Humans of Sackler: Patrick Davis, “I’ve been Accused of being a Science Robot”

Humans of Sackler, 23 March 2017

Patrick Davis, Neuroscience, Fifth-Year M.D./Ph.D. Student: “I’ve been Accused of being a Science Robot”

For this issue of Humans of Sackler, I had the opportunity to sit down with Patrick Davis, an M.D./Ph.D. student in the Neuroscience program. Although I see medical students coming and going around Sackler every day, I confess I haven’t gotten to know many of them – or much at all about the medical school curriculum. So it was a great pleasure to learn more about this from somebody who is as passionate about medicine as he is about science research; Patrick and I had a particularly engrossing conversation about the differences between these two kinds of higher education, and I hope you, dear reader, enjoy and benefit from it as much as I did!

 

Young Pat with the Chestnut Hill Academy Theoretical Physics Group

AH: How did you become interested in studying science?

PD: I had a physics teacher in 11th and 12th grade – Marty Baumberger – who was just the best teacher ever. He got me so into physics that I started a Theoretical Physics group at Chestnut Hill Academy… I went to Brown University as a physics major. I loved the open curriculum, but I was a terrible student. I didn’t do well my first year, so I switched to an economics major for about a year, and that was completely unfulfilling. Eventually I came to my senses and switched to biology… The thing about Brown: it’s chaos. There are no required classes, so you just mix and match and do whatever. There are requirements for your major, but you could theoretically never take a math class if you never wanted to. What happened to me was the best-case scenario: the first year and a half made me a more dedicated student. I learned that if I’m not doing something I really want to do then I’m going to be lazy, and if I don’t work hard then I’m not going to do well.

 

At a Macklis Lab get-together, chatting with friend and mentor Alex Poulopoulos (left)

AH: What was your first experience with neuroscience research?

PD: When I graduated from Brown, I didn’t know right away that I wanted to do med school or neuroscience. I ended up working at Jeff Macklis’s lab at Mass General Hospital for two years after college, and that was my first real exposure to neuroscience. Jeff made his name with a series of studies on induction of neurogenesis in the neocortex. I met Alex Poulopoulos there, who has been a mentor ever since, and a very good friend. I would credit Alex almost entirely with piquing my interest in neuroscience, but also with my development as a scientist. I love to come up with an idea, test it, go through the whole process myself, interpret my own data, talk to other people about their data – I like the actual scientific process. Alex just started his own lab at University of Maryland School of Medicine; anybody reading this, please apply to his lab! You could not ask for a better person to work for. He’s interested in how neural circuits self-organize, which is extremely interesting to me as well.

 

With pals from Brown University

AH: Why did you choose the M.D./Ph.D. path and how have your medical and scientific training differed?

PD: I could never be just an M.D. because I love science too much. The fundamental quality of a scientist is curiosity; medicine is more like service and helping people, curiosity about the people themselves, empathy. The preclinical years are a lot of memorization, but once you get into the hospital, it’s more like an apprenticeship. You’re learning how to do the day-to-day things that a doctor does: how to walk through clinical decision-making, interview a patient, present that information to other doctors, how to work with your hands if you’re doing a surgery rotation… Because medicine is an applied science, the goal there is all oriented around the health of the patient; I don’t think that’s really what science is about. For a long time, medicine has been done in a very parochial way: people in this hospital do it this way, people in another hospital do it another way. Evidence-based medicine still gets a lot of pushback. Take stenting for example: doing a coronary artery stent for someone with angina. About half of the stents in this country are done for stable angina – chest pain when you exercise, but not an acute threat to your health – and it’s now been shown over and over again that that is no better, and possibly worse, than just giving them statins and blood pressure reduction medication and telling them to eat their vegetables and exercise a little bit. It’s because doctors think in terms of, ‘I see it happen, it intuitively makes a lot more sense to me, so it must be this.’ Of course the lines are blurred in real life, but a true scientist would say, ‘We have to trust the evidence, why don’t we look at what’s causing the increased risk of doing the stent, or why do statins work?’ The curiosity that is absolutely necessary to be a good scientist is not necessary to be a good doctor… The types of mind that are selected for by these two professions are almost non-overlapping, they’re completely different.

 

Even science robots enjoy a night on the town every now and then

AH: What do you like to do when you’re not studying medicine or neuroscience, and how do you find the time and energy to do it all?

PD: I love to teach, I really like being in the didactic role and seeing people learn and discover things for themselves. I tutor for the MCAT, I used to tutor for the SAT, I’ve volunteered for things like middle school science fair mentoring and the Brain Bee. These kids in the Brain Bee were extremely impressive; they knew more facts for this test than I would have! Thomas Papouin and I also started a class trying to teach grad students the basics of the scientific method. There’s a whole rich history of how to think formally and scientifically; and the more aware you are of it and the more you practice it – like by applying these things to your own rotation project or qualifying exam – the better you get at it. The notion that, by just reading papers, this will happen – for some people, maybe it will, but the purpose of the program is to maximize the probability of this happening for everybody… I’ve been accused of being a science robot: the joke between Alex Jones and me is that when I get home, I have a scotch and read PubMed… The M.D./Ph.D.s that I’ve spoken to, the ones that succeed, are recharging one half of their brain while the other one works. Like a shark, like a science shark!

 

Relaxing by a picturesque mountain lake in the Cordillera Blanca, Peru

AH: Have you had many chances to travel outside of the U.S.?

PD: I’ve traveled through Europe a bit, I’ve been to Peru, Brazil… I was in Berlin at one point, and I decided to just hop on a train and go to Prague. I spent two full days and a night there, and it was awesome. Most of the people spoke English at tourist-type places, but it was fun to walk around, take pictures, be completely by myself… I had a Cormac McCarthy book called “All the Pretty Horses”, and it was nice just being on the train, reading or watching the sites, then walking around the city and going to a café for a coffee or beer. I don’t know much else about Prague, but aesthetically, I can’t imagine a prettier city. Part of why I enjoyed the city so much was because I didn’t expect it to be that way: of course when you go to Rome, you know that one of the greatest civilizations existed here and that every step you take is rich with history, but I didn’t expect this in Prague.

 

Enthusiastically sharing data at the Society for Neuroscience annual meeting

AH: What topic have you studied for your thesis work?

PD: Under Leon Reijmers’ mentorship, I’m trying to figure out how ‘extinction learning’ happens in the brain: it’s a medically-relevant type of learning that underlies treatment for psychiatric disorders like PTSD. In extinction learning, the patient repeatedly gets exposed to the thing they’re afraid of, you gradually increase the ‘stimulus intensity’, and they learn that it’s safe. So for example, if they’re afraid of spiders, you would show them a picture of a spider at first, then maybe have them in a room where there’s a spider in a corner, then work your way up to having them handle a spider. What I’ve found is that there’s a particular cell type in the amygdala – the parvalbumin interneuron – which acts a critical hub for this kind of learning: if you silence these cells, then you shut down the process of extinction learning. Now I’m using that finding as a jumping-off point to really figure out what’s going on. I’m manipulating parvalbumin interneurons with different frequencies of stimulation and seeing how the amygdala – and the rest of the brain – responds to that. It looks like I can ‘toggle’ the fear state up or down just by controlling this specific type of neuron!

 

Contemplating the mysteries of the universe

AH: Where do you see the field of neuroscience heading in the near future?

PD: I think that we have tools in neuroscience that 15 years ago, you couldn’t have even fathomed. Not just optogenetics, but recording techniques, chemogenetics, optical electrophysiology, simultaneous local field potentials with single units, closed loop systems… The engineers like Ed Boyden have done us a great favor. But now it’s time for us to step up. I think that in the next 2, 5, 10, 15 years there are going to be many, many discoveries that are really going to blow things open. Once we fall out of love with the mere application of modern tools to hypotheses we already kind of assumed to be true, then we’re going to ask the question: how? You have to record neurons’ endogenous activity, then do experiments that are really informative about what’s going on. In neuroscience, because we have these techniques, we can start asking this kind of question.

A guide to making effective protest signs

With the first ever March for Science two weeks away, a lot of us are sitting and scratching our heads thinking up the perfect rhyme, or the perfect punchline to write on cardboard that would express our outrage or our incredulity against proposed cuts for the NIH, or our passion for our favorite scientific topic, or even why science is awesome and important. We have so much to say, except there is only so much space on the cardboard or even the banner. Given that brevity is the mother of wit, we believe that you can come up with awesome signs for the March by yourself. However, we just wanted to provide some tips to help you along the way! If you happen to make a sign similar to someone else, don’t lose heart. Repetition = reinforcement, so it will show your solidarity with others. 

1. Use literary devices – Parallelism is a great way to get your message across and make it memorable. If you can make it rhyme, even better since it can turn your message into a chant! As the linguist Daniel Midgley describes, both parallelism and rhyming make slogans readable and memorable. In addition to rhyming, clever usage of common memes will also help making your sign memorable, such as the one below. 

Source: L May/Twitter

2. Be Positive – While the proposed cuts to the NIH budget may not sound funny at all and the future of scientific research looks bleak under this administration, negativity will not help win supporters. Instead, spin your negativism into a humorous catch-phrase that either expresses your incredulity (eg – “OMG GOP WTF”) or your positive attitude (eg – “We Are Better Than This”). 

3. Use Symbols – Your message can be personal and defined based on what you want to say, but  you can still express your solidarity with the overall cause by including the symbols of the protest (eg – the Boston March for Science has incorporated the official logo of the March for Science with its own twist by adding the Zakim bridge over it).

Official March for Science logo
Boston March for Science logo

4.  Focus on the Issues – Emotional reactions to President Trump and his proposed changes are inevitable. However, given that he has been in office for 3 months, it would not help to make signs that say “Not My President”. Instead, make sure your signs reflect the issues at hand – climate change, funding for scientific research, evidence-based policymaking, etc. Your sign should tell the rest of us about the cause you support in the specific context rather than a knee-jerk reaction, which may be valid but out of context. So, be informed about the specific goals of the march, and use those points to shape your message. 

5. Don’t be Partisan – Remember, it’s a non-partisan march, but it is not apolitical. Both democrats and republicans have utilized science as a tool to make political gains. However, this march is beyond petty partisan politics. This is something much more fundamental – it is about the defense of basic truths. While the anti-vaxxers and climate change deniers seem to support the Republican party more often than the Democrats, such issues affect all of us and the March for Science will not achieve its goals by displaying partisanship. Alienation is not what we need right now, but rather, we need to be able to win over the other side. 

Just a quick note – the March for Science is taking place on Earth Day, April 22. So PLEASE MAKE SURE you take your signs with you after the march, or recycle them and if you would like, help with clean-up afterwards. This is also our responsibility, not only as scientists, but also as members of society taking part in a civic and political action. 

Hope to see you all at the March, with your awesome signs.

For Science, In Solidarity!

GSC Committee & Club Updates: April 2017

Tufts Biomedical Business Club (TBBC)

from Aaron BernsteinCMP

Upcoming Events

TBBC Case Study Group: Mondays – 5-7PM, Jaharis 508

Practice solving cases, gain insight and tips, and learn more about the field of consulting.

TBBC Tufts Biomedical Alumni Speed Networking Night: Th Apr 13 — 6-8PM, Sackler 114

TBBC, in collaboration with the Office of Alumni Relations will be hosting a speed networking night! Meet fellow students and Tufts alumni who are working in the biomedical field from across all of Tufts campuses and programs, including Sackler, Fletcher, Medical, Dental, Nutrition, and the Gordon Institute. Mingle with old friends and new. We look forward to seeing you! Food and drinks will be served at this facilitated networking event.

TBBC Biotech BUZZ with Lily Ting: F Apr 14 — 9AM, M&V Lobby (Stearns 108)

Dr. Lily Ting is a life scientist and entrepreneur with 12 years of experience in academia and industry. Lily received her PhD from New South Wales University in Sydney and a post doc in the Gygi Lab at Harvard Medical School. After her experience leading projects in the academic sphere, Lily worked in a business development role at Athletigen and is now an Associate at PureTech Health. PureTech is a venture creation firm focused on bringing innovative solutions to the fields of neuroscience, immunology, and gastrointestinal diseases. She is also an avid dragon boat racer and just won gold, silver, and bronze in Puerto Rico!

TBBC Consulting Seminar Series: ClearView Heathcare Partners: Tu Apr 18 — 5-6:30PM, Sackler 507

Representatives from ClearView Healthcare Partners will speak to students about consulting and ClearView’s Connect to ClearView program for advanced degree candidates. 

TBBC, the Sackler Dean’s Office, GSC “Sackler Speaks” Flash Talk Competition: M Apr 24 — 5PM, Sackler 114

A well-developed flash talk is an effective tool to quickly and easily communicate your work to others. These take time to develop and usually evolve over a series of iterations. Sackler students will have a chance to give their scientific flash talks before a judging panel and other students. All presenters will receive helpful feedback and compete for nice prizes. This will be a low-key, fun event with appetizers and beer, and a chance to network with other students and professionals.

Recent Events

TBBC Biotech Buzz with Joel Batson, PhD, of RA Capital

F Feb 24: TBBC hosted Joel Batson, Science Project Manager at RA Capital. Joel introduced students to a new web-based tool he is developing and offered students the opportunity to collaborate with him and his team.

TBBC Career Seminar: Teresa Broering, Director of R&D, Affinivax

Tu Apr 4: Teresa Broering, current Director of R&D at Affinivax, a Cambridage, MA-based company developing a next generation approach in vaccine technologies, and former Director of Immunology at AbVitro as well as Senior Director of Product Discovery at MassBiologics, joined us for a discussion of her career path and her current role with Affinivax, and the current state of the biotech industry.

CMDB and Genetics Programs Come Together in Portland, Maine

For the first time, the Genetics and CMDB programs came together for a retreat in Portland, Maine for the snow and slush-filled weekend of April 1st. The retreat brought together students from different programs to interact and learn more about one another’s’ research, as well as students from different campuses. Both the Boston and the Bar Harbor Jackson Laboratories contingents made it to Portland to join the Scarborough Maine Medical Research Center Institute (MMCRI) folks for a weekend of science and camaraderie. Students and faculty gave brief talks on their work, followed by a poster session and a fantastic keynote speech on storytelling was given by Christine Gentry. Read on for details on the weekend, written by Jessica Elman (CMDB, Boston Campus), Jessica Davis-Knowlton (CMDB, MMCRI), and Alexander Fine (Genetics, JAX).  

We kicked off the retreat with a marathon of 16 talks given by students in year four and up from the CMDB and Genetics programs. Given the challenge to present a summary of their work in seven minutes or less, the students delivered with presentations that were brief but pointed. Three winners were selected by Philip HInds, Ira Herman, and Rajendra Kumar-Singh for their exceptional clarity, creativity, and concision.

In third place, Melissa LaBonty, a 5th year CMDB student in Pamela Yelick’s lab, presented on her work studying Fibrodysplasia Ossificans Progressiva (FOP). In this rare and severely understudied disease, an abnormal wound repair mechanism results in bone ossification in soft tissue after damage or injury. LaBonty is working with zebrafish to create a model of FOP, which will help to better characterize the disease and understand the underlying mechanisms that drive its progression. In her presentation, LaBonty spoke clearly and at an even pace, with assisting powerpoint slides that displayed only the most essential words: together this style helped keep the group focused on her story and contributed to her ranking as one of the best speakers of the day.

 

Siobhan McRee, a 5th year Genetics student in Philip Hinds’ lab, came in second among the student presenters. McRee talked about her work in which she is elucidating the roles of different Akt isoforms in BRAF-mutant melanoma. Though this cancer is initially responsive to the drug Vemurafenib, which specifically targets cells with a BRAF-mutation, cells with other driving mutations manage to survive the drug treatment and clonally expand, resulting in significant and potentially deathly relapse of disease. Ultimately, McRee’s work will help to better understand how the Akt signaling pathway is involved in this disease and may result in more therapeutically targetable molecules. McRee’s story logically built from general facts and understanding of BRAF melanoma to ultimately culminate on more specific data showing her findings thus far as well as their implications. Furthermore, her even pace and well-organized slides made her an especially great presenter that day.

Coming in first place was Kayla Gross, a 4th year CMDB student in Charlotte Kuperwasser’s lab. Gross’s work involves understanding how aging contributes to the breast cancer development, and why certain subtypes of breast cancer are more prevalent in the aging population. Given the prevalence of breast cancer, the impactfulness of Gross’ research is immediately obvious. She worked with an aging mouse model to characterize their mammary tissue as well as performed an RNAseq experiment to uncover molecular mechanisms that might be differentially expressed in young and aging mouse tissue. Gross presented her data in a logical progression, and used illustrative cartoons and animations to her advantage to keep her audience focused and to get her point across. Besides for her brilliant and captivating powerpoint, Gross stood out for her speaking style: she had clearly chosen her words to be concise and to the point, which allowed her to make the most of the seven minutes allotted to her.

All in all, the student presentations were remarkably impressive: in just seven minutes, all the participating students managed to convey the most critical and interesting components of their research. This was a great opportunity for everyone to learn a little bit more about what our colleagues are working on, as well as a chance to practice our “flash talk” skills, which will come in handy whether it’s at a job interview or at Thanksgiving table when your uncle asks you to explain what you’re doing in graduate school for the third time.

The Story Collider’s Christine Gentry, PhD as keynote

It was suggested by Terry Pratchett, Ian Stewart, and Jack Cohen in The Science of Discworld II: The Globe that perhaps Homo sapiens as a name for our species is a bit of a misnomer considering we are not omnipotent beings. They suggest Pan narrans, the storytelling ape, because we gain understanding by fitting facts into a larger narrative rather than collecting and storing millions of pieces of disparate information.

As communicators of new knowledge to the world (i.e. our scientific findings), it is important for us to keep the nature of our listeners in mind. In her keynote presentation to the retreat, Story Collider’s Christine Gentry, PhD encouraged us all to think about how to frame our narratives to be more approachable and demonstrated some methods of drawing in an audience.

She immediately captured our attention and sympathy by describing the challenges she faced in a wending career path that started with her geek excitement to bring a black widow spider to her Texas elementary school show-n’-tell, traversed through public outreach on the topic of zoology, and has landed at teacher/storyteller in Boston.

She required us to engage with her material by highlighting snippets of stories that we examined in small groups to find the element that made them compelling. We saw that admitting to vulnerability helps to humanize us to our audience in the story from a researcher who relies on fresh donor tissue, that self identity makes us more honest in the story from a researcher who decided not to cover her tattoos, and that we can surprise our audience by not sticking to script in the story from David who refused to tell the inspiration arising from conflict story that reporters sought to box him into. The thread tying all these stories together is that at the core they are about relationships with others, ourselves, our work, and with the larger community.

Perhaps the most memorable take-home point from her talk is that anecdotes do not equal stories. The response to most anecdotes is naturally “so what?” In order for an event or experience to be a story, it must have changed you: “I was callus, this event happened, and now I am more thoughtful” rather than “I am amazing, I did this, and I am still amazing!”

Scientific inquiry must be done in an objective manner and it is imperative that we remain unbiased as possible when we review scientific evidence, but there is room for us to inject our personalities into our presentations and relate our findings to the people who care. Now it remains to us to decide when to do so and to what degree.

On Sunday morning, we took a break from data and lectures; it was time to start working together. The purpose of this retreat was cross-program cooperation, and in our final event of the weekend, we put that goal into action. We separated into breakout sessions, not by program or campus, but by what we are interested in. These small group discussions were designed to get people together with various strengths and experiences to think about how to solve some of the challenges that graduate students face.

So what are graduate students at Sackler interested in discussing? The topics of these breakout sessions varied. Some sessions focused on day-to-day problems that a graduate student might face, like using CRISPR/Cas9 or selecting a sequencing platform. In the CRISPR discussion, participants came to the conclusion that there are no specific shared standards for all the applications of CRISPR and identified strategies to address potential off-target effects.

Other discussions centered on how to accomplish broader training goals, including grant writing, mentoring, and communicating in science. The grant writing section reviewed general writing strategies, like setting short-term, realistic goals, and shared a need for a formalized grant-writing course at Sackler. The mentoring/leadership session discussed existing programs at Sackler where a student can find a mentor, like the Tufts Mentoring Circles and the Tufts Biomedical Business Club. Students expressed a need for a more accessible alumni network, including cross-institutional resources. In the scientific communication group, students were urged to get on social media platforms like LinkedIn, Twitter, and ResearchGate.

In two of the largest breakout sessions, participants concentrated on solving larger scale problems: designing coursework for a modern graduate program in biology and bridging the gap between science and medicine. To help bridge the gap between scientific research and medicine at Tufts, the discussion group recommended that faculty members be identified that can connect labs with clinicians and tissue banks. In addition, access to a course that provides a basic orientation to clinical research would benefit many students at Sackler. In the session on coursework for a modern graduate program, one topic became the clear center of the discussion: computational biology! Whether students had struggled through teaching themselves or were currently stuck with a dataset they didn’t know how to analyze, everyone in the room agreed that coursework in computational biology was crucial for a graduate student’s success in modern biology. In addition to new coursework, students from both programs expressed a need for a revision and update of their first year coursework.

While all of the breakout sessions at the retreat were productive, they are meant to be starting points for continued discussion and collaboration. This retreat should be the springboard that leads to action across programs and institutions. Sackler students are lucky to be in programs that span multiple states, campuses, and research focuses. The cross talk between these groups will make each of our programs stronger and better prepare us for our careers in the future.

What Scientists Can Learn From Fiction Writers

Scientists don’t often think of themselves as writers. Our employment responsibilities do not include crafting characters or building worlds from words, nor investigating the latest political scandal, nor travelling the globe and composing reflections on our experiences. Yet, we do write: grants, reports, manuscripts. It is how we distribute our knowledge and the science we have done, because graphs and images and data have little impact if not shared. We write and revise as much as any journalist or novelist; still, writer isn’t an identity most scientists would primarily claim.

We are, though. Scientists are writers. Scientists are storytellers. Each graduate student, post-doc, faculty member has a story they are telling through their science. The scale and impact differs, but the fact remains: we must spin a tale convincing enough for our science to be funded, to be published, to matter. We are  writers, and we don’t even realize it.

I was trained to be a writer in the classical sense, specifically fiction writing. There were certain lessons that we learned over and over again, because they were fundamental to crafting even the most basic story. What fascinates me is that I have encountered these components informally in my graduate school training, just in the guise of doing good science.

We use basic story structure in writing articles: our beginnings ask a question, which we then try to answer in the middle, and our ends show how we have changed our little corner of the science world with our answer. There may even be a cliffhanger in there–alluding to a sequel coming soon to a journal near you!–if we’ve created even more questions with our answer. Grant writing uses a similar structure, with more emphasis on the cliffhanger. Leaving your reader on the edge of his seat, wondering what could come next, is something both scientists and fiction writers want (equally for the validation of having intrigued your audience and the satisfaction that such engagement often results in financial investment).

Show, don’t tell. Rather than telling a reader that a character is angry or sad, a writer should describe the character’s balled-up fists or tear-stained cheeks. For scientists, our equivalent of ‘telling’ is ‘data not shown’–and we all know how much we should avoid that. We do our showing in our figures. A scientist knows that the more data you can include, all the better. A scientist also knows that the more visually appealing your data is, the better it represents your conclusions. No one likes to read tables, right? Those data become so much more interesting as a pie chart, a graph, or a schematic. We show as much as we can, and tell as little as possible, because the best case scenario is when the data speaks for itself, instead of the scientist speaking for it.

Stories are much more interesting when they start in media res, or in the middle: no boring leadup, no extensive exposition. It is why publications often start with describing a hit or two they discovered from a screen, instead of the million little steps that led up to and happened during the screen itself. Good papers do that, and so does good fiction. The first Harry Potter book does not walk the reader through Harry’s childhood; it just starts right at the moment his life is about to change. Relevancy and immediacy are key components to telling any story, and scientists know and practice these principles to the best of their ability.

Crafting things out of thin air to make a story is a staple of fiction, but we know that as data fraud in the science world. The ‘characters’ in our scientific writing, the ‘plot’, the ‘setting’, the ‘rising action’, the ‘falling action’, all of those things have to be based on facts and evidence, on carefully planned and painstakingly executed experiments. They are based on reality. We know this; every scientist knows this. What we as scientists may not realize, however, is the extent to which fiction writing is also rooted in reality. Creating characters or worlds out of thin air is in actuality rarely done. The foundation of so many characters–ordinary or fantastical–come from experiences and observations within the writer’s own realm. It is a different way of collecting and representing evidence, a different way of asking or answering a question about the world. This reality-turned-fiction is one of the best ways a novel writer can build a sense of believability even in the most far-fetched fiction. It also builds trust between author and reader, one of the most important–and difficult–parts of fiction writing. Scientists have these components within their works as well, though constructed and strengthened in a different manner. Trust in science is built through executing proper and thorough controls, validating via different experimental methods, and considering (and hopefully, systematically eliminating) alternate theories or explanations. So regardless of the method in which they are built, that believability and that trust are critical components to any story, be it science or fiction.

Fiction writing, creative nonfiction writing, journalistic writing are all still very different beasts than scientific writing. Still, it would benefit scientists to focus less on the differences and more on where our often polarized fields actually do intersect. So much of our work is to provide convincing answers to difficult questions, and that type of evidence-based persuasion can be drastically more powerful if we use the same tools that traditional writers do. Scientists need to learn these tools as undergraduate and graduate students through formalized, structured, specified, and required coursework. That training will carry us, and our work, miles farther in graduate school and in our careers beyond. We need to be trained as writers, maybe as much as we are trained as scientists. Communicating our work in a persuasive and captivating manner is more important the ever, given the disturbing loss of faith in evidence-based arguments. We, as scientists, need to win that trust back, and to do so, we better be able to tell one hell of a story–to our funding institutions, to our public–about our science. For science to progress, we need our stories to be loud, to be spellbinding, to be believed and trusted by the public. We need to be writers, otherwise we might one day read a story about science that starts with once upon a time…

 

 

 

 

 

 

 

 

 

 

 

PubMed Tip of the Month…Search or Filter by Funder

Funding information is recorded in two fields in a PubMed record: Grant Number and Publication Type. Limiting a search to these fields can help you find articles that were supported by a specific grant, funder or type of funder (e.g. non-U.S. government).

  • Grant Number: The Grant Number field records grant or contract numbers as published in the article, or derived from PubMed Central as a result of the NIH Public Access Policy. To find articles funded by a particular organization, search the Grant Number field for the organization’s name, acronym or 2-letter code (click on link above for complete list funding agency names, acronyms and codes). For example, to find studies supported by the National Institute on Aging, search PubMed for: AA[gr].
  • Publication Type: Medical Subject Headings (MeSH), the standardized terms used to describe articles for MEDLINE, include Publication Types to identify financial support when that support is mentioned in the article. A list of publication types, including those for Research Support, can be viewed from the link above. To filter a search by one of the funding Publication Types: in the left-hand column of a results page, click ‘Customize’ under Article types. Scroll down and check the box next to the types of Research Support you would like to view. Click ‘Show’. The types of research support that you selected should now be visible under Article types. Click the research support type to filter your results.

Notes from the Library…Finding Funding & Writing Grant Proposals

Finding funding and writing grant proposals is a necessary, time-consuming, and at times frustrating, part of doing research. Our ‘Finding Funding & Writing Grant Proposals’ guide lists resources available at Tufts and beyond for locating funding opportunities, discovering projects that have been funded, and writing grant proposals. The full guide can be viewed at: http://researchguides.library.tufts.edu/findfunding. Here are a few highlights from this guide:

Finding Funding

  • COS Pivot: Comprehensive database of national and international funding opportunities from government and private funders. Advanced search features allow you to restrict your search to a particular funder, funding type or applicant type (e.g. graduate student). Profiles section may help you identify potential collaborators within or outside of Tufts. Use your Tufts email address to create an account, which will allow you to build a profile, view potential funding matches, save searches and schedule funding alerts.  Log in with Tufts username and password for off campus access.
  • Graduate & Postdoctoral Extramural Support (GRAPES): Compiled by the University of California at Los Angeles, GRAPES is a database of scholarship, grant, award, and fellowship opportunities for graduate students and postdocs.

Discovering Funded Projects

  • National Institutes of Health RePORTER: Research Portfolio Online Reporting Tool Expenditures and Results (RePORTER) is a searchable database of research projects funded by the NIH as well as the Centers for Disease Control (CDC), Agency for Healthcare Research and Quality (AHRQ), Health Resources and Services Administration (HRSA), Substance Abuse and Mental Health Services Administration (SAMHSA), and Department of Veterans Affairs (VA).
  • National Science Foundation (NSF) Award Search: Complete data on active and expired NSF awards from 1976 to present; some information available for pre-1976 awards.

Books on Writing Grant Proposals

  • The Grant Application Writer’s Workbook: This popular workbook guides applicants through a NIH grant application, providing examples of each component of the application. Updated to reflect recent changes to application requirements.
  • Guide to Effective Grant Writing: How to Write a Successful NIH Grant Proposal: Covering all aspects of the proposal process, from the most basic questions about form and style to the task of seeking funding, this book offers clear advice backed up with excellent examples. Based on the author’s experience serving on NIH grant review panels, it covers the common mistakes and problems he witnessed while reviewing grants.
  • Writing the NIH Grant Proposal: Hands-on advice that simplifies and demystifies writing a NIH grant proposal.

On the Shelf…The New York Times

The New York Times

Tisch Library in Medford recently subscribed to The New York Times academic pass program. This means that Tufts students, faculty and staff can register for a personal account to access The New York Times from their computer or mobile device, on and off campus. For instructions on creating a personal account using the Tufts academic pass and answers to FAQ about our access, see this page: http://researchguides.library.tufts.edu/nytimes.   Note: When creating an account, be sure to choose the correct link based on your location when registering (i.e. on or off campus).

CAR-T from A to Z

Often touted as a “miracle therapy” for certain cancers, CAR-T treatment has created a lot of buzz in the immuno-oncology field. There are over a hundred CAR-T clinical trials open in the U.S. and the first commercial CAR-T could possibly be approved by the end of this year. Initially, the advent of the therapy in 2012 had some warranted safety concerns. The technology is inherently aggressive and can become unruly if not it’s not properly monitored. For this reason, the first clinical trials of CAR-T created damaging side effects and in some cases the therapy was associated with patient deaths. However, therapy design has been revamped over the past five years and researchers are finding ways to dampen the level of toxicity the therapy produces. Despite the risks associated with CAR-T, clinical trials have shown to be effective at treating the targeted cancer. Recently, clinical trials have shown remissions rates of up to 94% and as a result the therapy has attracted millions of dollars from investors. Although the technology is not perfect, there is optimism in the field that CAR-T can radically improve cancer patient care.

CAR-T treatment involves the infusion of transgenic T-cells that express a Chimeric Antigen Receptor (CAR) on their cell membrane into the patient. The most common procedure involves isolation of the patient’s own T-cells, which are then genetically modified and expanded in vitro. These transgenic T-cells are then infused back into the patient to specifically target tumor cells. The CAR-T receptor of the transgenic T-cell contains three domains: (1) a target-binding domain externally exposed to the extracellular environment, (2) a transmembrane domain, and (3) an activation domain that is intracellular contained. The target-binding domain is engineered to recognize a specific tumor antigen; it is structurally different than endogenous T-cell receptors because it recognizes antigens independent of major histocompatibility complex (MHC). The antigens CAR-T recognizes are instead proteins, carbohydrates, and gangliosides on the tumor cell surface. The transmembrane domain and activation domain of the CAR-T receptor are more structurally similar to endogenous T-cell receptors—they are responsible for activating and triggering T-cell proliferation when the receptor binds to its target antigen. When activated, the T-cells mediate killing of tumor cells by two mechanisms: (1) secretion of granzymes and (2) activation of death receptor signaling in the tumor cell. These killing strategies are potentiated by additional signaling receptors on the T-cells that can improve T-cell proliferation and cytokine release. As of now, research teams have designed third-generation CAR-Ts that contain costimulatory receptors that ameliorate antitumor activity and proinflammatory cytokine secretion.

Ilustration of a cytotoxic T cell (purple), also called a CD8 T or killer T cell, investing a tumor cell.

 

The high success rate of CAR-T therapy in clinical trials has prompted several companies to compete for commercialization and introduction of the therapy into the market. At the moment, Novartis is leading in the race of clinical development and commercialization. In November, the company successfully completed Phase II trial of the CAR-T candidate for B-cell acute lymphoblastic leukemia (ALL) and Novartis is currently preparing to submit applications to the FDA this year. Kite Pharma also recently completed their Phase II clinical trials for CAR-T therapy against lymphoma and Kite Pharma have also started regulatory submissions with the FDA. Both companies have created a lot furor and excitement around their respective CAR-T therapies. However, some researchers are skeptical that FDA approval will be granted to these companies because severe side effects still exist and deaths have been reported in the clinical trials. Juno Therapeutics, a company that was initially in the stiff CAR-T race, terminated their research and development program for this very reason—5 patients died of cerebral edema caused by the therapy. Alternatively, companies like Cellectis and Bellicum Pharmaceuticals have taken the approach to mitigate harmful CAR-T side effects. Cellectis has developed a CAR-T therapy with a switch control system that only activates the transgenic T-cells when rampamycin is present. This therapy is currently in Phase I clinical trails and has already shown a lot of promise after saving two infants from leukemia. Bellicum Pharmaceuticals is also developing a similar technology that requires rimiducid to be present for CAR-T cell activation.

A technical limitation of CAR-T technology is that it is challenging to target solid tumors. The therapy is most effective against hematological cancers. However, in other cancers that have solid tumors, there is low T-cell infiltration and additionally an immunosuppressive environment prevents the immune system from attacking the solid tumor. To solve this problem, the company Celyad is developing a CAR-T that expresses Natural Killer Receptors (NKR) that can bind ligands of solid tumors. The company is currently beginning clinical trials with these NKR expressing CAR-Ts. Researchers have also suggested combining the checkpoint inhibitor drugs such as PD-1 with CAR-T therapy as a multi-pronged method to attack solid tumors; however the side effects of this combination therapy are unknown.

From a patient’s and physician’s point of view, another limitation of CAR-T therapy is that it expensive and lengthy process because the CAR-Ts are developed from the patient’s own cells. Cellectis and Celyad are offering a solution to the expense of CAR-T by developing an allogeneic CAR-T therapy—that is, the T-cells are derived from a healthy donor and are immediately available when they are needed. This technology is still at its early stages and is scientifically challenging to develop since foreign donor T-cells can be readily attacked by the patient’s immune system. Additionally, the manufacturing, transportation, and banking of the allogenic CAR-T would also prove to be tricky. The plethora of different CAR-Ts in clinical trials has given hope to patients, physicians, and investigators that the therapy will be introduced to the market fairly soon. Although several limitations exist for CAR-T, ongoing research and clinical development continues to refine the therapy and encourage the public that CAR-T has the potential to revolutionize the immuno-oncology field.

 

Citations

Yu et al. Journal of Hematology & Oncology (2017) 10:78

http://labiotech.eu/car-t-therapy-cancer-review/

http://www.the-scientist.com/?articles.view/articleNo/47788/title/Opinion–Balancing-Risks-and-Rewards-of-CAR-T-Cell-Therapy/

https://nihrecord.nih.gov/newsletters/2016/11_18_2016/story1.htm

https://www.statnews.com/2016/08/23/cancer-car-t-side-effects/

http://www.the-scientist.com/?articles.view/articleNo/42462/title/The-CAR-T-Cell-Race/