A microtubule-regulating enzyme integral to spermiogenesis may be target for future male contraceptive or fertility treatments, according to research published today (May 24) in PLoS Genetics. An international team of researchers identified a new enzyme, KATNAL1, which appears to regulate spermatid maturation in mice by controlling the cytoskeleton dynamics central to sperm cell development.  Scientists hope elucidation of KATNAL1’s role in spermiogenesis may illuminate previously unknown causes of male infertility or provide a target for non-hormonal male contraceptive strategies.

“It’s an important study,” said Yan Cheng who investigates male contraception at the Population Council in New York and was not involved with the study. Cheng noted that it is the first study to report how loss of a microtubule-regulating enzyme affects sperm maturation and opens the possibility of using strategies to block or delete the enzyme as reversible or permanent contraception.

“It’s often hard to work out why [men are infertile],” explained lead author Lee Smith of Queen’s Medical Research Institute in Edinburgh, Scotland. In order to shed more light on possible mutations responsible for male infertility, Smith and his collaborators treated mice with a mutagenic chemical and screened males for infertility. A point mutation conferring male-only infertility and smaller testis size was mapped to a new gene, which Smith’s group called KATNAL1 (KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1), after its high homology to KATANIN p60, an enzyme known to regulate microtubule dynamics.

Though KATNAL1 was expressed in a variety of tissues, including brain and liver, only the testes of mice with a mutated form of the gene appeared grossly abnormal, with smaller than normal testes. Overexpression of KATNAL1 in a human embryonic kidney cell line demonstrated a similar effect on the cytoskeleton as KATANIN, which regulates microtubule dynamics by severing microtubule filaments.

The mutation in the infertile mice is localized to the ATP-binding domain of KATNAL1, and appears to ablate its function. In the KATNAL1-mutated mice, mature sperm cells were largely absent. Instead, the researchers found prematurely-exfoliated immature cells in the epididymis, and fluorescent imaging of microtubules in Sertoli cells showed that mutated KATNAL1 expression correlated with fewer stable microtubules.

Cytoskeleton dynamics are a critical regulator of sperm cell maturation. A specialized set of polarized cells, called Sertoli cells, chaperone post-meiotic sperm cells as they develop from a round, cytoplasm-rich immature state to their lean mature state, having grown tails and lost excess cytoplasm. Sperm are closely associated with Sertoli cells during their development, like apples on an apple tree, explained Smith, and rely on them for nutrients and transport to the lumen of the seminiferous tubules. Like apples, mature sperm will “drop off” (known as exfoliation) when “ripe.” The transport and delivery of nutrients to the sperm depends on dynamic microtubule filaments.

“We’ve identified a novel pathway important in male fertility,” said Smith, who said he hopes that further investigations will illuminate other players involved in KATNAL1 regulation and microtubule dynamics in sperm maturation. It may be possible that KATNAL1, or a different component of this microtubule-regulating pathway, could be a non-hormonal target for a male contraceptive drug, Smith added.

Non-hormonal male contraceptive strategies are appealing for several reasons, said Mara Roth, an endocrinologist at the University of Washington who did not participate in the research. Many men respond well to hormone treatment, but about 5 to 10 percent of men don’t show a drop in sperm counts in response to hormones, she explained. In contrast to female hormonal contraception, which targets one egg per month, male contraceptive strategies need to deal with the extraordinary number of sperm produced on a daily basis—upwards of 1000 per second. And even after vasectomies, Roth noted, some men don’t follow up to make sure their sperm count has dropped. The challenge in using KATNAL1 as a possible target of contraceptive drugs, she said, is in ensuring that their action will be both reversible and restricted to the testes.

Other scientists agreed that determining KATNAL1’s role in cells beyond Sertoli cells is an important next step. Cytoskeleton regulation within sperm cells is also an important component of germ cell maturation, said Ann Sperry, who studies sperm head shaping at East Carolina University and was not involved with the study. Some sperm did appear to mature in KATNAL1-mutant mice, but it’s unclear if their cytoskeletons are also dysregulated, and whether this also contributes to the infertility phenotype.

“KATNAL1 opens promising and interesting avenues to further research on this theme as demonstrated in this beautiful scientific contribution,” R.-Marc Pelletier, who investigates sperm maturation and infertility at the University of Montreal and was not involved with the research, wrote in an email. “Additional information on the systemic and topical enzymatic activity of the enzyme could contribute to clarify its real implication in the regulation of male fertility. However, the full resonance for future treatment of male fertility and the development of non-hormonal male contraceptives based solely on the use of KATNAL1 may require more supportive investigation.”

In the meantime, Smith hopes that KATNAL1 may help researchers understand more mechanisms underlying human male infertility. He and his collaborators hope to discover more regulators of microtubule dynamics in Sertoli cells. If this pathway proves to underlie infertility in men, there is a possibility of using gene therapy to reverse it, said Smith, whose group is currently attempting this feat in KATNAL1-mutated mice.

L.B. Smith et al., “KATNAL1 Regulation of Sertoli Cell Microtubule Dynamics Is Essential for Spermiogenesis and Male Fertility,” PLoS Genetics, 8(5): e1002697, 2012.

Scientists studying mice genetically engineered to lack an anti-inflammatory factor have stumbled upon an unexpected secondary function for the protein—it slows down aging. The surprising discovery, which is reported online today (May 24) in Molecular Cell, has implications for inflammatory and age-related diseases, but also for cancer.

“We were [shocked], to put it mildly,” said Robert Schneider of New York University, who led the study. “This is certainly not something anybody would have ever anticipated.”

Schneider and his team had been analyzing mice that lacked a protein called AUF1 and they’d shown that it was critical for binding to and degrading mRNA transcripts encoding inflammatory proteins. But besides having a dampened inflammatory response, mice lacking AUF1 displayed some unusual characteristics.

“We noticed that they aged very rapidly,” said Schneider. “Every cell in this animal’s body was undergoing senescence.” Furthermore, “with each subsequent generation the ability to produce mice decreased quite dramatically,” he said. These attributes, which appeared to have nothing to do with inflammation, began to ring some bells, said Schneider. They reminded him of reports about mice that lack telomerase—an enzyme that maintains the repetitive DNA sequences (telomeres) that cap and protect the ends of chromosomes. Without telomerase, telomeres become shorter with each cell cycle, which eventually damages the chromosomes and triggers cellular senescence.

“I suspect that there are some people who wouldn’t have been broad enough in their knowledge to be able to make that leap,” said Joan Steitz, a molecular biologist at Yale University, who did not participate in the study. “I found that impressive.”

Schneider’s team discovered that their AUF1-lacking mice did indeed have lower levels of telomerase than wild type mice as well as shorter telomeres, which was the most likely explanation for their rapid aging. They also found that the AUF1 protein associated with the promoter region of the telomerase gene and could activate transcription.

That an mRNA binding protein can also bind to DNA is not too surprising, said Myriam Gorospe a molecular biologist at the National Institute on Aging who did not participate in the research. “There are a number of examples of RNA binding proteins that have affinity for nucleic acids in general.” More surprising, however, was that it could regulate transcription. “It is pretty unusual,” said Steitz. “It will undoubtedly spur lots of people to look at their RNA binding proteins and figure out whether they too have additional transcriptional functions.”

Exactly how AUF1 recognizes and binds the telomerase promoter is unknown, but Schneider’s team found that two particular isoforms of the protein appear to be responsible. These isoforms are different to the ones that degrade mRNA, explained Gary Brewer a molecular geneticist at the University of Medicine and Dentistry of New Jersey who was not involved in the work. “I think it’s really exciting,” he said. “You’ve got one gene, four isoforms—two that have one function and two that appear to have a completely different function… Nature works in some kooky ways.”

The discovery of AUF1’s dual functionality “has huge ramifications and will have an impact on many areas of biology and gerontology and pathology,” said Gorospe. One example is cancer, she said. “In cancer we see more telomerase activity, because cancer cells need healthy telomere ends so that they can continue dividing.” And, she went on, “AUF1 is generally higher in cancer tissues compared with their healthy counterparts.” The discovery that AUF1 can activate telomerase transcription would now, at least in part, explain that link. “In the light of this role [for AUF1] in maintaining telomerase function, I think we’re all going to be looking at it a lot more closely,” she said.

A. R. Pont et al., “mRNA Decay Factor AUF1 Maintains Normal Aging, Telomere Maintenance, and Suppression of Senescence by Activation of Telomerase Transcription,” Mol. Cell doi: 10.1016/j.molcel.2012.04.019, 2012.

A new genetic assay will soon help the European fish industry determine the geographical origin of fish that are stocking the supermarkets. Developed by researchers associated with FishPopTrace, an international consortium that monitors the illegal fish trade, the assay can distinguish between different populations of cod, hake, herring, and sole by scanning for single-nucleotide polymorphism (SNP) signatures unique to groups of fish. In a trial of the assay, published earlier this week in Nature Communications, researchers were able to distinguish between legal and protected populations of fish with 93 to 100 percent accuracy.

“This is a tremendous breakthrough,” Kimberly Warner, a senior scientist at the international advocacy group Oceana, told ScienceNOW. “These are critical tools in our fight against illegal fishing and mislabeling and enable us to put some teeth into our fisheries laws and eco-certifications.”

The United Kingdom will be employing the new tool in the near future in a pilot study designed to vet the authenticity of fish origin labels.

The radiation emitted during the Fukushima nuclear accident is unlikely to lead to increases in cancer, according to two separate studies conducted by the World Health Organization (WHO) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Based on estimates of radiation doses received after the accident, even cases of cancer in the nuclear plant workers highest exposed will be difficult to attribute to radiation, according to the reports on radiation exposures in the first year after the accident.

Both the WHO and UNSCEAR assessed public exposure. “If there’s a health risk, it’s with the highly exposed workers,” Wolfgang Weiss, UNSCEAR’ chair, told Nature. More than 150 nuclear plant workers received high enough exposures to slightly raise their risk of cancer, but most civilians did not, according to the WHO’s evaluation.

UNSCEAR’s report calculated that the Japanese government’s estimates of exposure were correct within a factor of ten, but surveys and interviews examining public attitudes show continuing distrust of official numbers. Residents are reporting high levels of PTSD symptoms, and some feel that reports on radiation exposure, though independent, may not be thorough enough. “I think international organizations should stop making hasty reports based on very short visits to Japan that don’t allow them to see what is happening locally,” Tatsuhiko Kodama, head of the radioisotope centre at the University of Tokyo, told Nature.

Read more about how the Fukushima accident may be affecting wildlife, the changing reports of radioactive pollution, how scientists are using monkeys to track radiation, at http://classic.the-scientist.com/.

Advocates of open access have started an online petition that can be signed by US and non-US citizens, urging President Obama to implement policies making all publicly-funded research open access.  With a more than 14,000 signatures to date, the petition is well on its way to meeting its 25,000-name goal.

The Administration’s Office of Science and Technology is taking an interest in open access, having put out two calls for public information on the topic in the past two years. And the president’s science advisor John Holdren— believed to be sympathetic to the cause, according to The Guardian–has already met several times with open access advocates.

The National Institutes of Health already has a policy requiring federally funded research to be made publicly accessible within 12 months of publication, and the United Kingdom is considering similar measures. In addition, a bill called the Federal Research Public Access Act (FRPAA) wending its way through Congress would require any publicly funded research to be deposited in open access repositories within 6 months of publication.

“There are good reasons for optimism in this case,” writes Mike Taylor at The Guardian. “Demonstrating public support will strengthen this legislation’s chances.”

Hat tip to Genomeweb

Recent discussions debating the value of advanced degrees show why it’s so important to at least be familiar with the kinds of marketable skills that are needed to succeed beyond an academic setting. Universities across the country are taking note, offering programs in a wide range of academic disciplines that not only infuse post-graduates with knowledge, but equip them with the “soft” skills demanded by the spectrum of global industry.

True, scientific research has always been most advanced because the value of advanced degrees is evident all the time. In labs, as experiments unfold and discoveries are made, those with the highest credentials are often behind the most critical work. But even science industry is dramatically changing, and an advanced degree is only part of what’s needed to market yourself in an increasingly flexible and competitive workforce. Especially within the largest science companies in the world, the days of the long-term strategic hire, when an organization had the luxury of molding the perfect employee over time, are gone. In order to compete for the best jobs and opportunities, scientists at all levels today must also know how to navigate a multitude of seemingly non-science issues, from company culture to social etiquette, in order to continue advancing their careers.

Acquiring and strengthening these so-called soft skills should be a high priority for any scientist in the search for their next job or promotion. The difficulty in transitioning from academia to industry demonstrates why.

Scientists with the highest credentials often present themselves to companies, thinking that their narrow focus and expertise in one area will be enough to land them a job.

From an absolutely technical perspective, this approach may be fine. Life sciences companies certainly value and seek out specialized knowledge. But the problems companies face in global business demand that their workforce be much more versatile today. This means companies are looking beyond candidates’ technical skills and academic credentials for evidence that they can understand the big picture.

So what does this new thinking really boil down to? Companies want to know if you truly understand the unique business issues behind their goals and how your abilities could contribute to reaching those goals. Scientific research in most settings, after all, is not simply an academic pursuit–it’s big business. So even if a researcher has published 53 papers in the top scientific journals, the ultimate question from an organization’s view will always be: “How are you going to apply that knowledge to help us?”

Companies are also looking for someone who has the social skills to fit into the culture of the workplace, and who knows how to communicate effectively with colleagues to accomplish the task at hand. As in most business environments, strengthening these core social skills will strengthen practically every aspect of a scientist’s career.

Also, because of the incredible pace of scientific research and advancement, employers want someone who can hit the ground running. That means knowing the current issues the company is going through, and having the ability to transfer your skills and be immediately productive in your new position.

Leaving the academic setting is not as daunting as it seems. By taking the time to hone skills that are critical in virtually every industry, you’ll see your opportunities grow exponentially in the sciences.

 Alan Edwards is vice president and science leader, Americas Products Group, Kelly Service®. Kelly Services, Inc., a staffing and management solutions company, is headquartered in Troy, Michigan.

Researchers at the University of California, San Francisco, have alleviated chronic pain in mice by transplanting neurons into their spinal cords. The study, which is published today in Neuron, could lead to better treatments for neuropathic pain, the persistent condition caused by nerve injuries, where pain occurs spontaneously or at the lightest touch.

The transplanted cells released a signalling chemical called gamma aminobutyric acid (GABA), which silences excitable neurons. This inhibition is often missing in neural diseases like epilepsy and chronic pain, leading to uncontrolled neural activity.

Many drugs for chronic pain also increase GABA signalling, but these “alleviate the symptoms without acting on the cause,” said Allan Basbaum, who led the new study. “In contrast, our approach restores the inhibitory control that is missing in the injured tissue. We can expect much longer and conceivably permanent effects.”

“It is a milestone paper,” said Hanns Zeilhofer from the University of Zurich, who was not involved in the study. “It demonstrates very impressive pain relief. In the long run, it may pave the path to a cell-based therapy of otherwise intractable pain.”

Other groups have reduced epileptic seizures in mice by implanting foetal GABA-releasing neurons into their brains. Basbaum wanted to see if the same neurons could be successfully transplanted into the spine to treat chronic pain.

Joao Braz, a postdoc in Basbaum’s lab, extracted immature precursors of GABA-releasing neurons from the brains of fetal mice, and injected them into adults with injured spinal nerves, whose paws were extremely sensitive to touch. He delivered the neurons to the dorsal horn—a structure in the spine that receives sensory information from around the body. Loss of GABA signalling in the horn is thought to underlie many hard-to-treat pain conditions.

The transplanted neurons survived and gave rise to mature GABA-releasing cells, which formed connections with the local spinal circuits. Within a month, the sensitivity brought on by the rodents’ injured nerves had been completely reversed.

The transplants did not alleviate the symptoms of inflammatory pain, caused by injuries to tissues rather than nerves. This suggests that rather than providing general pain relief, the new neurons were addressing the root cause of neuropathic pain: a lack of GABA.

Theodore Price from the University of Arizona said the study settles a debate about how nerve injuries alter GABA signalling in the spinal cord. “Some studies might have been construed to suggest that enhancing GABA signalling would actually enhance pain rather than inhibit it,” he said. Braz’s work clearly shows that the latter is correct. “I think it has exciting therapeutic applications for not only neural transplants [to reduce pain] but also generation of novel pharmacological therapies targeting the GABAergic system,” Price added.

Some existing drugs can already boost GABA signalling but they do not work for many patients with chronic pain. Even for those who do respond to treatment, the effects are temporary, so drugs need to be taken regularly for a long time. Furthermore, by activating GABA receptors in the brain, the drugs can cause unwanted side effects like sedation or addiction.

“The transplantation of neurons which release GABA into the spinal cord would circumvent these problems,” said Zeilhofer. “Apparently, the neurons survive for long periods and their action remains restricted to the spinal dorsal horn.”

Other groups have tried to use viruses to introduce GABA-producing genes into spinal neurons, or engineered human stem cells to produce the chemical. Both approaches have alleviated neuropathic pain in rodents. However, Basbaum said, neither technique produces neurons that integrated into the animals’ nervous systems, so they are unlikely to produce long-lasting effects. Both methods could also increase the risk of cancer, as the viruses can disrupt important genes, and the stem cells can keep on growing after they are transplanted. Transplanting fetal neurons avoids both problems.

Basbaum now plans to follow the fates of the transplanted mice to see if they improve further or deteriorate. He also wants to see if transplants from human fetal tissues will work as well as those from mice, and he has approval to begin such experiments.

“It will definitely be a very long way until such approaches can be applied in human patients,” said Zeilhofer. He doubts that the technique will become a routine part of pain treatment, since it will require surgery, immune suppression, and a source of donor cells. However, he adds, “in the far future, it may offer a promising alternative for cases in which no other satisfactory treatment can be found, and these may be very many.”

J. Braz et al., “Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain,” Neuron doi:10.1016/j.neuron.2012.02.033, 2012.

Human mesenchymal stem cells (hMSCs) have become a popular potential therapy for numerous autoimmune and neurological disorders. But while these bone marrow-derived stem cells have been studied in great detail in the dish, scientists know little about how they modulate the immune system and promote tissue repair in living organisms.

Now, one research team has uncovered a molecular mechanism by which hMSCs promote recovery in a mouse model of multiple sclerosis (MS).

According to research, published online Sunday (May 20) in Nature Neuroscience, a growth factor produced by hMSCs fights MS in two ways: blocking a destructive autoimmune response and repairing neuronal damage. The finding could help advance ongoing clinical trials testing hMSCs as a therapy for MS.

The researchers have identified “a unique factor that has surprisingly potent activity mediating neuron repair,” said Jacques Galipeau, a cell therapy researcher at Emory University in Atlanta, Georgia, who was not involved in the research. “The magnitude of the effect on a mouse model of MS is a big deal.”

MS is an autoimmune disease in which the immune system attacks myelin sheaths that surround and protect nerve cells. The attack leaves nerves exposed and unable to send signals to the brain and back, resulting in the loss of motor skills, coordination, vision, and cognitive abilities. There is no cure for MS, and most current therapies work to simply suppress the immune system, preventing further neuronal damage. None have demonstrated an ability to also repair damaged myelin and promote recovery.

In 2009, Robert Miller and colleagues at Case Western Reserve University in Cleveland, Ohio, demonstrated that hMSCs dramatically reversed the symptoms of multiple sclerosis in a mouse model of the disorder. “The animals got better,” recalled Miller. The team hypothesized that the stem cells suppress the immune response and promote remyelination.

But Miller wanted to know exactly what the cells were doing. To find out, his team isolated the medium on which the hMSCs were grown to determine if the cells or something they secreted was responsible for the observed recovery. The medium alone was enough to induce recovery in mice, pointing to the latter.

To find out exactly which molecule or molecules in the medium were responsible, the researchers separated the proteins in the fluid based on the molecular weight and injected each isolate into mice exhibiting symptoms of MS. The mid-weight solution, of proteins with masses between 50 and 100 kilodaltons (kDa), caused recovery. “That eliminated a huge number of potential candidates,” said Miller.

The researchers then narrowed the field again with a literature search for a molecule that fit their criteria: secreted by hMSCs, 50-100 kDa in size, and involved in tissue repair. They identified hepatocyte growth factor (HGF), a cytokine made by mesenchymal cells that has been shown to promote tissue regeneration and cell survival in numerous experiments. Sure enough, HGF alone was enough to promote recovery in the MS mouse models, and blocking the receptor for HGF in those mice blocked recovery. The team also demonstrated that HGF suppresses immune responses in vivo and accelerates remyelination of neurons in vitro. Finally, they saw that HGF causes remyelination in rats with a lesion on their spinal cord.

“I feel quite confident that HGF suppresses the immune response and also drives myelin repair,” said Miller. There are likely other hMSCs-produced factors that contribute to the cells’ beneficial effect, but HGF is certainly critical, he said. “The data are compelling,” added Galipeau.

There are currently several clinical trials testing hMSCs in MS patients around the world, including a phase I trial at the Cleveland Clinic in Ohio that emerged from the work in Miller’s lab. The new mechanistic information could help researchers designing those therapies to select cells that produce high levels of HGF, said Miller, which should promote remyelination and maximize symptom reversal.

But the research begs a question: why not simply forgo the cells altogether? That point is up for debate. Miller argues that stem cells act as vehicles to transport HGF, and other potential factors, directly to the central nervous system and maintain production there. But a single protein is a far more practical therapy—cheaper and easier to produce—than a cell therapy, countered Galipeau. “The best cell therapy is one done without a cell,” he said. “Identifying these factors and testing them as single agents is an important short-term deliverable of stem cell science.”

To find out more about which cell therapies are in clinical trials, stay tuned for the July issue of The Scientist, featuring an analysis of the growing cell therapy industry.

L. Bai et al., “Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models,” Nat Neuro, doi:10.1038/nn.3109, 2012.

The Device: Although nature can inspire great design solutions, it often needs a bit of tweaking. When researchers at the University of Washington wanted to create a system to move miniscule amounts of liquid, they looked to the lotus leaf with its extremely hydrophobic surface for inspiration. But while water can move along the leaf’s surface without getting stuck, there is no way to control its flow—a necessary quality for designing small portable biomedical devices.

The researchers first created a hydrophobic surface that mimicked the lotus leaf by building micro-scale pillars whose surface texture helped keep water droplets spherical. Amidst those pillars they added a track of arched lines, like a stack of parentheses, which helped the droplets stay in place.  The researchers could make the droplets move forward along the track by vibrating the surface at a particular frequency.  Once on a track, each droplet moves in one direction and remains separate from the others, and can even travel forward if the chip is upside down or curved. The researchers showed that they could also build tracks that dead ended into each other, forcing the droplets to merge and mix, a desirable outcome for microfluidics applications.

“This is an interesting new way to create new kinds of structured surfaces to be able to manipulate droplets in various directionalities,” said Evelyn Wang, a mechanical engineer from Massachusetts Institute of Technology who was not involved in the study.

What’s New: Earlier concepts for moving distinct droplets of liquid involve applying electricity or heat to the sample, which can alter the chemistry or denature proteins, and thus may not be suitable for biological applications. “We wanted something that was very gentle,” said lead author Karl Böhringer of the University of Washington.

While temperature can be increased, to build a miniaturized PCR chamber, for example, “we want the ability to heat our samples to be separate from our ability to move them,” he said.

Importance: The chip is made of a material called polydimethylsiloxane (PDMS), which is “really inexpensive,” said Wang. “Each chip would cost a few dollars to make.  If you scale it up, it would bring [the cost] down to cents,” said Böhringer, making it ideal for applications requiring cheap, disposable materials.

The research proves that liquids of different viscosity can be transported using vibrations, such as from a cell phone, but Böhringer has not designed an application just yet. The chip would need to be outfitted with sensors or electrodes, which would be a good deal more expensive than the surface itself.

Needs Improvement: Different sized droplets require different frequencies of movement. For example a 5-microliter droplet will travel at a resonance frequency of about 80 hertz, said Böhringer. Once the appropriate frequency is determined for the liquid being used, it should be straightforward to control its movement along the chip. But being able to control the size of the droplets entering the chip initially may not be so easy on such a small scale. “We’d have to see how to adjust to the existing technology” of spraying or splitting droplets in order to make it work with the chip, said Böhringer.

T.A.  Duncombe et al., “Controlling Liquid Drops with Texture Ratchets” Adv Mater, 24, 1545–50, 2012.

All clinical trial findings—even negative ones—will be made public, author contributions to manuscripts will be made clear, and study authors will have full access to all trial data in industry-funded clinical trials if a list of recommendations hashed out by editors at top medical journals and eight major pharmaceutical companies are actually implemented.

A team of 11 authors from the worlds of Big Pharma and biomedical publishing listed 10 such recommendations in a recent article that ran in the current issue of Mayo Clinic Proceedings. The recommendations arose from the Medical Publishing Insights and Practices Initiative, launched in 2008, which includes input from representatives at Merck, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Pfizer, and Takeda, as well as editors from 65 biomedical journals, among them The Lancet and the Journal of Clinical Oncology, and other members of the International Society for Medical Publication Professionals.

The eight pharmaceutical companies all affirmed their commitment to the recommendations, such as ensuring that clinical studies and publications address clinically important questions, improving understanding and disclosure of authors’ potential conflicts of interest, educating authors on how to develop quality manuscripts and meet journal expectations, reporting adverse event data more transparently and in a more clinically meaningful manner, and transparently reporting statistical methods used in analyses, among others.

But the proof of Big Pharma’s commitment to these principles will, as always, be in the pudding. “The [recommendations] all seem fine,” Jerome Kassirer, former editor-in-chief of The New England Journal of Medicine told American Medical News. “The question is whether the pharmaceutical companies will practice what they preach. They don’t always do this, as is evident from the multiple multimillion-dollar suits we hear about, year after year.”