The November publication has generated a passionate debate in the scientific community over whether such research should be published or kept outside the pages of reputable scientific journals, where it may find undeserved legitimacy and only encourage further questionable science to flourish.

The latest study is the third published since 2003 in Stereotactic and Functional Neurosurgery, which isn’t the only journal chronicling results from the procedure, which is known as ablation of the nucleus accumbens. In October, the journal World Neurosurgery also published results from the same researchers, who are based at Tangdu Hospital in Xi’an.

The authors, led by Guodong Gao, claim that the surgery is “a feasible method for alleviating psychological dependence on opiate drugs.” At the same time, they report that more than half of the 60 patients had lasting side effects, including memory problems and loss of motivation. Within five years, 53% had relapsed and were addicted again to opiates, leaving 47% drug free.

(MORE: Addicted: Why We Get Hooked)

Conventional treatment only results in significant recovery in about 30-40% of cases, so the procedure apparently improves on that, but experts do not believe that such a small increase in benefit is worth the tremendous risk the surgery poses.  Even the most successful brain surgeries carry risk of infection, disability and death since opening the skull and cutting brain tissue for any reason is both dangerous and unpredictable. And the Chinese researchers report that 21% of the patients they studied experienced memory deficits after the surgery and 18% had “weakened motivation,” including at least one report of lack of sexual desire. The authors claim, however, that “all of these patients reported that their [adverse results] were tolerable.” In addition, 53% of patients had a change in personality, but the authors describe the majority of these changes as “mildness oriented,” presumably meaning that they became more compliant. Around 7%, however, became more impulsive.

The surgery is actually performed while patients are awake in order to minimize the chances of destroying regions necessary for sensation, consciousness or movement.  Surgeons use heat to kill cells in small sections of both sides of the brain’s nucleus accumbens.  That region is saturated with neurons containing dopamine and endogenous opioids, which are involved in pleasure and desire related both to drugs and to ordinary experiences like eating, love and sex.

(MORE: A Drug to End Drug Addiction)

In the U.S. and the U.K., reports the Wall Street Journal, around two dozen stereotactic ablations are performed each year, but only in the most intractable cases of depression and obsessive-compulsive disorder and after extensive review by institutional review boards and intensive discussions with the patient, who must acknowledge the risks. Often, a different brain region is targeted, not the nucleus accumbens. Given the unpredictable and potentially harmful consequences of the procedure, experts are united in their condemnation of using the technique to treat addictions. “To lesion this region that is thought to be involved in all types of motivation and pleasure risks crippling a human being,” says Dr. Charles O’Brien, head of the Center for Studies of Addiction at the University of Pennsylvania.

David Linden, professor of neuroscience at Johns Hopkins and author of a recent book about the brain’s pleasure systems calls the surgery “horribly misguided.”  He says “This treatment will almost certainly render the subjects unable to feel pleasure from a wide range of experiences, not just drugs of abuse.”

But some neurosurgeons see it differently. Dr. John Adler, professor emeritus of neurosurgery at Stanford University, collaborated with the Chinese researchers on the publication and is listed as a co-author.  While he does not advocate the surgery and did not perform it, he believes it can provide valuable information about how the nucleus accumbens works, and how best to attempt to manipulate it. “I do think it’s worth learning from,” he says. ” As far as I’m concerned, ablation of the nucleus accumbens makes no sense for anyone.  There’s a very high complication rate. [But] reporting it doesn’t mean endorsing it. While we should have legitimate ethical concerns about anything like this, it is a bigger travesty to put our heads in the sand and not be willing to publish it,” he says.

(MORE: Anesthesia Study Opens Window Into Consciousness)

Dr. Casey Halpern, a neurosurgery resident at the University of Pennsylvania makes a similar case. He notes that German surgeons have performed experimental surgery involving placing electrodes in the same region to treat the extreme lack of pleasure and motivation associated with otherwise intractable depression.  “That had a 60% success rate, much better than [drugs like Prozac],” he says. Along with colleagues from the University of Magdeburg in Germany, Halpern has just published a paper in the Proceedings of the New York Academy of Sciences calling for careful experimental use of DBS in the nucleus accumbens to treat addictions, which have failed repeatedly to respond to other approaches. The paper cites the Chinese surgery data and notes that addiction itself carries a high mortality risk.

DBS, however, is quite different from ablation.  Although it involves the risk of any brain surgery, the stimulation itself can be turned off if there are negative side effects, while surgical destruction of brain tissue is irreversible. That permanence—along with several other major concerns — has ethicists and addiction researchers calling for a stop to the ablation surgeries, and for journals to refuse to publish related studies.

Harriet Washington, author of Medical Apartheid:  The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present, argues that by publishing the results of unethical studies, scientists are condoning the questionable conditions under which the trials are conducted. “When medical journals publish research that violates the profession’sethical guidelines, this serves not only to sanction such abuses, but to encourage them,” she says. “In doing so, this practice encourages a relaxing of moral standards that threatens all patients and subjects, but especially  the medically vulnerable.”

(MORE: Real-Time Video: First Look at a Brain Losing Consciousness Under Anesthesia)

Shi-Min Fang, a Chinese biochemist who became a freelance journalist and recently won the journal Nature‘s Maddox prize for his exposes of widespread fraud in Chinese research, has revealed some of the subpar scientific practices behind research conducted in China, facing death threats and, as the New York Times reported, a beating with a hammer. He agrees that publishing such research only perpetuates the unethical practices. Asked by TIME to comment on the addiction surgery studies, Fang writes that publishing the research, particularly in western journals, “would encourage further unethical research, particularly in China where rewards for publication in international journals are high.”

While he doesn’t have the expertise to comment specifically on the ablation data, he says “the results of clinical research in China are very often fabricated. I suspect that the approvals by Ethics Committee mentioned in these papers were made up to meet publication requirement. I also doubt if the patients were really informed in detail about the nature of the study.” Fang also notes that two of the co-authors of the paper are advertising on the internet in Chinese, offering the surgery at a cost of 35,000 renminbi, about $5,600.  That’s more than the average annual income in China, which is about $5,000.

Given the available evidence, in fact, it’s hard to find a scientific justification for even studying the technique in people at all. Carl Hart, associate professor of psychology at Columbia University and author of the leading college textbook on psychoactive drugs, says animal studies suggest the approach may ultimately fail as an effective treatment for addiction; a 1984 experiment, for example, showed that destroying the nucleus accumbens in rats does not permanently stop them from taking opioids like heroin and later research found that it similarly doesn’t work for curbing cocaine cravings. Those results alone should discourage further work in humans. “These data are clear,” he says, “If you are going to take this drastic step, you damn well better know all of the animal literature.” [Disclosure:  Hart and I have worked on a book project together].

(MORE: Top 10 Medical Breakthroughs of 2012)

Moreover, in China, where addiction is so demonized that execution has been seen as an appropriate punishment and where the most effective known treatment for heroin addiction— methadone or buprenorphine maintenance— is illegal, it’s highly unlikely that addicted people could give genuinely informed consent for any brain surgery, let alone one that risks losing the ability to feel pleasure. And even if all of the relevant research suggested that ablating the nucleus accumbens prevented animals from seeking drugs, it would be hard to tell from rats or even primates whether the change was due to an overall reduction in motivation and pleasure or to a beneficial reduction in desiring just the drug itself.

There is no question that addiction can be difficult to treat, and in the most severe cases, where patients have suffered decades of relapses and failed all available treatments multiple times, it may make sense to consider treatments that carry significant risks, just as such dangers are accepted in fighting suicidal depression or cancer.  But in the ablation surgery studies, some of the participants were reportedly as young as 19 years old and had only been addicted for three years.  Addiction research strongly suggests that such patients are likely to recover even without treatment, making the risk-benefit ratio clearly unacceptable.

The controversy highlights the tension between the push for innovation and the reality of risk. Rules on informed consent didn’t arise from fears about theoretical abuses:  they were a response to the real scientific horrors of the Holocaust. And ethical considerations become especially important when treating a condition like addiction, which is still seen by many not as an illness but as a moral problem to be solved by punishment.  Scientific innovation is the goal, but at what price?
Read more: http://healthland.time.com/2012/12/13/controversial-surgery-for-addiction-burns-away-brains-pleasure-center/#ixzz2ExzobWQq

Thanks to Dr. Lutter for bringing this to the attention of the It’s Interesting community.

 

 

Researchers report they have developed in mice what they believe might one day become a breakthrough for humans: a retinal prosthesis that could restore near-normal sight to those who have lost their vision.

That would be a welcome development for the roughly 25 million people worldwide who are blind because of retinal disease, most notably macular degeneration.

The notion of using prosthetics to combat blindness is not new, with prior efforts involving retinal electrode implantation and/or gene therapy restoring a limited ability to pick out spots and rough edges of light.

The current effort takes matters to a new level. The scientists fashioned a prosthetic system packed with computer chips that replicate the “neural impulse codes” the eye uses to transmit light signals to the brain.

“This is a unique approach that hasn’t really been explored before, and we’re really very excited about it,” said study author Sheila Nirenberg, a professor and computational neuroscientist in the department of physiology and biophysics at Weill Medical College of Cornell University in New York City. “I’ve actually been working on this for 10 years. And suddenly, after a lot of work, I knew immediately that I could make a prosthetic that would work, by making one that could take in images and process them into a code that the brain can understand.”

Nirenberg and her co-author Chethan Pandarinath (a former Cornell graduate student now conducting postdoctoral research at Stanford University School of Medicine) report their work in the Aug. 14 issue of Proceedings of the National Academy of Sciences. Their efforts were funded by the U.S. National Institutes of Health and Cornell University’s Institute for Computational Biomedicine.

The study authors explained that retinal diseases destroy the light-catching photoreceptor cells on the retina’s surface. Without those, the eye cannot convert light into neural signals that can be sent to the brain.

However, most of these patients retain the use of their retina’s “output cells” — called ganglion cells — whose job it is to actually send these impulses to the brain. The goal, therefore, would be to jumpstart these ganglion cells by using a light-catching device that could produce critical neural signaling.

But past efforts to implant electrodes directly into the eye have only achieved a small degree of ganglion stimulation, and alternate strategies using gene therapy to insert light-sensitive proteins directly into the retina have also fallen short, the researchers said.

Nirenberg theorized that stimulation alone wasn’t enough if the neural signals weren’t exact replicas of those the brain receives from a healthy retina.

“So, what we did is figure out this code, the right set of mathematical equations,” Nirenberg explained. And by incorporating the code right into their prosthetic device’s chip, she and Pandarinath generated the kind of electrical and light impulses that the brain understood.

The team also used gene therapy to hypersensitize the ganglion output cells and get them to deliver the visual message up the chain of command.

Behavioral tests were then conducted among blind mice given a code-outfitted retinal prosthetic and among those given a prosthetic that lacked the code in question.

The result: The code group fared dramatically better on visual tracking than the non-code group, with the former able to distinguish images nearly as well as mice with healthy retinas.

“Now we hope to move on to human trials as soon as possible,” said Nirenberg. “Of course, we have to conduct standard safety studies before we get there. And I would say that we’re looking at five to seven years before this is something that might be ready to go, in the best possible case. But we do hope to start clinical trials in the next one to two years.”

Results achieved in animal studies don’t necessarily translate to humans.

Dr. Alfred Sommer, a professor of ophthalmology at Johns Hopkins University in Baltimore and dean emeritus of Hopkins’  Bloomberg School of Public Health, urged caution about the findings.

“This could be revolutionary,” he said. “But I doubt it. It’s a very, very complicated business. And people have been working on it intensively and incrementally for the last 30 years.”

“The fact that they have done something that sounds a little bit better than the last set of results is great,” Sommer added.  “It’s terrific. But this approach is really in its infancy. And I guarantee that it will be a long time before they get to the point where they can really restore vision to people using prosthetics.”

Other advances may offer benefits in the meantime, he said. “We now have new therapies that we didn’t have even five years ago,” Sommer said. “So we may be reaching a state where the amount of people losing their sight will decline even as these new techniques for providing artificial vision improve. It may not be as sci-fi. But I think it’s infinitely more important at this stage.”

http://health.usnews.com/health-news/news/articles/2012/08/13/retinal-device-restores-sight-to-blind-mice

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.