The Fake Drug Problem

 

By Gesa Junge, PhD

Tablets, injections, and drops are convenient ways to administer life-saving medicine - but there is no way to tell what’s in them just by looking, and that makes drugs relatively easy to counterfeit. Counterfeit drugs are medicines that contain the wrong amount or type of active ingredient (the vast majority of cases), are sold in fraudulent packaging, or are contaminated with harmful substances. A very important distinction here: counterfeit drugs do not equal generic drugs. Generic drugs contain the same type and dose of active ingredient as a branded product and have undergone clinical trials, and they, too, can be counterfeited. In fact, counterfeiting can affect any drug, and although the main targets, particularly in Europe and North America, have historically been “lifestyle drugs” such as Viagra and weight loss products, fake versions of cancer drugs, antidepressants, anti-Malaria drugs and even medical devices are increasingly reported.

The consequences of counterfeit medicines can be fatal, for example, due to toxic contaminants in medicines, or inactive drugs used to treat life-threatening conditions. According to a BBC article, over 100,000 people die each year due to ineffective malaria medicines, and overall, Interpol puts the number of deaths due to counterfeit pharmaceuticals at up to a million per year. There are also other public health implications: Antibiotics in too low doses may not help a patient fight an infection, but they can be sufficient to induce resistance in bacteria, and counterfeit painkillers containing fentanyl, a powerful opioid, are a major contributor to the opioid crisis, according to the DEA.

It seems nearly impossible to accurately quantify the global market for counterfeit pharmaceuticals, but it may be as much as $200bn, or possibly over $400bn. The profit margin of fake drugs is huge because the expensive part of a drug is the active ingredient, which can relatively easily be replaced with cheap, innate material. These inactive pills can then be sold at a fraction of the price of the real drug while still making a profit. According to a 2011 report by the Stimson Center, the large profit margin combined with comparatively low penalties for manufacturing and selling counterfeit pharmaceuticals make counterfeiting drugs a popular revenue stream for organized crime, including global terrorist organizations.

Even though the incidence of drug counterfeiting is very hard to estimate, it is certainly a global problem. It is most prevalent in developing countries, where 10-30% of all medication sold may be fake, and less so in industrialized countries (below 1%), according to the CDC. In the summer of 2015, Interpol launched a coordinated campaign in 115 countries during which millions of counterfeit medicines with an estimated value of $81 million were seized, including everything from eye drops and tanning lotion to antidepressants and fertility drugs. The operation also shut down over 2400 websites and 550 adverts for illegal online pharmacies in an effort to combat online sales of illegal drugs.

There are several methods to help protect the integrity of pharmaceuticals, including tamper-evident packaging (e.g. blister packs) which can show customers if the packaging has been opened. However, the bigger problem lies in counterfeit pharmaceuticals making their way into the supply chain of drug companies. Tracking technology in the form of barcodes or RFID chips can establish a data trail that allows companies to follow each lot from manufacturer to pharmacy shelf, and as of 2013, tracking of pharmaceuticals throughout the supply chain is required as per the Drug Quality and Security Act. But this still does not necessarily let a customer know if the tablets they bought are fake or not.

Ingredients in a tablet or solution can fairly easily be identified by chromatography or spectroscopy. However, these methods require highly specialized, expensive equipment that most drug companies and research institutions have access to, but are not widely available in many parts of the world. To address this problem, researchers at the University Of Notre Dame have developed a very cool, low-tech method to quickly test drugs for their ingredients: A tablet is scratched across the paper, and the paper is then dipped in water. Various chemicals coated on the paper react with ingredients in the drug to form colors, resulting in a “color bar code” that can then be compared to known samples of filler materials commonly used in counterfeit drugs, as well as active pharmaceutical ingredients.

Recently, there have also been policy efforts to address the problem. The European Commission released their Falsified Medicines Directive in 2011 which established counterfeit medicines as a public health threat and called for stricter penalties for producing and selling counterfeit medicines. The directive also established a common logo to be displayed on websites, allowing customers to verify they are buying through a legitimate site. In the US, VIPPS accredits legitimate online pharmacies, and in May of this year, a bill calling for stricter penalties on the distribution and import of counterfeit medicine was introduced in Congress. In addition, there have also been various public awareness campaigns, for example, last year’s MHRA #FakeMeds campaign in the UK,  which was specifically focussed on diet pills sold online, and the FDA’s “BeSafeRx” programme, which offers resources to safely buying drugs online.

In spite of all the efforts to raise awareness and address the problem of fake drugs, a major complication remains: Generic drugs, as well as branded drugs, are often produced overseas and many are sold online, which saves cost and can bring the price of medication down, making it affordable to many people. The key will be to strike the balance between restricting access of counterfeiters to the supply chain while not restricting access to affordable, quality medication for patients who need them.


3D printed model of Cas9 from CRISPR

We need to talk about CRISPR

By Gesa Junge, PhD

You’ve probably heard of CRISPR, the magic new gene editing technique that will either ruin the world or save it, depending on what you read and whom you talk to? Or the Three Parent Baby, which scientists in the UK have created?

CRISPR is a technology based on a bacterial immune defense system which uses Cas9, a nuclease, to cut up foreign genetic material (e.g., viral RNA). Scientists have developed a method by which they can modify the recognition part of the system, the guide RNA, and make it specific to a site in the genome that Cas9 then cuts. This is often described as “gene editing” which allows disease-causing genes to be swapped out for healthy ones.

CRISPR is now so well known that Google finally stopped suggesting I may be looking for “crisps” instead, but the real-world applications are not so well worked out yet, and there are various issues around CRISPR, including off-target effects, and also the fact that deleting genes is much easier than replacing them with something else. But, after researchers at Oregon Health and Science University managed to change the mutated version of the MYBPC3 gene to the unmutated version in a viable human embryo last month, the predictable bioethical debate was reignited, and terms such as “Designer Babies” got thrown around a lot.

A similar thing happened with the “Three Parent Baby,” an unfortunate term coined to describe mitochondrial replacement therapy (MRT). Mitochondria, the cells’ organelles for providing energy, have their own DNA (making up about 0.2% of the total genome) which is separate from the genomic DNA in the nucleus, which is the body’s blueprint. Mitochondrial DNA can mutate just like genomic DNA, potentially leading to mitochondrial disease, which affects 1 in 5000-10000 children. Mitochondrial disease can manifest in various ways, ranging from growth defects to heart or kidney to disease to neuropsychological symptoms. Symptoms can range from very mild to very severe or fatal, and the disease is incurable.

MRT replaces the mutated mitochondrial DNA in a fertilized egg or in an embryo with the healthy version provided by a third donor, which allows the mitochondria to develop normally. The UK was the first country to allow the “cautious adaption” of this technique.

While headlines need to draw attention and engage the reader for obvious reasons, oversimplifications like “gene editing” and dramatic phrases like “three parent babies” can really get in the way of broadening the understanding of science, which is difficult enough as it is. Research is a slow and inefficient process that easily gets lost in a 24-hour news cycle, and often the context is complex and not easily summed up in 140 characters. And even when the audience can be engaged and interested, the relevant papers are probably hiding behind a paywall, making fact checking difficult.

Aside from difficulties communicating the technicalities and results of studies, there is also often a lack of context in presenting scientific studies - think for example of chocolate and red wine which may or may not protect from heart attacks. What is lost in many headlines is that scientific studies usually express their results as a change in risk of developing a disease, not a direct causation, and very few diseases are caused by one chemical or one food additive. On this topic, WNYC’s “On The Media”-team have an issue of their Breaking News Consumer Handbook that is very useful to evaluate health news.

The causation vs. correlation issue is perhaps a little easier to discuss than big ethical questions that involve changing the germline DNA of human beings because ethical questions do not usually have a scientific answer, let alone a right answer. This is a problem, not just for scientists, but for everyone, because innovation often moves out of the realm of established ethics, forcing us to re-evaluate it.

Both CRISPR and MRT are very powerful techniques that can alter a person’s DNA, and potentially the DNA of their children, which makes them both promising and scary. We are not ready to use CRISPR to cure all cancers yet, and “Three Parent Babies” are not designed by anyone, but unfortunately, it can be hard to look past Designer Babies, Killer Mutations and DNA Scissors, and have a constructive discussion about the real issues, which needs to happen! These technologies exist; they will improve and eventually, and inevitably, play a role in medicine. The question is, would we rather have this development happen in reasonably well-regulated environments where authorities are at least somewhat accountable to the public, or are we happy to let countries with more questionable human rights records and even more opaque power structures take the lead?

Scientists have a responsibility to make sure their work is used for the benefit of humanity, and part of that is taking the time to talk about what we do in terms that anyone can understand, and to clarify all potential implications (both positive and negative), so that there can be an informed public discussion, and hopefully a solution everyone can live with.

 

Further Reading:

CRISPR:

National Geographic

Washington Post

 

Mitochondrial Replacement Therapy:

A paper on clinical and ethical implications

New York Times (Op-Ed)

 


Can Chocolate be Good for You? The Dark and Light Side of the Force

By Jesica Levingston Mac leod, PhD

It is this time of the year again: San Valentin (aka Valentine's Day) -  the best excuse to give and more importantly to EAT a lot of chocolate. But, maybe a better gift that receiving chocolate,  is to know that eating chocolate might be good for your health.

In the beginning chocolate was "created" as a medicine -  a healthy beverage -  around 1900 BC by Mesoamerican people. The Aztecs and Mayas gave it the name of “xocolatl”, it means bitter water, as the early preparations of the cacao seeds had an intense bitter taste. Almost one year ago, a longitudinal study, done in the US East Coast, connected eating chocolate with better cognitive function. Yay! Great news, right? The scientists gathered information over a period of 30 years (starting in 1976) from 968 subjects (aged 23-98 years) in the Syracuse-Maine area. The results showed that more frequent chocolate consumption was meaningfully associated with better performance on the global composite score, visual-spatial memory and organization, working memory, scanning and tracking, abstract reasoning, and the mini-mental state examination. Importantly, they pointed out that with the exception of working memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors across the participants.

More good news arrived last summer: an Italian research team announced that flavanol-rich chocolate improves arterial function and working memory performance counteracting the effects of sleep deprivation. The researchers investigated the effect of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation in 32 healthy participants, who underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were assigned to consume high or poor flavanol chocolate bars. During the tests the participants were evaluated by the psychomotor vigilance task and a working memory task, systolic blood pressure (SBP) and diastolic blood pressure (DBP), flow-mediated dilation and pulse-wave velocity. As you might know, sleep deprivation increased SBP/DBP. The result was that SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment sleep deprivation impaired flow-mediated dilation, flavanol-rich, but not flavanol-poor chocolate counteracted this alteration. Flavanol-rich chocolate mitigated the pulse-wave velocity increase. Also, flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition.

The European Food Safety Authority accepted the following statement for cocoa products containing 200 mg of flavanols: “cocoa flavanols help maintain the elasticity of blood vessels, which contributes to normal blood flow”. This statement means that flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. In another study led by Columbia University Medical Center scientists,  dietary cocoa flavanols—naturally occurring bioactives found in cocoa—reversed age-related memory decline in healthy older adults. One possibility is that the improvement in cognitive performance could be due to the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow. Following on this other chocolate attribute, it was shown than weekly chocolate intake may be beneficial to arterial stiffness.

But, there are some bad news!  A review of 13 scientific articles on this topic, provided evidence that dark chocolate did not reduce blood pressure. However, the reviewers claimed that there was an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Specifically, their analysis showed that chocolates containing around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure if consumed over longer periods: “Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, you will need to consume  100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin). Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin”.  The method of manufacturing dark chocolate retains epicatechin, whereas milk chocolate does not contain substantial amounts of epicatechin.

The first epidemiological “indication” for beneficial health effects of chocolate were found in Kuna natives in Panama with low prevalence of atherosclerosis, type 2 diabetes, and hypertension. This fact correlated with their daily intake of a homemade cocoa. These traits disappear after migration to urban and changes in diet.

 

There are many  claims about the potential health benefits of chocolate, including anti-oxidative effect by polyphenols, anti-depressant effect by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. Chocolate contains quercetin, a powerful antioxidant that protects cells against damage from free-radicals. Chocolate also contains theobromine and caffeine, which are central nervous system stimulants, diuretics and smooth muscle relaxants, and valeric acid, which is a stress reducer. However, chocolate also contains sugar and other additives in some chocolate products that might not be so good for your health.

 

Oh well, maybe the love of chocolate is like any other romantic affair: blind and passionate. Apparently, the beneficial dosage is 10 g of dark chocolate per day (>70% cocoa), so enjoy it as long as the serotonin boost for rewarding yourself with a new treat last.

 

Happy Valentine's Day!

 

 


Forging a Connection Between “Doing” and “Feeling”: How Behavioral Activation Therapy Can Alleviate Depression

 

By Lauren Tanabe, PhD

 

A few weeks ago, I stumbled across a short description of a recent study published in The Lancet out of the University of Exeter: researchers found that behavioral activation (BA) therapy works as well as cognitive behavioral therapy as therapeutic intervention for depression. Cognitive behavioral therapy (CBT) has been previously shown to be as effective as antidepressants.

 

According to the Society of Clinical Psychology, depression may cause people to “disengage from their routines and withdraw from their environment.” Over time, this isolating avoidance behavior can intensify depression as people “lose opportunities to be positively reinforced through pleasant experiences, social activity, or experiences of mastery.” Behavioral activation therapy aims to alter the patient’s avoidance behavior by increasing exposure to “sources of reward.” As well as by helping people to understand the connection between their behavior and their mood.

 

In lay-terms, activity will influence how you feel. If you sit at home alone, this may worsen depression. If you coax yourself to engage in some kind of social activity, or to work towards a goal (chores, hobby, work), this may lessen depression symptoms.

 

This seems straightforward enough. When I first learned of the study, scrolling through a blurb in Scientific American entitled, Depressed? Do What You Love, I must admit, I audibly scoffed, Really? We need a study to tell us this? At the time, it seemed rather obvious and mostly common-sense that doing what you love would lead to feelings of happiness (or if not happiness, a lessening of depression). I reached out to the lead author on the study, Dr. David Richards of Exeter University and proceeded to pose question after skeptical question. Dr. Richards patiently and thoroughly answered each one. I was most curious about how he would respond to one question in particular:

 

Some might say that it's not surprising that doing what you enjoy can ward off depression. Why do we need a study to tell us this?

 

“If it were that obvious, then why would we have got to the point of recommending complex therapies like CBT [cognitive behavioral therapy] which focus on changing the way we think? Or why wouldn’t people have figured it out for themselves? … BA is not just doing what you enjoy. It is increasing the opportunities for positive reinforcement and reducing avoidance caused by aversive experiences. Depression is self-reinforcing and before you know it you can find yourself in a position where you cannot see a way out, just by having started on what at the time seemed like a sensible path of avoiding things you don’t like. Although there is an element of the common sense to BA that you suggest, in actual fact people often get stuck and what BA does is help them make some important connections between activity and mood which then leads to a personalised programme of re-activation …

 

As I read his email, my emotions ranged from incredulous to enlightened.  I mulled over his words in the following days. Perhaps, like most who suffer from depression, I want to believe that I am actively doing what I can to wriggle my way out of its clutches. Especially since it often takes an inordinate amount of effort and cognitive calisthenics for me to admit to myself (or anyone else) that I need help in the first place. I’ve painstakingly evaluated my thoughts and actions with a therapist and I know in great detail why I’m depressed. I’ve finally filled that antidepressant prescription, that old, familiar frenemy I hate to get in touch with again, after so many independent years. These actions should be enough to cure me. And yet, each morning, as I wash down my pill, vicious thoughts gnaw into me for being weak, followed by the washing over of a listless acceptance in the belief that I am broken, followed by the eking seepage of a meek hope. That tiny bit of hope – that these tyrannical thoughts will dissipate and I’ll finally be free – carries me through the day. The daily ritual of self-flagellation even (especially) for seeking help is simply exhausting. So, maybe there is something more I could be doing to help myself.

 

Dr. Richards went on to write, “Western tradition often stresses that if we are ‘ill’ we must cure the sickness inside us before taking our place in the world again. What BA does is tell people that they do not need to do this. So although you might think that is common sense, you would be surprised at how many people are applying a ‘fix me first’ principle and are surprised by the BA rationale …”

 

Behavioral activation therapy highlights a subtle, yet significant, shift in how treatment for depression is viewed, in general. A common analogy used in describing this type of therapy is that it works from the “outside-in” rather than the “inside-out.” That is, if you’re depressed you don’t wait to feel better and then participate in fulfilling activities (a common and somewhat intuitive strategy). Rather, the participation in meaningful work will alter your outlook and mitigate the depression. This, I could relate to.

 

I could recall myriad examples of times when I knew that sitting on the couch and binge-watching bad TV or going to bed at 7 pm was not going to lead to fulfillment of any kind, and much more likely just make me feel worse about myself, but I did it anyway. Why? Likely a strange dichotomy of wanting to make myself feel better from a quick-fix of escapism coupled with a twisted hatred of myself – I couldn’t possibly excel at anything other than existing as a gluttonous zombie, so why bother? And then, of course, there is not wanting to be a burden to others or to bring them down. Practicing self-imposed isolation in order to avoid becoming the archetypal “Debbie Downer” feels necessary to preserve relationships and save face.

 

But, clearly, this approach doesn’t work for most. It certainly didn’t for me.

 

The Exeter study was a well-controlled, randomized analysis of over 400 men and women who either received CBT or BA therapy. One year after treatment, both groups reported at least a 50% reduction in symptoms and were equally likely to experience remission. Both groups also contained some participants already taking antidepressants (ADs).

 

I asked Dr. Richards if he thought that being on medication could make someone more receptive to the therapy. He did not believe so, “We stratified the randomisation to ensure both groups had the same likelihood of being on ADs. The key thing is that for most of them, the drugs had not worked, evidenced by the fact that they had been on them for a considerable while before starting BA. We chose this because this is the reality of clinical services – psychological therapists have to work with patients who are on tablets as well as undergoing therapy. It’s the real world.”

 

The real world is replete with people suffering from depression (approximately 350 million worldwide). Of those, many do not have access to adequate treatment. According to the study, BA therapy is a more cost-effective option (about 20% less expensive than CBT), as treatment can be delivered by less specialized health workers. This is important. Wide-scale treatment options are critical, especially in low income countries where the treatment gap can be as much as 80 - 90%.

 

When I first read about BA, I mistakenly thought the goal was to do what makes you happy. But this is not the case. I asked Dr. Richards about this: “It’s not at all about making you happy. It’s about the function of behaviour in the short- and long-term. People learn to see the connection between activity and mood and choose activities where their experience is that this will be a more positive experience – achieving things, reducing avoidance.”

 

When asked why he believes BA therapy works, Dr. Richards responded, “It is because what we do has a profound connection with how we feel. Experiencing this connection is the core.”

 

I think I’ll be adding aspects of BA therapy to my current repertoire. As much as I sometimes want to avoid others, I’ll make the extra (albeit sometimes painful) effort to socialize with friends and to engage in tasks that “rational me” knows will lead to fulfillment (even if “depressed me” fights it). It will be a slow process, but no better time than the new year to forge new habits, new behaviors, and hopefully, resurrect a happier version of myself.


Happy Science: Turn That Frown Upside Down

 

By Lori Bystrom, PhD

Although 2016 may have been rough for some, most of us are still optimistic about 2017. We all want to start the New Year happy. Fortunately, more and more businesses, institutions, and even countries and cities are focusing on happiness. Companies, such as Happy City in Bristol, England, aim to keep people content. The Center for Health and Happiness at Harvard is gaining a lot of interest (see The Atlantic  article). Many countries and cities are being ranked based on happiness (check out the happy planet index). And just look at the United Arab Emirates, which appointed its first "minster for happiness" early in 2016. All of this sounds wonderful and promising, but what about the happiness of scientists?

 

I am not sure that many people would equate "science" with “happiness." As an academic scientist, I recall happy moments of scientific discovery, but those are memorable partly because they are rare. I particularly recall one glorious moment during the last month of a project — after many failures and nearly passing out — when I was finally able to get publishable results. Oh how long I waited for that happy day!  More often, however, the scientific work environment can be tough, especially in academia, with little positive feedback, low pay, and competitive/high pressure work. This is all compounded with constant trials and tribulations of everyday science, all of which can take a toll on the mental health of scientists.

 

It may seem grim to view scientific work as so difficult, but this does not stop many scientists from loving science. In fact, I think science would probably be very boring if amazing results were so easy to achieve all the time (well, it would be a little bit exciting). I think many scientists would agree that there is something appealing about the challenge of discovering and exploring the unknown in order to reach that happy eureka moment. That being said, though, science research does not need to be as depressing as it is. This is to say: there is much that could be done to make scientists less unhappy.

 

So what can be done to make or keep scientists more content with their job? More money is always nice, of course, but this is not always the answer, nor is it always feasible. There are, however, other approaches that may improve work conditions for scientists. Here are a few ideas for promoting happiness in the lab, especially for academic scientists.

Listen to all; respect all

This may seem obvious, but this was often a major problem in the labs where I have worked.  I think it is always good to listen to what everyone has to say about a project. I have witnessed people at all levels in the academic institution fail to encourage this kind of healthy discourse. Everyone should have a voice. Not only that, but scientific discovery comes in many shapes and forms. Even a young scientist may see something that a more experienced scientist might not, because they are too lost in the detail. Different perspectives may help shed light on problems that initially seem too complex to solve.

 

Excluding people from intellectual discussion hinders the creative flow in research and leads to unhappy scientists. Most researchers would like to provide some feedback about projects in the lab.  Scientists should not be treated like robots. This   only makes scientists angry. And once a few colleagues are upset, they are liable to take it out on everyone else, leading to a lab infested with unhappy scientists.

 

Define and communicate expectations

All mentors should have their students and/or employees define what kind of expectations they have of each other at the beginning of a project. These expectations should be reviewed over time, as they will likely change. You may not see eye to eye with your mentor, but they are also not mind readers. This is why expectations from both sides should be reviewed. And if you are not a good match then it is better to find out early.

 

In addition to short-term goals, both mentor and mentee should also define their long-term goals. Not everyone wants to go to medical school, be a PI/advisor, or stay in the lab, and therefore scientists should work on projects that are relevant to their long-term and short-term interests. Furthermore, if you need advice you should ask, and if someone asks for advice, you should respond. No one has a crystal ball and so dead silence does not help anyone. Ultimately, good communication prevents miscommunication and an unhappy lab environment.

 

Aim to achieve little goals

It is not reasonable for everyone in a lab to expect to be the first author on a paper in a high-ranking journal after a short stint in research (I have had many summer students expect this!) For this reason, I think it is important for scientists to aim for small goals, especially at the beginning of a project or career. By starting out small you can build a strong foundation for a big project. For students that are new to a particular field of science, or even science at all, it may be good  for them to work on projects already in progress by developing small and relevant side projects, as well as providing them small incentives (e.g., name on poster or something that they can put on their CV). This way there is less confusion in the lab and the outcome of the project is more likely to keep everyone happy.

 

More senior scientists can also benefit from taking on smaller projects within or outside of their own research. This can help because many scientists may not see the light at the end of the tunnel when their project is not working as planned. In such an eventuality, having smaller projects on the side allows them to take a break from their main project by using their expertise in small doses to help other projects, especially those close to being finished. This, in turn, may help them better visualize their problem, keep their publication record up, and boost their morale.

 

Keep everything organized and transparent

I think organization is crucial in a lab. This not only pertains to cleaning the lab space, decluttering lab supplies and maintaining instruments, but also to finances. It would be nice if someone at the institution other than the PI had to deal with this. Unfortunately, this is not usually the case. It is a lot to ask that one person manage research, lab drama, and also lab finances. I find that academic scientists (myself included) are not trained how to do this very well. Therefore, it may be good if everyone in the lab sat down and discussed what is needed for various projects in order to make sure the money is well spent. If financial conditions are becoming a problem in lab — as they often are, even in the most prosperous labs — it may also be good to have everyone write a budget for their project. Transparency about the financial situation of the lab also helps people understand the state of the lab (and perhaps the mood of their PI/boss), and may encourage scientists to think again about paying extra for something not necessary (do we really need pink pipettes?). A lab that is organized and financially transparent helps prevent unnecessary stress and avoids a lot of unnecessary resentment.

 

Don't forget to socialize… and take a break!

I know that I could not have survived my lab experiences without the support of other fellow scientists. I found that lunchtime was something I looked forward to every day because not only could I eat (nom nom), but I could vent about experiment problems, laugh, or learn from other colleagues. I think all mentors should encourage this and celebrate any scientific achievement with some kind of social event, even if it only occurs during lab meeting. A friendly and social environment makes for happier scientists.

 

Additionally, overworking scientists leads to less efficient and productive work. Before a big deadline is about to approach, it might be good for scientists to take a few hours off to recompose themselves. This might be a good time to take a walk or eat a nice dinner. Otherwise, if there is no time for that it might be good to take a longer vacation after the deadline is over so you can come back more refreshed and ready to tackle more challenging moments in science. I know I have denied myself vacations many times because I thought maybe if I just kept on working I would get the data I needed sooner. Unfortunately, this often led to less productive work. This is why it might be good to enforce that all researchers take vacations, especially after stressful periods.

 

Perhaps in the future, there will be organizations to help manage the happiness of scientists, although I am not holding my breath for something like this to appear anytime soon. Maybe the first step, however, is acknowledging that there is a lot of unnecessary unhappiness in the lab and that we should try to do something about it. The future of science will be better if we keep scientists smiling :)


How to Live Long and Prosper - a Vulcan's Dream

 

By Jesica Levingston Mac leod, PhD

 

A new Harvard study found that we are living longer and better, too. In fact, the life expectancy for a 65 year old in USA grew a lot in the last 20 years: the life expectancy for females is now 81.2 years and for males it's 76.4 years. The 3 pillars of this improvement are the less smoking, healthier diet and the medical advances. Going straight into the deep science latest developments, two start ups (BioViva and Elysium Health) were in the news recently for their cutting-edge “anti-aging” approaches. The first group to research  telomeres gene therapy is Maria Blasco's group. A study by Bernardes de Jesus et al. demonstrated how telomerese gene therapy in adult and old mice could delay aging and increase longevity, without the collateral effect of increasing the propensity of developing cancer.

In the study, the scientists showed how the treatment of 1- and 2-year old mice with an adeno associated virus expressing mouse telomerase reverse transcriptase (TERT) had beneficial effects on health and fitness, with an increase in median lifespan of 24% and 13%, respectively. Some other benefits included better insulin sensitivity, reduced osteoporosis, improved neuromuscular coordination and improvements in several molecular biomarkers of aging. In cancer cells, the expression of the telomerase is enhanced, giving this protein a bad reputation as having a “tumorigenic activity”. Elizabeth Parrish, the CEO of BioViva, went all the way to Colombia, to receive two gene therapies that her company had developed: one to lengthen the telomeres and the other to increase muscle mass. The results of the treatment were very positive: the telomeres in leukocytes grew from 6.71 kb to 7.33 kb in seven months. As a side note, petite leukocyte telomere length may be associated with several psychiatric disorders (including major depressive disorder) and with poor response to psychiatric medications in bipolar disorder and schizophrenia.

In a nutshell, human telomeres are composed of double-stranded repeat arrays of “TTAGGG” terminating in a single-stranded G-rich overhang. The fidelity of that sequence is maintained by the enzyme telomerase, which uses an intrinsic RNA molecule containing the CAAUCCCAAUC template region and the reverse transcriptase component (TERT), to synthesize telomeric DNA de novo onto the chromosome terminus. The telomeres were named after the greek words télos (end, extremity) and méros (part). Take home message: Telomerase adds DNA to the ends of telomeres and by lengthening telomeres, it extends cellular life-span and/or induces immortalization. The telomerase is not active in normal somatic cells while active only in germ-line, stem and other highly proliferative cells.

 

Last year, Dr. Fagan and collaborators, published in PLoS One that the transcendental meditation and lifestyle variations stimulate two genes that produce telomerase (hTERT and hTR). Even cheerier news were reported in Nature for thanksgiving: the edible dormouse (super cute, small, long tail mouse - Glis glis) telomere length significantly increases from an age of 6 to an age of 9 years. As they state in the paper "the findings clearly reject the notion that there is a universal and inevitable progressive shortening of telomeres that limits the number of remaining cell cycles and predicts longevity".  These species of mouse skip reproduction in years with low food availability, this “sit tight” strategy in the timing of reproduction might pushed "older" dormouse to reproduce, and this could facilitate telomere attrition, this strategy may have led to the evolution of increased somatic maintenance and telomere elongation with increasing age.

The other company, Elysium, co-founded by MIT professor Lenny Guarente, is focus in the mitochondria and the NAD (nicotinamide adenine dinucleotide). Mitochondria are our energy generators and they get crumbly as we age. Dr. Guarente demonstrated in mice how it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of NAD, like nicotinamide riboside (NR, a precursor to NAD that is found in trace amounts in milk), resveratol (a red wine ingredient) or pterostilbene (present in berries and grapes). Elysium has just realized the results of the clinical trial that was placebo-controlled, randomized, and double-blinded, where they evaluated the safety and efficacy of BASIS (the diateary supplement with nicotinamide riboside (NR) and pterostilbene) in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene) or double the dose. In both cases, the intake of Basis resulted in the increase of NAD+ levels in the blood safely and sustainably, 40% and 90% respectively.

 

A former Guarante's postdoc -  Dr. Sinclair - has just published in Science the discovery of a NAD binding area in a protein that regulate NAD's interactions with other proteins related to aging. The Sinclair's lab reported that the binding of NAD+ to DBC1 (Deleted in Breast Cancer 1 protein) prevents it for inhibiting another protein -  PARP1, an important DNA repairing protein. Furthermore, they have shown that as the mice aged, the concentration of NAD+ decreased, and more DBC1 was available to bind to PARP1, culminating in the accumulation of DNA damage. On a brighter note, this process was reversed by restoring higher levels of NAD+. The good news are that NAD+modulation might protect against cancer, radiation and aging.

 

Although all these advances are great, they won’t make you live longer in the next 10 years, so what can you do to live longer/healthier? Science comes again to answer this question! Harvard studies have shown that living “meaningful lives” helping others, having aims/motivations (and been conscious about the fact that we are taking our own decisions), been grateful, enjoying the present and significant relationships with other humans are key aspects to have a happy live. Obviously, exercising and having natural environments around us, as well as healthy eating are crucial points in a healthy life.

It might be an oversimplification, but 70% of your risk of disease is related to diet: soda and processed food are related with shortening the telomeres. Good news: you can slow down aging with a healthier life style: “Switch to a whole-food, plant-based diet, which has been repeatedly shown not just to help prevent the disease, but arrest and even reverse it” claims Dr. Greger’s, author of the Daily Dozen—a checklist of the foods we should try to consume every day. The super food list includes: Cruciferous vegetables (such as broccoli, Brussels sprouts, cabbage, cauliflower, kale, spring greens, radishes, turnip tops, watercress), Greens (including spring greens, kale, young salad greens, sorrel, spinach, swiss chard), other vegetables (Asparagus, beetroot, peppers, carrots, corn, courgettes, garlic, mushrooms, okra, onions, pumpkin, sugar snap peas, squash, sweet potatoes, tomatoes), beans (Black beans, cannellini beans, black-eyed peas, butter beans, soyabeans, baked beans, chickpeas, edamame, peas, kidney beans, lentils, miso, pinto beans, split peas, tofu, hummus),  Berries: (including grapes, raisins, blackberries, cherries, raspberries and strawberries),  other fruit (such as apples, apricots, avocados, bananas, cantaloupe melon, clementines, dates, figs, grapefruit, honeydew melon, kiwi, lemons, limes, lychees, mangos, nectarines, oranges, papaya, passion fruit, peaches, pears, pineapple, plums, pomegranates, prunes, tangerines, watermelon),  Flax seeds, nuts, spices (like turmeric), whole grains (Buckwheat, rice, quinoa, cereal, pasta, bread) and the almighty: water.

As you can expect, a lot of research is needed to get a magic pill that might boost your life expectancy but you can start investing in your future having a positive attitude, healthy diet, exercising and all the other things that you already know you should be doing to feel better, without forgetting that life is too short, so eat dessert first.

 


The Danger of Absolutes in Science Communication

 

By Rebecca Delker, PhD

Complementarity, born out of quantum theory, is the idea that two different ways of looking at reality can both be true, although not at the same time. In other words, the opposite of a truth is not necessarily a falsehood. The most well known example of this in the physical world is light, which can be both a particle and a wave depending on how we measure it. Fundamentally, this principle allows for, and even encourages, the presence of multiple perspectives to gain knowledge.

 

This is something I found myself thinking about as I witnessed the twitter feud-turned blog post-turned actual news story (and here) centered around the factuality of physician-scientist Siddhartha Mukherjee’s essay, “Same but Different,” published recently in The New Yorker. Weaving personal stories of his mother and her identical twin sister with experimental evidence, Mukherjee presents the influence of the epigenome – the modifications overlaying the genome – in regulating gene expression. From this perspective, the genome encodes the set of all possible phenotypes, while the epigenome shrinks this set down to one. At the cellular level – where much of the evidence for the influence of epigenetic marks resides – this is demonstrated by the phenomenon that a single genome encodes for the vastly different phenotypes of cells in a multicellular organism. A neuron is different from a lymphocyte, which is different from a skin cell not because their genomes differ but because their transcriptomes (the complete set of genes expressed at any given time) differ. Epigenetic marks play a role here.

 

While many have problems with the buzzword status of epigenetics and the use of the phrase to explain away the many unknowns in biology (here, here), the central critique of Mukherjee’s essay was the extent to which he emphasized the role of epigenetic mechanisms in gene regulation over other well-characterized players, namely transcription factors – DNA binding proteins that are undeniably critical for gene expression. However, debating whether the well-studied transcription factors or the less well-established epigenetic marks are more important is no different than the classic chicken or egg scenario: impossible to assign order in a hierarchy, let alone separate from one another.

 

But whether we embrace epigenetics in all of its glory or we couch the term in quotation marks – “epigenetics” – in an attempt to dilute its impact, it is still worth pausing to dissect why a public exchange brimming with such negativity occurred in the first place.
“Humans are a strange lot,” remarked primatologist Frans de Waal. “We have the power to analyze and explore the world around us, yet panic as soon as evidence threatens to violate our expectations” (de Waal, 2016, p.113). This inclination is evident in the above debate, but it also hints at a more ubiquitous theme of the presence of bias stemming from one’s group identity. Though de Waal deals with expectations that cross species lines, even within our own species, group identity plays a powerful role in dictating relationships and guiding one’s perspective on controversial issues. Studies have shown that political identities, for example, can supplant information during decision-making. Pew Surveys reveal that views on the issue of climate change divide sharply along partisan lines. When asked whether humans are at fault for changing climate patterns, a much larger percentage of democrats (66%) than republicans (24%) answered yes; however, when asked what the main contributor of climate change is (CO2), these two groups converged (democrats: 56%, republicans: 58%; taken from Field Notes From a Catastrophe, p. 199-200). This illustrates the potential for a divide between one’s objective understanding of an issue and one’s subjective position on that issue – the latter greatly influenced by the prevailing opinion of their allied group.

 

Along with group identity is the tendency to eschew uncertainty and nuance, choosing solid footing no matter how shaky the turf, effectively demolishing the middle ground. This tendency has grown stronger in recent years, it seems, likely in response to an increase in the sheer amount of information available. This increased complexity, while important in allowing access to numerous perspectives on an issue, also triggers our innate response to minimize cost during decision-making by taking “cognitive shortcuts” and receiving cues from trusted authorities, including news outlets. This is exacerbated by the rise in the use of social media and shrinking attention spans, which quench our taste for nuance in favor of extremes. The constant awareness of one’s (online) identity in relation to that of a larger group encourages consolidation around these extremes. The result is the transformation of ideas into ideologies and the polarization of the people involved.

 

These phenomena are evident in the response to Mukherjee’s New Yorker article, but they can be spotted in many other areas of scientific discourse. This, unfortunately, is due in large part to a culture that rewards results, promotes an I-know-the-answer mentality, and encourages its members to adopt a binary vision of the world where there is a right and a wrong answer. Those who critiqued Mukherjee for placing too great an emphasis on the role of epigenetic mechanisms responded by placing the emphasis on transcription factors, trivializing the role of epigenetics. What got lost in this battle of extremes was a discussion of the complementary nature of both sets of discoveries – a discussion that would bridge, rather than divide, generations and perspectives.

 

While intra-academic squabbles are unproductive, the real danger of arguments fought in absolutes and along group identity lines lays at the interface of science and society. The world we live in is fraught with complex problems, and Science, humanity’s vessel of ingenuity, is called upon to provide clean, definitive solutions. This is an impossible task in many instances as important global challenges are not purely scientific in nature. They each contain a very deep human element. Political, historical, religious, and cultural views act as filters through which information is perceived and function to guide one’s stance on complex issues. When these issues include a scientific angle, confidence in the institution of science as an (trustworthy) authority plays a huge role.

 

One of the most divisive of such issues is that of genetically modified crops (GMOs). GMOs are crops produced by the introduction or modification of DNA sequence to incorporate a new trait or alter an existing trait. While the debate spans concerns about the safety of GMOs for human health and environmental health to economic concerns over the potential disparate benefits to large agribusiness and small farmers, these details are lost in the conversation. Instead, the debate is reduced to a binary: pro-GMO equals pro-science, anti-GMO equals anti-science. Again, the group to which one identifies, scientists included, plays a tremendous role in determining one’s stance on the issue. Polling public opinion reveals a similar pattern to that of climate change. Even though awareness of genetic engineering in crops has remained constantly low over the years, beliefs that GMOs pose a serious health hazard have increased. What’s worse, these debates treat all GMO crops the same simply because they are produced with the same methodology. While the opposition maintains a blanket disapproval of all engineered crops, the proponents don’t fare better, responding with indiscriminate approval.

 

Last month The National Academy of Sciences released a comprehensive, 420-page report addressing concerns about GMOs and presenting an analysis of two-decades of research on the subject. While the conclusions drawn largely support the idea that GMOs pose no significant danger for human and environmental health, the authors make certain to address the caveats associated with these conclusions. Though prompted by many to provide the public with “a simple, general, authoritative answer about GE (GMO) crops,” the committee refused to participate in “popular binary arguments.” As important as the scientific analysis is this element of the report, which serves to push the scientific community away from a culture of absolutes. While the evidence at hand shows no cause-and-effect relationship between GMOs and human health problems, for example, our ability to assess this is limited to short-term effects, as well as by our current ability to know what to look for and to develop assays to do so. The presence of these unknowns is a reality in all scientific research and to ignore them, especially with regard to complex societal issues, only serves to strengthen the growing mistrust of science in our community and broaden the divide between people with differing opinions. As one review of the report states, “trust is not built on sweeping decrees.”

 

GMO crops, though, is only one of many issues of this sort; climate change and vaccine safety, for example, have been similarly fraught. And, unfortunately, our world is promising to get a whole lot more complicated. With the reduced cost of high-throughput DNA sequencing and the relative ease of genome editing, it is becoming possible to modify not just crops, but farmed animals, as well as the wild flora and fauna that we share this planet with. Like the other issues discussed, these are not purely scientific problems. In fact, the rapid rate at which technology is developing creates a scenario in which the science is the easy part; understanding the consequences and the ethics of our actions yields the complications. This is exemplified by the potential use of CRISPR-driven gene drives to eradicate mosquito species that serve as vectors for devastating diseases (malaria, dengue, zika, for example). In 2015, 214 million people were affected by malaria and, of those, approximately half a million died. It is a moral imperative to address this problem, and gene drives (or other genome modification techniques) may be the best solution at this time. But, the situation is much more complex than here-today, gone-tomorrow. For starters, the rise in the prevalence of mosquito-borne diseases has its own complex portfolio, likely involving climate change and human-caused habitat destruction and deforestation. With limited understanding of the interconnectedness of ecosystems, it is challenging to predict the effects of mosquito specicide on the environment or on the rise of new vectors of human disease. And, finally, this issue raises questions of the role of humans on this planet and the ethics of modifying the world around us. The fact is that we are operating within a space replete with unknowns and the path forward is not to ignore these nuances or to approach these problems with an absolutist’s mindset. This only encourages an equal and opposite reaction in others and obliterates all hope of collective insight.

 

It is becoming ever more common for us to run away from uncertainty and nuance in search of simple truths. It is within the shelter of each of our groups and within the language of absolutes that we convince ourselves these truths can be found; but this is a misconception. Just as embracing complementarity in our understanding of the physical world can lead to greater insight, an awareness that no single approach can necessarily answer our world’s most pressing problems can actually push science and progress forward. When thinking about the relationship of science with society, gaining trust is certainly important but not the only consideration. It is also about cultivating an understanding that in the complex world in which we live there can exist multiple, mutually incompatible truths. It is our job as scientists and as citizens of the world to navigate toward, rather than away from, this terrain to gain a richer understanding of problems and thus best be able to provide a solution. Borrowing the words of physicist Frank Wilczek, “Complementarity is both a feature of physical reality and a lesson in wisdom.”

 


science behind meditation

Meditation and Science - Crossing Pathways

 

By Jesica Levingston Mac leod, PhD

Good news (as of February 22, 2016): finally science is starting to explain how mindful meditation can be good for your health. Last month, a study published in the Biological Psychiatry journal proved that  mindfulness meditation combines the default state network (a network of interacting brain regions known to have activity highly correlated with each other)  with a region known to be important in top-down executive control at rest (the left dorsolateral prefrontal cortex), which in turn is associated with improvements in Interleukin -6 levels. Interleukin-5 is  a marker of inflammatory disease risk. They recruited 35 jobless adults, who were separated in 2 groups: one group  was immersed in a 3-day intensive residential mindfulness meditation and the other group in a relaxation training program.  Blood samples and a resting state scan test were taken before and after the  program. The key findings indicated that  mindfulness meditation training, and not relaxation training, increased posterior cingulate cortex  resting state functional connectivity with left dorsolateral prefrontal cortex (region important in top-down executive control). According to this study "these pre-post training alterations  statistically explained 30% of the overall mindfulness meditation training effects on Interleukin-6 at follow-up after 4 months". In healthy men, elevated levels of Interleukin-6 are related to  increased risk of future Myocardial infarction, for example heart attack.

 

More than 9 years ago I read a study that completely changed my point of view about meditation. I am very lucky to have an open-minded meditation-practicing mother who taught me the basic techniques when I was very young, but as a researcher I did not connect the power of meditation with any "biological" or scientifically proved alteration. Many people meditate to reduce psychological stress and health problems, but my mother taught me to meditate to reach a nirvana-like moment of peace and clarity. We focused on the moment - not searching for fixing any problem - and just enjoyed the experience.

 

Meditation can be defined in psychological terms as the practice of disciplining one's attention in an effort to attain a certain state of mind. There are two different types of meditation: spiritual (known for the presence of mantras and thoughts about God and God’s attributes) and secular meditation independent of any religious motivation. In the study that changed my view of this practice, Wacholtz and Pargament (1, 2) studied how these 2 types of meditation helped people deal with pain. They asked the participants to meditate for 20 minutes each day over a period of 2 weeks. One group was told to practice spiritual meditation and a second group would practice secular meditation. A third group of people were asked to not meditate as a control. Then, the researchers performed the simple "please introduce your hand in this cold ice water and try to hold it there as long as you can" method. How long could the participants keep their hand in this very uncomfortable situation? Well, the "spiritual" group had greater decreases in anxiety and more positive mood, spiritual health, and spiritual experiences, plus they tolerated pain almost twice as long as the other two groups. Of course, just meditation gave the participants a better tolerance to the -2C water. In 2008 they published another study where they showed that spiritual meditation was more effective than secular meditation at reducing the severity of migraines in chronic patients.

 

Recently, a variety of studies are proving that meditation is an effective treatment for stress and pain. For example in Nature Review NeurologyJensen et al. reviewed a number of publications on this very topic. First of all, they note that meditation is not an invasive therapy, moreover they conclude that the "evidence indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain".

 

On the other hand, a meta analysis published this year by Goyal et al. in JAMA Internal  Medicine (they included 47 trials with 3515 participants) found that mindfulness meditation programs had moderate evidence of improved anxiety, depression and pain. They detected low evidence of improved stress/distress and mental health-related quality of life, and low evidence of no effect or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits, sleep, and weight. In conclusion, they found no evidence that meditation programs were better than any active treatment, like medicine or workout.

 

Let's face it: the happiest guy in the world, Dr. Matthieu Ricard (yes, he has a PhD in molecular biology), meditates often as the basis of his awesomeness, so let's follow his example... or in scientific language: he has being proving his hypothesis with 100% success, and we can reproduce his experiment at any time in our own lives.

To find a meditation group near you and more information check the free mediation info website.

This post was originally published on June 4, 2014. 


How Can You Make Money and Help Others with Your Shit?

And other very important poop updates.

 

By Jesica Levingston Mac leod, PhD

First, you have to be a healthy pooper… Second, you have to live in the Boston area. Your stool can help a person suffering from recurrent C. difficile infections, which is a bacterium that affects 500,000 Americans every year.  Where antibiotic treatment has failed to help, a new treatment called “fecal microbiota transplantation” has shown a cure rate of 90%.  In this procedure, a fecal microbiota preparation using stool from a healthy donor is transplanted into the colon of the patient.  OpenBiome, the startup company based in Boston, helps facilitate this procedure by screening and processing fecal microbiota preparations for use in this treatment. After joining the registration you and your stool will be screened and if you are healthy and a good candidate you will became a donor. If you can succeed with all the tests and you can provide “supplies” quite often then you can exchange money for you poo.

Lately, the study of the human microbiota has been all over the news, specially related with weight control, pregnancy and the infant’s diet. In fact, it's estimated that the human gut contains 100 trillion bacteria, or 10 times as many bacteria as cells in the human body. Yes, I know what you are thinking: “More of them that my own cells, that cannot be right, right?”

These bacteria, or microbiota, influence your health in many ways, from helping to extract energy from food to building the body's immune system, to protecting against infection with harmful, disease-causing bacteria.

Researchers are only just beginning to understand how differences in the composition of gut bacteria may influence human health. From what we know so far, here are five ways gut flora can affect your wellness:

 

Weight Changes

Yes, your gut bacteria affect your eating disorders (or orders if you are lucky). For example the diversity of gut bacteria is higher in lean people compared to obese people. Also, some specific bacteria groups, the Firmicutes and the Bacteroidetes, are linked with obesity. The famous study were they transplanted gut bacteria from obese and lean people to mice, making the host of the first kind of poo gain more weigh that the mice who received the “lean fecal bacteria”, was a shocking confirmation of the importance of the gut bacteria in the body weight regulation. They discovered that the gut bacteria from obese people increase the production of some amino acids, while the material from lean people increases the metabolism of “burning” carbohydrates.

 

Preterm Labor

Realman and col. found that pregnant women with lower levels of bacteria Lactobacillus in their vagina had an increased risk of preterm labor, compared with women whose vaginal bacterial communities were rich in Lactobacillus. Apparently, the absence of Lactobacillus allows the grown of other species that would have different effects in the pregnancy.

 

Crying Babies

In a funny study on how diet may affect babies, Pertty and col. showed that giving probiotics to your baby does not change the daily crying time, around 173 minutes, compare to the placebo group (174 min), according to the parental diary. They enrolled 30 infants with colic during the first 6 weeks of life.  However, parents reported a decrease of 68% in daily crying in the probiotic and 49% in the placebo group.

 

Heart Attacks

Gut Bacteria produce compounds can even affect your heart. One of these compounds is the trimethylamine-N-oxide (TMAO), and the presence of it in the blood of the subjects of a recent research study, increased 2.5 times the probability of having a heart attack, stroke or to die over a three-year period compared with people with low levels of TMAO. They have also shown that the metabolism of the gut bacteria changes according of the host’s (your) diet. For example, the consumption of high cholesterol and fatty food can increase the bacterial production of TMAO.

 

The Immune System

A recent review published in Cell rang the alarm about the negative effect of the “rich countries” diet in the microbiota influencing the immune system. In ideal and normal conditions the immune system-microbiota association allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. In rich countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected.

 

Lungs and Asthma

The gut bacteria can affect your lungs: The low levels of 4 gut bacteria strains (FaecalibacteriumLachnospiraVeillonella, and Rothia) in kids was been recently related to an increase in the risk for developing debilitating asthma. The introduction of these 4 bacteria in mice induced to suffered asthma shown protection as the mice’s lungs did not present inflammation.

The question is: how bacteria IN the guts can affect your other tissues and organs? One study that was just published shows  that these bacteria produce chemicals that may help the immune system to battle against other germs. Without this training, the immune system could fail and create inflammation in the lungs. As a follow up from the latest research it may be possible in the near future to predict asthma, and other diseases, as well as cure some illnesses with gut bacteria.

Be ready to give a shit about your shit.


From Bed[side] to Bench: Involving Patients and the Public in Biomedical Research

By Celine Cammarata

 

Many of us doing biomedical science never really see patients, the very people our work will hopefully one day help. But what if we did – what if those individuals who will eventually be using our research on a daily basis were in fact involved in the work from the start? How would research change?

 

This is the concept underlying the movement toward Patient and Public Involvement or PPI, a title that (logically enough) refers to efforts by researchers and institutions to engage patients and members of the public in the process of biomedical research and, in doing so, fundamentally change the way scientific information is created and disseminated. Traditionally, the flow if information between science and society was seen as relatively unidirectional, with researchers passing scientific knowledge down to an uninformed, receptive public. More recently, however, there has been a growing recognition that information flow from the end-users of research back to investigators is also critical.

 

One way to accomplish this is to directly incorporate those users – broadly defined as patients, caregivers, members of the public rather than clinicians or practitioners - into the research process. A prominent definition of PPI is “research being carried out ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them” (INVOLVE). Individual instances of PPI can be quite variable, though most engage users in some form of advisory role, often through interviews, surveys, focus groups, and hosting users alongside researchers on regularly-meeting advisory groups (Domecq et al., 2014). PPI is represented at all stages of research, from inception of project ideas through the data collection process to implementation of findings and evaluation and is most prevalent in research that is either directly related to health or social issues and services.

 

A primary driving force behind PPI is the belief that input from users will push research toward questions that are more relevant to those users. Individuals with first-hand experience of an illness or other condition are thought to hold a particular kind of expertise and therefore able to craft more immediately relevant research questions than an academic investigator in the field might.

 

One important stage at which patients and the public are having an impact is by working with funding agencies to establish research priorities. For instance, the UK’s NHS Health Technology Assessment program involves users alongside clinicians and researchers in the development and prioritization of research priority questions. Members of the public were engaged in several different stages of the process, from initial suggestion of research ideas through to selecting topics that would be developed into solicitations for research. Analysis revealed that overall these lay members exerted an influence on the research agenda approximately equal to that of academic and clinical professionals (Oliver, Armes, & Gyte, 2009).

 

PPI can also increase the relevance of individual studies, with specific examples including: users of mental health services shifting outcome measurement in a study of therapies to improve cognition away from psychological tests in favor measuring performance on daily activities; the investigation of environmental factors such as radiation, which researchers originally considered negligible, in a study of breast cancer; and the development of new assessment tools to measure the mental and psychological condition of stroke victims in a study that initially planned to focus only on physical health outcomes (Staley, 2009).

 

Users may express particular suspicions or hunches about their condition that they believe should receive further investigation, may increase pressure on investigators to clearly state how their work will contribute to the public, and may challenge whether a project is even conceptualized in a way relevant to those who experiencing the situation in question, helping to determine whether a research problem is truly a “problem” at all. An excellent example of the impacts of PPI in research commissioning is the Head Up project, an entirely user-driven project in which patients with motor neuron disease working with one of the CCF programs pushed for research on an improved supportive neck collar.

 

PPI may also help increase the up-take of research findings because user’s are generally able to relate to and communicate with other users and practitioners in a uniquely meaningful way. Patients and members of the public may help to write up study findings, present at conferences or, importantly, bring findings directly to the user community.

 

Of course, nothing comes without a cost. A number of challenges in conducting PPI have consistently been identified, including: insufficient time and funding; tension over roles on the project and difficult relations between academic researchers and users; lack of training for both users and researchers; and a tokenistic attitude toward PPI on the part of investigators. Still relatively little is known about the precise effects of PPI or best practices. However, these are active areas of scholarship. Also of note is the relative lack of PPI in basic science research; PPI is predominantly relegated to applied health and social research. An important step in furthering PPI would be to establish who the “users” of basic research are, whether PPI in basic research is likely to be beneficial, and how the practice could be implemented.

 

Overall, it is clear that the end-users of research can be incorporated into setting the research agenda, designing studies and communicating results, and suggests that such user engagement can increase the relevance of research and the dissemination and adoption of findings.


Flintstones Kids Vitamins

How the Flintstones can Help the Jetsons: History Lessons for Modern Medicine

By Lori Bystrom, PhD

Many of us look forward to a future of convenience with magical gadgets and miracle cures, perhaps something akin to the lifestyle of the cartoon characters on The Jetsons. The show's optimistic portrayal of the future depicts our fascination with modern technology – an interest that stems not only from our desire for new and improved modes of transportation and communication, but also from our desire for new and better medicine.

 

The future of medicine may seem promising, but understanding the past may be vital for making medical dreams come true. Just as the stone-age characters from The Flinstones are capable of helping the futuristic characters of The Jetsons fix their time machine (see The Jetsons Meet The Flinstones clip from 1:00 to 1:17), so too can our long-departed ancestors help us in ways that will benefit us in the future (perhaps in less barbaric ways than hitting something with a club). In other words, medical advancements, although conventionally based on research using modern technology, can also be derived from medical information of the ancient past.

 

Nowhere is this better exemplified than in the recent discovery of a plant-based eye infection remedy found in a 1,000 year old medical text. This finding was recently presented at the British Society for General Microbiology Annual Conference by researchers at the University of Nottingham in England and Texas Tech University in the United States. They found that the 9th century Anglo-Saxon book, known as Bald's Leechbook, contained a remedy for an eye infection that consisted of a mixture of garlic, onion or leeks, wine, and bile (from cow’s stomach) that was boiled and fermented in a brass vessel. Amazingly, the recreation of this ancient remedy proved to be effective against the resilient methicillin-resistant Staphylococcus aureus (MRSA), both in vitro and on wounds. In fact, it was found to be more effective than one of the antibiotics (vancomycin) currently used to treat the modern day superbug (see this article). Although clinical trials need to be conducted to confirm the beneficial effects of this medicinal preparation, this is an extraordinary start for a potential drug.

 

Should we be surprised that some of these ancient remedies actually have therapeutic value? Back in the day, when clinical trials did not exist and ethical practices were not necessarily enforced, there was probably a great deal of trial and error as people tried medicines on each other. The only medicines that were recorded were probably those that worked, while ineffective treatments may or may not have been noted. Interestingly, some of the traditional medicines may have been inspired by how animals treated their ailments (an area of study known as zoopharmacognosy). There also may have been minimal repercussions for failed treatments (no lawsuits?), and therefore maybe more freedom for finding medical cures. Moreover, if a treatment was found to be effective nobody probably had to wait for approval from any organization such as the Food and Drug Administration (FDA).

 

Regardless of what happened in the past, it is apparent there are valuable lessons we can learn from our ancestors. For instance, the ancient practice of fecal transplantation is now gaining acceptance in modern medicine. As far back as the 4th century, Ge Hong, a traditional Chinese medicine doctor, used fecal material to treat his patients with food poisoning or severe diarrhea. Just recently, the FDA approved the use of fecal transplants for specific gastrointestinal problems. The use of leeches for the treatment of venous congestion, among other ailments, is another example of modern medicine embracing old technology (see this article). There are numerous conventional medications that also have roots in the distant past (e.g. aspirin). Any book on the history of medicine will provide more information on this subject matter.

 

All of these examples suggest that medical research is limited if it turns a blind eye to the past. Moreover, the medical community needs to address the polar opposite views on traditional/natural medicines: those that think all natural products/traditional remedies are safe and those that think all traditional medicines/natural therapies are inherently bad. What it really comes down to is what is effective and not what resonates better to different patients or doctors. More scientific research needs to assess whether these treatments are safe and effective, while identifying those that may be snake oil. The journalist and information designer, David McCandless, beautifully illustrates some of these differences on his website.

 

Modern medicine should keep an open mind while researchers continue to investigate ancient remedies and screen out the good from the bad. It is appropriate that a small division of the National Institute of Health, known formerly as the National Center for Complementary and Alternative Medicine, was renamed as the National Center for Complementary and Integrative Health. Unconventional or traditional medicines that are effective are not the ‘alternative’, but perhaps the best option or one that can be integrated with other medical treatments.

 

As we move forward in medicine, we might want to keep digging up the past so we are prepared to combat new diseases and improve current treatments. The future of medicine may just need, as George Jetson puts it nicely, “a little stone-age technology.”


HPV vaccine now covers 9 strains

Extra Protection: New HPV Vaccine Extends Protection to Nine Strains of The Virus

 

By Asu Erden

The human papillomavirus (HPV) is responsible for 5% of all cancers. Until, 2006 there were no commercially available vaccines against the virus. That year, the Food and Drug Administration (FDA) approved the first preventive HPV vaccine, Gardasil (qHPV). This vaccine conveys protection against strains 6, 11, 16, and 18 of the virus and demonstrates remarkable efficacy. The Centers for Disease Control (CDC) estimates that this quadrivalent vaccine prevents 100% of genital pre-cancers and warts in previously unexposed women and 90% of genital warts and 75% of anal cancers in men. While this qHPV protects against 70% of HPV strains, there remains a number of high-risk strains such as HPV 31, 35, 39, 45, 51, 52, 58 for which we do not yet have prophylactic vaccines.

 

In February of this year, a study by an international team spanning five continents changed this state of affairs. The team led by Dr. Elmar A. Joura, Associate Professor of Gynecology and Obstetrics at the Medical University, published its study in the New England Journal of Medicine. It details a phase 2b-3 clinical study of a novel nine-valent HPV (9vHPV) vaccine that targets the four HPV strains included in Gardasil as well as strains 31, 33, 45, 52, and 58. The 9vHPV vaccine was tested side-by-side with the qHPV vaccine in an international cohort of 14, 215 women. Each participant received three doses of either vaccine, the first on day one, the second dose two months later, and the final dose six months after the first dose. Neither groups differed in their basal health or sexual behavior. This is the immunization regimen currently implemented for the Gardasil vaccine.

 

Blood samples as well as local tissue swabs were collected for analysis of antibody responses and HPV infection, respectively. They revealed the same low percentage of high-grade cervical, vulvar, or vaginal. Antibody responses against the four HPV strains included in the Gardasil vaccine were similar in both treatment groups. Of note is that participants in the 9vHPV vaccine group experienced more mild to moderate adverse events at the site of injection. Dr. Elmar A. Joura explained that these effects are due to the fact that the “[new] vaccine contains more antigen, hence more local reactions are expected. The amount of aluminium [editor’s note: the adjuvant used in the vaccine] was adapted to fit with the amount of antigen. It is the same amount of aluminium as used in the Hepatitis B vaccine.”

 

These results confirm that the novel 9vHPV vaccine raises antibody responses against HPV strains 6, 11, 16, 18 that are as efficacious as the original Gardasil vaccine. In addition, the novel vaccine also raises protection against HPV strains 31, 33, 45, 52, and 58. Importantly, the immune responses triggered by the 9vHPV vaccine are as protective against HPV disease as those raised by the qHPV vaccine.

 

Yet we are all too familiar with the contention surrounding the original qHPV vaccine. And no doubt, this new 9vHPV vaccine will reignite the debate. Those who specifically oppose the HPV vaccine question its safety and usefulness. In terms of its safety, the HPV vaccine has been tested for over a decade prior to becoming commercially available and has been proven completely safe since its introduction a decade ago. Adverse effects include muscle soreness at the site of injection, which is expected for a vaccine delivered into the muscle…

 

As for its usefulness, don’t make me drag the Surgeon General and Elmo onto the stage. The qHPV vaccine has been shown to be safe and to significantly impact HPV-related genital warts, HPV infection, and cervical complications, “as early as three years after the introduction of [the vaccine]” in terms of curtailing the transmission and public health costs of HPV infections and related cancers.   “HPV related disease and cancer is common. It pays off to get vaccinated and even more importantly to protect the children,” noted Dr Elmar A. Joura.

 

Other opponents to the HPV vaccines raise concerns regarding the use of aluminium as the adjuvant in the formulation of the vaccine. This inorganic compound is necessary to increase the immunogenicity of the vaccine and for the appropriate immune response to be raised against HPV. Common vaccines that include this adjuvant include the hepatitis A, hepatitis B, diphtheria-tetanus-pertussis (DTP), Haemophilus influenzae type b, as well as pneumococcal vaccines.

 

The only question we face is that given the availability of Gardasil, why do we need a nine-valent vaccine? In order to achieve even greater levels of protection in the population at large, extending coverage to additional high-risk HPV strains is of central importance for public health. The team of international scientists that contributed to the study underlined that the 9vHPV vaccine “offers the potential to increase overall prevention of cervical cancer from approximately 70% to approximately 90%.” Thus the novel 9vHPV vaccine offers hope in bringing us even closer to achieving this epidemiological goal. “With this vaccine cervical and other HPV-related cancers could potentially get eliminated, if a good coverage could be achieved. This has not only an impact on treatment costs but also on cervical screening algorithms and long-term costs,” highlighted Dr. Elmar A Joura.


Germs on the subway

Buggy Transportation

All the bugs in the metro, tube, subway, from NYC to Asia

By Jesica Levingston Mac leod, PhD

The New York City (NYC) subway is use for more than 5 million passengers per day. Passengers being humans, pets, bacteria, parasites, viruses and other unknown creatures. Consequently infectious diseases, like influenza can be easily transmitted in this transportation method. Other dangerous circumstances are the black carbon and particle matter concentrations, which In Manhattan are considerably higher than in the urban street level. If you have just ridden the subway, I recommend that you check you washed your hands before continue reading…because, literately, this article is about shit!

Last Month a great research team from Cornell published the studies on microorganisms from 466 subway stations where they found 76 known pathogens (aka “bad” bacteria), and, more interestingly, they found a lot of unknown organisms. This means that almost half of all DNA present on the subway’s surfaces matches no known organism. As they could identified some of the microorganisms, they described that these bacteria were originated in some metropolitan citizen food, pet, workplace… you can actually check which kind of bacteria was found in your favorite/closest subway station... just to be sure what to tell to your doctor next time that you have some infection….

During a year and a half, Dr. Mason, the leader of the group, took samples from materials like the metal handrails in order to collect DNA for the big data genetic metropolitan profile project, aka the Pathomap project. From the 15,152 types of life-forms, almost half of the DNA belonged to bacteria—most of them harmless; However, the scientists said the levels of bacteria they detected pose no public-health problem. The most prevalent bacterial species was Pseudomonas stutzeri, with enrichment in lower Manhattan (aka finance species ;)), followed by strains from Enterobacter and Stenotrophomonas. Notably, all of the most consistently abundant viruses (only 0.03%) were bacteriophages, which were detected concomitant with their bacterial hosts.

Other study done in 2013 in Norway, found that the airborne bacterial levels showed rapid temporal variation (up to 270-fold) on some occasions, both consistent and inconsistent with the diurnal profile. Airborne bacterium-containing particles were distributed between different sizes for particles of >1.1 μm, although ∼50% were between 1.1 and 3.3 μm. Anthropogenic activities (mainly human passengers) were the major sources of airborne bacteria and predominantly contributed 1.1- to 3.3-μm bacterium-containing particles. The peaks are at 8 am and 5 pm, following the rush hours.

Other great discovery was that the human allele frequencies in the subway mirrored US Census data. Within the neighborhoods they found African American and Yoruban alleles correlation for a mostly black area in Brooklyn, Hispanic/Amerindian alleles in the Bronx and they observed that Midtown Manhattan showed an increase in British, Tuscan, and European alleles.

In this globalized world, you won't be surprised that in the London's Tube a group of journalist and researchers found more than 3 million bacteria. These data suggested that the average train or bus seat could have more than 70 types of bacteria, plus cold and flu viruses. The North-South Victoria line was the only one that passed the hygiene test.

In a study at the Hong Kong subways system, researchers analyzed aerosol samples in order to find the taxonomic diversity of the "under" microbes. Each bacterial community within a line was dependent on architectural characteristics, nearby outdoor micro biomes, and distance to other lines, and were influenced by temperature and relative humidity.

Altogether these results sound really scary, but I hope that the reader won’t react panicking, but just being aware of the bad pathogens around him/her and carry a hand sanitizer/mask/cleaning aerosol/wipes or just wash your hands with soap! Actually, health officials from the FDA, believe washing hands with soap and water is the best method to get rid of germs.


Dengue It: Dengue-Specific Immune Response Offers Hope for Vaccine Design

 

By Asu Erden

The dengue virus is a mosquito-borne pathogen that infects between 50 and 100 million people every year. Furthermore, the World Health Organization estimates that approximately half of the global population is at risk. Yet there are currently neither vaccines nor medicines available against this disease, whose symptoms range from mild flu-like illness to severe hemorrhagic fever. The central challenge in designing a vaccine against dengue is that infection can be caused by any of four antigenically related viruses, also called serotypes. Moreover, prior infection with one serotype does not protect against the other three. In fact, such heterotypic exposure can result in much more severe secondary infections – a phenomenon called antibody-dependent enhancement. The lack of knowledge about naturally occurring neutralizing antibodies against dengue viruses has hindered the development of an efficient vaccine. A new study published in the journal Nature Immunology by Professor Screaton’s team at Imperial College, London, may allow the field to overcome this barrier.

 

In this month’s issue of Nature Immunology, Dejnirattisai and colleagues present their characterization of novel antibodies identified from seven hospitalized dengue patients. They first isolated monoclonal antibodies – antibodies made by identical immune cells derived from the same parent cell – from immune cells in the blood of these patients. Among the isolated antibodies, a group emerged that recognized a key component of the dengue virus envelope known as dengue E protein. But unlike previously identified antibodies, this group specifically recognized the envelope dimer epitope (EDE) of dengue, which results from the coming together of two envelope protein subunits on the mature virion rather than a single E protein.

 

The novelty of the study lies in its identification of a novel epitope – EDE – a potent immunogen capable of eliciting highly neutralizing antibodies against dengue. Previously identified antibodies did not show great efficacy against the virus. Antibodies that do not bind dengue antigens sufficiently strongly or are not present at a high enough concentration end up coating the virus through a process named opsonization. This is believed to lead to a more efficient uptake of the virus by immune cells thus fostering a more severe infection by infectious and sometimes also by non-infectious viral particles. This is the issue facing the field. An effective dengue vaccine would have to elicit a potent antibody response able to neutralize the virus while circumventing antibody-dependent enhancement. The antibodies characterized in this study present the peculiarity of efficiently neutralizing dengue virus produced in both insect cells and human cells – both relevant for the lifecycle of the virus – and being fully cross-reactive against the four serotypes.

 

The identification of highly neutralizing antibodies with an efficiency of 80-100%, cross-reactive against the dengue virus serocomplex, and able to bind both partially and fully mature viral particles offers hope for the design of a putative subunit vaccine. Mimicking potent immune responses seen in patients facilitates the process of vaccine development since it removes the need for identifying viral antigens relevant for protection not seen in nature. The naturally occurring responses already point in the right direction. Of the two dengue vaccine trials, neither relied on insight from such immune responses in patients infected with the virus. Based on the present study, it seems that the next step facing the field is to efficiently elicit an immune response that specifically targets EDE. If the antibodies identified here are shown to initiate protection in vivo, Dejnirattisai et al.’s study will have brought the field forward incommensurably.


You Can Help Cure Ebola!

 

By  Jesica Levingston Mac leod, PhD

Since the start of the outbreak last March, Ebola virus has already taken more than 8.000 lives and infected more than 21.200 people, according to the  Center for Disease Control (CDC). The panic raised from this situation rushed the testing of therapies to stop the outbreak and the research on the Ebola virus has seen a rebirth. Some research groups that have been working in this field for a long time can now openly ask for help. One of these groups is the one lead by Dr. Erica Ollman Shaphire at The Scripps Research Institute, California. In 2013 they published in Cell an analysis of the different conformations of Ebola VP40 (Viral Protein 40) aka the shape-shifting “transformer” protein. They reported 3 different conformations of this protein, and how this variety allows it to achieve multiple functions in the viral replication circle. This Ebola virus protein along with the glycoprotein would be used as target for anti viral research. In order to find new anti-virals, their approach is an in-silico scrutiny of thousands of compounds, using viral protein crystal structures in the in silico docking to find leads that may be tested in the lab as inhibitors. IBM is already helping them in this project, generating the World Community Grid to find drugs through the Outsmart Ebola Together project.  Here is where you can start helping, as this project involves a huge amount of data and computing time, they need volunteers that can donate their devices spare computing time (android, computer, kindle fire, etc) to generate a faster virtual supercomputer than can accelerate the discover of new potential drugs. This approach has been shown to be successful for other diseases like HIV and malaria, so you are welcome to join the fight against Ebola virus: https://secure.worldcommunitygrid.org/research/oet1/overview.do.

If you do not have any of these devices (I hope you are enjoying the public library free computers), you can still help Dr. Shapire quest to discover new therapies against Ebola. Her group is now “working to support the salary of a computer scientist to help process the data we are generating with the world community grid” as she describes it. To help identify the most promising drug leads for further testing you can donate money on: www.crowdrise.com/cureebola.

Other groups that were mostly working on other viruses, like Flu, also joined the race to discover efficient therapies. For example, last month, the Emerging Microbes and Infections journal of the Nature Publishing Group published the identification of 53 drugs that are potential inhibitors of the Ebola virus. One of the authors of this paper is Dr. Carles Martínez-Romero, from Dr. Adolfo García-Sastre’s lab in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. In the study, Dr. Martínez-Romero and collaborators described how they narrowed the search from 2.816 FDA approved compounds to 53 potential antiviral drugs. This high-throughput screening was possible thanks to the use of the Ebola viral-like particle (VLP) entry assay. This allows studying Ebola viral entry without using the ”real”, full replicative virus. These 53 compounds blocked the entry of Ebola VLPs into the cell. Understanding how these market-ready compounds can inhibit Ebola entry and its infectious cycle will pave the way for a new generation of treatments against Ebola virus-associated disease.

Dr. Martínez-Romero had an early interest in science; “Since I was a child, I showed great interest in biological sciences and a great desire to question and discover. This led me to pursue my studies in Biotechnology in order to become a successful researcher.”Viruses are very interesting to me because, although they are not strictly living organisms, they are as old as life itself. Even though they are the origin of many illnesses in mammals and other organisms alike, we are tightly interconnected with viruses and they will continue shaping our evolution throughout the years to come.

I also asked him about advice to his fellow researchers, and he answered: “There is a famous quote of Dr. Albert Einstein: “If we knew what we were doing, it wouldn’t be called Research”. As postdocs and researchers in general, we are constantly pursuing new hypotheses. It is a very arduous path with its ups and downs but full of rewards and new challenges ahead.” About the future of the antiviral research, he keeps a positive view: “Several antiviral therapies are being developed to combat the current Ebola outbreak, such as antibody cocktails (Zmapp), antiviral drugs, and specific Ebola vaccines. Together with re-purposing screens like the one we published, a combination of therapeutic drugs can be used to obtain better antiviral strategies against the Ebola virus.”