The Language of Scientific Discovery

 

By Asu Erden

Most of us are aware of the political controversies surrounding the human papillomavirus (HPV) vaccine. Some of us even have personal anecdotes relating to this highly charged subject. “I remember my aunt calling me to ask me about the vaccine. She was worried about what it meant for her children’s health and why her son should get an immunization aimed at preventing cervical cancer,” said Dr. Heather Marshall, a postdoctoral fellow at the Yale Department of Immunology. The confusion is all too common. As scientists, we have failed Dr. Marshall’s aunt and millions like her. In fact, the HPV vaccine has been extremely poorly marketed despite its astounding efficacy. The Centers for Disease Control (CDC) estimates that the quadrivalent vaccine offered in the US has an efficacy against genital pre-cancers and warts of nearly 100% in previously unexposed women, as well as 90% against genital warts and 75% against anal cancer in men. Despite the remarkable efficacy of the vaccine, not all parents in the US want to have their sons and daughters vaccinated. The scientific achievement that a vaccine embodies is not enough. This is one of the tragedies brought about by the failure of science communication. The HPV vaccine has been marketed towards young girls. Why has it not been made clear that both women and men should get the vaccine and that the early age of vaccination is only meant to increase vaccine efficacy? Men and women can actually be immunized up until the age of 26, after which it is assumed that you have most likely been exposed to one or more of the HPV strains that the vaccine protects against. In reality, you can still get the vaccine after this age. It will just not be as efficacious.

 

“The contribution of science is to have enlarged beyond all former bounds the evidence we must take account of before forming our opinions” wrote British biologist Sir Peter Medawar in Pluto’s Republic. In this day and age, the Internet provides readers around the world with a spate of resources – most of which not peer-reviewed – on just about anything. Unlike newspapers and books, blogs are most often not fact-checked. Just have a look at the Natural News blog and you’ll see how harmful misinformation disguised in a professional layout can be. As Dr. Marshall notes “a hundred years ago, it took weeks or months for a piece of scientific news to reach the other end of the country or the other side of the Atlantic. Fifty years ago it took a few hours or days. Twenty years ago it became one second but that sort of news still had a very narrow audience. Today you can literally reach 100 million people within a few seconds, which is really scary.” It is scary because it comes with a duty to inform that too many scientists choose to ignore out of frustration and because of the lack of any tangible benefits to their career. Dr. Schatz, professor of Immunobiology and Molecular Biophysics and Biochemistry at Yale, deplored that the connection is very tenuous between talking to students at local high schools and increasing interest and funding for scientific research. It inevitably comes down to scientists’ intrinsic motivations to go out there and share their research with the public.

 

As a graduate student at Yale and as a scientist, I find these realities challenging. I am unsure as to when I first came to realize the widening mismatch between how scientists talk to the public about their research and how they should talk about it. But this is something that every budding and established scientist is aware of. Yet we are seldom taught how to translate scientific concepts back into the vernacular. Science truly has a separate language that facilitates talking about complex concepts with peers that share the same premises. It is easy to forget that this has been taught to us and does not come naturally. I discussed this with Will Khoury-Hanold, a graduate student in my lab. His involvement with the Science in the News initiative – which trains Yale graduate students to give talks to high school students about a broad range of current scientific topics – taught him a lot in this regard. He described science as requiring a greater leap than other disciplines. “Anyone can pick up a history book and read about the elements that led to the Civil War. It’s not the same with science. […] With science, it’s about translating it back to English.” This is hard to do, and we often shy away from talking to the public. But in a world where Jenny McCarthy is hired by The View and has access to a 3 million viewer platform to spread her anti-vaccine views, scientists have to speak up and as loudly as they can to provide the public with fact-checked truths. Of course entertainers can aptly serve the cause: if you have not seen this vaccine-related video by Penn & Teller I strongly encourage you to do so. Nevertheless, the duty to inform the public about these matters should fall on scientists.

Scientists are partly responsible for the failures of science communication. Clearly, we have a tendency to revel in esoteric statements about our research and about science more generally. If you take the word “theory” for instance, its scientific meaning widely differs from its colloquial understanding. For non-scientists, a theory is something that has yet to be proven. For scientists, a theory is “a well-substantiated explanation of some aspect of the natural world that can incorporate facts, laws, inferences, and tested hypotheses […] theories do not turn into facts through the accumulation of evidence. Rather, theories are the end points of science. They are understandings that develop from extensive observation, experimentation, and creative reflection,” as pointed out by the National Academy of Sciences. Our arcane vocabulary makes it seem as though understanding science were a luxury. We need to use more accessible language so that such misrepresentations of scientific truths do not happen. Is it the fault of scientists that the HPV vaccine was poorly marketed? Perhaps not directly but we should have made it clearer to journalists why the vaccine is so important and how it is significantly reducing the incidence of cervical cancer. Another infamous example is that of the alleged correlation found between the measles, mumps, and rubella (MMR) vaccine and autism. While the study published by Mr. Wakefield in 1998 has been debunked and his medical license was stripped, most people still don’t know why his results were wrong. Not only did he not comply with the clinical trial rules for his study, the putative correlation he claimed to have found was based on a confounding factor. What is that you say? That would be an example of scientific jargon but what it really means is this: the MMR vaccine usually gets administered around the age of 2, which is also the age at which most children start speaking. One of the clearer symptoms of autism is to not start speaking when you are supposed to. Thus, autism inherently gets diagnosed around the age of 2. This is what underlines the correlation Wakefield reported. The confounding factor was the age of the children. When it comes down to their kids’ health, reminding parents that “correlation is not causation” achieves little. Having the population actually exposed to that concept more generally would achieve much more.

 

As Dr. Marshall emphasized, “a lot of the time it can come down to the scientist. If you had asked me [about it] a couple of years ago, I might not have said this as easily.” As scientists we never get properly trained to know how to answer that phone call we might get from journalists who under the pressure of publication might perform less than optimal fact-checking. By not being as clear as possible we inadvertently provide ground for sensationalism. But this reflects a broader failure to communicate science to the public. We live in a world where it is acceptable not to know what a gene is or how evolution actually works. To remedy this, scientists need to make concepts they are familiar with more accessible and report their research aptly.

 

 

But the language of scientific discovery and science communication is not solely beneficial to the public. It can help scientists better share their research with people beyond the realm of their own department. A good talk fosters cross-fertilization between fields. Scientists have a tendency to narrowly focus on their thought-processes and dig a deeper and deeper hole to burrow themselves into. As a result, we lose the forest for the trees. Many graduate students, postdoctoral fellows, professors, and department chairs have encountered this somewhere along the line. Insufficient training in writing and in giving public speeches results in science talks that fail to convey their points across. The problem is that scientists are asked to give many talks and presentations. What happens most often is that they regurgitate PowerPoints they prepared for specialists in their field and use them to give talks to an unspecialized audience.

 

The challenge and art of giving a good talk is to know your audience and to aptly choose the level of detail versus abstraction that suits said audience. “We as a species – by which I mean scientists –,” added Professor Schatz “are so programmed to show the data that it takes effort not to.” That skill is not just useful when communicating science to a lay audience. It fosters collaborations and thus important breakthroughs within the field of scientific research. Professor Schatz recalled an immunology meeting organized by the Federation of American Societies for Experimental Biology he was at a few months ago. One of the speakers at that conference was Dr. Margaret Goodell who specializes in the field of stem cell research and therefore stood out as not being an immunology-related speaker. She gave such an inspiring and thought-provoking talk that immunology professors were lining up to discuss potential collaborations with her lab. This does not happen when content prevails over format. At a time when knowledge within the sciences has become so specialized, collaborations become a necessity. If as scientists we are unable to communicate our research to people outside our field – whether they are scientists or not – we prevent such collaborations from budding. It also prevents good scientists from getting grants because they are unable to write well enough about their research.

 

Most scientists get into their field with the hope to increase the spectrum of human knowledge about the world surrounding us, even if only by a little bit. And most of us thrive on the possibility of understanding something about nature that no one had understood previously and of sharing it with the rest of the world. But somewhere along the line, this humanistic ideal wanes or at least no longer suffices. “You make a scientific discovery and you can’t wait to share it with your peers” said Will. Why this does not necessarily translate into a desire to talk about your research to the public remains somewhat elusive. So to those scientists out there, I must ask: do you remember your personal statement for college and for graduate school? You meant it when you said that you wanted to save the world by increasing our understanding of worm neurobiology or by curing cancer. Don’t forget it!

The Earth and Moon Have Been Reunited, and It Feels So Good

 

By Knicole Colon, PhD

 

There has been a long-held theory that the proto-Earth was plowed by another proto-planet about the size of Mars some 4.5 billion years ago, and out of the debris from that collision the Moon was born.  Models of this giant collision predict that the Moon’s composition should include a significant fingerprint of this other planet, which is commonly referred to as Theia (who in Greek mythology is the mother of Selene, the goddess of the Moon).  However, the Earth and the Moon have always appeared to be very similar (at least chemically), and there has been no direct evidence to support the existence of Theia… until now!  This new evidence comes from a very detailed analysis of lunar rocks that were collected by astronauts that landed on the Moon back in the 1960s and 1970s.  This study has been published in Science and was led by Daniel Herwartz.

 

You might be asking yourself, if we have had these rocks in our possession for decades, why are we just studying them now?  Well, lunar rocks have indeed been studied before.  However, earlier analyses were not sensitive enough to measure any differences between the chemical composition of lunar rocks and rocks from Earth, differences that would be evidence of Theia.  The new analysis by Herwartz et al. involved the use of advanced electron microscopes and a precise laser-based method for analyzing the rock samples.  The end result was the measurement of 12 +/- 3 parts per million more of a rare isotope of oxygen (oxygen-17) in lunar rocks than is found in rocks on Earth.  This finding is what supports the idea that the lunar rocks contain remnants of the planet Theia.

 

It is really not surprising to find evidence that a Mars-size planet collided with Earth in the early days of the Solar System.  For reference, Mars is about half the size of Earth, and there were likely many similar objects swinging around the Solar System during its formation.  This is because planets form out of a swirling disk of gas and dust that is orbiting around a star.  Planet formation is ultimately a very chaotic process, and objects continuously collide and get destroyed and debris gets formed into new objects, like the Moon.  However, because of this chaos, an alternative theory for differing oxygen isotope abundances in the Moon and Earth is that Earth may have initially had an oxygen chemistry similar to the Moon/Theia but was affected post-collision by an impact from a water-rich comet or asteroid.

 

This is only one argument against the evidence presented by Herwartz et al.  Some scientists are questioning simply the significance of their measurements, since its such a small difference (12 +/- 3 parts per million).  Regardless of whether the results from Herwartz et al. hold up, a debate like this can be good since it can inspire more scientists to pursue similar studies.  To me, it also brings to light another debate, which is really the conspiracy theory that the Moon landing was a hoax.  The study by Herwartz et al. involved analyzing rocks that astronauts brought back from the Moon.  Yes, astronauts did in fact land on the Moon.  No, the landings were not a hoax.  An argument I often hear is, if we did go to the Moon, why haven’t we gone back?  The answer lies in the facts: humans did land on the Moon not once, but six different times.  Humans have not gone back to the Moon since the 1970s for many reasons, including that it is expensive and that we are looking towards exploring new parts of the Solar System now, like Mars.  Plus, we are clearly still learning from those manned missions to the Moon that took place decades ago thanks to studies like that led by Herwartz.  Now we may finally have the first direct evidence to support the existence of Theia.  I will say that since these findings are somewhat debatable, maybe this is a good selling point to send humans back to the Moon.  I would not object to seeing that happen in my lifetime!

Top 3 Concepts in Becoming a Successful Networker

 

By Kelly Jamieson Thomas, PhD

 

Networking, the cultivation of productive relationships for employment or business, is undeniably vital to career development. Successful networking helps us advance our current career, develop a career outside our wheelhouse, and maintain relevance in our field of expertise.

 

As a teenager, I learned the importance of networking by accident. An acquaintance, who was leaving for college, was no longer be able to continue the summer business she started—teaching swim lessons to children. Initially, I met her through life-guarding and competitive swimming, but we stayed in touch outside of those experiences. Instead of shutting down her business, she taught me the nuances of instructing children and recommended her clients hire me. She was confident in recommending me because she knew I had the skill base (I was a certified lifeguard, had swum on a competitive team for 9 years, and babysat young children frequently) and I was actively looking for employment. Ultimately, I was able to continue her business, earn much more money than I would have life-guarding, and develop my teaching skills. Although at the time I did not recognize that it was networking that put me in the position to build my own business, I now fully appreciate how connecting with her and cultivating our relationship benefited us both.
Over the years since that successful venture in networking, I’ve learned that there are three key components to successfully networking. To become a successful networker: seek opportunities to actively network, make an initial and meaningful connection with others, and cultivate a long-term professional relationship. All three components are critical to developing a network that will not only benefit you, but, equally as important, also benefit those in your network.

 

Create Opportunity

Strategically place yourself in social situations that potentially expose you to other professionals with whom you may develop productive relationships. To do this, think outside the proverbial box. Expect that if you attend a career panel, you will have to vie for the attention of those with whom you’d like to connect. In those scenarios, it’s best to make contact at the very beginning of the schmoozing.

 

If you’re interested in becoming a writer or working in publishing, find a book signing that interests you at the local Barnes & Noble and attend. Not only will the author be there, but also most likely his/her publisher will be there. Sit down with one of the deans at your school, discuss your career after you graduate, and ask if he/she can connect you with alumni who currently work in the field in which you are interested. Look for Social Media Week events—they tend to have some that are science-focused. Attend DOC (drop out college) events if there are any nearby. When you are attending conferences at other universities, email scientists or deans with whom you would like to have a one-on-one conversation and ask them if they have any spare time to meet. If it’s industry that peaks your interest, look for career fairs before your graduation is imminent, and attend. Remember to connect with friends who work at companies that may have positions in which you’re interested and ask if they can connect you with their colleagues. Update your LinkedIn profile to include any experience that will strengthen your resume and help you to connect with professionals whose careers interest you. These are only some of the opportunities that may allow you to connect.

 

Make a Connection

Once you’ve found some unique opportunities to broaden your network, be sure to make a memorable connection. Always look people in the eye when you speak with them and dress appropriately for the event. I understand that as graduate students and postdoctoral fellows, the salaries are meager, but there’s no excuse for stained or messy clothes.

 

Often, at events that are obviously networking events, it seems impossible to speak with the professional you’d like to because everyone in the room is on the same quest. Act swiftly and attempt to find them at the beginning of an event. If they were already engaged in conversation, I would recommend against blatantly interrupting to inject yourself. Instead make eye contact, wait for a natural break in the conversation, and then introduce your self. If you’ve been standing by for a few minutes, offer something to the conversation that was already ongoing. Once you’ve had a few minutes to speak, don’t be shy about offering your business card and asking for theirs. Yes, even if you’re a student, have a business card. It’s inexpensive to have cards made and it demonstrates a level of professionalism that many lack. My card during graduate school had the school logo and name, my name with PhD Candidate underneath, mobile number, and email address.

Cultivate your relationship

Now that you’ve successfully connected with other professionals, stay in touch through emails, calls, or a chat over coffee. Occasionally, share your favorite articles and insights through email. Please be conscience of others’ privacy and if you must mass email, bcc your recipients so that you don’t share their email address with those they don’t know. Ideally, personal communication is best. If you publish, give a talk at a conference, or receive grant money, be sure to update your network. With communication regarding research that you know intimately, but the person to whom you’re explaining does not, be concise, clear, and brief. I’ve found that many people who aren’t scientists are interested in hearing about complicated research, but they don’t know the language of science. Find a way to communicate your accomplishments in a manner everyone can understand. This is not only much more interesting for your audience, but great practice for interviews and almost any career path.

 

Maintaining your network is similar to gardening. As every flower in a garden requires different amounts of light, water, and pruning, each professional in your network requires different types of communication. By consistently cultivating the network you’ve worked so hard to create, you increase the chance that when someone in your network hears about an opportunity that you’d love to interview for, they’ll contact you.

 

While networking may seem daunting if you’ve traditionally avoided professional social interaction, remember that many of those with whom you’d like to network were most likely in your shoes at one point. I’ve always found that people are happy to connect with and offer a helping hand to those that they find engaging and promising as professionals.

10 Must-See Microscopy Images: The Body

 

By Michael Burel

 

As they saying goes: “Beauty is in the eye of the beholder.” No, literally. It’s probably in your eye. At the microscopic level, cellular structures—such as those found in the retina—form breathtaking patterns, taking on color and shapes when combined with fluorescent markers and high-definition capturing techniques. Here are ten must-see microscopy images from the bodies of mammalians to flies.

 

1. Retinal ganglion cells from a mouse retina

Retinal ganglion cells (RGCs)
Josh Sanes, Harvard University
Image courtesy Cell Picture Show.

Retinal ganglion cells (RGCs) relay signals from the rods and cones in the eye to the brain. In this image, RGCs can be seen “pointing” to a single direction and respond best to objects that move in the direction that these cells point.

 

2. Epithelial cells in a developing mouse embryo

Evan Heller, Rockefeller University Image courtesy Nikon 2012 Small World Competition.
Evan Heller, Rockefeller University
Image courtesy Nikon 2012 Small World Competition.

This genetically engineered mouse embryo allows for the visualization of epithelial cells, showing the pattern of whisker placement on the face.

 

3. Crypts and villi of a mouse colon

Paul Appleton, University of Dundee Image courtesy Nikon 2006 Small World Competition.
Paul Appleton, University of Dundee
Image courtesy Nikon 2006 Small World Competition.

This 740-maginified view of the mouse colon was captured using two-photon excitation microscopy. Individual cells making up the villi can be seen protruding out of the screen.

 

4. Utricle from a mouse ear

Jeffery Holt, University of Virginia Image courtesy Olympus BioScapes 2006 Competition.
Jeffery Holt, University of Virginia
Image courtesy Olympus BioScapes 2006 Competition.

The utricle, located deep within the mammalian inner ear, uses small hairs to relay information regarding balance, motion, and spatial orientation.


5. Little skate embryo

Katherine O’Shaughnessy and Martin Cohn, University of Florida Image courtesy FASEB 2013 BioArt Competition.
Katherine O’Shaughnessy and Martin Cohn, University of Florida
Image courtesy FASEB 2013 BioArt Competition.

Researchers in developmental biology turn to cartilaginous fish like skates to understand how complex organisms arise from just a single cell. Little skates are useful in this endeavor because they can develop outside their egg casing, allowing researchers to observe organ formation and development as it occurs.

 

6. Fruit fly ovaries

 

Denise Montell, University of California, Santa Barbara Image courtesy Nikon 2012 Small World Competition.
Denise Montell, University of California, Santa Barbara
Image courtesy Nikon 2012 Small World Competition.

Nearly 85% of cancers derive from epithelial cells that line our organs, and when cancers become aggressive, they can lose their epithelial characteristics and metastasize. Fruit fly ovaries are an excellent model system to study this phenomenon as groups of epithelial cells detach and migrate during egg development.

 

7. Rat cerebellum

Hiroaki Misono, Doshisha University Image courtesy Olympus BioScapes 2006 Competition.
Hiroaki Misono, Doshisha University
Image courtesy Olympus BioScapes 2006 Competition.

This image taken with confocal microscopy shows a section through the rat cerebellum with different neurons and support cell types.

 

8. Blood vasculature from a mouse retina

Michael Bridge, University of Utah Image courtesy  Olympus BioScapes 2012 Competition.
Michael Bridge, University of Utah
Image courtesy Olympus BioScapes 2012 Competition.

In the developing retina, astrocytes (support cells of the nervous system) must establish a framework before blood vessels can grow, much like tracks must be laid down before a train can run. In this three-week-old mouse retina, blood vessels can be seen at different depths: red to green vessels form the primary layer while cyan to purple vessels form the underlying layer.


9. Early brain structures of a developing zebrafish

Michael Hendricks, National University of Singapore Image courtesy Nikon 2007 Small World Competition.
Michael Hendricks, National University of Singapore
Image courtesy Nikon 2007 Small World Competition.

Fluorescent markers reveal details of the midbrain and diencephalon, early structures in nervous system development, in a zebrafish embryo.

 

10. Muscle fibers in a developing fruit fly

Timothy Mosca, Stanford University Image courtesy Nikon 2012 Small World Competition.
Timothy Mosca, Stanford University
Image courtesy Nikon 2012 Small World Competition.

Sacromeres allow muscles to contract and relax, providing a means for locomotion. In this fruit fly larva, sacromeres appear as the thin, striped bands within the red muscle tissue along the body wall. Flying insects have sacromeres that are built with a limited range of motion to assist in wing movement during flight.

 

Is the Fountain of Youth in the Blood of Youth?

 

By Elaine To

Although the rumors of the Countess of Bathory bathing in virgin blood to restore her beauty are unfounded, there may actually be scientific merit in the myth. In two separate publications in the same issue of Science, researchers investigating aging have shown that blood, brain, and muscle tissues in elderly mice can be regenerated by the GDF11 protein found in the blood of young mice.

The researchers begin by creating parabiotic pairs of mice who are joined surgically to share a circulatory system. Pairs were created between mice of the same age (isochronic) or different ages (heterochronic), resulting in young-young (Iso-Y), old-old (Iso-O), or young-old pairs (Het-Y and Het-O). The young mice were 2 months of age and the old mice were 15 months old. After 5 weeks of being surgically joined, the mice were separated and their characteristics analyzed for the hallmarks of aging. Throughout the study, the Iso-O mice are compared to the Iso-Y and Het-Y to understand the effects of aging. Then the Het-O mice are compared to the other three and they are found to consistently resemble the Iso-Y and Het-Y mice more closely than the Iso-O mice.

In the first publication, the researchers focus on effects on neural and vascular cell and tissue regeneration. Neural progenitor cells identified by Ki67, Sox2, and Olig2 markers are noticeably decreased in the Iso-O mice, and Het-O mice recover these cell populations. Examining the olfactory bulb revealed that Iso-O mice have fewer newborn neurons, and Het-O mice have more than the Iso-O mice, though they don’t quite recapitulate neuron counts of the Het-Y and Iso-Y mice. When mice were exposed to small amounts of an aroma, the Iso-O mice ignored the stimulus while both the Het-O and Iso-Y mice spent time exploring the scent. This indicates that the Het-O and Iso-Y mice had greater sensitivity towards the smell.

Examining vasculature in the brain showed that Iso-O mice had lower blood vessel volume than Iso-Y and Het-Y mice, whereas Het-O mice were similar to Iso-Y and Het-Y. Iso-O mice also have much decreased cerebral blood flow versus Iso-Y, which is equal between Het-O and Iso-Y mice.

It became clear that the regeneration factor was in the blood serum, and GDF11 was identified as the responsible protein. 21-month old mice treated with GDF11 had increased blood vessel volume and Sox2 progenitor cells versus the untreated controls. GDF11 also increased the number of phosphor-SMAD2/3+ cells, showing that GDF11 acts through the SMAD/TGF beta signaling pathway.

The second publication focused on muscular degeneration in elderly mice. The stem cells responsible for muscle regeneration, especially after injury, are known as satellite cells. The Iso-Y, Het-Y, and Het-O mice had greater amounts of satellite cells than the Iso-O. Aging satellite cells were also associated with increased DNA damage and phosphorylation of histone H2AX. The Het-Y, Iso-Y, and Het-O mice had much less of both as compared to the Iso-O mice.

Treating elderly mice with GDF11 increased the frequency of satellite cells and decreased their DNA damage versus the untreated mice. There were also more regenerating muscle fibers after an injury. Electron micrographs of muscles showed fewer swollen mitochondria and more regular muscle fiber patterning in the GDF11 treated mice. There were greater amounts of PGC-1alpha, a regulator of mitochondrial biogenesis, and a greater LC3-II over LC3-I ratio, indicating enhanced autophagy. Lastly, the GDF11 treated mice had greater endurance while running and demonstrated greater grip strength.

This collection of papers provides strong evidence for GDF11’s ability to regenerate neurons, blood vessels, and muscles. While it may have potential to greatly improve quality of life for elderly individuals, further studies must first prove that these effects occur in humans as well and examine long term effects.

Disclaimer: we do not condone bathing in the blood of virgins, or anyone else for that matter!

 

Drosophila Diaries: Pray for Elves

 

By Michael Burel

 

Have you ever just sat down at your bench, put your head in your hands, and heaved a big sigh? (This is not a live broadcast of my current state, I swear). You sit for a moment—flanked by unread papers stacked high enough to be a booster seat for a small child at a restaurant and developed blots that look like they were sneezed on by someone with a sinus infection—wondering how in the world you will manage to get everything done. Your friend walks over and asks in a quiet, maternal tone, “…Is everything okay?”

 

You scream: “No, Barbara, everything is not okay!” You walk Barbara to your desk. “Do you see this to-do list?” You walk Barbara to the stack of papers. “Do you see these articles I still have to read?” You walk Barbara to your recently developed western blot. “Do you see the band at 75 kDa? Trick question, Barbara! The band is supposed to be there. And it isn’t!”

 

Aside from contacting human resources for an expedited transfer to a different lab, Barbara at least gets the idea that you’re overwhelmed. And surely she can empathize; after all, researchers are forced to simultaneously wear a variety of hats: The scientist (obviously this hat is just oversized goggles), the writer (awkward pencil-behind-the-ear), the conference socialite (your biggest, fakest smile), the presenter (an overtly positive attitude when confronted with questions you don’t know how to answer at the end of your talk), and the post-seminar food scrounger (a general disheveled, desperate appearance). Especially around this time of year, graduate students must also prepare for qualifying exams, compounding the already endless array of experiments left to complete before the exam can even take place. It’s soon a slippery slope to existentialism: Am I even qualified to be a scientist? Do I deserve to be here? What is my purpose…?

 

To avoid this potentially dangerous rabbit hole, wouldn’t it be nice if there were, I don’t know, five of you so that each clone were assigned certain tasks? Considering the ethics of human cloning are far from resolved (and the fact that you have self-trust issues and aren’t sure if Clone B can really crank out that proposal without intense micromanaging), there may be another solution: elves. Yes, elves. Tiny, magical elves (you can’t prove they don’t exist, so the possibility remains that they do, right?). Minions that know exactly what you want done, how you want it done, and when to get it done. Santa knows what’s up.

 

This installment of Drosophila Diaries will cover the gene Pray for Elves (PFE). Don’t worry; I’ve already anticipated your immediate question: “…Huh?” PFE was named for that same multitasking struggle shared by all scientists and the natural subsequent desire for magical elves. Let me explain:

 

FlyBase, the Fountain of Knowledge for Drosophila geneticists, is an enormous online bioinformatics tool with the explicit goal of annotating the entire Drosophila genome. This tour de force began in 1993 and has since seen several revisions through the tireless work of a consortium of Drosophila researchers. In 2002 while working on the third release of the annotated genome, bioinformatician Suzanna Lewis sent this e-mail  to the FlyBase community regarding one gene in particular:

 

[quote]The name for my gene is PrayForElves…It is the middle of the night (2:38 to be precise), I am away from friends and family, it has been this way for over 2 years, I can’t sleep because of all the work there is yet to do, and there is no end in sight. So when do the magic little elves appear out of nowhere and get everything done?
-S
P.S. I am serious.[/quote]

 

In compassion for her plight, the name stuck. Interestingly, the phenotype of mutations in PFE was not fully described until 2006 by Daniel Eberl’s group in their study of ocelli, which are three small photoreceptors located at the top of a fly’s head. A classical mutant called reduced ocelli had been established in the past, but what gene contributed to the malformation of ocelli in this mutant remained unknown. In their study, Eberl’s group mapped the mutations to the PFE gene where they explicitly stated in their manuscript: “Pray For Elves was named by Suzanna Lewis… [who] prayed for magic elves to help her finish her work.” (Yes, that was actually published in a scientific journal). Eberl’s group continued studying the genetic region in which PFE lies and named the immediately upstream gene elfless in homage to Suzanna’s original desperation, which will now probably live in infamy next to Legolas and Dobby.

 

Indeed, frustration takes many forms. It can make you more productive; it can make you want to quit everything and open a bakery; or it can make you hallucinate that Will Ferrell is actually from the North Pole and is here to help you with your experiments. Either way, feeling overworked and wishing for help is a commonality shared by all scientists. One just got lucky enough to have her prayers heard.

 

Jill Tarter: A Leader for the Search for Life Beyond Earth

 

By Knicole Colon, PhD

 

I first knew I wanted to become an astronomer when I was 12 years old.  The main driver behind my desire to study the universe came from watching the movie Contact, which was released in 1997 and stars Jodie Foster and Matthew McConaughey.  The movie (based on the book of the same name by Carl Sagan), tells the tale of a female scientist fighting for her right to conduct research on a topic she is passionate about: the search for extraterrestrial life.  She faces heavy opposition from both scientists and politicians who believe her research ideas are more like science fiction than fact.  Spoiler alert: eventually she detects an extraterrestrial signal that leads to her traveling through a wormhole and visiting the extraterrestrial beings.  However, things are complicated and not many people believe her trip through the universe actually took place.  There is much more to the story, and I highly recommend seeing the movie or reading the book.  The story offers a fascinating (and fairly realistic) portrayal of the life of an astronomer while also exploring the never-ending debate of science versus religion (in light of making contact with an alien species).  For me, the best part is that the female protagonist in the story (Ellie Arroway) was actually inspired by the real-life scientist Dr. Jill Tarter.

 

Dr. Jill Tarter, who is now 70 years old, has been involved with the search for extraterrestrial life ever since her graduate school years (in the 1970s) at the University of California, Berkeley.  She has been involved in various projects like SERENDIP (Search for Extraterrestrial Radio Emissions from Nearby Developed Intelligent Populations) and Project Phoenix (a search for extraterrestrial messages in radio signals).  The latter project was run by the SETI (Search for ExtraTerrestrial Intelligence) Institute, which Tarter helped found and where she was the Director from 1999 until 2012.  On top of that, she has received numerous awards and honors for her work, including being named one of the 100 most influential people in the world in 2004 by Time Magazine.  Clearly she has had a successful career, but not without some hardships.

 

Tarter’s career was just beginning in the 1970s, and she had to make her way through a field that was (and still is, but less severely so) dominated by males.  That alone is a daunting task, but then you add in trying to get funding for something that seems like science fiction — searching for signs of intelligent life beyond Earth.  In 1993 the  government decided to no longer fund SETI programs, so Tarter has been leading efforts to find private funding to support the research at the SETI Institute since then.  One major scientific breakthrough that has helped her cause is the discovery of extrasolar planets.  Before 1995, all the research at SETI was based on the statistical likelihood that intelligent life existed elsewhere in the universe, but there was no scientific evidence for planets that could host such life.  Now that over 1500 planets have been discovered orbiting other stars, astronomers at SETI are strategically searching stars that are known to have planets!  That makes this a very exciting time to search for signs of alien life.

 

These new prospects are in part what motivated Tarter to retire as Director at SETI and instead focus on the continuous task of finding funding for SETI research.  As she has discussed in recent interviews, the continued operation of SETI is important not just to know whether other intelligent life exists in the universe, but to know that it can survive and thrive for a significant amount of time.  If we can detect signs of intelligent life from a planet orbiting a star that is hundreds of light years away, then that gives us a glimpse of that civilization’s past (due to the time it has taken the signal to travel from that star and reach Earth).  Such a detection would suggest that advanced civilizations may be common and long-lasting, compared to the relatively young technological age of life on Earth.  Of course, a null detection would be just as significant.  That would suggest technologically-advanced civilizations are few and far between.  In either case, I think humans would be motivated to continue growing technologically because we will either know it is possible to survive, or because we will want to defy the odds by surviving.   Only time will tell what new discoveries will be made.  I have a feeling we will make a significant discovery in my lifetime, and I hope Dr. Jill Tarter is also able to enjoy the fruits of her labor!

 

What If Science Could Save the World?

 

By Florence Chaverneff, PhD

Despite the fact that science has been used as a diplomatic tool for decades, not only is the field of science diplomacy (SD) unbeknownst to the general public, but more surprisingly, as a quick survey among fellow postdocs revealed, to scientists themselves. To be sure, SD is at least as effective as the so-called ‘panda diplomacy’ long-practiced by China through gifting of members of the endangered species. China recently suspended this form of diplomacy with Malaysia following tensions over disappearance of airliner MH370 transporting many Chinese citizens. SD is no weirder than panda diplomacy. It can actually be quite a powerful and long-term diplomatic tool, albeit trickier to execute than panda gifting.

 

One thing in this world is sure, tensions between nations will always exist. John Lennon’s imagined world with “no countries […] nothing to kill or die for, and no religion too” and with “all the people living life in peace”, where conflicts would disappear, certainly is appealing. However, those values and causes people have been fighting for since the beginning of civilization have a good chance of sticking around, well…till the end of civilization. Therefore, it seems highly likely that diplomacy and diplomatic endeavors between nations and people will always be necessary. And what best way to go about such undertakings, than through science? As Louis Pasteur puts it:

[quote]Science knows no country, because knowledge belongs to humanity, and is the torch which illuminates the world.[/quote]

 

Science Diplomacy, you say?

What was the case in Louis Pasteur’s time still holds nowadays. Science, more so now than ever before, is part of a global culture, a universal truth, which rises above cultural and political differences. While it seems a constant challenge for politicians to gain the general public’s trust, scientists, thanks to the values commonly associated with scientific pursuit, have it easier. This is exemplified by a 2007 public opinion poll conducted in several Middle-Eastern countries, where, despite negative opinions on US politics, people viewed the US Science & Technology sector favorably. What are these values that are particular to scientists? Well, as scientists, we conduct our work with integrity and research ethics, intellectual honesty and sensible judgment. These values that are part of the ‘scientific method’ cannot be taught; they are both intangible and elusive, and are gradually acquired during one’s scientific training. Scientists are also problem-solvers, trained to think critically to resolve issues. These skills are particularly valuable in diplomatic endeavors, where tensions and differences need to be overcome, and where emotions and personal opinions need to be left aside so that agreements can be reached. Thus, science may act as a ‘soft power’, to establish lasting dialogue, and eventually peace and security between nations, in a way politics cannot.

 

Science Diplomacy: it works!

Interface between science and diplomacy occurs at three different levels: science in diplomacy, which consists in providing scientific advice to foreign policy actors, diplomacy for science, which is used to promote scientific cooperation, and science for diplomacy, which relies on ‘diplomacy for science’ to ease tensions between states.

 

Although some SD initiatives are directly related to peace-keeping efforts (e.g. curbing of nuclear proliferation and spread of biological and chemical weapons), others are purely scientific. One can gather hope in SD from the growing list of successful examples of large-scale international scientific collaborations, some of which involve countries at odds. These projects span the fields of physics (CERN or European Organization for Nuclear Research; ITER or International Thermonuclear Experimental Reactor with China and the US ), space science (International Space Station with Russia and the US; European Spatial Agency; European Southern Observatory http://www.eso.org/public/), biology (Human Genome Project  involving the US, China and Japan; International Cooperative Biodiversity Groups; Secretariat of the Pacific Regional Environment Programme) and climatology (International Climate Science Coalition). These are some of the most visible instances of international scientific collaborations, however, a plethora of smaller-scale efforts have led to valuable diplomatic accomplishments. In recent news, combined efforts between laboratories in China, the US, France and the UK yielded a synthetic yeast chromosome. Despite the long-running US embargo on Cuba hampering relationships between the two countries, an agreement for cooperation in the life sciences between Cuba’s Academy of Science and AAAS was recently signed. This agreement is based on Cuba’s thriving biotechnology sector and expertise in infectious diseases, both of which are of concern to the US where funding and scientific capacities could benefit Cuban research. An even more surprising example of SD, several years in the making, lies in capacity-building agreements between North Korea and the US to start scientific collaborations between the two countries, teach English to North Korean scientists, and enable their access to online scientific publication databases through a virtual science library. From these agreements, the US gains improved relationship with the belligerent and closed North Korea, who itself benefits by providing improved quality of life for its citizens. This case highlights a necessity for successful SD: all parties implicated need to benefit from the efforts in one way or another, provided they are achieved in a genuine manner, devoid of political undertones. Most countries around the world grasp the importance of science, technology and innovation for economic development, as evidenced by the often high percentage of Gross Domestic Product devoted to R&D, and might therefore be eager to engage in sustained SD efforts.

 

Who are the Science Diplomats?

Science diplomacy is practiced by a spectrum of institutions in the US, from non-governmental organizations (AAAS which has a center dedicated to science diplomacy and Civilian Research and Development Foundation), to non-for-profit organizations (NYAS, US National Academies) to universities (e.g. USC), think tanks (Rand Corporation, Brookings), consulates and embassies, to the government (USAID, US State Department, White House Office of Science and Technology Policy). This diversity in the nature of organizations practicing SD is a strength, as each institution brings its own capacities, network and agenda. Additionally, actors of SD from different sectors often cooperate to conduct their efforts. SD is a dominant part of the Obama administration and the state government’s mission to boost ‘cooperation in science & technology’. But what is necessary for SD to prevail as a bona fide diplomatic tool? First and foremost, SD needs to be recognized by relevant agencies as an effective avenue to reach their goals, so that they integrate it into their agenda. Critical areas where SD can be successful need to be identified, and a federal budget needs to be devoted to SD initiatives. Lastly, SD practices and language need to be developed. A noteworthy example of integration of SD in a country’s diplomatic agenda, which countries around the world could learn from, is that of Switzerland with Swissnex.

 

It doesn’t take belonging to one of these institutions to practice SD. Academic scientists can also do their part, albeit on a smaller, yet significant scale. Such efforts may be accomplished by establishing collaborations with researchers from countries experiencing difficult relations with the US, by maintaining communication with former labmates and collaborators that have returned to their home country, more generally, by harnessing the potential of scientific diaspora in the US.

 

I believe this is an exciting time to be doing research, as thriving technologies across different fields are offering unprecedented opportunities worldwide. So why not take our scientific training and use it to achieve another type of ‘greater good’ than pure scientific discovery?

 

 

 

Sensationalized Science

 

By Elizabeth Ohneck, PhD

 

In a recent Letter to Nature, researchers from the Scripps Research Institute announced that they had successfully engineered a bacterium that could recognize and replicate DNA containing an unnatural base pair (UBP). Their publication, entitled “A semi-synthetic organism with an expanded genetic alphabet”, demonstrated that E. coli could recognize, take up, and utilize man-made nucleotides to reproduce a plasmid containing a base pair of the synthetic nucleotides, faithfully replicating the UBP for over 20 generations (read more about it in our post about the paper).

 

The findings presented by the authors are incredibly exciting and have huge implications for future research in genetics, microbiology, and medicine. The presentation, however, is concerning. The authors refer to their strain of E. coli as “semi-synthetic.” Such a term could, for non-scientists (or even the scientist with a highly active imagination), conjure up images of some half bacterium-half robot, a sort of Frankenstein’s monster bacterium manufactured by man in the lab. What they actually have is a strain of E. coli carrying two plasmids, one that expresses an algal transporter able to import the synthetic nucleotides, and one containing the UBP. The introduction of plasmids into bacteria is a staple of biological research, and non-native proteins are regularly expressed in microorganisms from E. coli to yeast for countless research and industrial purposes. Are these microorganisms, then, also considered semi-synthetic? Referring to this E. coli strain as such actually does the findings a disservice, as part of what makes this report so exciting is that a common organism could recognize and utilize synthetic nucleotides with its own DNA replication machinery. The idea of an “expanded genetic alphabet” is also somewhat of a stretch, as the second plasmid contained a single UBP but was otherwise composed of canonical, naturally occurring A-T/G-C base pairs. This single UBP wasn’t utilized in any biological or genetic function; it was merely maintained during plasmid replication. Can we consider this UBP a true expansion of the genetic alphabet if it is not interpreted for inclusion in a bacterial function? Do the lofty terms used in the title sensationalize the story in an effort to attract an audience?

 

For trained scientists, this issue may seem minor; after all, would anyone outside of the research sector truly read or pay attention to this paper? If the research results become a news story, they might. In fact, the bigger problem is the communication of this research to the general public by the media, which further sensationalized the story. CNN even published an article entitled “New life engineered with artificial DNA.” One merely needs to glance through the comments section of the online article to understand the backlash of such a claim. Is this organism really “new life?” Is “artificial DNA” perhaps an overstatement?

 

The current climate of public attitude toward health science and genetic research is bitterly divided. Consider, for example, the well-publicized, acrimonious debates over vaccination, pharmaceuticals, and GMOs. Articles that imply scientists are “playing God” by “creating new life” only increase suspicion and inflame anti-science sentiment among groups already wary or contemptuous of health and science research. While it’s important to draw readers and sell stories, sensationalizing the science inhibits fair dialogue over the subject and detracts from the value of the scientific discovery.

 

The advancement of science needs public support – financially, politically, and even in terms of morale – which we can only gain through transparency and the communication of accurate information in the interest of educating the public. As research scientists, good communication starts with us. We have the responsibility to ensure our findings are clearly and truthfully conveyed to any audience, including among the research community. In turn, it is up to science writers and journalists to ensure the appropriate communication of scientific research to the public, in a manner intended to do more than sell stories. Science, itself, is sensational. Let’s not allow fabricated drama to take away from the excitement and wonder of scientific discovery.

DNA is made of A, C, T, G…X, and Y?

 

By Elaine To

 

In biology classes, everybody is taught that deoxyribonucleic acid (DNA, AKA the genetic information of a cell) has four and only four nucleotide bases. Adenine (A) and thymine (T) base pair together and cytosine (C) and guanine (G) base pair together. For the first time ever, researchers have expanded the genetic alphabet to include two additional bases: dNaM (X) and d5SICS (Y).

The researchers have previously shown that DNA polymerases, the enzymes responsible for replicating DNA, successfully replicate DNA containing the dNaM-d5SICS base pair. However these reactions were not carried out within living cells. The researchers decided to try this in the bacterium Escherichia coli due to the simplicity of the cells. Multiple factors had to be optimized in preparation for carrying out these reactions inside cells.

Firstly, the unnatural bases must be present inside the bacteria for DNA polymerase to use them as raw materials. Cells normally obtain A, C, T, and G from breaking down food or recycling previously used nucleotides. Both these pathways were not options for X and Y, so the researchers first tried passive diffusion across the cell membrane. Once X and Y diffused into the cell, they could then be phosphorylated by naturally occurring enzymes to their triphosphate form, which is the form that DNA polymerases recognize and use. The phosphorylation was unsuccessful.

The researchers then explored the idea of transporting the triphosphate forms (XTP and YTP) directly into the cells. Uptake of XTP and YTP by nucleotide triphosphate transporters from multiple other species was screened. The PtNTT2 transporter from the diatom Phaeodactylum tricornutum was most efficient at bringing XTP and YTP into the cells.

The next issue was the instability of XTP and YTP in the culture medium, especially when the E. coli were actively growing. Tests were first carried out on the natural triphosphate ATP. It was determined that addition of KPi to the culture medium increased ATP stability significantly and that KPi had the same effect on XTP and YTP.

And with that, the researchers were ready to generate their E. coli organism containing X and Y. They prepared two circular pieces of DNA, known as plasmids, which are easy to transport into bacteria. One plasmid contained the gene for the PtNTT2 transporter and the other contained a gene with an A-T base pair replaced by X and an analog of Y. Since YTP is the provided substrate, any newly produced plasmid will contain X and Y. This distinguishes it from the original template plasmid containing X and the Y analog.

After inserting both plasmids into the bacteria and growing them in KPi, XTP, and YTP containing medium, the plasmids were extracted from inside the cells. Analyzing the total nucleotide content with mass spectrometry showed that Y was clearly present. X was not detected, but it is known to fragment poorly and thus be difficult to detect with mass spectrometry.

To check the incorporation of XTP and YTP into the extracted plasmid, it was replicated in a PCR reaction using the natural nucleotides, YTP, and biotinylated XTP as substrates. The new product should contain biotin and thus react with streptavidin, which binds very strongly to biotin. As expected, streptavidin bound to the PCR product, confirming that the X-Y base pair is in the plasmid.

Sequencing of the plasmid shows that the nucleotide sequence is correct up until the expected location of the X-Y base pair. The sequencing reaction terminates at this location because there is no X nor Y provided in the sequencing reagents. This proves that X-Y is present in the right location in the plasmid.

In a series of landmark experiments, the researchers have shown replication of DNA containing an unnatural base pair inside living cells. The next step to be undertaken is the transcription of this DNA to mRNA and then hopefully translation into a functional protein. It is conceivable that the incorporation of X-Y into mRNA will soon transpire due to the similarity of DNA and RNA. Subsequently, work that has already been done in incorporating unnatural amino acids could be leveraged to facilitate the use of X-Y in codons that result in proteins.