Innovation150 series on the RED blog: As Canada celebrates 150 years we look back on Canadian innovations in transfusion medicine over the years. A series of posts over the next few weeks feature remarkable Canadian progress in transfusion medicine past, present and future. #Innovation150.
Science papers—the everyday tales of slaying research dragons and finding buried treasures. Not just for stereotyped nerds in white coats, or wild-haired Einstein lookalikes. You can read them too. With the rise in open access publishing, more are available to lay readers outside academia’s ivory towers. But what are they all about? And why would you want to read one? Firstly, there are two types of science papers: primary research, where excited doctoral students and their senior advisors showcase their latest research and launch it into the international science world, and reviews, which round up current knowledge and up-to-date thinking in one subject area. Although the reviews give a broad overview of the current state of scientific play, the primary research papers are the ones that generate the excitement with their sensational headlines. And this is the reason you might want to take a peek at the primary source material itself—is the headline a fair summary of the paper? Is the press release an accurate Read More
Although daunting to non-scientists (and also to scientists not working in the field itself—just because we’re scientists doesn’t mean we understand every little bit of science), they’re not difficult to read, though it might take a little time. However, even real scientists go through a research paper several times, making notes and paying attention to comprehension. So you’re not slow or dim or uneducated if you need to read it more than once.
What is a primary research paper?
Primary research papers draw together a project or sub-project, announcing its results to a waiting audience of peers. They are usually submitted to and published by peer-reviewed journals, where the editorial process involves close scrutiny by experts active in the field. They make suggestions on style, writing quality and content; criticise experimental design and data analysis; correct errors; and request clarification, revision or even extra experiments before publication.
Why write primary research papers?
Glory? Staking a claim? Announcing an earth-shattering piece of scientific news? Documenting the process?
All of the above—a publication is the equivalent of a news piece announcing experimental results, and it also establishes ownership or primacy. A doctoral student may need a certain number of publications for a thesis. Publication is often a requirement for grant funding, academic tenure and general career advancement.
Primary research papers usually start with an abstract, then move into the introduction, materials and methods, and results, ending with a discussion of the work’s significance. A list of references, listing all the papers consulted in designing the experiment and analysing the results, follows, and there may be some kind of disclosure regarding affiliations, funding and so on. A beginning, a middle and an end.
Where do I start?
The abstract is an obvious place to start, but beware—this part is the foreword, the marketing paragraph designed to pull the reader in with all the juicy bits. It is a summary, highlighting all the key findings and usually with a tightly restricted word count. This is where you can see if the subject interests you—just don’t stop here.
Move on to the introduction, where the scientists answer the “Why?” behind their experiments. What made them research this particular problem in this particular way? Introductions usually summarise background material, giving a history of research in the subject and the reasoning behind a scientist’s interest. This is where you will find their quest, what makes them tick as a researcher. Look closely; there is nearly always a plot to follow.
Materials and methods is where you find out “how,” and it may seem like it is written in a completely foreign language…these are merely the tools a scientist takes on the quest, a little like some of the awesome text-driven role-playing games of early internet years. For “96-well plate,” read lump of coal, or short sword. They help get the job done, though might not be so good at fighting off dragons.
This is tricky. Unless you’re active within the field or have a good grasp of experimental design and statistical analysis, you probably won’t be able to analyse it in depth. But there are things you can pick up on that might give you a clue.
Does the abstract (or the press release) accurately reflect what is in the paper and the authors’ conclusions in the discussion?
Check out the references—depending on the uniqueness of the research, the following questions may be justified: Do the references seem valid? How recent are they? How many sources have the authors consulted, or do they just stick with their own work? Are they citing credible journals?
And the disclosure—How valid is a study on glucose-fructose funded by a large soft drinks manufacturer? Is the research sponsored by a strong advocacy group? Where is the grant from? Who does the senior author (usually the last person listed as an author) work for?
So next time you see a sensational headline announcing that if more people did XYZ then they wouldn’t die from diseases A, B or C, have a look for the primary source material and translate it for yourself.
Getting your hands on primary research papers:
Open access publishers like Public Library of Science, PLOS ONE and eLife are a ready source of peer-reviewed primary research papers. Other publishers may also make papers available online without requiring subscription or erecting a paywall. Your library subscription (academic or public) often gives access to papers for free if you don’t want to purchase access. Googling the paper’s title sometimes works too.
How to read a science paper—some great advice below:
Reading critiques of research papers
Want to see how scientists analyse published research results? Learning from professionals in action is a good way to hone your own observational skills. Check out the PubMed Health home page from the National Library of Medicine, or pay a visit to the UK’s National Health Services Behind the Headlines service.
Check out Ben Goldacre’s acerbic takedowns of bad science in The Guardian.
As mentioned, this is difficult, but if you’d like to learn more about appropriate application of statistical analysis, try Lior Prachter’s blog. And if you like infographics, Compound Interest’s Everyday Exploration of Chemical Compounds blog has a great poster, A Rough Guide to Spotting Bad Science.
The post’s author reviews two to three primary research and review papers each week, distilling the storyline into engaging summaries for one of Talk Science To Me’s clients, Go Communicate, over on Accelerating Science. After a year and more than 100 reviews, Amanda feels confident that she can find the hidden narrative behind any protein chemistry paper or food safety technique.
Thalidomide has a tragic history, but it’s still being used today in ways that point to future success in the world of clinical medicine.
I’d like to stretch the coincidence theme once more on the blog, so bear with me as I wander through some random but connected happenings from my own world of science communications.
What do you think of when you hear the name of this drug? What images come to mind?
If you’re a certain age, I’m sure that images of babies born with missing limbs or flipper-like appendages instead of arms or legs flash in front of you. Middle-aged adults may hold childhood memories of growing up around these kids, pointing to them in the street. Older women may shudder, thinking how close they came to taking the as-then wonderdrug that deformed so many lives in the late 1950s and early 1960s. For youngsters, it may just be a sad episode in modern medicine (if they’ve heard of it at all).
For me, thalidomide is the bogey-drug, the medication taken oh-so-innocently that blighted the lives of kids only a few years older than myself. It was available as a sleeping aid and morning sickness preventative around the same time my parents married and considered starting a family.
Thalidomide means tragedy; it means bad science; it means lack of protection from the pharmaceutical industry and policy-makers; it means danger.
But I’ve found recently that thalidomide also means change, it means hope, and it means pharmaceutical success—not quite the bogey-drug I thought, perhaps.
Back in August of this year, a news clipping caught my eye on my RSS reader. “FDA scientist who kept thalidomide off the market dies,” the headline read. Coming from the United Kingdom, I had automatically assumed that thalidomide was a global tragedy. As I read the news story, I learned that the United States had been largely spared, thanks mostly to the stubbornness of one scientist who refused again and again to approve licensing for thalidomide. The scientist, Frances Oldham Kelsey, was not only Canadian, but a woman. I clipped the story into Evernote and tagged it #Ada Lovelace Day.
What Kelsey did was refuse to take the drug company appeals at face value. She used her training and experience to ask for further details. Then, suspicious of the facts presented, kept denying approval. Once it was firmly linked with phocomelia, the birth defects experienced by thousands of children in Europe, thalidomide was withdrawn from the market and banned in 1962. Kelsey’s vigilance and professionalism in dealing with thalidomide paved the way for many of the stricter drug safety measures that protect consumers today.
Around the same time as I researched my Ada Lovelace Day post, I was also reviewing a paper on proteomics that dealt with a new strategy for destroying errant proteins and thus preventing cancer. Winter et al. (2015) targeted BRD4, a protein involved in activation of the C-Myc oncogene, an intracellular switch that can push cellular activity into cancer.1 The researchers found that by combining thalidomide with an experimental compound, they could tag BRD4 with a pharmaceutical “black spot” and sweep it into the cell proteasome for accelerated destruction. Not only did this strategy work well in the petri dish, but Winter et al. could also decrease the size and abundance of tumours in mice xenografted with human tumour cells by treating the animals with the drug conjugate.
This was the first time I had encountered a mention of thalidomide as a modern-day drug, so I did some hunting to find out if this was a unique occurrence.
Well, it wasn’t. In the mid-1960s, clinicians started using thalidomide to treat painful skin lesions in leprosy. Quite by accident, they found that alongside giving their patients a good night’s sleep, thalidomide also cleared up erythema nodosum leprosum. Then, research into cancer treatments that rely on disrupting the blood supply to tumours showed that thalidomide might indeed be useful. In 1998, the drug was finally approved for use in the United States…but with strict controls to prevent another tragedy.
Then another proteomics paper to review landed in my inbox: “Lenalidomide induces ubiquitination and degradation of CK1a in del(5q) MDS.”2 This one heralded a success story for a thalidomide derivative, lenalidomide, which has been used very successfully to treat patients with a form of myelodysplastic syndrome (MDS), del(q5) MDS. This MDS is a leukemia caused by the deletion of a region of chromosome q5. A shortage of the products encoded by one of the genes in this region renders affected cells incredibly sensitive to phthalimide drugs like lenalidomide.
As the research team, Krönke and co-authors, investigated the mechanisms behind this outstanding success, they found that the thalidomide derivative seemed to act once more by targeting the protein into proteasomal destruction. [reviewed here]
Furthermore, during their investigations in mice, they found that they could only replicate this effect when a certain human protein was added back into the experimental animals. This, they suggested, could explain why some of the initial research back in the 1950s failed to show the horrendous drug side effects that blighted so many families.
When I need to find out about medical research, drug information or experimental breakthroughs, I head to PubMed, the U.S. National Library of Medicine search engine that looks through the whole of the MEDLINE database of life science and biomedical topics. Simply typing “thalidomide” as a search term currently returns over 9,000 articles spread over the last 55 years.
While the first 5 years of thalidomide’s catalogue on MEDLINE mostly represent the dreadful exposure of its mutagenic effects and issues surrounding drug safety during pregnancy, more than two-thirds of records come from therapeutic success in the last 15 years.
Today, thalidomide is one of the most stringently controlled drugs available, with safeguards in place to protect developing fetuses. Unfortunately, this protection is not 100 per cent effective, and children affected by thalidomide continue to be born. Stronger controls are definitely needed.
However, the scope of the thalidomide family of drugs is only just being explored by medical science. Although the mechanisms by which thalidomide and its derivatives work explain its early tragic history, they also point to future success in the world of clinical medicine, with the ability to improve lives rather than damage them irreparably.
- Winter, George E., Dennis L. Buckley, Joshiawa Paulk, Justin M. Roberts, Amanda Souza, Sirano Dhe-Paganon, and James E. Bradner. 2015. “Phthalimide conjugation as a Strategy for in vivo Target Protein Degradation,” Science 348(6241):1376–81. doi: 10.1126/science.aab1433.
- Krönke, Jan, Emma C. Fink, Paul W. Hollenbach, Kyle J. MacBeth, Slater N. Hurst, Namrata D. Udeshi, Philip P. Chamberlain, D. R. Mani, Hon Wah Man, Anita K. Gandhi, Tanya Svinkina, Rebekka K. Schneider, Marie McConkey, Marcus Järås, Elizabeth Griffiths, Meir Wetzler, Lars Bullinger, Brian E. Cathers, Steven A. Carr, Rajesh Chopra, and Benjamin L. Ebert. 2015. “Lenalidomide Induces Ubiquitination and Degradation of CK1a in del(5q) MDS,” Nature 523: 183–188. doi:10.1038/nature14610.
Helium is a non-renewable resource, and an important one, as it’s used for gas chromatography, MRI diagnosis, smartphones, Internet communication, and more.
Don’t worry if this alarming piece of (non-)news slipped past your radar at the end of the year: the world is running out of seaweed!
Not just any old seaweed, but the red stuff beloved of microbiology labs.
— Stefanie Vogt (@StefanieVogt) November 19, 2015
As reported breathlessly in the lab and science media, worldwide stocks of red algae seaweed from the genus Gelidium are in short supply. Although it is found in intertidal and deep subtidal cold and tropical regions all over the world (apart from around the poles), most harvesting takes place in only a few areas: Spain, Portugal, South Africa and Mexico, with Morocco being the major supplier.
Apparently, trade restrictions, overharvesting and increased pressure from the food industry have come together to limit stocks of this lab staple. So much so that late last year, lab consumables supplier Thermo Scientific sent around a memo to customers warning them of the low seaweed stocks. Only when this letter was tweeted out by concerned microbiologist Dr. Adam Roberts did the world appreciate the true potential horror of the situation: bring back the potato.
Global shortage of agar. This could go quite bad fast!
Microbiologists be aware… pic.twitter.com/QwQKbiQG6e
— Adam P Roberts (@GCAGATGCAATG) November 19, 2015
An explanation and a bit of history
Recently, I haven’t had a lot to do with agar agar, a gelatin-like product made from seaweed that is used to make culture plates in microbiology—that is, not until this first bit of news crept into my feed readers. No, it wasn’t #agarpocalypse that I noticed hitting the headlines; instead, seaweed was making waves because of one of those “invisible women in science” posts.
In the beginning, microbiologists had a problem with studying bacteria: there was no way to culture them in the lab. Pioneers like Robert Koch would use potato slices to grow the microbes, that is until his laboratory assistant’s wife suggested that, from her experience with cooking, agar agar might be a better alternative.
The trouble with growing bacteria is that they need a substrate to grow on and in that holds enough nutrient to sustain the colonies but doesn’t disrupt morphology. Fanny Hesse’s suggestion, agar agar, proved ideal for the job—so simple, so ideal, that she was written out of microbiological history for
a few many years.
Her suggestion, agar agar, is perfect as a growth medium: it must be heat activated to generate its setting properties, and it is pourable when hot but remains a solid at room or, more importantly, incubator temperature. This means that batches of the stuff can be autoclaved for sterility, then poured into Petri dishes as a culture medium. Furthermore, the constituents of agar—sugar polymers derived from algae—are indigestible to most bacteria, preserving the growth substrate intact as colonies grow.
Better than both potatoes and gelatin.
And apparently irreplaceable.
— Stefanie Vogt (@StefanieVogt) December 9, 2015
Back to the potato?
Although a few snippets of news slipped out after Christmas, the Internet has grown silent on the impending algal catastrophe. Questioning the only microbiologist I meet regularly in real life was disappointing—no, she didn’t know any labs that were stockpiling the product ahead of lean times. Likewise, my call-out on Twitter went unanswered, even by the initial tweeter who did try to pin some blame on foodies overusing the lab staple in cooking.
In summary, my limited research shows that bacteria will continue to be grown and characterized in research labs all over the globe. Spuds can breathe a sigh of relief, though ant farm owners and jelly makers might have to spend a little more on their hobbies.
#clickbait #storminateacup #nothingtoseehere
* the other half of the sky, in case you were wondering
I must confess to being a little adrift over the gravity surrounding the recent news about gravitational waves.
While I have no difficulty understanding our previous blog post on ripples, I must confess to being a little adrift over the gravity surrounding the recent news. Although I’m totally caught up in the infectious scientific excitement of the whole announcement on detecting gravitational waves, it’s not something I could explain the importance of to the person next to me on the bus, for example.*
In a nutshell
The excitement arises from what the primary paper contains: news of not only the successful outcome of many research hours spent calibrating and recalibrating the detectors from data gathered in countless previous experiments, but also the confirmation of a 100-year-old theory. The detectors “saw” the gravitational ripples as predicted and were able to witness the birth of a new black hole. Furthermore, in addition to being the first gravitational data coming from gravitational waves, it is also the first observation of two black holes merging into one.
Yes, but why the excitement?
So—just for you, dear reader—instead of just exclaiming “yay, physics!” and scrolling to the next kitten video, I thought I would find out a little lot more about why this is indeed a Big Deal to more than just the physicists in our midst.
Or maybe it is just a scientific breakthrough that only a scientist can love, as @kirkenglehardt suggests?
— Kirk Englehardt (@kirkenglehardt) February 13, 2016
IMO, this is why the public should (and probably does) care
The news last week came from a massive collaborative study based on detecting the gravitational waves flooding across the universe that Einstein predicted from work back in 1915. His general theory of relativity, a geometric explanation of gravity across the universe complete with curvature of space-time, is still mostly beyond my grasp (and I’m content to let it lie there—I’m a scientist, but that doesn’t mean that I have to know everything). And the news from the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo (Italy) working groups appears to provide the first proof that he was right.
Let me say this again: modern physics has just proved him right on something he predicted 100 years ago.
The sheer number of authors alone on the paper is worth celebrating (over 1,000). As an illustration of the collaborative nature of scientific research, dispelling the myth of the lone genius in a basement laboratory, it’s powerful! Is that not an impressive et al.?
How many people does it take to find a gravitational wave? Here's the official list… pic.twitter.com/WexwAMprlr
— New Scientist (@newscientist) February 11, 2016
3. because.black holes
We’ve just witnessed two massive black holes colliding into one super black hole…okay, 1.3 billion years ago…but we were there (sort of). A truly Matthew McConaughey/Interstellar moment indeed, as in the video below showing some of the science moments recreated in the film in collaboration with Kip Thorne, a leading expert in the world of Einstein’s theory and gravitational physics.
Apparently, binary black holes go pop! The sound files below give the “chirp” as the waves increase frequency and thus pitch, with a “ringdown” as the new black hole stabilizes. Moreover, it’s the volume that gives researchers the clue to how long ago this event happened.
(this is probably the most important reason why the news should knock your scientific socks off)
Now that physicists can “hear” these events taking place and have seen Einstein’s gravitational ripples in action, it opens up a completely new way of looking out into the universe from this pale blue dot. There is undoubtedly a whole slew of validation work going on right now to further confirm the data just released, but even if you don’t understand the complicated theories, just appreciate that there are some scientists getting very excited at what Georgia Tech calls a “new window on the universe.” Indeed, the short video in the Georgia Tech press release likens it to being able to hear for the first time—possibly the best analogy ever to explain why you should be popping the champagne corks along with the boffins.
Bob McDonald from CBC’s Quirks and Quarks chats with Michael Landry, detection lead scientist at the LIGO Hanford observatory.
If you’re not ready to take my word on this, then there are some great resources out there that make an excellent job of explaining. Therefore, I’ll let you, dear reader, scan through them rather than wade through my own interpretation of bouncing on rubber sheets (stay with me on this one…).
- The original press conference: listen to the scientists themselves explain what’s going on.
- The LIGO website has some details on the why, what and whoopee of it all. Share the excitement with a gravitational waves ringtone for your phone!
- Gabriela González, spokesperson for the LIGO Scientific Collaboration, explains the news at the recent AAAS meeting.
- Cartoons from the UK’s The Independent newspaper.
… and maybe you should check out the primary sources too (for a little light reading and listening)
- Primary research paper: Abbott, B. et al. 2016.** “Observation of Gravitational Waves from a Binary Black Hole Merger.” Physical Review Letters 116. doi: 10.1103/PhysRevLett.116.061102
- LIGO press release
* Science communicators note: I am avoiding the whole “explain it to your mother/grandmother” stereotype here. Just don’t get me started on how insulting this terminology is…
** Note: this is the year of publication, not the number of scientists involved in the project (though it could be…)