Tips for reducing talk anxiety (2b, more responses to reader comments)

This is a follow-up to the original piece.

 

Dr. Krishna Kumari Challa wrote: Well, if you are an introvert, your brain goes haywire with the great stimulation given by larger audiences (an introvert’s mind needs less stimulation to have the same level of understanding about a situation). Controlling it is more important, according to psychologists, before thinking about the points given in the blog. Only when the stimulation is controlled you can control other things. That is why introverts try to hide behind something, look at their papers or at the screen instead of the audiences in the initial stages. They try to reduce the stimulation by doing so.
I would be grateful to you if you could give tips on how to reduce this ‘too much stimulation’ issue.

 

Hi Krishna – an excellent point! My experience with students suggests that there are surely “types”, such as those you call introverts, who dislike being the focus of attention and whose brains experience an exaggerated response that powerfully influences their bodies and behavior in public presentations and similar situations. Usually giving them help requires close observation, then developing an individual plan of practice that addresses specific behavioral symptoms – like those mentioned in the earlier post. This will take time and patience. Here, too, it can be useful to help them focus on the content of their presentation, and this is a theme to be covered in a future post. That said, I’m not a psychologist, and some types of anxiety clearly have very deep roots that need to be addressed therapeutically before any satisfying “cure” is really achieved.

But still there are things that can help: It’s crucial to try to define the parameters of the problem as precisely as possible. Are there any situations in which the person manages to handle their anxiety? Are they equally affected if they give the presentation to two or three close friends, or their lab? Is one of the issues trust: with people they know, does a fear of disapproval or a negative response disappear? If they can handle small groups, then this can become a cornerstone of practice. They need to give the talk as often as possible in such settings in a way that helps them internalize the positive effects and extend the experience to situations with larger audiences.

Personally I learned something about this through music. My first violin teacher, Lewis Hoyt, said that one of his teachers had always told him to imagine the heads in the audience as cabbages! Later he began studying through a new method which took exactly the opposite approach – enjoying the presence of an audience and fully engaging them as human beings in your personal music, work, or story. Over the long term, if one can manage it, this tends to work better than pretending like they aren’t there.

Your point about “control” reminds me of the student I discussed in point 9 of the original article – where the issue was managing all of the ideas bombarding his brain and the flow of the content. A few simple strategies to ensure that you can stay on track (point 8) and won’t get lost go a great way toward reinforcing confidence. The trick is to extend them to behaviors that are really hard to control: blushing, stammering, shaking, etc.

Each speaker needs to build on the strengths she/he has and use them to support areas of weakness. Can you tell a joke? Can you tell a funny little personal story about something that happened during the project? If some weird little accident happens, can you improvise and get people to laugh? There are lots of potential methods to change the atmosphere – disasrming a stressful situation – which can almost instantly relieve a lot of the tension. As a teacher or speaker you may have to dig deep into the rhetorical repertoire to find something that works, but there’s often something there to draw on.

A lot more needs to be said about this; I’ll keep thinking about it, and the comments on the piece have been extremely helpful in pulling out essential points for consideration. I’ll be teaching several courses over the next couple of months and will be able to report more specific examples from actual practice.

 

If you like these pieces, you might be interested in the article:

“The Dinner Party: Learning to explain your work to a general audience can make you a better scientist.”

 

If you’d rather enter the bizarre, twilight world where science collides with humor, check out the Devil’s Dictionary of Scientific Words and Phrases, or the text of a talk I gave in Oslo in 2015, plus everything else in the categories “Hilarious moments in science communication” or satire.

 

And if you haven’t yet seen the most popular post so far from this blog, check out the “God” article:  “Even God’s first paper got rejected.

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Tips for reducing talk anxiety (part 2a, first feedback from readers)

Wow! The article on performance anxiety is getting a lot of traction; thanks very much for the feedback and I’m hoping for a lot more. (See the full article here or just scroll down if you’ve landed at the blog main page. Click here for a list of other pieces devoted to teaching and training.)

Two readers have provided tips that I include here with a couple of comments:

From Jennifer Kirwan, the head of the Metabolomics Unit at the Berlin Institute of Health, come two pointers:

Two tips I was given years ago when public speaking:

1)      Never ever use a laser pointer or wooden stick. Instead, use powerpoint animations to circle or otherwise highlight the point of interest. Not only does this eliminate the issue of shaky hand syndrome, but it also serves to engage your audience more as frequently people have to struggle to see the laser dot on the screen, especially when it’s moving.

2)      Many people tend to find they blush when faced with public speaking. We were advised if we have this problem to wear clothes that cover our shoulders and avoid low cut clothes. It makes the blushing less obvious and, if you are less worried about people seeing you blush, you’re less likely to start.

Great points. A couple of remarks:
To 1: It’s absolutely true that the spot from a laser pointer can be hard to see – especially under certain lighting conditions and on some slide backgrounds. And a pointer can be terribly distracting in the hands of speakers with that awful habit of drawing really fast circles around the thing they want you to look at. (…which may be an unconscious strategy they’ve adopted to hide trembling – or the effect of a major caffeine overdose). And the pointer is often a lazy person’s way of compensating for a slide that’s crammed with too much information, or whose design is unclear and hard to scan. (And, of course, if the audience is looking at the laser dot, they won’t be looking at you.)
Caveats: Some people (including me) aren’t very fond of PowerPoint. I’m not as fanatical about this as other people (including the peerless Edward Tufte), but they make very good points. It’s crucial to map out content and your message before you choose the template for each slide and the talk in general. When you do, you’ll often find that none of the templates really fits. Most people do it the other way around. They pick some template, or simply start with the default that some other user set up long ago, and try to fit their information into it. This can impose a structure on the message that doesn’t fit it at all, and you may not even be aware of it.
But for anyone who does use PowerPoint, or another system with similar animation features, Jennifer’s advice has some clever added benefits. Picking spots to animate or highlight will force you to plan a rhetorical path through the information on the slide – those points represent the key landmarks in this chapter of your story. Defining that path can help you distinguish important information from unnecessary details, showing you things that can be left out. (General rule: leave out as much as possible, and then a little bit more.) Animations can also help during your presentation. If, God forbid, you do have a blackout, the next highlight will point you back into the story.
Even so, I would always have a pointer on hand: you may need it for other reasons. Someone may pose a question that requires you to return to a slide and focus on something you haven’t anticipated; you may need to point it out for the rest of the audience. Secondly, something can happen that makes you abandon your original plan. If time gets short you may need to skip things
Suppose, for example, the topic of the last speaker overlaps with yours. You  may want to build a bridge between the talks that you hadn’t anticipated: “The previous speaker addressed this question at the level of the transcriptome. At the level of the proteome, however, we didn’t see any upregulation of pathway components – as you can see here, and here.” (Since the focus of your talk is slightly different, you hadn’t highlighted those particular molecules.)
To 2); I really like Jennifer’s second point about using your wardrobe to cover blushing. That makes great sense.
(Although in my personal case, I’d need a different strategy, being the kind of person who rarely bares his shoulders or exposes much cleavage during a talk. Maybe I could wear a bright scarlet suit that made my face look pale, or go to the Solarium and get a mild sunburn beforehand, or blind the audience with my laser pointer, etc. etc. … Sorry, Jennifer, I couldn’t resist.)

The second comment came from my friend and former colleague Alan (aka Rex) Sawyer, and is interesting on several levels: cultural, pharmacological, and rhetorical:

I needed this advice 25 years ago while preparing for my first paid gig as a counter-tenor soloist (Friedenskirche, Handschusheim, Johann Sebastian Bach, BWV 4, “Christ Lag in Todesbanden”). But what broke the ice as I went on stage was that the stagehand had failed to provide a seat for me. The audience laughed good-humouredly, which totally banished my case of nerves as it got the audience on my side. Later I got a top tip to eat three bananas about an hour before going on stage. Bananas contain trace quantities of a natural beta blocker. The effect is subtle, but it really works.
To that I can only say: if you’re already taking beta blockers, consult your physician before eating bananas; otherwise you may be comatose when it comes time to give your talk. Wait several hours before operating any heavy equipment. A laser pointer is probably safe.
And don’t get confused and eat three watermelons by mistake. The effects might resemble those of another pharmaceutical product: reports claim that a substance called citrulline in watermelon acts as a sort of natural Viagra. Although you’d probably have to eat an awful lot of it to experience the effects. And at that point, you might not want to walk onstage to give a talk.
If you like these pieces, you might be interested in the article:
If you’d rather enter the bizarre, twilight world where science collides with humor, check out the Devil’s Dictionary of Scientific Words and Phrases, or the text of a talk I gave in Oslo in 2015, plus everything else in the categories “Hilarious moments in science communication” or satire.

Tips for reducing talk anxiety (part 1)

This is part of a series of articles on the blog (a few already published, more in the works) devoted to didactics and the communication of science (and other things). I am currently working on a handbook that includes ideas such as these and explores in depth the myriad problems of presenting content. More pieces to come on that.

The tips given here are related to performance anxiety and represent just a sample of things I’ve learned from my own excellent teachers, from my experience in training lots of scientists and other types of speakers, from my own experiences in public speaking, and from the process by which I completely eliminated my own stage fright when performing as a musician (yes, it’s possible – and that’s when the fun and the real music begin!). In the courses I give we always find a way to adapt these principles to individuals and their problems.

Please help me by contributing your own experiences and tips, so we can build a useful, very practical resource that will help as many students and teachers as possible! I will add your points to the list and mention their sources!

The first step in learning is to identify any barriers that exist – to define the problem as clearly as possible. So it’s crucial to carry out some self-exploration: you need to carefully study your own body in situations of fear, anxiety and stress.

These mental and physical techniques require practice, and they work best if you imagine yourself as concretely as possible in the environment you will face when giving a talk. Visualise the room – ideally, visit it ahead of time, and maybe go to another talk there. Sit toward the back and listen. If you can’t visit the room, then imagine various scenarios: a large classroom, an intimate seminar room, a packed auditorium, an almost empty auditorium.

Next close your eyes and imagine the moment before you are invited to speak. Imagine someone getting up and introducing you; you’re sitting there and will be headed onstage in 30 seconds. Find out if possible whether you will be standing or sitting down; imagine the size of the audience you will be facing, mentally prepare for a moment where the beamer doesn’t work and needs to be fiddled with, if the microphone suddenly doesn’t work, etc. Have some strategy for “vamping” the time, with a joke or some other device that engages the audience. (“While we’re waiting, I’d like to conduct an informal survey about a question of tremendous scientific relevance: Where does that stuff in your belly button come from, anyway?” There’s actually a very interesting study out about this… )

  1. Nervousness is usually accompanied by various physiological and mental symptoms, and here the goal is to deal with common and specific symptoms such as stress and tension, a nervous voice, a wavy pointer, and blackouts. By removing these symptoms you can trick your body into thinking it’s comfortable, and the cognitive issues often fade along with them. But there are clear strategies for dealing with blackouts, too.
  2. The first step is to try to replicate the condition of your body when you’re nervous, by imagining you’re in the situation, or remembering the feelings you had the last time.
  3. Anxiety is usually marked by muscle tension in very specific parts of your body. The first goal is to be aware of their positions and consciously relax them. My own technique is very simple: I totally relax my ankles, letting go of all tension in my ankles and then my feet. When I do this – and it’s true for most other people as well – it is very hard to maintain tension anywhere else – in my back, my vocal chords, etc. Try it – totally relax your ankles, and while doing so try to make a muscle tense in your back, or your arms. If it’s difficult, that means you can use this approach as well. If not, you need to find some other part of your body that you can deliberately relax and thus force yourself to relax the stressed muscles as well. Stand up and relax your ankles. This should be the first thing you do after you’re standing at the lecturn or whatever, and you’ll have to practice remembering to do it.
  4. Remember that the first 30 seconds or so of a talk are less about the content than about the audience learning to listen to your voice and style. If you realize that, then you realize that it’s also a time that you can use to get comfortable. First of all, BREATHE. Then speak SLOWLY and CLEARLY and have a clear strategy prepared to invite your listeners to engage with you right from the beginning. This is something you have to practice as well – people are usually most nervous at the beginning of a talk, and that’s when they usually talk the fastest. Additionally, for predictable reasons, they tend to say the highly technical terms they are most familiar with the fastest – and these are just the words that need to be spoken the most clearly and distinctly. Practice the beginning of your talk with a metronome or by slowly pacing around in a way that forces you to slow the rate of syllables as you speak. You’ll have to practice this a lot of times until you instinctively start slowly rather than with the rush of nervousness.
  5. Engagement #1: try to engage the listeners at the very beginning. Before you speak, look around at some of their faces and smile. If you’re not fixed to a podium or a position at the front, move toward them, as if you’re in a more informal setting.
  6. Engagement #2: if possible, start off with a real question that interests you and has motivated the work, if you can find one that’s general enough to be grasped by the entire audience. Why? If you’re lucky, they’ll actually try to come up with an answer in their own minds, or focus on the question. This immediately draws the audience into the content, rather than a focus on you and your behavior. At that point you’ve engaged them in the subject matter. If they really try to answer the question, they’ll think something like, “Oh, that’s interesting; I would have tried to do it this way…” and you’ll immediately have set up a dialogue that will continue throughout the talk and will provide plenty of good feedback at the end.
  7. Engagement #3: Rhetorically speaking, most data slides are also shown to answer specific questions. (“Does protein A interact with protein B?” Well, to find out, here’s what we did. You see the results here, which provides the following answer…) Unfortunately, most speakers don’t realize that this is what’s happening. They use the ANSWER to the question as the title of the slide, and often start trying to explain the answer before clearly presenting either the question, the methodology, and the results. This confuses the rather simple story-line inherent in the slide. It can also disrupt the talk as a whole because an answer (end of slide) usually stimulates the next question (beginning of next slide). You don’t have to make all the titles of your slides questions, but you should realize this is what is going on (and actually, why not do it?). It has the benefit of gluing separate slides together in a smooth story. And it also can stop a big problem that occurs if the order of information on a slide is different from the order you are using while speaking. When that happens, people are trying to read and listen at the same time, are getting different information from those two channels, and probably won’t remember anything.
  8. Boiling a talk down into a big question and many sub-questions can have a huge effect on anxiety when you’re worried about content blackouts. All you need to remember (or have on tiny cards in your hand) are the questions. You know the answers – that’s what you’ve been doing for the past 100 years. The question-answer method serves to create a real dialogue that engages the public and also an outline of your talk.
  9. Practice other specific performance problems that you are aware of. The first step in finding a cure is to identify what has been disrupted at the right level (it’s just like practicing music that way). A while back I had a student who was having what looked like blackouts during a talk. Later he explained that they weren’t blackouts – instead, every idea was bombarding his brain at once, and he couldn’t figure out where to start. I suggested a method by which he put up a slide and practiced fixing his eyes precisely on the thing he would talk about first, then moving them to the next thing, and so on. The very next day he gave a talk in front of 400 people without a single glitch or “brain freeze.”
  10. Shaky voice. If your voice quavers or trembles while you speak, the problem may be tension in some part of your body (see number 3 above). Often there is another problem, especially (but not only) if you are speaking in a foreign language. You may be pitching your voice too high or too low, which puts tension on your vocal cords and that will extend into your face and throat and shoulders and then the rest of your body – and then you’re doomed! This often happens in a foreign language, where people sometimes choose a “base pitch” (the tone – in a musical sense – at which you would speak if you were talking in a monotone) that is at the wrong place of the spectrum. This is really likely to happen if you subjectively consider your voice too high or too low (to be “sexy”) and try to place it differently. How do you know the right base pitch that your voice should have? A friend who has become a well-known speech pathologist gave me this tip. Go to a piano, and find the highest and lowest keys that you can comfortably The appropriate ground tone for your voice should be between the half-way mark and a third of the way from the bottom of this range. If you try to speak at a pitch that’s too low, you’ll experience the “creaky voice” phenomenon. If your voice is too high, in general, you’ll strain your vocal chords and eventually get hoarse or lose your voice. If either of these things happens to you anyway on a regular basis, you may be pitching your everyday voice too high or low. Also try different volumes of voice. You may arrive in a big room with no microphone, and you’ll have to project. Aim your voice at the person in the back, without shouting at the people in the front row. Your diaphragm and vocal cords have the potential to cause all the air in the room to vibrate and communicate your message. Singing teachers know the secrets of projection. I don’t, but it has a lot to do with breathing deeply and comfortably, and not tightening your throat or larynx.
  11. Shaky pointer syndrome. The reason a pointer shakes is because of tension in the muscles that control your arm and hand. The solution is to let your shoulder hang, without any muscular activity from the back or upper arm, and imagine that all the weight is on your elbow, and that it’s sitting on a table. Now use only the muscles you need to raise your forearm (preserving this feeling of all the weight in your elbow) and aim the pointer at a spot on the wall. Let it remain on the same point for a while. If it shakes, there’s probably some tension still in your upper arm (it’s really hard to make the forearm tense if your upper arm and shoulder are relaxed). Once you can hold the point relatively still, try moving it back and forth in a horizontal line. Here, too, you should imagine that your elbow is resting on the table, taking all the weight from your shoulder, and you’re just sliding your forearm back and forth.
  12. Those nerdy, highly technical slides… Although most scientists tell me that nowadays, most of the talks they give are to mixed, non-specialist audiences, you’re bound to have a few slides that are complex or obscure and you won’t have time to teach people “how to read them.” Example: I’m working with scientists who are developing mathematical models of biological processes, and at some point in their talks they want to show the real deal – math and formulas. They know a lot of people will be intimidated by this, but they still need to show the real work. On the other hand, they don’t want people to “tune out” and give up on understanding the rest of the presentation. At this point what I recommend is to say something like, “Now my next slide is specially made for you math nerds out there; the rest of you can take a short mental vacation and I’ll pick you up in just a minute on the other side.”
  13. Imagine the “personality” you’ll project when you become the leading expert in your field. Pretend like you’ve given the talk a hundred times to enormous success, and now you’re on the lecture circuit, giving it to audiences that think you’re the Greatest and are eager to provide input and their own ideas. How will you look up there? What kind of voice will you have? What types of rhetorical devices can you use to project “modest authority”? When a musician has practiced and practiced a piece for months, and gets stuck, sometimes all you have to do to make the next big step is to imagine what it will sound like when you play it a year from now. If you can imagine that, as concretely as possible, usually the next time you play it will be much closer to that vision. The same thing goes for giving talks.
  14. Criteria for success… If I give someone directions to a party, there’s a simple test that reveals whether I’ve done a good job or not – whether they arrive on time, on the right day… What’s the equivalent for a talk? (Pause while you think about it a minute…) The best answer I’ve heard is this: Imagine you leave the room and there’s somebody waiting outside who says, “Damn! I really wanted to hear that talk; what did he/she say?” At that point a member of the audience should be able to give the person a short summary, and it should fit two criteria: 1) the speaker would agree with it, and 2) most members of the audience should give very similar answers. As a speaker, how do you ensure that this happens? Well, the most obvious way – which few people really ever consider – is to close your talk by saying this: “Now imagine when you leave the room, there’s somebody standing outside who tells you, ‘Damn, I really wanted to hear that talk; what did he/she say?’ Well, here’s what you should tell them…” And then sum it up in a nice little package that’s tight enough to be remembered, with a clean, predictable story line. Remember you’re not trying to simply communicate single facts! You’re trying to answer a question – which you have to be able to articulate very precisely – and you need to explain the meaning of that question in terms of models and concepts that you share with the audience. You need to put information into a structure that can be grasped and remembered, in a way that holds the attention of the audience and engages their intelligence. This means you have to provide information in a relational, coherent structure – and if they don’t share your background and models, you’ll have to provide it. If you do that, you’ll get the kind of smart questions and feedback you’d like, the kind that will help you improve your thinking and your research.

The last points relate to content, which will be the subject of more articles very soon.

ALL of these points require practice – numerous repetitions while mentally imagining the real-life situation as it will feel, as closely as possible. You may always feel anxious before or during a talk; it may never go away. But most people can deal with the symptoms, using strategies like these, and that makes all the difference.

Two final points: First, remember what it’s like to be in the audience when a speaker is really nervous. Everybody is rooting for him or her – they’re on your side! Take comfort in that and try to engage people in the sense that “you’re all in this together”: you’re inviting them to think about an interesting question with you, rather than waiting for them to throw rocks (or shoes) at you.

Secondly, you’ve got to be engaged in the content. Even when you think your story isn’t that great or sexy, or leaves lots of questions up in the air – well, that’s what most science is like, folks! Remember that you’re presenting something that has an inherent interest to a lot of scientists. And negative results are useful as well because they can save your colleagues a lot of time; it will prevent them from following the same old leads, time and time again, without realizing that other labs have tried and failed and been unable to publish their results. Closing off blind alleys is a great service to scientists everywhere – it’s a key step toward progress by forcing people to rethink and revise the basic models they are using.

These are some of the very basics I’ve learned through experience in many performance situations of my own as well as working with a lot of students with different problems over the years. I have learned a lot from the fantastic teachers I have had the privilege of studying with (and continue to do so in the life-long process of learning). I also absorbed a lot from a fantastic book about performance anxiety, whose focus is music but every bit of it is applicable to public speaking, which I highly recommend here:

The Inner Game of Music
Overcome obstacles, improve concentration and reduce nervousness to reach a new level of musical performance
Barry Green with Timothy Gallwey (co-author of the Inner Game of Tennis)
London: Pan Books, 2015.
ISBN: 978-1-4472-9172-5

At Amazon, also available on Kindle

For other articles on science communication teaching, click here.

An animal that runs on hybrid fuel

Research highlight from the MDC – a great story from Gary Lewin’s group in the current issue of Science

 

When oxygen gets scarce, the naked mole-rat throws a metabolic switch to draw energy from fructose rather than glucose

The naked mole-rat, a rodent native to Africa, can survive with little or no oxygen far longer than other mammals. The secret lies in its metabolism: in addition to the basic system by which animals generate energy from glucose, naked mole-rats have a backup system based on fructose. This discovery comes from Gary Lewin’s lab at the Max Delbrück Center (MDC), in a collaboration with the groups of Michael Gotthardt (MDC), Stefan Kempa (MDC and BIH), and Thomas Park (University of Illinois in Chicago), as well as scientists from several other countries. The work is published in the April 21 edition of the journal Science.

Oxygen is so essential to life that a very short deprivation is fatal to animals. Their cells need a constant supply to drive the chemical reactions that produce energy from food. In ancient times, cells evolved a form of metabolism that used the sugar glucose as a source of fuel and the high reactivity of oxygen atoms to extract its energy. This process was so efficient that glucose-based metabolism could fuel the bodies of humans and even larger animals, and it has been maintained over the course of evolution.

But life in a harsh environment can alter even very basic aspects of an animal’s biology. Long ago, something drove the ancestors of the naked mole-rat underground. There the rodent’s biology and behavior began an evolutionary dialogue with the extreme conditions it encountered. This led to some highly unusual adaptations. Naked mole-rats are insensitive to some forms of pain, and have lifespans that exceed 32 years – ten times the norm for most other rodents. Only one or two cases of cancer have ever been detected in the species. And now MDC scientists have discovered that the animal can go with little or no oxygen for extraordinary lengths of time.

Such characteristics have attracted the interest of scientists around the globe – including neurobiologist Gary Lewin. Over several years, his laboratory has gained deep insights into the biology of pain by comparing the nervous system of the naked mole-rat to that of mice and humans. Upon learning that the naked mole-rat could cope with little or no oxygen, he was immediately intrigued – and his lab was well prepared to pursue the biology behind this unique attribute.

Linking oxygen deprivation to a unique metabolic system

Oxygen deprivation was clearly connected to the animal’s biology, lifestyle and environment. “Naked mole-rats huddle in huge, underground colonies of up to 280 individuals,” Lewin says. “This means that they continually experience sharp declines in levels of oxygen and dramatic increases in carbon dioxide. Without adaptations, this would be just as deadly to the naked mole-rat as it is to other animals.”

Most organisms on Earth are suited to the surface atmosphere, composed of about 21% oxygen and only tiny amounts of carbon dioxide (about 0.04%). Reducing oxygen to about 5% is fatal for a mouse within about 15 minutes; total deprivation causes fatal damage within about a minute. The naked mole-rat, however, can cope with as little as 5% oxygen and high levels of carbon dioxide for hours on end with no apparent distress or ill effects. And amazingly, it can survive at least 18 minutes without any oxygen at all.

“Under these conditions the animal enters a sort of suspended animation,” says Jane Reznick, a postdoc in Lewin’s group and a lead author on the current paper. “It falls asleep and its heartbeat slows to about a quarter of the normal rate. When oxygen is restored the heart rate rises, and the animal quickly wakes up and goes about its normal behavior.”

This hinted that some backup system was protecting its heart and brain – two organs that are highly sensitive to oxygen in other species. Without it, their cells cannot produce energy and rapidly suffer fatal damage.

Hitting the stop button on an assembly line

There had to be some fundamental difference in the naked mole-rat’s metabolism. To find it, the scientists enlisted help from the MDC’s Metabolomics Unit, headed by Stefan Kempa. His team uses advanced technology to capture global and quantitative snapshots of cellular metabolism. Their methods reveal the presence of tiny metabolites: molecules that are created through the processing of fuels like glucose. Networks of enzymes break glucose down into small products that move through the metabolic pipeline, generating energy along the way.

“These experiments are a bit like hitting the ‘stop’ button on an assembly line,” Kempa says. “If you were to do that in a factory, then look at partially assembled pieces and the bits that were tossed out, you’d get an idea of what was being built, and how it was constructed.” Further experiments traced the remnants of the sugars as they flowed through an alternative metabolic route that generated energy without consuming oxygen.

Comparing mouse and naked mole-rat tissues under conditions with and without oxygen revealed some curious differences. In naked mole-rats, oxygen deprivation triggered a shutdown of cellular energy factories called mitochondria. In the mouse they continued to operate but quickly malfunctioned – mitochondria need oxygen to run.

But the most startling finding had to do with the sugar molecules found in the animals’ blood and tissues. Overall, naked mole-rats had a lot less glucose than mice, which hinted that other sugars might be providing an alternative source of energy. During oxygen deprivation, there was a significant rise in levels of other sugars. Naked mole-rats had more sucrose – and truly stunning was the amount of fructose, which had skyrocketed.

Can tissues run solely on fructose fuel?

Could the naked mole-rat be using fructose rather than glucose as a source of energy? The two sugars weren’t that different – even our own bodies make use of fructose-based metabolism, although this only happens in the kidney and liver. These organs have an enzyme called ketohexokinase, or KHK, which can trim fructose into a form that can be plugged into the energy production line. From that point on the modified fructose, called F1P, is handled like glucose. Since the subsequent stages of processing don’t require oxygen, it wouldn’t be absolutely necessary in a metabolic system based on fructose.

“In humans, fructose metabolism occurs only in the kidney and liver because they’re the only tissues that contain KHK,” Lewin says. “We found that brain tissue from the naked mole-rat contained high levels of F1P – suggesting that KHK was at work – but only under oxygen deprivation. This told us two things: that their brains might really be using fructose as a source of energy, and that the switch only happened when oxygen grew scarce.”

The evidence for fructose metabolism was accumulating, but so far it was all indirect; the next step would be to determine whether the animals were actually using the alternative source of fuel. First the scientists performed experiments using brain tissue to test whether neurons could function if they were deprived of glucose and fed exclusively on fructose. While an hour of this treatment severely damaged the cells of mice, naked mole-rat neurons continued to show activity. Experiments carried out in Michael Gotthardt’s group showed even more dramatic results for the naked mole-rat heart, which could beat just as well when supplied with fructose as it could using glucose.

“This was proof that fructose can replace glucose as an energy source in the naked mole-rat brain and heart,” Reznick says. “It helps explain how these organs – and the animal as a whole – can recover from long periods of oxygen deprivation.”

A two-part system for switching to alternative fuel

Cells can only use fructose as an energy source if they can absorb it from their surroundings. This requires a protein called GLUT5, which snatches fructose and draws it into the cell. In mice and humans, GLUT5 appears in kidney and liver cells, but other tissues have almost none. It’s another factor that restricts fructose metabolism to the kidney and liver in humans and prevents it from serving vital organs such as the brain and heart. In the naked mole-rat those tissues – and most other cells – have at least ten times as much GLUT5.

“This gives the naked mole-rat a two-part system that allows it to survive long periods of oxygen deprivation,” Lewin says. “Throughout its body you find both the GLUT5 transporter and the KHK enzyme that converts fructose into a usable energy source.”

Fructose metabolism has been encountered in human diseases including malignant cancer, metabolic syndrome, and heart failure. This hints that there might be some link between the naked mole-rat’s metabolism, its resistance to cancer, and possibly even its extraordinary lifespan.  Only further research will tell – but the current study provides an interesting new handle on such questions.

“It’s important to understand how these unusual animals make the metabolic switch without any obvious long-term damage to their tissues,” Lewin says. “We might learn something about how our own cells attempt to cope with situations in which they are deprived of oxygen, such as strokes or heart attacks. Our work raises questions about the biology of fructose metabolism that will ‘fuel’ research for years to come.”

 

Russ Hodge

Thanks to Jana Schlütter and Martin Ballaschk for comments on an earlier draft.

Reference:

Thomas J. Park1, Jane Reznick2, Bethany L. Peterson1 , Gregory Blass1 , Damir Omerbašić2, Nigel C. Bennett3, P. Henning J.L. Kuich4, Christin Zasada4, Brigitte M. Browe1, Wiebke Hamann5, Daniel T. Applegate1, Michael H Radke5,10, Tetiana Kosten2, Heike Lutermann3, Victoria Gavaghan1, Ole Eigenbrod2,  Valérie Bégay2, Vince G. Amoroso1, Vidya Govind1, Richard D. Minshall7, Ewan St. J. Smith8, John Larson9, Michael Gotthardt5,10, Stefan Kempa4, Gary R. Lewin2,11 (2017): „Fructose driven glycolysis supports anoxia resistance in the naked mole-rat.“ Sciencedoi:10.1126/science.aab3896

1Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America; 2 Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 3Department of Zoology and Entomology, University of Pretoria, Pretoria, Republic of South Africa; 4Integrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 5Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 7Departments of Anesthesiology and Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America; 8Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom; 9Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, United States of America; 10DZHK partner site Berlin, Germany; 11Excellence cluster Neurocure, Charité Universitätsmedizin Berlin, Germany

Breaking the temperature barrier

With an advanced ERC grant, Thoralf Niendorf’s group will aim ultrahigh-field MRI at a critical, yet largely unexplored dimension of life

 

Temperature is one of the most rigidly controlled aspects of life, as seen by the very narrow range maintained in the tissues of warm-blooded animals. The heat briefly rises through fevers and inflammations as a part of immune responses to infections. But there has been a major obstacle to exploring this crucial dimension of life: scientists have not had a method to alter temperatures within living tissues.

Soon that may change thanks to an advanced ERC grant just awarded to Thoralf Niendorf’s group and his team, who work at the high end of magnetic resonance imaging (MRI) technology. “Every time a doctor takes an image using MRI, there’s a generation of heat,” Niendorf says. “The unknown impact of this has led to strict regulations governing the amount that can reach patient tissues. We’re hoping to take this side effect and turn it into a tool for research, new forms of diagnosis, and hopefully even therapies.”

That will require an instrument which can focus exact amounts of energy on precise, microscopic targets inside animal bodies. The group has found a way to build it: start with a new ultrahigh-field MRI instrument, then add a custom-designed array of radiofrequency transmitters to shape and focus its powerful magnetic field. The scientists have already worked out the theory and tested designs; now, with the new grant, they can build the machine.

At that point they will enter uncharted scientific territory. The first projects will involve thermal phenotyping studies – a term coined by the group – carried out in collaborations with scientists working on a range of systems. The goal is to determine whether various tissues have unique thermal properties that can be detected by MRI and might have diagnostic value. The next step will be to observe how tissues respond to highly focused increases in temperature. Disease-related processes may be susceptible in ways that could usher in new MRI-based therapies. A unique feature of this strategy would be the ability to deliver a treatment and monitor its effects simultaneously, using the same instrument.

Another part of the project will involve an ongoing collaboration with scientists in Sydney, Australia and Berlin who are building temperature-responsive polymers to deliver drugs or other molecules. These “nano-vehicles” can be introduced into the body, where they remain inactive until heated. They can be loaded with several substances which are released at different temperatures upon activation through MRI. The interest for research is that scientists could alter tissues in a step-wise manner, to control complex processes over time. And the same strategy could be used to strike a disease with successive blows, targeting different weaknesses.

“Planning this project has already drawn together a group of people with diverse expertise,” Niendorf says. “We’re excited about exploring this dimension of life in a truly interdisciplinary way. We can’t predict what we’ll find. But the fact that organisms keep temperature under such tight control hints at vitally important functions across the body.”

 

The original version of this article was published on the MDC website and can be seen here.

 

Before and after: Scientific writing

Here’s another text from a young scientist who is aiming to improve her writing. The intent of publishing it here is to show other students, teachers, and scientists the kind of work we do in communications courses. Most of the time we work individually, but here the author, Ekaterina Perets, has very generously allowed me to print the version of the text she wrote before we began working on it, alongside my comments and the final version. That text was recently published in the MDC newsletter Insights. You can see it here.

Ekaterina is a PhD student in Enno Klussmann’s lab at the MDC. As she began writing her doctoral thesis, she decided to produce a version of her abstract for non-specialists. It’s a useful exercise that challenges you to put your work into a broader perspective and look at it through other eyes.

Ekaterina wrote a solid first version of the text that we worked on for several days to produce the final draft that was published. Her goal was to tell her story clearly and accurately, in a way that would make sense to non-scientists and other researchers as well.  I have painstakingly gone through the drafts again to elaborate on some of the issues that arose and her solutions. These are things that pop up all the time in my courses on science writing. They are usually more difficult to see – and solve – in your own writing, which is why Ekaterina’s willingness to share is so valuable.

Considered in isolation, most of the problems aren’t too significant. In combination, though, they make more work for a reader who is already challenged by all the new ideas. The changes build a story that is easier to read and presents information at a pace that can be digested by a careful reader.

Enno helped by providing comments along the way. A particular challenge in the text arose from the fact that the work hasn’t been published yet, so Ekaterina had to remove some passages from the first draft – she didn’t want to reveal anything that might interfere with getting her article into a good journal.

It’s always possible to do more with a text; there are still passages that could be fuller, simpler, and clearer. But that’s the way it always is. As Mark Twain said, “The time to begin writing an article is when you have finished it to your satisfaction.” Somewhere he also stated, I believe, something to the effect that publication is the only way to force a writer to stop editing his piece.

(Mark Twain also advised writers to “Substitute ‘damn’ every time you’re inclined to write ‘very’; your editor will delete it and the writing will be just as it should be,” but perhaps that doesn’t apply here.)

So thanks, Ekaterina and Enno!


I’ve used the following structure: first comes Ekaterina’s complete original text (except for the passages that were removed). As you’re reading the original, make a note of anything that you think might cause problems for her target audience.

After the full original text I go it paragraph by paragraph, identifying specific issues that came up and showing how Ekaterina addressed them in her next draft.

That new version is assembled at the end. If you’re still alive at that point, it’s interesting to read the two side-by-side.


 

FIRST VERSION

An A-kinase anchoring protein regulates metabolism and motility in cancer cells

The ability of cancer cells to detach themselves from the initial tumor site, migrate and invade adjacent tissues signifies the first step of usually fatal distant metastasis. In order to achieve this, a complex organization of multiple intracellular processes initiates. Collectively, this transition is termed EMT (Epithelial-Mesenchymal Transition) and the ultimate goal of modern cancer research is to gain further insight into EMT induction and regulation.

While breaking bonds between cancer cells and initial tumor predicts poor prognosis, many proteins inside the cell require physical attachment to other proteins in order to function. Also, certain proteins have different roles depending on their location inside the cell and the switch between these roles occurs when the protein attaches itself to one cellular structure or to another. These kinds of attachments are usually facilitated by scaffolding proteins.

One example of location-dependent protein is GSK3β. When GSK3β is in the cytoplasm of the cell or in the nucleus, it has a main role in transferring biochemical information important for cells’ development as well as EMT. This information circuit is called the Wnt signaling pathway and it has been reported to malfunction in various tumors. However, when GSK3β in located in the cellular structures called the mitochondria, it transmits information required for survival or death of abnormal cells.

In addition to being location-dependent, GSK3β activity depends on physical interaction with other proteins. Under normal conditions GSK3β remains active and can be inhibited by a phosphate molecule placed on it by one of the proteins called kinases. One example of such a kinase protein is Protein Kinase A (PKA). The scaffolding protein in charge of bringing GSK3β and PKA in close proximity to each other in order to insure the transfer of the phosphate molecule from PKA to GSK3β belongs to the A-kinase anchoring proteins (AKAPs) family. AKAPs have in common the ability to bind PKA and direct it to a particular location inside the cell. Since this AKAP is able to regulate GSK3β activity via PKA by direct binding of the two proteins, elucidating the AKAP’s exact function in tumorigenesis is compelling.

Interestingly enough, when we delete the AKAP gene in a model cell line, thereby preventing the formation of the AKAP protein, …

(Here a section has been removed)

Reprogramming of cellular metabolism is another hallmark of cancer. Back in 1929, Otto Warburg first noted that rapidly growing cancer cells rely on different energy production methods than healthy slow-growing cells. He stated that cancer cells produced most of their energy in a process called anaerobic glycolysis, in contrast to healthy cells which preferred the highly-efficient energy production via oxidative phosphorylation (OXPHOS) which takes place in the mitochondria. The advantage of glycolysis over OXPHOS is the high speed in which energy is produced. While Warburg thought that all cancer cells switch to high-rate glycolysis, recent studies have shown that this is not entirely true; only rapidly growing and dividing cancer cells use glycolysis, while non-dividing or metastasizing cancer cells, prefer OXPHOS.

(Section removed)

In summary, this research demonstrated that the AKAP is required for both migration and metabolic control of lung cancer cells. However, the direct target protein of the AKAP remains to be found. Therefore, future work will aim to answer the “chicken or the egg” question; who was affected first by the AKAP, the EMT or metabolism?

Prospectively, our approach contributes to elucidating mechanisms underlying EMT and metabolic reprograming regulation in tumorigenesis and proposes this AKAP as a potential therapeutic target.


 

COMMENTS

In this section I walk through the text and comment on each issue as it arises. In classroom teaching it’s better to cluster problems of the same type and cover several examples before moving on to each new issue. This helps a student decontextualizes a problem and recognize it in their own writing. Here, for the sake of simplicity, I’ll stick to the order of the text. I’ll break it into paragraphs to discuss the overall information structure and transitions, then work through the sentence level to cover issues there.

First paragraph:

The ability of cancer cells to detach themselves from the initial tumor site, migrate and invade adjacent tissues signifies the first step of usually fatal distant metastasis. In order to achieve this, a complex organization of multiple intracellular processes initiates. Collectively, this transition is termed EMT (Epithelial-Mesenchymal Transition) and the ultimate goal of modern cancer research is to gain further insight into EMT induction and regulation.

 

I found this beginning logical; it starts with a concept that most readers are probably familiar with (“metastasis”) and moves to something that is probably new (EMT) that is crucial to the paper. Some of the sentences are dense, partly because they use words that are familiar but rather uncommon. If you can replace such words with more common terms without losing the meaning, it requires less “processing” by the reader. In a single sentence this may not be too important, but using such words constantly in a text makes it “heavier” and a bit tougher going overall.

In my own writing, I aim to compose sentences that make a point as clearly as possible, that can be understood the first time they are read, and whose structure links to the sentences that precede and follow them.

The first sentence will probably be accessible to the target audience (students and others who have no specialist knowledge of the field). It isn’t the easiest type of sentence for readers to decode because the subject (a list) goes on for a line and a half before we get the verb. There are several ways to avoid this:

Metastasis, which is usually the fatal stage in cancer, begins when...

Cancer cells take the first step toward metastasis… when they…

The sentence also contains several words and constructions that have alternates in more typical daily language: “The ability of… detach themselves (free themselves, break away from)… initial tumor site (the tissue where a cancer originally appears)… signifies (is)…” I wasn’t too concerned about this, but the phrase “usually fatal distant metastasis” compresses several ideas into a compound that is looser and will surely be easier to cope with after Ekaterina changed it to:

The ability of cancer cells to detach themselves from an initial tumor site, migrate and invade other tissues signifies the first step of metastasis, which is often the fatal step in cancer progression.

It’s always good to take out extra information if it doesn’t really contribute to the point at hand; here she has removed “adjacent” and “distant” and loosened the dense compound at the end of the first sentence by starting with a single, familiar word (metastasis) and adds a clause to provide the clarification or definition.

The second sentence begins with, “in order to achieve this,” which has unnecessary words (“To achieve this” would mean the same thing). “This” is vague because it refers to a complex process with many parts. “A complex organization of multiple intracellular processes” will be abstract to most readers, and it is dense because it compresses a sentence into a noun phrase. An alternative would be something like, “A number of complex processes within cells must be reorganized…” In the original version, again we have to wait quite a while for the verb (“initiates”), and most readers will find the sentence easier to scan with a shorter subject placed closer to its verb.

Here’s her solution:

Cells must reorganize a number of internal processes to initiate metastasis.

The next sentence starts with “collectively,” a word that’s common in scientific texts and a little more unusual in other styles. Its meaning should be clear, so we’ll leave it. But the reader must completely understand “what is being collected,” and there are ways to make this easier to scan.

I was worried that “the ultimate goal of modern cancer research” might be overstating her case: cancer is a vast field, whose ultimate goal is probably to cure the disease. EMT is surely a crucial step along the way, but other labs working on other aspects of cancer might have other “ultimate goals” and disagree. In her final version, she has toned this down.

“Initiate” and “regulate” are less-familiar than more common words such as “start” and “is controlled”, but it’s important to note that “regulation” has a particular scientific meaning. This is similar enough to the way most people understand the word that she might not necessarily want to change it. Here is her final version:

The ability of cancer cells to detach themselves from an initial tumor site, migrate and invade other tissues signifies the first stage of metastasis, which is often the fatal step in cancer progression. Cells must reorganize a number of internal processes to initiate metastasis. Collectively, the steps in this process are called the Epithelial-Mesenchymal Transition (EMT). An important goal of modern cancer research is to learn more about the molecules and processes that initiate EMT and influence the way it develops in a tissue.

 

Second paragraph:

While breaking bonds between cancer cells and initial tumor predicts poor prognosis, many proteins inside the cell require physical attachment to other proteins in order to function. Also, certain proteins have different roles depending on their location inside the cell and the switch between these roles occurs when the protein attaches itself to one cellular structure or to another. These kinds of attachments are usually facilitated by scaffolding proteins.

The connection between the introductory paragraph and this one is a crucial step along the way to Ekaterina’s complete, logical story. Her strategy raises an issue that often appears in writing about biomedical themes. When the experiments are finished and the results interpreted, it’s often possible to link something you have learned to cancer or another disease. That may have been the original intent of a project, or the connection may turn up while you’re pursuing some other question.

Either way, the claim will only be taken seriously if specific types of evidence are provided. In the type of work carried out at the MDC, this usually starts at a very basic level of a biological system, identifying a molecule, studying its activity in healthy cells, demonstrating what happens if it is missing or unable to perform its functions, and showing that the same type of disruption occurs in a disease.

This provides a logical framework to explain what you did – providing you approach things from the bottom up, from the lowest level of structure in an organism to one of the highest levels (health). But if your text starts with a disease, your entry point is high, and it’s harder to build the logic this way.

There are reasons to do so anyway: In popular science writing, diseases presumably attract readers out of a sort of diffuse self-interest: people are afraid of diseases and interested in progress toward cures. In scientific texts, diseases are often hung over a project like a big banner, perhaps to attract the attention of a wide community of cancer researchers, or to open the coffers of agencies that prefer to fund projects that will lead to real medical applications.

Whatever your reason, starting with the disease can introduce a structural problem in a story that is more logical when told the other way around. Ekaterina needs to jump from tumors and metastases to a scale that is millions of trillions of times smaller: interactions between proteins in cells. She wants to do that in the fewest steps possible so that she can start talking about her work. Her original draft uses a sort of logical slight-of-hand: she has introduced metastases and the notion that cancer cells have to detach themselves from their neighbors, and jumps to the idea that proteins have to attach themselves to structures inside cells. It’s awkward because she’s talking about things at vastly different scales, in different locations, and hasn’t provided any other logical connection between these events.

Ekaterina found a great solution to the problem by linking the two themes at a more profound level: cellular attachments and detachments depend on interactions between proteins – whether they bind to each other or not. Adding that connection makes the transition to the molecular scale much more logical:

Before a cancer cell can migrate away from its tumor, it has to detach itself by breaking its bonds to other cells, and this is generally a sign that the patient’s prognosis will be poor. The cell is usually tied to its neighbors and material in the space between them by proteins that are bound to each other; now these connections must be broken. The binding and unlinking of proteins, inside the cell as well as outside, is a general phenomenon that is crucial to every aspect of cellular life and has to be carefully controlled. Whether a protein binds to the right partner, and when and where it does so, can make the difference between life and death for a single cell or an entire organism.

A molecule’s location influences its ability to carry out its tasks, and its location is determined by interactions with other proteins that help attach it to a cellular structure or compartment. This often requires the participation of a “scaffolding” molecule which can bind to both the protein and the target membrane or structure it should be attached to; the scaffold provides a way of bringing them together.

Third paragraph:

One example of a location-dependent protein is GSK3β. When GSK3β is in the cytoplasm of the cell or in the nucleus, it has a main role in transferring biochemical information important for cells’ development as well as EMT. This information circuit is called the Wnt signaling pathway and it has been reported to malfunction in various tumors. However, when GSK3β in located in the cellular structures called the mitochondria, it transmits information required for survival or death of abnormal cells.

Here Ekaterina uses the concept of localization as a bridge between paragraphs; she just mentioned it, so readers should be able to follow her logic. Here I was concerned about the number of ideas that might be new which she introduced, and whether she had connected them to each other in the clearest possible way. Sometimes the simplest things make a text challenging to readers unfamiliar with basic concepts: What do they imagine when they read “transferring biochemical information,” and will they instantly relate it to the “information circuit” in the next sentence? The author can help by making connections excruciatingly explicit; readers who can’t follow your logic will have to invent one on their own, and rather than invest the effort, they may give up.

There are countless ways to build connectivity and make transitions. A lot of them don’t need to be as explicit when writing for scientists from your field. They are already familiar with concepts such as protein-protein binding and the logic that connects this theme to events at the scale of cells, including metastases.

Even in this type of communication, however, the writer has to be intensely aware of the logic that connects ideas to each other and the larger story; at that point you can make an intelligent decision about each transition. Is a connection really implicit, from the text? Would there be anything wrong with making it explicit? When giving someone directions to a party, it’s usually better to give too many directions than too few – within limits. If everyone you’re inviting lives in town and is familiar with the same landmarks nearby, you won’t need to start with a map of contintental Europe. In the same way, a scientist doesn’t need to be told that your body is made of cells.

As always, the amount of information and logic you choose to present should be guided by a realistic guess about the knowledge of your intended audience. Ekaterina added more linkage and rearranged some of the points within sentences to produce this version:

One example of a protein whose activity depends on its location is a molecule called GSK3β, which has been found to malfunction in various tumors. When GSK3β is in the cytoplasm or the nucleus, its main role is to transmit information needed during cells’ development and for the regulation of EMT. In these two locations, the main function of GSK3β is mainly to send signals along a molecular “information circuit” called the Wnt signaling pathway. But GSK3β can also be found within other cellular structures called mitochondria. There it transmits information along a different route, with different effects: the signal helps determine whether abnormal cells survive or die. Both locations and signals play a role in whether cancer cells grow, survive, and metastasize. They may only be able to do so by interrupting the signals that GSK3β normally transmits to other proteins. Therefore, ensuring that GSK3β is in the proper location and functions correctly is probably crucial in cancer prevention and treatment.

 

Fourth paragraph:

In addition to being location-dependent, GSK3β activity depends on physical interaction with other proteins. Under normal conditions GSK3β remains active and can be inhibited by a phosphate molecule placed on it by one of the proteins called kinases. One example of such a kinase protein is Protein Kinase A (PKA). The scaffolding protein in charge of bringing GSK3β and PKA in close proximity to each other in order to insure the transfer of the phosphate molecule from PKA to GSK3β is a member of the family of A-kinase anchoring proteins (AKAPs).

Here there are clear links to the previous paragraph (GSK3β and localization) and Ekaterina connects this to a topic introduced earlier: protein-protein binding. But within the paragraph, it’s not always immediately clear how each new idea arises from the previous one – at least until you have read the whole sentence. The first sentence, for example, ends with protein interactions, a theme also taken up in the next sentence – but only after the introduction of a new idea (phosphorylation), and the link between the two ideas comes at the end. The reader has to wait for the author to close the gap. The alternative is simply to change the order of information within sentences to get a better flow.

English permits great flexibility in the arrangement of phrases within sentences. Word order can be used to establish (or at least support) the logical flow and to transmit other kinds of meaning. Each sentence is like a story that begins somewhere and takes us somwhere else, and the next sentence can start right at that point and move on.

That is much more difficult in a language like German, where sentence structure is much more rigid: putting almost anything before a subject requires an inversion that pushes the main verb all the way to the end – so you often have to process entire sentences to grasp their connections. German readers are used to this and may, fundamentally, be better at it.

Ekaterina’s native language is not German, but she has used this type of sentence structure. To represent the problem symbolically, an arrangement of ideas is probably easiest to follow if it looks something like this:

A – B; B – C; C – D… etc.

If a sentence contains three pieces of information as Ekaterina’s does, this may be harder. But the arrangement in the first two sentences look more like this:

A – B – C. D – B – A

(A = localization. B = activity. C = protein interactions. D = phosphorylation. B = activity. A = interactions)

Rearranging this to create a more linear storytelling structure would change this:

In addition to being location-dependent, GSK3β activity depends on physical interaction with other proteins. Under normal conditions GSK3β remains active and can be inhibited by a phosphate molecule placed on it by one of the proteins called kinases.

….to something like this:

GSK3β’s activity depends on both its cellular location and its direct physical interactions with other proteins. By binding to a protein called a kinase, for example, it acquires a chemical tag called a phosphate group. This has an important fact: it inactivates GSK3β and switches off signals when a message has been received.

It’s not easy to carry this approach through to the end of the paragraph, because most of the sentences convey more than two ideas. That means shuffling and combining them in other ways. And a linear structure isn’t always appropriate: it’s good when describing a sequence of events, or when “zooming in” from a general idea to a specific one. Sentences that introduce lists, however, would be structured differently.

Suppose Ekaterina had introduced the topic this way: “In different cellular locations, GSK3β interacts with different sets of proteins and has different functions.” If examples follow, the clearest structure would be to construct the information the same way: “In the cell nucleus, GSK3β binds to specific proteins as a way of transmitting signals… In the cytoplasm it functions the same way. But when it is located in structures called mitochondria, …”

Ekaterina’s found a different solution that has the same effect: within sentences, the order of ideas reflects the logic that connects them:

GSK3β’s location and activity are the result of interactions with other proteins. When GSK3β binds to a molecule called Protein Kinase A (PKA), for example, PKA transfers a chemical tag called a phosphate group to it, which switches off the signaling activity of GSK3β. The tag can only be transferred if the two molecules are brought into direct contact, a process that is arranged by scaffolding proteins such as members of the family of A-kinase anchoring proteins (AKAPs).

This brings Ekaterina directly to the heart of her project. At this point the reader has been introduced to all the main players in the story, and now she is going to guide us to the specific question she is asking and the way she chose to pursue it.

 

Fifth paragraph:

AKAPs have in common the ability to bind PKA and direct it to a particular location inside the cell. Since this particular AKAP is able to regulate GSK3β activity via PKA by direct binding of the two proteins, elucidating the AKAP’s exact function in tumorigenesis is compelling.

Here there is another dense cluster in the first sentence: “A-kinase anchoring protein (AKAP) family,” which she will loosen in the final draft. In the second, “have in common the ability to” is awkward (and grammatically suspect because a phrase is interposed between the verb and its object).

The third sentence is interesting for another reason. It seems to fit the principles we have covered – it begins with points that have already been introduced and then builds a link to the overarching topic: the development of tumors and metastases. This raises a different issue related to information density. “Since the AKAP is able to regulate GSK3β activity via PKA by direct binding of the two proteins” combines several pieces of information that the reader has learned moments ago. That integration is important, but readers will only understand it if they have digested what they’ve learned. It’s a bit like introducing someone to three new words in a foreign language and a new grammar rule, and then immediately presenting him with a sentence that combines them all. He may understand it, but you shouldn’t expect him to.

Here’s how Ekaterina loosened it up:

AKAPs share a common feature: the ability to bind PKA and transport it to a particular location inside the cell. This means that the AKAP not only interacts with both GSK3β and PKA – it also directs them to specific locations in the cell. That’s interesting because PKA also has many roles in the development of tumors.

In the new draft she decided to expand on this by reminding readers of a point she had raised earlier:

Now three molecules are bound together: the AKAP, PKA and GSK3β. This puts PKA close enough to transfer a phosphate group onto GSK3β and block its activity. Since both of these molecules have been implicated in the development of tumors, it makes sense to wonder whether the AKAP, the protein that brings them together, might also have a role in the disease. If so, we would probably expect to find a disruption of the normal activity of the AKAP, but its functions in healthy cells have been unclear.

 

Sixth paragraph

At this point Ekaterina has introduced the main question of her research, which is something like this: “Are the cancerous effects of GSK3β sometimes related to the fact that it is in the wrong place and/or its ability to interact with important partners such as PKA? And if so, could defects in the AKAP be responsible?”

Her thesis project required breaking this question down into smaller parts, designing experiments to address each part, and then assembling the results into a satisfactory answer. In the sixth paragraph she introduces part of the experimental strategy:

Interestingly enough, when we delete the AKAP gene in a model cell line, thereby preventing the formation of the AKAP protein, …

She hasn’t explicitly explained the rationale for this experiment – which any scientist will understand, but what about non-specialists? There’s an easy way to make sure they get the point:

A common method to discover the function of a molecule is to remove it from cells where it is normally found and observe what happens to them. We did this with the AKAP by deleting its gene in a line of cells that we use as a model in the lab, which left the cells incapable of producing the AKAP protein. We discovered that its removal affects a number of processes that are specifically involved in metastasis and other aspects of the development of tumors.

Next Ekaterina confronts a technical problem: She can’t describe some of her experiments or present the results until they have been published in a scientific journal. Giving away too many details, even in the MDC newsletter, would be grounds for the rejection of her paper by a journal – which typically refuses to publish work that has already appeared.

Her solution is to address the reader directly and frankly, explaining why she doesn’t go deeper into the project:

For the details you’ll have to wait for the paper. For now we can say that the silencing of the AKAP affects the behavior of other proteins that play crucial roles in signaling, EMT, and also cell metabolism, the process by which cells produce the energy they need. Cancer cells have different energy needs than healthy cells, and the reprogramming of cellular metabolism is another hallmark of cancer.

Metabolism is another theme she wants to introduce because it has an important role in her thesis, and she finds a great way to do so using history:

Back in 1929, Otto Warburg first noted that rapidly growing cancer cells rely on different energy production methods than healthy slow-growing cells. He stated that cancer cells produced most of their energy in a process called anaerobic glycolysis, in contrast to healthy cells which preferred the highly-efficient energy production via oxidative phosphorylation (OXPHOS) which takes place in the mitochondria. The advantage of glycolysis over OXPHOS is the high speed in which energy is produced. While Warburg thought that all cancer cells switch to high-rate glycolysis, recent studies have shown that this is not entirely true; only rapidly growing and dividing cancer cells use glycolysis, while non-dividing or metastasizing cancer cells, prefer OXPHOS.

This is a good storytelling because it gives readers a character to latch onto. By placing her project in a historical context, she is also saying more, by implication: her work addresses an issue so fundamental in cancer research that it has occupied scientists for nearly a century.

All along the way Ekaterina confronts important decisions about the amount of information a reader really needs to get the gist of her work. Here she decides to introduce two types of metabolism that she names without going into much detail; it’s enough to contrast them based on the sites in cells where they occur and a parameter that is related to cancer (speed). I recommended sharpening the contrast by expanding on the idea in this sentence:

The advantage of glycolysis over OXPHOS is the high rate at which energy is produced.

Here’s what she came up with:

This link was discovered back in 1929, when the German scientist Otto Warburg became the first to note that rapidly growing cancer cells rely on methods of energy production that are different than those used by healthy, slow-growing cells. He stated that cancer cells produced most of their energy in a process called anaerobic glycolysis. Healthy cells, on the other hand, favored a type of energy production based on a process called oxidative phosphorylation (OXPHOS), which takes place in the mitochondria. The difference has to do with speed and efficiency: glycolysis produces energy at a very high rate, while OXPHOS is geared toward efficiency, and is more sustainable over the long term. While Warburg thought that all cancer cells switch to high-rate glycolysis, recent studies have shown that this is not entirely true; only rapidly growing and dividing cancer cells use glycolysis. Non-dividing or metastasizing cancer cells prefer OXPHOS. When you read the paper you’ll see how we demonstrated the AKAP’s effects on metabolism and how we interpret them in terms of the dysregulation of metabolism and EMT.

(Section removed)

The reader has to guess how this might relate to her project, but some clues are available: OXPHOS takes place in the mitochondria, which is one of the sites where GSK3β is found… Hmm…

Now all that’s left is to sum up. The conclusion is crucial because it gives the author a chance to put everything back together, to show how she has answered the scientific question posed at the beginning, and to frame the story she wants the reader to remember it. Here’s what she wrote for the first draft:

In summary, this research demonstrated that the AKAP is required for both migration and metabolic control of cancer cells. However, the direct target protein of the AKAP remains to be found. Therefore, future work will aim to answer the “chicken or the egg” question; who was affected first by the AKAP, EMT or metabolism?

Prospectively, our approach contributes to elucidating mechanisms underlying EMT and metabolic reprograming regulation in tumorigenesis and proposes the AKAP as a potential therapeutic target.

The main changes she ends up making have to do with phrasing, word order, and making sure her logic (which would be clear to any scientist) will also make sense to readers less familiar with buzzwords like “elucidating mechanisms” and “potential therapeutic target.” She gets rid of clusters like “contributes to elucidating mechanisms underlying EMT and metabolic reprogramming regulation in tumorigenesis.” By now most of those terms will have confronted the reader, but the conclusion is the last place you want the text to get dense.

A lot of questions remain: other proteins directly affected by the AKAP have yet to be found. The project raises a “chicken-or-egg” question, in which EMT is the chicken and metabolism the egg: which process does the AKAP influence first? Our approach should contribute to understanding the mechanisms that produce some of the changes in these processes that are observed as tumors arise from healthy tissue and then become metastatic. And it hints that the AKAP might make a therapeutic target. This would be useful because AKAPs have features that might permit fine-tuning their effects with drugs. By doing so, it might be possible to alter the behavior of GSK3β in one location, where its activities contribute to disease, without affecting its healthy functions.

Below I provide the final version. As Ekaterina lives with this text, she’ll find that she could come back time and time again and improve it with editing. It’s a writer’s curse – to recognize weaknesses in old texts that have been published and you can no longer change. The important thing is what you learn when you mak the effort.


 

FINAL VERSION

Can a small A-kinase anchoring protein play a big role in cancer? A report from the lab bench

The ability of cancer cells to detach themselves from an initial tumor site, migrate and invade other tissues signifies the first stage of metastasis, which is often the fatal step in cancer progression. Cells must reorganize a number of internal processes to initiate metastasis. Collectively, the steps in this process are called the Epithelial-Mesenchymal Transition (EMT). An important goal of modern cancer research is to learn more about the molecules and processes that initiate EMT and influence the way it develops in a tissue.

Before a cancer cell can migrate away from its tumor, it has to detach itself by breaking its bonds to other cells, and this is generally a sign that the patient’s prognosis will be poor. The cell is usually tied to its neighbors and material in the space between them by proteins that are bound to each other; now these connections must be broken. The binding and unlinking of proteins, inside the cell as well as outside, is a general phenomenon that is crucial to every aspect of cellular life and has to be carefully controlled. Whether a protein binds to the right partner, and when and where it does so, can make the difference between life and death for a single cell or an entire organism.

A molecule’s location influences its ability to carry out its tasks, and its location is determined by interactions with other proteins that help attach it to a cellular structure or compartment. This often requires the participation of a “scaffolding” molecule which can bind to both the protein and the target membrane or structure it should be attached to; the scaffold provides a way of bringing them together.

One example of a protein whose activity depends on its location is a molecule called GSK3β, which has been found to malfunction in various tumors. When GSK3β is in the cytoplasm or the nucleus, its main role is to transmit information needed during cells’ development and for the regulation of EMT. In these two locations, the main function of GSK3β is mainly to send signals along a molecular “information circuit” called the Wnt signaling pathway. But GSK3β can also be found within other cellular structures called mitochondria. There it transmits information along a different route, with different effects: the signal helps determine whether abnormal cells survive or die. Both locations and signals play a role in whether cancer cells grow, survive, and metastasize. They may only be able to do so by interrupting the signals that GSK3β normally transmits to other proteins. Therefore, ensuring that GSK3β is in the proper location and functions correctly is probably crucial in cancer prevention and treatment.

GSK3β’s location and activity are the result of interactions with other proteins. When GSK3β binds to a molecule called Protein Kinase A (PKA), for example, PKA transfers a chemical tag called a phosphate group to it, which switches off the signaling activity of GSK3β. The tag can only be transferred if the two molecules are brought into direct contact, a process that is arranged by scaffolding proteins such as the members of the family of A-kinase anchoring proteins (AKAPs).

AKAPs share a common feature: the ability to bind PKA and transport it to a particular location inside the cell. This means that the AKAP not only interacts with both GSK3β and PKA – it also directs them to specific locations. That’s interesting because PKA also has many roles in the development of tumors.

Now three molecules are bound together: the AKAP, PKA and GSK3β. This puts PKA close enough to transfer a phosphate group onto GSK3β and block its activity. Since both of these molecules have been implicated in the development of tumors, it makes sense to wonder whether AKAP, the protein that brings them together, might also have a role in the disease. If so, we would probably expect to find a disruption of the normal activity of the AKAP, but its functions in healthy cells have been unclear.

A common method to discover the function of a molecule is to remove it from cells where it is normally found and observe what happens to them. We did this with the AKAP by deleting its gene in a line of cells that we use as a model in the lab, which left the cells incapable of producing the AKAP protein. We discovered that its removal affects a number of processes that are specifically involved in metastasis and other aspects of the development of tumors.

For the details you’ll have to wait for the paper. For now we can say that the silencing of the AKAP affects the behavior of other proteins that play crucial roles in signaling, EMT, and also cell metabolism, the process by which cells produce the energy they need. Cancer cells have different energy needs than healthy cells, and the reprogramming of cellular metabolism is another hallmark of cancer.

This link was discovered back in 1929, when the German scientist Otto Warburg became the first to note that rapidly growing cancer cells rely on methods of energy production that are different than those used by healthy, slow-growing cells. He stated that cancer cells produced most of their energy in a process called anaerobic glycolysis. Healthy cells, on the other hand, favored a type of energy production based on a process called oxidative phosphorylation (OXPHOS), which takes place in the mitochondria. The difference has to do with speed and efficiency: glycolysis produces energy at a very high rate, while OXPHOS is geared toward efficiency, and is more sustainable over the long term. While Warburg thought that all cancer cells switch to high-rate glycolysis, recent studies have shown that this is not entirely true; only rapidly growing and dividing cancer cells use glycolysis. Non-dividing or metastasizing cancer cells prefer OXPHOS. When you read the paper you’ll see how we demonstrated the AKAP’s effects on metabolism and how we interpret them in terms of the dysregulation of metabolism and EMT.

A lot of questions remain: other proteins directly affected by the AKAP have yet to be found. The project raises a “chicken-or-egg” question, in which EMT is the chicken and metabolism the egg: which process does the AKAP influence first? Our approach should contribute to understanding the mechanisms that produce some of the changes in these processes that are observed as tumors arise from healthy tissue and then become metastatic. And it hints that the AKAP might make a therapeutic target. This would be useful because AKAPs have features that might permit fine-tuning their effects with drugs. By doing so, it might be possible to alter the behavior of GSK3β in one location, where its activities contribute to disease, without affecting its healthy functions.

 

The dinner party: Learning to explain your research to a general audience can make you a better scientist

Nobel Prize winners customarily deliver two talks about their work during the official award ceremonies in Stockholm. One is a scientific statement about the research for which they have won the award and their perspective on its importance to their field. The second is the “banquet speech,” aimed at a more general audience. These banquet speeches are often remarkable examples of scientific communication and are the best refutation of the idea that it takes convoluted language to express complex ideas. Clarity is, in fact, a much harder art to master.

After interviewing a number of these exceptional people, I have become convinced that the connection between excellent science and clear communication is no accident. What links them is a style of thought that always manages to “see the forest for the trees:” the choice of just the right experiment, at just the right time, which suggests an important new model or clarifies an existing one, resolves some important debate within a field or establishes an entirely new direction for research.

Contrast this with another type of “banquet speech,” a dinner party at which someone asks you about your work. Well, what you did today was try for about the 50th time to get an experiment to work. As you fumble for an explanation, you realize that the person you’re talking to has never heard of the things you’re working on and lacks a real understanding of basic concepts like genes, signaling pathways, and transcription factors. You’re lucky if they’ve heard of the type of cell you’re working on, and why on Earth would somebody care about the biology of a worm?

You’ve been at your project so long that it’s often hard even to see the tree, let alone the forest, for all the leaves. At some point you notice that the person who asked the question has a glazed look on his face and is drinking a lot of wine.

Is there an easy solution? And if it’s true that excellent science and good communication go hand in hand, can you become a better scientist by improving your communication skills? After many years of helping researchers develop their writing and presentations, I think the answer is a resounding “yes”. While communications courses are often lumped into a broader category of “soft skills,” they ought to be regarded as central components of a scientific education. In some countries that is the case, but other educational systems – particularly in mainland Europe – scientists receive little or no help in learning “a skill that is inherent to every field,” to cite writer and educator William Zinsser.

Very few of us have the kind of mind that quickly and naturally sorts information into a clear structure and – on the first try – translates our thoughts into the linear form of language, in a way that allows a reader or listener to reconstruct complex ideas. (An amazing exception is Barack Obama; look at the word-for-word transcripts of his Presidential debates and compare both the conceptual structure and syntax of his answers with those of other candidates.) But even professional writers don’t normally have to get everything fine the first time. It’s usually fine to start with a rather scrambled draft and recover or introduce structure in revisions.

Even when you’re finished, however, there is no guarantee that your text will be suitable as a “dinner speech;” this requires something more. Explaining your science at a dinner party requires a certain style of thinking that is a sort of worst-case scenario for other communicative situations. It can be made easier by preparing properly for the task – a process that is equally important and useful when communicating with experts. That process is crucial both to successful communication and successful science.

* * * * *

Most biomedical research is devoted to working out the exacting details of some biological process. Experiments generally aim to answer a very specific question, but both the question and any answer you might receive only make sense in the context of an intricate set of assumptions and models. Most projects aim to validate a particular hypothesis, or extend an existing model to a new situation, or refute it. You may be applying a new technology to quantify something that couldn’t be measured before, or using a new tool to explore a set of data. Whatever your project, it acquires its meaning through a particular type of dialogue with what scientists already know as they try to expand current knowledge to fit a new situation, or venture into unexplored territory.

Students absorb a number of models during the course of their studies, usually becoming so familiar with a framework of ideas that certain patterns become habitual, stylized, practically subconscious, and thus “invisible”. For example, the connection between DNA, RNA and proteins is so common that scientists use the same name to identify three different types of molecules, in different species, and switch comfortably back and forth between them as they discuss their functions in model organisms and humans. Along the way they often completely lose a listener who does not have the relationships of these molecules firmly in mind.

Subconscious models and structures may create obstacles as you do science because a scientist might not fully comprehend the architecture of assumptions on which an experiment is based in the first place. This might make it difficult to understand results that run counter to expectations. Does the problem lie with an experimental setup, or the way a model has shaped a hypothesis, the model itself, or some far more general assumption? It may be impossible to decide without a very clear understanding of the relationship between a question and much more general structures of thought.

Even the most fundamental links between ideas in a field may be unclear to non-scientists and hinder communication at a very basic level. When this is likely to happen, the underlying frameworks need to be exposed and articulated. This suggests a strategy for communication that can work with a range of target audiences. Below I will describe one means by which we achieve this in science writing and presentation courses.

The first step is to force students to articulate a precise scientific question as clearly as possible. Take, for example, the following: “What small molecules could disrupt the binding of a protein to a transcription factor, and what chemical/structural features permit them to do so?”

As a grammatical sentence, this can be decoded, to a certain degree, by any native speaker – but its meaning to a scientist depends on both knowing particular facts and relating them to a much broader base of knowledge. The two go hand in hand. Defining a “transcription factor” requires placing a type of protein into the context of a larger story about cell structure and behavior. “Binding” and “structural features” have to do with the chemical subunits of molecules, the three-dimensional arrangement of atoms in these subunits, and how this architecture influences a protein’s activity.

To give a sense of the meaning of this question to a non-specialist, a researcher needs to relate it to a hierarchy of more general questions, models, and “stories” that scientists agree on. There will be several possible approaches, because any given question is usually embedded in different types of schemes. For example, the interaction between two molecules is part of a “chemical” story about the features that allow them to bind. Another type of story has to do with biological functions. Transcription factors usually are usually the penultimate steps along “biochemical signaling pathways.” These information routes through the cell usually start with a stimulus at the cell surface, trigger a signal that is passed from one molecule to the next, and then alter the transcription factor so that it moves to the cell nucleus. There it docks onto DNA and changes the pattern of active and silent genes. All of these pieces of information need elaboration – the scientist’s job in a communication exercise! – and below is an example of how it can be done.

Either type of story can be converted into a hierarchical “tree” that starts with the specific form of the question and links it to higher-level themes. Each step in the list below represents a way of connecting the specific question to a more general question or a larger story:

• What chemical/structural features determine whether a specific protein can bind to a specific transcription factor?

• What proteins can bind to this transcription factor, how do they change its behavior, and what genes does it go on to activate?

• How do molecular signals or environmental factors change gene expression patterns?

• How do cells respond to changes in their surroundings during development, the onset of a disease, stress, or some other situation?

• What are the basic components of our bodies and how do they influence our lives and our health?

This process of moving from the specific to the very general provides a structure for extending the meaning of findings both “horizontally” (to other molecules and processes with similar structures and functions), and “vertically” (to more basic principles of living systems). It also provides a system that can be used when dealing with a particular target audience. Everyone is probably interested in the last question, which involves very basic aspects of life and our bodies. This provides a level at which you can “meet” the listener and guide him or her into the story in a structured way, as a sort of dialogue headed for more specific questions and answers.

After stating that you’re trying to study life by understanding its basic components – molecules – you can point out that our bodies begin as single cells that differentiate. This usually happens through a process by which cells receive molecular signals from their surroundings. Those signals begin at the cell surface and are passed along from molecule to molecule inside the cell, until they reach a transcription factor. The role of this protein is to activate new sets of genes, changing the components of cells, and thus giving different types of cells new structures and functions. The aim of your work is to understand what characteristics allow a molecule to activate the transcription factor. Why is this interesting? Well, one reason is just to learn basic things about cell functions and fates. And of course diseases often disrupt signaling pathways, and your work may help explain why this happens – as well as suggest points at which therapies can intervene.

This description simply moves upward through the tree, from the general to the specific, and it provides a structure for the story. The information will need to be enhanced, broken down into “digestible” bits, and compared to things that the audience is familiar with, using metaphors and other tools. But at least you have told a story that is logical and gets to the point – what you have actually done, and its relevance.

Where you start in the hierarchy depends on your best guess about the level of prior knowledge of your audience. If you have overestimated what they know, and start with a point that is too specific, you will lose listeners right away. When talking to biologists, on the other hand, you can assume that they already understand basic concepts like signaling pathways and their effects. They may not, however, be familiar with the specific pathway you are interested in, the molecules that are involved, or its particular biological functions. At this point you can start close to the end, with the second question in the list above.

I’ve often heard students “throw in the towel” when they try to explain their work to non-specialists: “To understand what I’m doing, you’d have to have a complete course in molecular biology.” Again, using the example of a transcription factor, it’s probably enough to discuss how a molecule is related to the activation of different sets of genes, that this changes populations of molecules in a cell, and those in turn change a cell’s form and functions. You don’t really need to explore what happens next – alternative splicing, or the many other levels of post-transcriptional regulation – to get the point across.

If you’re talking to biologists, going too far in the other direction and explaining a point like, “Cells respond to environmental stimuli” would seem silly. Saying something far too general such as, “I’m trying to cure cancer,” when what you’re really doing is studying a particular transcription factor, would be equally ridiculous. Of course your work may have implications for a disease – note all of those sentences that typically come at the end of the discussion section of a paper: “So this study suggests new potential targets in the development of rational therapies in the treatment of cancer.” But it doesn’t explain the real scientific relevance of what you have done.

* * * * *

Communication is most effective when you regard it as a dialogue rather than a one-way transmission of information. The hierarchical tree suggests a dialogue structure in which you begin with a question that your target audience might really ask, or at least be interested in, and then guide them to the particular point you want to make. It also helps you make logical decisions about what information is necessary – and especially what isn’t! – in making a particular point.

There are many more elements in successful communication – including the use of powerful images and metaphors that capture the essence of a particular biological entity or process. Metaphors are crucial as scientists learn about their field and try to convey complex ideas to their colleagues. But the first step in convincing scientists to develop their communication skills depends on showing them that even the “dinner party talk” can improve their science.

The link lies in connecting the general to the specific, in relating a piece of work to a hierarchy of models and stories in which it is embedded, and here is the connection between doing better science and communicating it well. It is an essential strategy in the courses I am developing. It is always wise to clearly articulate the models and mental structures upon which a particular piece of work is based; these relationships tell you how far a particular result can be extended to other molecules, processes, or biological functions. They are equally useful in developing strategies to communicate science to just about anyone. Nobel laureates understand this very well, and we can all learn something from their example.