Reckless Research Race, Results in Rising Retractions. Reform Required?

As our regular readers know, SRxA’s Word on Health loves nothing more than a good alliteration to start the day!  Although the blog post title may rank as one of our more classic tongue twisters, there is nothing amusing about the content.  As involved as we are in medical communications and peer-reviewed, scientific publishing, we are saddened to report on the rise of a recent trend of falsified research. An unsettling pattern is emerging. The rate at which articles are retracted (meaning the study was published, only to later be dubbed unfit for print — typically due to either deliberate misconduct or an honest scientific mistake) is increasing. To our knowledge, at least three scientific journals have published articles over the past two years warning of the rise in retractions and misconduct by researchers who have fudged results.

Last year Nature reported a tenfold increase in retractions over the past decade even though the number of published papers only increased by 44%. Before that, the Journal of Medical Ethics published a study in 2010 that said a rise in recent retractions was the fault of misconduct and “honest scientific mistakes.” It calculated that the number of retractions had more than tripled from 50 in 2005 to 180 in 2009.

The latest publication to highlight this issue is Infection and Immunity. In the fall of 2010, Dr. Ferric C. Fang, editor in chief of the journal made an unsettling discovery – one of his authors had doctored several papers. The journal wound up retracting six of the papers from the author, Naoki Mori of the University of the Ryukyus. It soon became clear that Infection and Immunity was hardly the only victim of Dr. Mori’s misconduct. Since then, according to the blog Retraction Watch, other scientific journals, including the International Journal of Cancer  have retracted another 24 of his papers. This was a new experience for Fang. Prior to this incident Infection and Immunity had only retracted nine articles over a 40-year period. “Nobody had noticed the whole thing was rotten,” said Fang, a professor at the University of Washington School of Medicine. Dr. Fang became curious how far the rot extended. To find out, he teamed up with a fellow editor at the journal, and before long they reached a troubling conclusion: not only that retractions were rising at an alarming rate, but that retractions were just a manifestation of a much more profound problem.

Dr. Fang’s colleague, Dr. Arturo Casadevall, said he feared that science had turned into a winner-take-all game with perverse incentives that led scientists to cut corners and, in some cases, commit acts of misconduct. Last month, in a pair of editorials in Infection and Immunity, the two editors issued a plea for fundamental reforms. While no one claims that science was ever free of misconduct or bad research, the new raft of retractions appears to be a mix of misconduct and honest scientific mistakes. Several factors are at play here, scientists say. One may be that because journals are now online, bad papers are simply reaching a wider audience, making it more likely that errors will be spotted. But other forces are more pernicious. To survive professionally, scientists feel the need to publish as many papers as possible, and to get them into high-profile journals. And sometimes they cut corners or even commit misconduct to get there. To measure this claim, Drs. Fang and Casadevall looked at the rate of retractions in 17 journals from 2001 to 2010 and compared it with the journals’ “impact factor,”  – a score based on how often their papers are cited by scientists. The higher a journal’s impact factor, the higher its retraction rate. The highest “retraction index” in the study went to one of the world’s leading medical journals, The New England Journal of Medicine.

The scramble to publish in high-impact journals may be leading to more and more errors. Each year, every laboratory produces a new crop of Ph.D.s, who must compete for a small number of jobs, and the competition is getting fiercer. In 1973, more than half of biologists had a tenure-track job within six years of getting a Ph.D. By 2006 the figure was down to 15 percent. In such an environment, a high-profile paper can mean the difference between a career in science or leaving the field. The scramble isn’t over once young scientists get a job. “What people do is they count papers, and they look at the prestige of the journal in which the research is published, and they see how many grant dollars scientists have, and if they don’t have funding, they don’t get promoted,” Dr. Fang said. “It’s not about the quality of the research.”

With all this pressure on scientists, they may lack the extra time to check their own research. Instead, they have to be concerned about publishing papers before someone else publishes the same results. Adding to the pressure, thousands of new Ph.D. scientists are coming out of China and India, countries that offer cash rewards to scientists who get papers into high-profile journals. Dr. Fang worries that the situation could be become much worse if nothing happens soon. To change the system, Fang and Casadevall say graduate students need a better understanding of science’s ground rules. They would also move away from the winner-take-all system, in which grants are concentrated among a small fraction of scientists by putting a cap on the grants any one lab can receive. A little bit of old fashioned honesty wouldn’t hurt either!

Synchrotron scientists suggest solution to sneezing sans sleepiness

As allergy sufferers we know all too well that although many over-the-counter antihistamines relieve symptoms, we’re are often too groggy to enjoy the respite. Now, thanks to some sleuth work by a team of international scientists, the way has been paved for antihistamines with fewer side-effects.

An international team of scientists has successfully cracked the  code for the complex 3-D structure of the human histamine H1 receptor protein. Using an X-ray beam 100 billion times stronger than normal,  at Diamond Light Source, the UK’s national synchrotron facility, researchers were able to get a 3D picture of the shape of H1 receptors.

Published this week in Nature, this discovery opens the door for the development of ‘third-generation’ antihistamines.

The H1 receptor protein is found in the cell membranes of various human tissues including airways, vascular and intestinal muscles, and the brain. It binds to histamine and has an important function in the immune system. However, in susceptible individuals it can cause allergic reactions such as hay fever, food allergies and pet allergies. Antihistamine drugs work because they prevent histamine attaching to H1 receptors.

Dr. Simone Weyand, postdoctoral scientist at Imperial College London, who conducted much of the experimental work at Diamond, said: “First-generation antihistamines are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side-effects including sedation, dry mouth and arrhythmias.”

The team comprised of leading experts from The Scripps Research Institute in California, Kyoto University, Imperial College London and Diamond worked for 16 months on the project.

Professor So Iwata, Director of the Membrane Protein Laboratory at Diamond, said: “It took a considerable team effort but we were finally able to elucidate the molecular structure of the histamine H1 receptor protein and also see how it interacts with antihistamines. This detailed structural information is a great starting point for exploring exactly how histamine triggers allergic reactions and how drugs act to prevent this reaction.”

Word on Health’s allergy prone bloggers will be eagerly awaiting developments and will bring you news as it happens…assuming of course we can stay awake to do so!

What Are Your Telomeres Telling You?

When it comes to the science of aging, there are few discoveries as intriguing as telomeres.  These caps at the ends of chromosomes protect genes from being eroded each time a cell divides. When telomeres are finally eaten away after many years, cells begin to show signs of aging. This process is thought to be a key part of what makes us grow old.

 Telomeres’ partner in crime is the enzyme telomerase, which helps keep telomeres long and healthy, a property that’s made it the subject of almost science-fictional fascination.  Telomerase confers immortality on cancer cells and has even been shown to reverse aging in telomerase –deficient rats.

Now, in a move that brings these questions into sharper focus for the general public, Telome Health, founded by Elizabeth Blackburn, who won the 2009 Nobel Prize for Medicine for her work in this area, has announced that it will bring to market a test for telomere length.

The company already provides such a test for research use, but according to its website it will release a test for the general public this fall

News of the test’s release has spurred a flurry of misleading reports suggesting that we’re on the cusp of being able to learn how long we’ll live — and whether we can ward off the irksome outward signs of aging.

While scientists are divided over the value of the test for individuals, no serious researchers are saying a telomere test will be some kind of crystal ball. However, if people can monitor their telomere length, perhaps they can make lifestyle changes to alter that risk by boosting their cells’ longevity.

SRxA’s Word on Health is asking its readers: Would you take the test?  Let us know.

Dozing Off or Going Off Line?

If, like us, you’ve ever “misplaced” your keys or stuck the milk in the cupboard and the cereal in the refrigerator, we have good news for you. According to new research, chances are you’re not going mad, or showing signs of early Alzheimer’s – your brain may simply have been taking a nap!

The study published this week in Nature suggests that certain napping neurons in an otherwise awake brain may be responsible for the attention lapses, poor judgment, mistake-proneness and irritability that we’ve all experienced when we haven’t had enough sleep.

Doctors at the University of Wisconsin-Madison say they have found that some nerve cells in a sleep-deprived, yet awake, brain can briefly go “off line,” into a sleep-like state, while the rest of the brain appears awake.

“Even before you feel fatigued, there are signs in the brain that you should stop certain activities that may require alertness,” says Dr. Chiara Cirelli, Professor of Psychiatry at the School of Medicine and Public Health. “Specific groups of neurons may be falling asleep, with negative consequences on performance.”

Until now, scientists thought that sleep deprivation generally affected the entire brain. EEGs typically show network brain-wave patterns typical of either being asleep or awake.  Micro sleep, a term used to describe momentary periods of sleep that can occur at any time, typically without significant warning was thought to be the most likely cause of accidents due to falling asleep at the wheel while driving.

But the new research found that even before that stage, brains are already showing sleep-like activity that impairs them.  In the current study, researchers inserted probes into the brains of freely-behaving rats. After the rats were kept awake for prolonged periods, the probes showed areas of “local sleep” despite the animals’ appearance of being awake and active.
And there were behavioral consequences to the local sleep episodes. When they kept the rats up beyond their bedtime, the rats started to make mistakes. When challenged to do a tricky task, such as reaching with one paw to get a sugar pellet, they began to drop the pellets or miss in reaching for them, indicating that a few neurons might have gone off line.

“This activity happened in few cells,” Cirelli adds. “Out of 20 neurons we monitored in one experiment, 18 stayed awake. From the other two, there were signs of sleep—brief periods of activity alternating with periods of silence.”

So, the next time you do something dumb, don’t blame yourself, just tell people your brain was off-line!

He who felt it, probably smelt it

On the other hand, people who can’t feel pain, due to a rare genetic defect, also lack the sense of smell.  At least this seems to be the case according to a new small scale study just published in Nature. The unexpected discovery shows that nerves that detect pain and odors rely on the same protein to transmit information to the brain.

Researchers examined three people with mutations in the SCN9A gene which means they can’t feel pain.  All those studied had suffered multiple broken bones without feeling any pain, and two had gone through childbirth birth painlessly. However they weren’t aware that they also couldn’t smell a thing.

None of the study participants could distinguish balsamic vinegar, orange, mint, coffee or perfume from plain water, even when researchers poured on so much perfume and vinegar that the scents were unbearable to people with a normal sense of smell.

It may not be so strange that none of the people realized that they lacked a sense of smell. “If this was a genetic defect from birth they wouldn’t even know what they were missing,” says Graeme Lowe, a neurophysiologist at the Monell Chemical Senses Center in Philadelphia who was not involved in the study.

As oblivious as the patients were to their smell deficit, the scientists had been equally clueless that smell and pain shared a common communication gateway.

Researchers had previously shown that SCN9A controls pain sensitivity in people. The gene makes a sodium channel that lets sodium pass in through a nerve cell’s membrane when the nerve detects something painful. That flood of sodium sends an electrical signal racing toward the brain.

In the new study, the team discovered that odor-detecting nerve cells have the same sodium channel.

Because the sodium channel is missing in people with SCN9A mutations, the messages sent by pain and odor-sensing nerves never actually make it to the brain.

“It was completely surprising that these two sensory systems would use the same sodium channel,” says Frank Zufall, a neurophysiologist at the University of Saarland School of Medicine in Homburg, Germany. “But it’s clearly not needed for all senses.” None of the people with the faulty gene had hearing or vision problems. The researchers next plan to test whether those people have a sense of taste, and whether taste cells also use the sodium channel to communicate.

These findings are particularly interesting given that some drug companies are working on painkilling drugs that block the sodium channel’s activity.  The results of this study suggest that such drugs could have the side effect of eliminating smell, and could also compromise people’s ability to taste.

Imagine going though life never knowing the smell of newly baked bread, or the delights of freshly ground coffee?  Now that would be painful!

The skinny on blood transfusions: a modern day miracle?

Most of us have read the biblical accounts of water being turned into wine.  Now Canadian scientists have discovered how to turn skin into blood.  This miraculous breakthrough could revolutionize cancer treatments and solve the blood donor shortage.

What is more because the blood is made from the patient’s own cells, there is no danger of either rejection or infection.

The team from McMaster University, Ontario say that the process has been so successful that treatment could be available within two years.

Dr Mick Bhatia who headed the team said “People will effectively become their own donors. We are very excited and very enthusiastic about it. There is a lot of work to be done but I would be disappointed if we were not trying it on patients by 2012.”

The research, published in Nature, is part of ongoing attempts across the world to revert adult cells back to their original stem cell form. Stem cells are “master cells” which can potentially be manipulated in a laboratory to become any other cell in the body.

Human Skin Cells

What’s unique about this process is that it misses out the “in-between” stage of turning the skin cells back to stem cells and then converting them to blood cells. Instead, the cell is reprogrammed directly by inserting a specific transcription factor – a protein that interacts with DNA to activate genes – and applying cytokines or signaling molecules.

The result – within a month the skin is converted to blood.

Leukemia patients are likely to be the first to receive transfusions of perfectly matched blood generated from their own skin. In future, laboratory manufactured blood could help to plug the gap caused by donor shortages. The technique also holds out the promise of making other kinds of cell, including neurons with the potential to treat brain diseases such as Parkinson’s and Alzheimer’s.

Skin cells from both young and old people were used in the research to prove that age of donor made no difference to the process.

Next the team plans to assess what kind of production capacity might be possible with the cells, and whether they can successfully be stored in deep freeze.

As always, SRxA’s Word on Health will be watching these developments and bringing them straight to you.