Goals and Habits: A Scientific Take on New Year’s Resolutions

 

By Gesa Junge, PhD

Happy New Year! Did you make any New Year’s Resolutions? Are they exactly the same ones as last year? Maybe science can help you actually keep them this year (so you can make new ones for 2018).

Giving up on New Year’s Resolutions is incredibly common. Statistics suggest that about half of us make New Year’s Resolution, but less than 10% keep them. Still, there are some ways that psychologists, behavioral scientists and even economists suggest can help you actually make some lasting changes.

Setting the right goals is an important first step. There is a whole TED article on the science behind goal-setting, but the key issues are to pick a meaningful goal, and figuring out exactly why it is so important to you to make this change in order to stay motivated. Also, goals need to strike a balance between too easy and too hard – research from the 1980s shows that more difficult goals can make you work harder. Similarly, specific goals lead to better outcomes than vague and generic goals, probably because it is easier to measure success.

But realistically, in order to make long-term changes, you need to change your habits. Neurologists distinguish between goal-oriented and habitual actions, and according to a 2006 study, almost half of our behavior is habitual. Routines allow our brains to function more efficiently. This makes sense – if we had to focus on all the little actions that are required to for everyday things like making a cup of tea or taking the subway to work, that would be incredibly exhausting.

So a lot of processes can become automated, often even without you noticing. Studies show that rodents trained to find a food reward in the left arm of a T-maze will quickly get into the habit of running straight down to the left arm even if the reward is no longer there. The basal ganglia are thought to play a key role in habit formation, although there is still some controversy around which brain regions are specifically responsible for habit formation. NIH researchers found that, on a molecular level, the endocannabinoid system plays a role. Endocannabinoids are endogenous signalling molecules that stimulate activity via cannabinoid receptors, and mutations in the CB1 cannabinoid receptor prevented mice from forming habits in a lever-press test for a sucrose reward.

As we probably all know habits can be pretty difficult to change. Researchers at MIT trained rats to turn left for chocolate or right for sugar water in a T-maze, depending on which one of two audio signals they received. If the rats are later given chocolate milk mixed with enough lithium chloride to make them nauseous, they will still follow the audio cue to the left (even if they did not always drink the milk), indicating the behavior had become habitual. However, this behavior was lost when the researchers interfered with the infralimbic cortex, and the rats soon started habitually turning right for the sugar water, regardless of the sound cue. But once this new habit was broken (again by interfering with the infralimbic cortex), the animals reverted back to the original habit of going left or right depending on the sound cue. This suggests that habits are really replaced as opposed to lost, and that they can come back, which would explain why it is a) quite hard to break a habit in the first place and b) not to fall back into old habits later.

So a good strategy might be to change or replace habits rather than trying to get rid of them completely. In order to achieve this, there are various commitment devices, that is, measures that make you do the things you would otherwise probably not feel like doing. There is a very interesting Slate article that gives more examples, but one that sounds particularly effective is a website called StikK, founded by behavioral economists from Yale. Here, you can formulate a commitment and put money on the line which, if you don’t reach your goal, is donated to a charity, person or – probably most effective – an anti-charity. An anti-charity is a cause you truly despise (think political parties, lobbying groups, sports teams…).

Another interesting tool is “temptation bundling”, essentially combining activities you like to do with activities you know you should do but don’t particularly enjoy, e.g. only binge-watching Netflix while ironing or cleaning the house. This was evaluated in a study at the University of Pennsylvania that showed that allowing people to only listen to engaging audio books at the gym (by means of a locked-away iPod) caused them to spend more time at the gym than control groups. Unfortunately, all the effects were lost after Thanksgiving break, but November is a while away, so maybe it would be worth a try.

So it may take some effort, but hopefully you can find a way to stick to your resolutions longer than last year. Or at least past Ditch New Year’s Resolutions Day which apparently is January 17th. Good luck, and all the best for 2017!

 

Scizzle’s Christmas Gift Guide 2016

By Sally Burn, Gesa Junge, and Deidre Sackett

 

Ho ho ho, science lovers! It’s that time of year again: panic buying gifts for your nearest and dearest! If your intended recipient happens to be a scientist or a fan of all things science, we have a veritable selection of gift ideas. Or perhaps you yourself are angling to receive a science-themed present and want to point the buyer in the right direction. Then look no further: behold, Scizzle’s 2016 Christmas gift guide!

 

Culinary Science

Turn any kitchen into a lab with our handpicked selection of geeky culinary gifts. Spice up your cooking with the Chemist’s Spice Rack from ThinkGeek or whip up some cosmic cookies with these 3D spaceship cookie cutters. Then put a smile on the mathematician in your life’s face by serving them festive dessert on the i eight sum pi plates. Finally, prevent your Christmas lunch leftovers from being stolen from the communal fridge by taking them to work in this human organ for transplant insulated lunch bag.

 

Technical Tipples

Bring out the crazy scientist mixologist in you this festive season with a Chemist’s Cocktail Kit, then serve up your creations in drinking glasses that are out of this world. The Planetary Glass Set contains ten gorgeous tumblers – representing all eight planets in our solar system, plus the sun and Pluto. Pair the glasses with an anatomically informative coaster set to avoid marking your table – we heart these cardiac anatomy coasters, although the more cerebral minded may prefer a set of Brain Specimen Coasters.

 

Science Bling

Wear the whole solar system around your neck with this fabulous Solar Orbit Necklace or just keep Pluto’s heart close to your own with a Pluto pendant. Like DNA? Put a ring on it with this simple DNA helix ring available on Etsy.

 

Science Apparel

Help the female neurobiologist in your life stand out from the crowd in this Neurons Glow-in-the-Dark-Dress. Or go all out science with the Nerdy Science Dress, festooned with Erlenmeyers, microscopes, formulae, and DNA helices. And for sir, may we suggest the Too Molecule for School Men’s Socks.

 

For Kids (Both Little and Big)

You’re never too young or old to cuddle up with a plush brain, spleen, rectum, or any of the thirteen adorable soft organs available from Uncommon Goods. Or how about a crochet Erlenmeyer flask?

 

SciArt

Check out the Etsy store of the ultra-talented Ella Maruschchenko, whose illustrations have been featured on the cover of many leading journals, for science-themed prints and mugs. For an even greater range of SciArt gifts, head over to the Artologica Etsy store where you will find gorgeous paintings, silk scarves, and petri dish ornaments.

 

High End Geek Gadgetry

The Smartphone Instant Photo Lab is at the higher end of the gift budget ($169.99 and $24.99 for film) but worth it for the thrill of printing your candid Christmas party shots direct from your phone to Polaroid-style paper.

 

Under $10 – for Secret Santa and Stuffing Stockings

Finally, for $3 you can be the proud gifter of an infectious disease stress ball and for under $10 you can pick up a set of five solar power toy cars, a cute Space Capsule Tea Infuser, or even this super chic chemistry lab beaker vase.

 

The Phase That Makes The Cell Go Round

 

By Johannes Buheitel, PhD

 

There comes a moment in every cell’s life, when it’s time to reproduce. For a mammalian cell, this moment usually comes at a ripe age of about 24 hours, at which it undergoes the complex process of mitosis. Mitosis is one of the two main chromosomal events of the cell cycle. But in contrast to S phase (and also to the other phases of the cell cycle) it’s the only phase that is initiated by a dramatic change in the cell’s morphology that, granted, you can’t see with your naked eye, but definitely under any half-decent microscope without requiring any sort of tricks (like fluorescent proteins): Mitotic cells become perfectly round. This transformation however, as remarkable as it may seem, is merely a herald for the main event, which is about to unfold inside the cell: An elegant choreography of chromosomes, which crescendoes into the perfect segregation of the cell’s genetic content and the birth of two new daughter cells.

 

To better understand the challenges behind this choreography, let’s start with some numbers: A human cell has 23 unique chromosomes (22 autosomes and 1 gonosome) but since we’re diploid (each chromosome has a homolog) that brings us to a total of 46 chromosomes that are present at any given time, in (nearly) every cell of our bodies. Before S phase, each chromosome consists of one continuous strand of DNA, which is called a chromatid. Then during S phase, a second “sister” chromatid is being synthesized as a prerequisite for later chromosome segregation in M phase. Therefore, a pre-mitotic cell contains 92 chromatids. That’s a lot! In fact, if you laid down all the genetic material of a human cell that fits into a 10 micrometer nucleus, end to end on a table, you would wind up having with a nucleic acid string of about 2 meters (around 6 feet)! The challenge for mitosis is to entangle this mess and ultimately divide it into the nascent daughter cells according to the following rules: 1) Each daughter gets exactly half of the chromatids. 2) Not just any chromatids! Each daughter cell requires one chromatid of each chromosome. No more, no less. And maybe the most important one, 3) Don’t. Break. Anything. Sounds easy? Far from it! Especially since the stakes are high: Because if you fail, you die (or are at least pretty messed up)…

 

Anatomy of a mitotic chromosome
Anatomy of a mitotic chromosome

To escape this dreadful fate, mitosis has evolved into this highly regulated process, which breaks down the high complexity of the task at hand into more sizable chunks that are then dealt with in a very precise spatiotemporal manner. One important feature of chromosomes is that its two copies – or sister chromatids – are being physically held together from the time of their generation in S phase until their segregation into the daughter cells in M phase. This is achieved by a ring complex called cohesin, which topologically embraces the two sisters in its lumen (we’ll look at this interesting complex in a separate blog post). This helps the cell to always know, which two copies of a chromosome belong together, thus essentially cutting the complexity of the whole system in half, and that before the cell even enters mitosis.

Actual mitosis is divided into five phases with distinct responsibilities: prophase, prometaphase, metaphase, anaphase and telophase (cytokinesis, the process of actually dividing the two daughter cells, is technically not a phase of mitosis, but still a part of M phase). In prophase, the nuclear envelope surrounding the cell’s genetic content is degraded and the chromosomes begin to condense, which means that each DNA double helix gets neatly wrapped up into a superstructure. Think of it like taking one of those old coiled telephone receiver cables (that’s your helix) and wrapping it around your arm. So ultimately, chromosome condensation makes the chromatids more easily manageable by turning them from really long seemingly entangled threads into a shorter (but thicker) package. At this point each chromatid is still connected to its sister by virtue of the cohesin complex (see above) at one specific point, which is called the centromere. It is this process of condensation of cohesed sister chromatids that is actually responsible for the transformation of chromosomes into their iconic mitotic butterfly shape that we all know and love. While our butterflies are forming, the two microtubule-organizing centers of the cell, the centrosomes, begin to split up and wander to the cell poles, beginning to nucleate microtubules. In prometaphase, chromosome condensation is complete and the centrosomes have reached their destination, still throwing out microtubules like it’s nobody’s business. During this whole time, their job is to probe the cytoplasm for chromosomes by dynamically extending and collapsing, trying to find something to hold on to amidst the darkness of the cytoplasm. This something is a protein structure, called the kinetochore, which sits on top of each sister chromatid’s centromere region. Once a microtubule has found a kinetochore, it binds to it and stabilizes. Not all microtubules will bind to kinetochores though, some of them will interact with the cell cortex or with each other to gradually form the infamous mitotic spindle, the scaffold tasked with directing the remainder of the chromosomal ballet. Chromsomes, which are attached to the spindle (via their kinetochores) will gradually move (driven by motor proteins like kinesins) towards the middle region of the mother cell and align on an axis, which lies perpendicular between the two spindle poles. This axis is called the metaphase plate and represents a visual mark for the eponymous phase. The transition from metaphase to anaphase is the pivotal moment of mitosis; the moment, when sister chromatids become separated (by proteolytic destruction of cohesin) and subsequently move along kinetochore-associated microtubules with the help of motor proteins towards cell poles. As such a critical moment, the metaphase-to-anaphase transition is tightly safeguarded by a checkpoint, the spindle assembly checkpoint (SAC), which ensures that every single chromatid is stably attached to the correct side of the spindle (we’ll go into some more details in another blog post). In the following telophase, the newly separated chromosomes begin to decondense, the nuclear envelope reforms and the cell membrane begins to restrict in anticipation of cytokinesis, when the two daughter cells become physically separated.

 

Overview over the five phases of mitosis.
Overview over the five phases of mitosis (click to enlarge).

To recap, the process of correctly separating the 92 chromatids of a human cell into two daughter cells is a highly difficult endeavor, which, however, the cell cleverly deals with by (1) keeping sister chromatids bound to each other, (2) wrap them  into smaller packets by condensation, (3) attach each of these packets to a scaffold a.k.a. mitotic spindle, (4) align the chromosomes along the division axis, so that each sister chromatid is facing opposite cell poles, and finally (5) move now separated sister chromatids along this rigid scaffold into the newly forming daughter cells. It’s a beautiful but at the same time dangerous choreography. While there are many mechanisms in place that protect the fidelity of mitosis, failure can have dire consequences, of which cell death isn’t the worst, as segregation defects can cause chromosomal instabilities, which are typical for tissues transforming into cancer. In future posts we will dive deeper into the intricacies of the chromosomal ballet, that is the centerpiece of the cell cycle, as well as the supporting acts that ensure the integrity of our life’s code.

 

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.

 

Have Yourself a Merry Literature Christmas

By Gesa Junge, PhD

 

Now that Halloween and Thanksgiving are over, it seems that the world is moving full-speed towards Christmas. And while TV has Christmas adverts and Christmas specials, and the frequency of Christmas songs on the radio has been steadily increasing, what does Christmas look like in the world of scientific publishing? Interestingly, a Pubmed search for “Christmas”, has over a thousand results with “Christmas” in the title.

Some of these papers focus on holiday-related injuries, such as burns or falls. For example, one study analysed burn injuries due to Christmas decorations-associated fires, and while these are fairly rare, the majority of them actually occur after the holiday, presumably due to trees and wreaths drying out and becoming more flammable. Researchers in Calgary observed that several trauma patients were injured while installing Christmas lights, and this along with statistics showing increased risk of falls during winter months, prompted them to study this correlation. Most people in this study fell off of ladders or roofs, and most patients were male and middle-aged. The study also found that several patients sustained serious injuries, with  20% of patients requiring admission to the ICU and the median duration patients stayed in hospital being just over 2 weeks (15.6 days, range 2-165). This

Another study looked into blood alcohol content after consumption of commercially available (notably not homemade) Christmas pudding for lunch, measuring ethanol content of the pudding and then calculating what the blood alcohol content would be immediately after pudding consumption and 30 minutes later. The maximum blood alcohol content did not exceed 0.05g/dL  and the authors conclude that “[h]ospital staff should feel confident that the enthusiastic consumption of Christmas pudding at work in the festive season is unlikely to affect their work performance […]”, as long as they ate less than 1kg of it.

There is also an interesting paper which addresses the question of how to win the Christmas cracker pull. This is a UK-based tradition, in which two people pull on opposite ends of a Christmas cracker until it splits into two uneven pieces, and the person who ends up holding the larger piece wins the usually completely useless plastic toy inside the cracker. The study distinguishes between three techniques: The QinetiQ strategy (two-handed pull, slightly downwards), the passive-aggressive strategy (two-handed grip, but letting the other person pull) and the control strategy (both sides pull approximately parallel to the floor). Turns out, the passive aggressive strategy is the one most likely to lead to a win (92% probability, 95% CI 0.76-1), at least with regards to Christmas crackers.

The results of the Christmas cracker and Christmas pudding studies are published in the same issue of the Medical Journal of Australia alongside a few other brilliant Christmas-related papers, one of which offers a diagnosis of “patient R”, suffering from a shiny lesion on his nose that severely affected his quality of life. The paper suggests lupus pernio may be the unifying diagnosis.

Finally, a group of researchers in Denmark set out to show that there is indeed such a thing as “the Christmas spririt”. This is not a well-defined state, but rather a generally joyful state brought about by decorations, food and smells associated with Christmas. The researchers showed people images with a Christmas theme (e.g. a street in the dark decorated with lights, or a plate of Christmas cookies decorated with a Santa figure and Christmas baubles) and similar images with nothing Christmas-associated (e.g. a regular street, or a plate of cookies on a kitchen counter with no decoration) while monitoring brain activity in a functional MRI scanner. They studied ten people who had celebrated Christmas from a young age (the Christmas group) and ten people who did not celebrate Christmas (the non-Christmas group). Both groups showed increased activity in the primary visual cortex when being shown Christmas-themed images compared to everyday images, but the Christmas group also showed greater activity in several brain regions that did not occur in the non-Christmas group, including the primary motor and premotor cortex, the right inferior/superior parietal lobule, and the bilateral primary somatosensory cortex. This suggests that people who have a strong association with Christmas traditions and celebrations respond differently to Christmas-themed images than people who have no association with Christmas. However, how exactly those brain areas bring about the mysterious Christmas spirit is not clear.

So in conclusion, please be safe when installing holiday lights and keep an eye on the candles, but do feel free to eat Christmas pudding while passive-aggressively pulling Christmas crackers, and if you still can’t seem to find the Christmas spirit, go get a functional MRI scan. Merry Christmas and Happy Holidays!

Science Holidays to Celebrate in 2017

 

By Deirdre Sackett

The holiday season is upon us! Whether you’re celebrating with family, friends, or your experiments, there’s no denying the festive spirit in the air. But, after celebrating the winter holidays, we scientists can continue the celebrations and look ahead to all the wonderful and weird science holidays of 2017. Mark your calendars!

Mathematical Holidays

Math is one of the most vital and oldest aspects of science, so it makes sense that there are holidays to celebrate its importance!

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  • Probably the most famous science holiday, Pi Day falls on March 14, 2017, which represents the first three numbers of Pi (3.14). Pi is a value that represents the ratio of a circle’s circumference to its diameter. People celebrate Pi Day by baking — you guessed it — pies.
  • Pi Days’ status as the most famous science holiday also brings with it some drama. Two other days contend with Pi Day’s fame: Pi Approximation Day and Tau Day. Pi Approximation Day falls on July 22, 2017, and represents the fraction that would equal Pi (7/22). Tau Day falls on June 28, 2017, and celebrates tau, the symbol that represents 6.28 (double pi’s value).
  • Want to celebrate a sensible measurement system? National Metric Week falls on the week of October 10th (the tenth day of the tenth month).
  • Mole Day celebrates Avogadro’s Number (the mole, 10^23 atoms of a substance) on October 23.
  • Pythagorean Theorem Day celebrates the famous equation we were all taught in middle school algebra. Just as a refresher, this theorem states that the square of the hypoteneuse of a right triangle is equal to the sum of the square of its two sides. In 2017, it falls on August 15, because 8*8 + 15*15 = 17*17. [/unordered_list]

 

Space Holidays

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  • Yuri’s Night falls on April 12 and celebrates Yuri Gagarin, the first man to go to space. Yuri’s Night is celebrated across the globe as a recognition of our achievements in space travel and looking toward humanity’s future as a space-faring species.
  • Probably the most unusual on this list, National Create A Vacuum Day falls on February 4. It’s a day to celebrate and understand the science behind vacuums — spaces where the pressure is lower than atmospheric pressure. Celebrators are encouraged to use their household vacuums to “create a vacuum”…and also clean their houses. [/unordered_list]

Nature Holidays

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  • Hagfish Day is October 18, and celebrates one of the ugliest creatures on the planet: the hagfish. The holiday is designed to help everyone appreciate the evolution of the hagfish, and to look past its unpleasant exterior – a valuable life lesson.
  • Coral Reef Awareness week is the third week in July, and celebrates the preservation of the world’s precious coral reefs.
  • Earth Day and Arbor Day are the most famous nature holidays. Earth Day is on April 22, and Arbor Day follows a week later on the 29th. You can celebrate these holidays by doing something nice for the planet, like planting a tree or cleaning up trash.[/unordered_list]

Science Education Holidays

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  • DNA Day is April 20, and is celebrated by scientists and educators worldwide. It falls on the anniversary of the human genome’s completion in 2003, and the discovery of the double helix structure in 1953. The day is dedicated to the knowledge and appreciation of DNA and genomics. The month of April is “Human Genome Month.”
  • Darwin Day is February 12, and celebrates Charles Darwin’s birthday as well as his theory of evolution.[/unordered_list]

Geeky Holidays

While not entirely scientific, these holidays can be celebrated by people who love science and nerdy things.

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  • May 4, 2017 is Star Wars Day. May the Fourth be with you!
  • Geek Pride Day falls on May 25, 2017. Get your geek on and celebrate all things nerdy![/unordered_list]

How Science Trumps Trump: The Future of US Science Funding

 

By Johannes Buheitel, PhD

I was never the best car passenger. It’s not that I can’t trust others but there is something quite unsettling about letting someone else do the steering, while not having any power over the situation yourself. On Tuesday, November 8th, I had exactly this feeling, but all I could do was to sit back and let it play out on my TV set. Of course, you all know by now, I’m talking about the past presidential election, in which the American people (this excludes me) were tasked with casting their ballots in support for either former First Lady and Secretary of State Hillary Clinton or real estate mogul and former reality TV personality Donald Trump. And for all that are bit behind on their Twitter feed (spoiler alert!): Donald Trump will be the 45th president of the United States of America following his inauguration on January 20th, 2017. Given the controversies around Trump and all the issues he stands for, there are many things that can, have been  and will be said about the implications for people living in the US but also elsewhere. But for us scientists, the most pressing question that is being asked left and right is an almost existential one: What happens to science and its funding in the US?

The short answer is: We don’t know yet. Not only has there been no meaningful discussion about these issues in public (one of the few exceptions being that energy policy question  by undecided voter-turned-meme Ken Bone), but, even more worryingly, there is just not enough hard info on specific policies from the future Trump administration to go on. And that means, we’re left to just make assumptions based on the handful of words Mr. Trump and his allies have shared during his campaign. And I’m afraid, those paint a dire picture of the future of American science.

Trump has not only repeatedly mentioned in the past that he did not believe in the scientific evidence around climate change (even going as far as calling it a Chinese hoax), but also reminded us of his position just recently, when he appointed  known climate change skeptic Myron Ebell to the transition team of the Environmental Protection Agency (EPA). He has furthermore endorsed the widespread (and, of course misguided) belief that vaccines cause autism. His vice president, Mike Pence, publicly doubted  that smoking can cause cancer as late as in 2000, and called evolution “controversial”.

According to specialists like Michael Lubell from the American Physical Society, all of these statements are evidence that “Trump will be the first anti-science president we have ever had.” But what does this mean for us in the trenches? The first thing you should know is that science funding is more or less a function of the overall US discretionary budget, which is in the hand of  the United States Congress, says  Matt Hourihan, director of the R&D Budget and Policy Program for the American Association for the Advancement of Science (AAAS). This would be a relief, if Congress wasn’t, according to Rush Holt, president of the AAAS, on a “sequestration path that […] will reduce the fraction of the budget for discretionary funding.” In numbers, this means that when the current budget deal expires next year, spending caps might drop by another 2.3%. Holt goes on to say that a reversal of this trend has always been unlikely, even if the tables were turned, which doesn’t make the pill go down any easier. Congress might raise the caps, as they have done before, but this is of course not a safe bet, and could translate to a tight year for US science funding.

So when the budget is more or less out of the hands of Donald Trump, what power does he actually possess over matters of research funding? Well, the most powerful political instrument that the president can implement is the executive order. But also this power is not unlimited and could for example not be used to unilaterally reverse the fundamentals of climate policy, said David Goldston from the Natural Resources Defense Council (NRDC) during a Webinar hosted by the AAAS shortly after the election. Particularly, backing out of the Paris agreement, as Trump has threatened to do, would take at least four years and requires support by Congress (which, admittedly, is in Republican hand). And while the president might be able to “scoop out” the Paris deal by many smaller changes to US climate policy, this is unlikely to happen, at least not to a substantial degree, believes Rush Holt. The administration will soon start to feel push-back by the public, which, so Holt during the AAAS Webinar, is indeed not oblivious about the various impacts of climate change, like frequent droughts or the decline of fisheries in the country. There was further consensus among the panelists that science education funding will probably not be deeply affected. First, because this matter usually has bipartisan support, but also because only about 10% of the states’ education funding actually comes from the federal budget.

So, across the board, experts seem to be a reluctantly positive. Whether this is just a serious case of denial or panic control, we don’t know, but even Trump himself has been caught calling for  “investment in research and development across a broad landscape of academia,” and even seems to be a fan of space exploration. Our job as scientists is now, to keep our heads high, keep doing our research to the best of our abilities but also to keep reaching out to the public, invite people to be part of the conversation, and convincing them of the power of scientific evidence. Or to say it with Rush Holt’s words: “We must make clear that an official cannot wish away what is known about climate change, gun violence, opioid addiction, fisheries depletion, or any other public issue illuminated by research.”

 

Immunotherapy: Using Your Own Cells to Fight Cancer – Part 2

 

By Gesa Junge, PhD

 

Part 1 of this post described passive immunotherapies like antibodies and cytokines, but there are also active immunotherapies, which re-target our immune system towards cancer cells, for example cancer vaccines. These can be preventative vaccines, offering protection against cancer-associated viruses such as Hepatitis B (liver cancer) or Human Papilloma Virus (HPV, cervical cancer). The link between HPV and cervical cancer was first described in 1983, and a vaccine was approved in 2006. By 2015, the incidence of HPV infections in women under 20 had decreased as much as 60% in countries that had 50% vaccination coverage, although it may still be too early to tell what the impact on HPV-associated cancer incidence is. There are also other factors to consider, for example screening programmes are also likely to have a positive impact on HPV-associated cancers.

Vaccines can also be therapeutic vaccines, which stimulate the immune system to attack cancer cells. To date, the only cancer vaccine approved in the US is Provenge, used for the treatment of metastatic prostate cancer. For this therapy, a patient’s white blood cells are extracted from the blood, incubated with prostatic acid phosphatase (PAP, a prostate-specific enzyme) and granulocyte macrophage colony stimulating factor (GM-CSF) in order to produce mature antigen presenting cells which are then returned to the patient and search and destroy tumour cells.

Many other therapeutic cancer vaccines are in development, for example OncoVax, which is an autologous vaccine made from a patient’s resected tumour cells. OncoVax has been in development since the 1990s and is currently in phase III trials. Another example is GVAX, an allogenic whole-cell tumour vaccine currently being studied in phase I and II trials or pancreatic and colorectal cancer. As an allogenic vaccine, it is not made from the patient’s own blood cells (like an autologous vaccine), and it does not target specific antigens but rather increases the production of cytokines and GM-CSF.

Another therapy which is based on re-programming the patient’s immune system is adoptive T-cell transfer. As with some cancer vaccines, a patient’s T-cells are isolated from the blood, and the cells with the greatest affinity for tumour cells are expanded in the lab and the re-infused in the patient. A recent modification of this technique is the use of chimeric antigen receptor (CAR) T-cells, where the T-cell receptors are genetically engineered to be more tumour-specific before re-infusion. This approached was especially promising in chronic lymphocytic leukaemia, where some patients experienced remissions of a year and longer. Later, CAR T-cells were also tested in acute lymphocytic leukaemia, where response rates were as high as 89%.

Finally, a new class of cancer drugs called immune checkpoint inhibitors has been making headlines recently, some of which are now approved for the treatment of cancer. Immune checkpoints are part of the mechanism by which human cells, including cancer cells, can evade the immune system. For example, the programmed cell death (PD) 1 receptor on immune cells interacts with PD1 ligand (PDL1) on cancer cells, which inhibits the killing of the cancer cell by the immune cell. Similarly, CTLA-4 is a receptor on activated T-cells which downregulates the immune response.

The first checkpoint inhibitor was an antibody to CTLA-4, ipilimumab, which was approved for the treatment of melanoma in 2011. PD1 antibodies such as pembrolizumab and nivolumab were only approved in 2014, and the only PDL1 antibody (atezolizumab) in 2016, so it is difficult to tell what the long-term effects of checkpoint inhibitor treatment will be. Numerous checkpoint inhibitors are still undergoing trials, most of the advanced (phase III) ones being targeted to PD1 or PDL1. However, there are other compounds in early trials (phase I or II) that target KIR (killer-cell immunoglobulin-like receptor) which are primarily being studied in myeloma, or LAG3 (lymphocyte activation gene 3), in trials for various solid tumours and leukaemias.

Immunotherapies all come under the umbrella of biological therapies. Biologics are produced by organisms, usually cells in a dish, unlike synthetic drugs, which are manufactured using a chemical process in the lab. This makes biologicals more expensive to manufacture. Ipilimumab therapy, for example, can cost about $100 000 per patient, with pembrolizumab and nivolumab being only slightly less expensive at $48 000 – $67 000. This puts considerable financial strain on patients and insurance companies. From a safety perspective, biologicals can cause the immune system to overreact. This sounds odd, as the whole point of immunotherapy is to activate the immune system in order to fight tumour cells, but if this response gets out of control, it can lead to potentially serious side effects as the immune system attacks the body’s organs and tissues.

All of these therapeutic approaches (antibodies, interleukins, vaccines, and checkpoint inhibitors) are usually not used alone but in combination with each other or other chemotherapy, which makes it difficult to definitively say which drug works best. But it is safe to say that collectively they have improved the lives of a lot of cancer patients. If you are interested in finding out more about the fascinating history of immunotherapy, from the discovery of the immune system to checkpoint inhibitors, check out the CRI’s timeline of progress on immunology and immunotherapy here.

 

Immunotherapy: Using Your Own Cells to Fight Cancer – Part 1

 

By Gesa Junge, PhD

 

Our immune system’s job is to recognize foreign, unfamiliar and potentially dangerous cells and molecules. On the one hand, it helps us fight infections by bacteria and viruses, while on the other hand it can leave us with annoying and potentially dangerous allergic reactions to harmless things like peanuts, pollen or pets. Tumor cells are arguably very harmful to our health, and yet the immune system does not always eliminate them. This is partially because cancer cells are our own cells, and not a foreign, unfamiliar intruder.

The immune system can recognize cancer cells; this was first postulated in 1909 by Paul Ehrlich and subsequently found by several others. However, detecting cancer cells may not be enough to prevent tumor growth. Recent research has shown that while detection can lead to elimination of cancer cells, some cells are not killed but enter an equilibrium stage, where they can exist undisturbed and undergo changes, and finally the cells can escape, if they have changed in a way that allows them to grow undetected by the immune system. This process of elimination, equilibrium and escape is referred to as “cancer immunoediting” and is one of the most active research areas in cancer, particularly in regard to cancer therapy.

Immunotherapy is a form of cancer therapy that harnesses our immune system to kill cancer cells, and there are various approaches to this. Probably the most established forms of immunotherapy are antibodies, which have been used for almost two decades. They generally target surface markers of cancer cells; for example, rituximab is an antibody to CD20, or trastuzumab, which targets HER2. CD20 and HER2 are cell surface proteins highly expressed by leukaemia and breast cancer cells, respectively, while normal, healthy cells have lower expression, making the cancer cells more susceptible. Rituximab was approved for Non-Hodgkins Lymphoma in 1997, the first of now nearly 20 antibodies to be routinely used in cancer therapy. In addition to this, there are several new antibodies undergoing clinical trials for most cancers. These are mainly antibodies to tumour-specific antigens (proteins that may only be expressed by e.g. prostate or lung cancer), and checkpoint inhibitors such as PD1 (more on that in part 2).

Initially, antibodies were usually generated in mice; however, giving murine antibodies to humans can lead to an immune response and resistance to the mouse antibodies when they are administered again later. Therefore, antibodies had to be “humanised”, i.e. made more like human antibodies, without losing the target affinity, and this was only made possible by advances in biotechnology. The first clinically used antibodies, such as rituximab, were chimeric antibodies, in which the variable region (which binds the target) is murine and the constant region is human, making them much better tolerated. Trastuzumab is an example of a humanised antibody, where only the very end of the variable region (the complementarity-determining region, CDR) is murine, and the rest of the molecule is human). And then there are fully human antibodies, such as panitumumab, an anti-EGFR antibody used to treat colorectal cancer. There is actually a system to labeling therapeutic antibodies: -ximab is chimeric, -zumab is humanised and –umab is human.

Antibodies can also be conjugated to drugs, which should make the drug more selective to its target and the antibody more effective in cell-killing. So far there are only very few antibody-drug conjugates in clinical use, but one example is Kadcyla, which consists of trastuzumab conjugated to emtansine, a cytotoxic agent.

Other examples of immunotherapy are cytokines such as interferons and interleukins. These are mediators of the immune response secreted by immune cells which can be given intravenously to help attack cancer cells, and they are used for example in the treatment of skin cancer. Interleukin 2 (IL-2) was the first interleukin to be approved, for the treatment of advanced melanoma and renal cancer, and research into new interleukins and their therapeutic potential is still going strong. Especially IL-2 and IL-12, but also several others are currently in clinical studies for both and various other indications, such as viral infections and autoimmune diseases.

In addition to passive immunotherapies like antibodies and cytokines, there are also active immunotherapies which re-target our immune system towards cancer cells, for example cancer vaccines. More on this, and on new drugs and their issues in part 2.

 

 

 

Putting The "In" in Industry: Top Tips for a Successful Transition

 

By Esther Cooke, PhD

 

The plight of early career researchers was magnified last month (October 2016) by demoralizing news features in Nature entitled “Young scientists under pressure,” and “Young, talented and fed-up….” New research shows that annual increases in science-related doctorates, coupled with flat-lining or faltering funding opportunities and full-time faculty positions, is creating stiffer competition and lower success rates for young scientists in academia. Unsurprisingly, more and more PhDs are exploring alternative avenues, notably within pharmaceutical/biotechnology companies.

Vice President of Diagnostic Development at Illumina, Karen Gutekunst, PhD shared insights with the Scripps Consulting Club on how to successfully flee to pharma.

Gutekunst completed her doctorate in molecular genetics at the Georgia Institute of Technology. Her first whiff of R&D in industry came from a headhunt call about a job in New Jersey. Although not ready to leave Atlanta, Gutekunst liked the idea of applying “tech” to real medical problems. She landed her first industry position at Roche and stayed with the company for 18 years, working in project management, development, and regulatory affairs. She then spent two years with Clarient before landing her current job. During the workshop, Gutekunst reflected on personal experiences to highlight key pieces of advice for grad students and postdocs considering a similar path:

 

  1. Be open to possibilities. We often hold back from opportunities because they don’t fully satisfy our criteria, or for FOMO – that is, fear of missing out – on the “perfect” job that could be just around the corner. Gutekunst advises to keep an open mind: “Don’t be afraid to branch out, as no decision you make is forever.” New opportunities will present, and things will happen in the future that you can’t plan for. It’s all good experience (even the application process) and could be an important step towards that dream job. To be successful in industry, Gutekunst admits, “You have to be willing to change direction on the fly.” Adaptability is a must.

 

  1. Broaden your skillset. Don’t be an out-and-out lab rat. Gutekunst emphasizes that transferable skills are just as important as research skills. “You need to be a well-rounded person to grow and succeed in industry. It’s not just about how smart you are,” she says. All of the applicants will be smart, so it comes down to how well you will fit in with the culture. Unlike academia, where for the most part you work independently on your own project, research in an industrial setting is much more collaborative – people work together for the good of the company. Look for creative ways to demonstrate communication skills, leadership and project management skills, problem solving ability, and teamwork.

 

  1. Learn the lingo. Familiarize yourself with insiders’ jargon and acronyms that you might run into during interviews, such as GLP, GMP and GCP (good laboratory, manufacturing and clinical practices, respectively). Gain an understanding of company frameworks and the processes of production, development, and life cycle management, bearing in mind that these may differ between small and large companies. Gutekunst suggests that you tailor your research: “If you’re interested in marketing, understand what product requirements are and why they’re important.” Once you’ve mastered the language, speak it with passion – you’ll need to be able to convince someone to give you a job!

 

  1. Network, network, network. This one gets drummed into us all of the time, and that’s because it really is important. “You never know what might come of a conversation,” says Gutekunst. Maintain good relations with your colleagues and collaborators, attend conferences, join clubs and societies, and get stuck into professional networking sites like LinkedIn. Be proactive in asking questions and reaching out to people; be willing to stick your neck out. Made connections already? Hold on to them! Speaking from experience, Gutekunst adds, “Connections lead to random phone calls, and random phone calls lead to jobs.”

 

  1. Don’t wait! When asked about the best time to make the transition, Gutekunst responds, “If you want to go into industry, I’d try to get in as quickly as you can.” The earlier you are in your career, the easier it is to get over the hump of academic stereotypes. It comes back to adaptability; employers are looking for candidates who will adjust quickly to their way of doing things, i.e. before the rhythms of academic research become ingrained. If you’re sure it’s the right direction, don’t wait for that next paper or fellowship – you’ll always put one more hurdle in front of you. Work with what you have, and get in!

 

  1. Believe in yourself. It’s as simple as that. Have confidence and don’t be intimidated!A career in industry is absolutely attainable for academic PhDs, but a smooth transition requires careful planning and consideration, with some gumption and flexibility thrown in the mix. Check with your graduate students or postdoc services office for more information and resources. If you’re struggling to make the call, the most important thing is to trust your instincts and strive to do what you love – you’ll be happier!