This week’s themes:
Structural biology, ion channels, and small-molecule screening!
Same rules as always: Feel free to use or repost, if you accompany the image with the citation:
copyright 2016 by Russ Hodge, http://www.goodsciencewriting.wordpress.com.
Feel free to repost and use, accompanied by the text “copyright 2016 by Russ Hodge” and a link to this blog!
And now some singles…
In honour of the ongoing CRISPR/Cas patent fight… Here’s another one anyone can use if you cite:
copyright 2016 Russ Hodge, goodsciencewriting.wordpress.com
Download and repost as you like, just remember to add “copyright 2016 by Russ Hodge” – and point people to this blog if you like.
Today I’m adding a new feature to the blog: Cartoons on themes related to molecular biology. Scientists, teachers, and others are welcome to download and use the images posted on the blog provided they are always accompanied by the following attribution:
copyright 2016 by Russ Hodge
These are usually “insider” jokes that require knowing something about biology, so I will accompany each with a very short text (and yes, having to explain a joke is the quickest way to kill humour… Ah, well…)
Chromatin is the form of DNA found in the cell nucleus, with a lot of proteins and other molecules attached to it. During phases of the cell’s life when genes are active, chromatin appears in a loose form – like a bunch of yarn spilled onto the floor. (It’s actually highly organised and scientists are currently learning a lot about how the locations of strands are controlled.) Before cell division, chromatin condenses into a tightly packed form – the chromosomes. After cell division it expands again, giving other molecules access to genes so that they can be transcribed into RNA molecules.
Mitosis is a crucial step in cell division. It takes place after the cell’s pairs of chromosomes have been copied. They are split into two equal sets that will form the genomes of the two new daughter cells. This requires pulling them to opposite sides of the cell. Usually this happens when microtubule “tow-lines” reach from the chromosomes to a cluster of molecules at either pole, called centrosomes. Disruptions of this process can lead to daughter cells with an unequal number of chromosomes, a condition called aneuploidy.
Festschrift
on the occasion of
Carmen Birchmeier’s 60th birthday
“It’s complicated.”
– Walter Birchmeier
Abstract
In 2013, unbeknownst to most of her colleagues, friends, enemies, distant cousins, and predoctoral students, although not necessarily in that order, Carmen Birchmeier adapted ancient procedures from Medieval alchemists, added some spices from old family recipes, and developed a method of extracting human brains from their natural environment and maintaining them in vitro in the lab. The second step was somewhat harder than the first. Debrainings have been performed before, of course, but the methods remain nearly as labor-intensive and time consuming as they were thousands of years ago. Birchmeier’s innovation was to develop an automated, high-throughput pipeline. But the more serious bottleneck was Step 2: keeping a human brain alive in the lab for more than, say, 10 seconds. That’s where the spices came in.
Once the brains were surviving long enough, Carmen’s carried out some relatively successful experiments to replace the brain in the head, usually that of the original owner, although in one case some sort of administrative error led to what is probably best termed an “involuntary exchange.” The problem was not detected for quite some time because as it turned out, each of the brains preferred its new habitat. Each brain knew that it was in the other body, but it didn’t know whether the other brain knew, and if it didn’t know, well what it didn’t know wouldn’t hurt it. This led to some strange conversations in which everyone was pretending to be someone else, which can be confusing, especially when you were sitting across from yourself. But you don’t need to know any of this. In fact, just forget the last paragraph, because nothing in it reached statistical significance.
The lab attempted to publish a paper on the subject, but reviewers rejected it on the grounds that it was “merely methodological” and “unlikely to have any practical clinical applications.”
Because she feels, however, that this work might be useful to other neuroscientists, her lab has collected a number of protocols describing the proper treatment of brains in the laboratory. This document is intended as a guide to other groups who might be interested in replicating her work.
– Russ Hodge, 2015
Hold the brain between your two hands and give it a gentle squeeze. A healthy brain should have the consistency of cauliflower. Is it firm or squishy? Does it smell like alcohol, garlic, or cigarette smoke?
Which type of cheese does the brain resemble most?
Perform the “drop test:”
Check overall symmetry by rolling the brain over a level surface. If the owner has worn a hat for many years, it may be squished on one side.
Before removing the brain, you should obtain a general sense of its overall function. Since brain functions are based on electrochemical energy, two simple tests can be performed:
2. Insert a USB cable into the ear and see if the brain appears as an external device on your Mac computer (OS X.7 or higher). If you do not see the “brain” symbol on your desktop, try to mount it using the Disk Utility. If this does not succeed, try another brain. If the brain is password-protected, ask the owner for permission to access it.
If kept outside the body for long periods of time, brains should be occasionally turned to avoid bedsores.
There is anecdotal evidence that brains enjoy an occasional massage.
If the brain is to be replaced in a new body, use a powerful magnet to erase old memories. The operating system may need to be reinstalled.
Brains may be frozen. For defrosting, use the LOWEST setting on the microwave oven.
The “three-second rule:” If a brain is accidentally dropped, but picked up within three seconds, it is unlikely to be contaminated. Simply brush off any visible dirt.
The brain’s expiration date should be written somewhere on the bottom. Check the date before reinstalling a brain. A brain may be kept past this date if it has been refrigerated and does not smell. Expired brains can be fed to pets.
Meticulously record all tune-ups and repairs in the service manual, which is generally found in a pocket inside the skull near the left ear.
Do not use the brain in games of Nerf basketball or other sports activities.
Do not allow pets to play with brains.
Don’t let the brain get bitten by mosquitoes. The itching will drive it insane.
Brains sunburn very easily, so any brain exposed to sunlight should be generously coated with a sun-blocker with a rating of 50 or above.
Advise patients to get brain insurance before any procedure so that they can receive compensation in case anything goes wrong, providing they remember.
Brains often shrink slightly when stored outside the body. Upon reimplantation, use bubble packing to make up for the extra space.
If the brain seems too large for the skull upon reimplantation, use Vaseline or some other petroleum-based lubricant to ease it in.
If you have replaced a brain and notice some extra parts lying around, such as the hippocampus, just put them in wherever there is space. They will automatically migrate back to the proper position.
A reimplanted brain may need to be reanimated with an electric charge to function. Any normal taser will do. Stick the business end in one ear and deliver a charge until the patient tells you to stop.
If upon brain removal you find a computer chip or some other electronic device, you should assume that it is government property. Destroying it is a federal offense accompanied by a mandatory sentence and a fine. Get rid of it, but make it look like an accident.
If the brain belongs to a friend or acquaintance, you may be tempted to carry out some slight alterations to improve its personality. Any such measures are, of course, unethical, unless they are intended to improve the person’s singing. Do not be tempted by additional suggestions for improvements from the patient’s spouse or family.
It is illegal to sell a brain, but you may pawn it for short periods of time. Do not bet a brain in a poker game, even among members of the lab.
Don’t dress it in a silly hat, doll’s clothes, or make distasteful drawings on it with a permanent marker. Only write on the brain with an erasable whiteboard marker.
There is no evidence that when a brain is removed from the body, it can control the minds of people around it. Of course, that’s what it would want us to think.
If the brain belongs to a famous person, don’t take it out in public and show it around, especially in a bar. You may, however, do whatever you like with the body, provided it is restored to its former condition before the brain is reinstalled.
Do not stick Post-its directly onto the surface of the brain.
Do not use a brain as a Halloween Jack-o’-lantern.
Although brains are highly similar in appearance, each brain is unique and gives off a distinct smell. Train a dog to distinguish them.
A brain is not a pet. Do not try to teach it tricks.
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.
Note: this piece continues the theme of learning the Kansas state song in the first grade, covered in an article below. In case you don’t remember, it’s Home on the Range, and the text goes like this:
Oh give me a home where the buffalo roam
And the deer and the antelope play,
Where seldom is heard a discouraging word,
And the skies are not cloudy all day.
First graders never understand the third line of our state song, but by the time you get to it you no longer care. “I’ll sing it first and then it’s your turn,” your teacher says, as if a flock of parrots has flown in and replaced her pupils. A few of us parrots put our hands over our ears. Barely 15 minutes into our academic careers, we’ve already learned a lot of interesting things : chalkboards can make a horrible screeching sound, a lot like our teacher’s singing, although not quite as bad.
“Where seldom is heeeeearrrrd a discouraging woooorrrrd,” she screeches, and the chorus, 25 tone-deaf first graders yowling at the limits of lung capacity, produces a sound that causes the fillings in your teeth to vibrate. The text is beyond us, but the last two lines were about animals, so this must be their herd. Seldom is a herd of what? A herd of buffalo?
You’d like to ask, but you’re supposed to raise your hand and now you discover you can’t. Learning the first two lines of the song has been exhausting work. There have been too many new facts, and hints that your family has been keeping things from you. Why have they never talked about Lucrezia Borgia, and all of the millions of buffalo and husbands she murdered? At home do you really speak English, or is it some foreign language? “I never want to hear the word ‘ain’t’ in this classroom,” your teacher said a minute ago. “Some of you don’t speak right. It’s not your fault, but we’re going to fix it, starting now.”
Are you one of the ones that needs fixing? Has your whole life been a lie?
You’ve made your first foray into the science of zoology, with a plan for a field study to count antelopes. And even before you’ve learned the alphabet, grammar has reared its ugly head. Buffalo or buffalos? Deer or deers? You used to know, but you’re no longer sure.
All this thinking has sapped your energy. Your brain burns up all the energy it has, then starts drawing what’s stored up in your body, even your toes, which hold only a little bit, and burns that. In just five minutes a whole day’s supply of energy has been used up, leaving your body as limp as a noodle. Only seven hours more hours until school’s out.
So we squeeze the third line through our ears and it makes a lump in our brains, like a pig swallowed by a python, in hopes it will be digested later. But that may never happen. The lump may have to be surgically removed. And some of us, tragically, may die without ever having understood the full meaning of “Home on the Range.” A brain scan of the corpse would reveal a small lump, shaped like a pig. That’s the third line of the song, which never got digested.
Usually you figure out what it means many years later, when you’re in the middle of something important and completely unrelated. You may be drinking beer while sitting in a fishing boat in your garage. Or giving a speech to the American Nephrological society. Or you’re a detective on a stakeout, wearing a walrus suit as a disguise, and that’s the moment when the moment of enlightenment strikes.
“A discouraging word,” you realize, means a curse word, or, in the first-grade venacular, a cuss word. Saying that it is seldom heard implies that Kansans don’t cuss as much as people in other states. As publicity goes, that kind of information will attract one type of person, and another will say, “No thanks, I’ll just stay in Missouri.” In the end, both states are happy.
You’d expect this claim about the amount of cussing to have some empirical data behind it, but I’ve never been able to track it down. In my experience, people in Kansas cuss plenty. Which makes you wonder how they talk in other places.
First graders in particular use a lot of cuss words, which compose most of your vocabulary, aside from a few nouns and verbs that have practical uses. You find cuss words everywhere: on the playground, or when someone injures himself, or when guys come over to watch football with your dad. Cuss words stick to you; you come home covered in them. You don’t know what they mean, but you discover that they have magical powers that make the people around you do interesting things.
Cussing takes many years to master because words have different degrees of power and affect various categories of people differently, much like pharmaceutical substances. Your mom, grandmother and minister have no tolerance at all, probably because of some immune deficiency.
The weakest cuss words are used to express pain, or in situations involving automotive vehicles: getting a parking ticket, locking yourself out of the car, or criticizing the driving of others on the road. Higher on the scale come words related to poop. Then come legal issues surrounding the marital status of your parents at the time of your birth. Close to the top are words for various parts of your anatomy, followed by the things that can be done with those parts, particularly in relation to family members or animals.
All these things are valid topics of discussion, but they’re considered uncivilized. Cultured folk have an entirely different set of words that mean exactly the same things but won’t make your mom go crazy. Why? Nobody knows. It’s magic.
First graders pick up all these words and bring them home without considering the potential consequences: embarrassment, the loss of dessert privileges, or extended periods of incarceration. But at that age you’re not even sure whether something is a cuss word; the only way to find out is to test it on your mom.
You come home from school and find her baking cookies. “Have one,” she says, and gives you a cookie. You stare up at her with big, grateful brown eyes.
“Mom?” you say.
“Yes, dear,” she smiles at you.
“What does mmm-mmm mean?” you say.
She turns pale and stares down at you, thinking, He can’t have said what I think he just said. “What did you say?” she asks, which is the wrong question, because to give an honest answer you have to say it again.
“WHAT did you say???” she says – she can’t help herself – but manages to clap a hand over your mouth, just in time. She takes back the cookie, which is unfair, and says, “I’m going to discuss this with your father.” In your family, that’s the equivalent of getting out the nuclear launch codes.
* * * * *
By the second or third grade you can usually tell if a word is a cuss word, and you’ve learned they’re about as welcome in the house as pet spiders or head lice; all three are better left in the garage. The arrival of puberty presents entirely new challenges. One is a change in the wiring of your brain, connecting it directly to your mouth, without first passing by the censorship bureau, which lies just above your tonsils. Anything in your mind, even in the subconscious part, can pop out at any moment: death threats, family secrets, and an entire reservoir of cuss words, dammed up in your brain and ready to break out at any moment.
This is also the period of your life in which for a week every summer, you’re shipped off to Scout Camp. For your parents, Scout Camp provides a brief respite from sharing their home with a person who exhibits all the symptoms of clinical insanity. For you, Scout Camp imparts the lesson that you never, under any circumstances, want to be sent to the Gulag, which is, in all essential respects, just like Scout Camp.
Scout Camp will be the subject of an article of its own in the near future. For now let me just say that you learn skills that will serve you throughout life. You learn to tie knots, in case you ever need to hang somebody. You learn how to survive in the wilderness, which is a patch of woods above the picnic area at the lake, with a pocketknife, a map, a compass, a roll of Saran wrap, and a single match. These items, used in the right order, provide a solution to any situation you’re likely to encounter. They also have many creative uses as instruments of torture.
In the Gulag, over 90 percent of the words you hear in the Gulag are profanities, so at the end of the week you’re covered with them. Combine that with the total loss of control over your mouth and you’ve got real problems when the Gulag commutes your sentence and sends you home.
You come in the door and your mom is baking cookies, and she smiles at you and says how much she missed you, and the first thing out of your mouth is a cuss word.
“One more filthy thing out of your mouth, young man, and I’m going to wash that mouth out with soap,” your mom says.
Basically it’s a dare. You don’t want to take her up on it, it’s absolutely the last thing you want to do, but your brain and mouth are not under your control. You can guess what happens next.
Your mother is a gentle soul, an angel, but her threat is absolute; it leaves no room for a retreat with dignity. She’s committed herself and there’s no going back. So she leads you into the bathroom and washes your mouth out with soap.
This is a life experience just as important as being sent to the Gulag. It gives you a chance to learn techniques for projectile vomiting, which will come in handy the first time you get drunk. If you’re not willing to zap your tongue with a Taser, soap is the only substance capable of breaking the brain-to-mouth circuitry. It activates the trauma center of your brain, which records every sensation with perfect fidelity and will replay this event when triggered by the proper stimulus. In this case, a cuss word.
For years and decades to follow, any time you start to say one, your mouth will be filled with a powerful taste of soap and cause violent projectile vomiting. You don’t even have to say the word: just thinking it will provoke the symptoms.
And it’s hard, very hard, not to think of a thing when you’re trying not to. The harder you try, the more you think of it. Even right now, sitting here writing this…
I think I’ll change the subject now.
How to organize a spontaneous scientific conference, in 27 easy steps
It was a sunny morning in mid-May, the S-Bahn wasn’t on strike, the air was thick with the scent of lilacs and millions of allergens and the songs of birds who hadn’t yet figured out how to find partners on-line. A perfect day for a barbecue or, as things turned out, a fire alarm. At around 11 am the doors of House 31.1 opened, ejecting about 400 scientists. In the spirit of quantitative biology, I’d like to provide a more precise number, but they didn’t hold still long enough to be counted. (I can tell you, however, that p = 0.0011.) Their behavior might have reminded you of the efflux of molecules from a ruptured, apoptotic cell. Or perhaps not.
Without any facts, it was difficult to formulate a hypothesis that could explain a sudden, mass exodus of biologists. Had everyone simply decided to go to lunch at precisely the same moment? That seemed highly unlikely, statistically speaking, but in a stochastic universe that’s 13.798 billion years old, it’s bound to happen once or twice. Or were we witnessing the effects of some as-yet unknown biological mechanism, one that stimulated spontaneous migratory behavior in scientists?
I saw Walter Birchmeier standing on the lawn – was Wnt signaling involved? It’s always a good candidate when you have a migratory phenotype. Wnt helps regulate the motility of cancer cells; if you augmented its activity a trillion-fold, would it have the same effect on cancer scientists? But why did it affect only House 31.1? Was some sort of parasitic microRNA on the loose? Was there any connection to the microbiome of the belly button? Or chickens?
If I were a scientist, I could have grabbed some piece of equipment from the lab – maybe a liquid chromatography mass spectrometer, or a magic-angle NMR machine, and headed out to look for the mechanism. But the only high-throughput technology in my office is the coffee machine. So I’d have to rely on more primitive methods of scientific discovery, like asking somebody what was going on.
I saw Undine Hill standing by the blue bear; that morning on the bus she’d told me she’d spent the whole night preparing for her PhD committee meeting. “How did it go?” I said.
“Everything was going okay,” she said. “Until the fire alarm.”
That’s serendipity in science for you: often the best way to get an answer is to ask the wrong question. The signal that had sent everybody outside was a fire alarm. This didn’t necessarily exclude Wnt, but it certainly shifted the research focus. Further investigation yielded the locus of the problem: a defective microwave oven on the fifth floor. “It wasn’t my fault,” said Luiza Bengtsson.
By now people were drifting over from other buildings to join in the festivities, like immune cells attracted to cytokines, dendritic cells to brain tumors, and neighbors to your barbecue. Scientists from different floors and labs formed brief aggregates out on the lawn, engaged in some mutual phosphorylation, and then drifted off to join some other group. This went on until a fire truck appeared, causing an amyloid-like formation on the side of the road.
People were discussing the standard topics among scientists: writing a dissertation, watching football, watching football while writing a dissertation, why the third referee on a paper is always a sadistic lunatic, where to buy impact points on the global black market, whether to leave science and become a sheep farmer, whether a union between a bioinformaticist and a Drosophilist could produce fertile offspring… that kind of thing. A student recounted his epic combat with the Experiment from Hell: a routine protocol that worked perfectly up to the moment you really needed it, at which point it always failed. Almost as if it knew, as if it were out to get you.
Somebody said, “Have you ever noticed that everything we work on is invisible? Sometimes I wonder if it’s really there,” to which his friend said, “It’s there unless you moved it,” which caused someone else to chime in: “Last week a technician dropped a molecule somewhere on the bench and we still haven’t found it – can somebody loan me an antibody?”
Here and there you’d hear a bit of real science; somebody would be describing a problem with a project and get a much-needed tip. I realized I wasn’t watching a cell – the lawn had become a spontaneous, self-organizing mini-conference. Like when you’re shopping in KaDeWe and suddenly, from three floors, a choir starts singing the Hallelujah chorus. Some of it’s out of tune – Doppler shifts from the sopranos on the escalators – but it’s still darned impressive.
Of course fire alarms cost money, disrupt committee meetings, and you may have to write them into your experimental protocols. But they also can pay off in ways you’d never predict. I’m sure that out there on the lawn, somebody got an idea, or started a relationship – I’m referring to a collaboration rather than a romance although the two aren’t mutually exclusive. If you were there and that happened to you (I’m talking about the science, not the romance), let me know and I’ll insert your story here. You can tell me about the romance, too, but I won’t reprint it.
It was good to be reminded of the importance of chance encounters in science – they’re an important reason for conferences, and they can be stimulated by institutional structures such as technology platforms, courses and workshops, and seminars. The most powerful catalysts, though, are often the informal ones, which is why some of us have long dreamed of a campus working café. With the right atmosphere and location, it would quickly become a hub of campus life – as has happened in so many other places.
The thing about a fire alarm or drill is that everybody has to go. As I stood out on the lawn, I realized that one thing would have made this even better: if House 31.1 were home to an equal number of PhDs and MDs. We’re developing a virtual house with the Berlin Institute of Health – in that project, what will be the equivalent of a fire drill? Will there be a real, physical lawn where everyone has to assemble when it rings? What sort of fire code will be needed to drive them out of their labs and onto the lawn?
Those issues aside, I’ll close with a central issue in fire alarms – namely, what to do when you’re confronted by actual flames. Here I refer you to a small book of etiquette written by Mark Twain, with an entire chapter on behavior at fires. It’s full of all sorts of useful tips, such as how to propose marriage to a woman while rescuing her from a burning building.
The most helpful part, though, is a list that ranks people according to the order in which they should be rescued. There are 27 items, starting with your fiancée, whom you should save first. Second on the list is any woman for whom you have affections that you have not yet expressed. (If you choose to propose to her on this occasion, he provides a brief speech that you should memorize in advance.) He also explains what to do if you accidentally save #12 on the list before #10 (no, you shouldn’t necessarily take #12 back into the fire, but you should apologize to #10, using another speech to be memorized).
Clergymen are to be rescued at position 19 – after pets, if I remember correctly – but my favorite part is the very end, which reads as follows:
24. Landlord
25. Firemen
26. Furniture
Finally, when every other individual and object has been brought to safety, you are free to rescue…
27. Mothers-in-law.
I have lived in Heidelberg for many years and it is certainly a charming place. The Old Town is small enough that you can walk from one end to another in half an hour. Except during Heidelberger Herbst. Then the same walk takes about six hours. For those unfamiliar with Heidelberger Herbst, it means “Heidelberg Autumn” and is a quaint tradition dating back to the 1980s or farther, to the 70s or perhaps the Middle Ages. Over one long weekend 1 million visitors squeeze onto a street that fits about a thousand, to buy things you could get at any normal time without feeling like a cow being driven to the slaughterhouse. That’s the type of festival we have back home in Kansas, but we call it “Hamburger Herbst.”
Otherwise the city is truly charming. In Heidelberg you can fall in love, you can visit the Beer Museum (where they have over 100 kinds of beer) and try to break the current record (25 beers within two hours, depending on whether you count restroom breaks and emergency resuscitations). There is even a wonderful university clinic where you can get a heart transplant. Yes, visitors to Heidelberg can enjoy all of these experiences, although it’s best not to try to squeeze them all into one weekend.
Sometimes, though, it happens. Take the case of an acquaintance of mine who came through town on one of those bus tours where the bus leaves the highway, drives straight into the city center, stops at McDonald’s so that everyone can go to the restroom, then gives them just enough time to stroll two or three blocks to the nearest Starbuck’s, check their Facebook pages, and get back on the bus. Then it’s off to the next big city.
On that kind of schedule you have to squeeze in all the culture you can, even if you’re on your honeymoon. My friend and his new wife had just gotten married that afternoon, during a slow moment in the bus tour, and were walking from McDonald’s to Starbucks when they spotted the Beer Museum. A bus tour doesn’t give you much time to see a bit of authentic German culture, so when you see a Beer Museum, you have to take advantage of it.
My friend and his new wife hadn’t known each other all that long; in fact they’d just met the week before, sitting next to each other on the bus tour, so they still had plenty of things to learn about each other. My friend’s wife, for example, had never witnessed the bar trick my friend had perfected in college, which involves nine empty beer bottles, drained in the traditional way, which you then stack on your head in an inverted pyramidal structure. There’s only one method of stacking known to work, and you have to be seriously drunk to accomplish it.
That night my friend gave a magnificent performance, demonstrating his proficiency at one thing, at least, which is a good thing, because after nine beers the performance he attempted to give later, on his wedding night in a hotel room, was a complete disaster. His wife burst into tears and fled for the airport. She left Germany while he was sleeping it off, a nap that lasted about a day and a half, and when he finally woke up, she was gone for good. Never to be found again, at least not by him, since he hadn’t known her long enough to learn her maiden name, the name of her hometown, her cell phone number, or even her address on Facebook or Skype. Not only was his new bride gone, the bus had left town. It broke his heart. I mean this quite literally. He was taken to the Heart Clinic, where they gave him a transplant.
If you need a transplant or some other medical intervention while visiting Heidelberg, you’ll find the clinics across the river in Neuenheimer Feld. Actually the in is part of the name, in Neuenheimer Feld, so you probably have to say they are across the river in in Neuenheimer Feld. But this looks suspiciously like one of those situations in German where you need to change the case, probably to in einer Neuenheimer Feld, or in einer anderer Neuenheimer Feld, or in some other anderer Neuenheimer Feld, so my advice is just ignore the German case system. I have learned that you can get by perfectly well without it, if you mumble your articles. Due to the somewhat inflexible nature of the brain after adolescence, it takes a long time to learn all of these complicated rules, and then all you’d have to show for it would be a bunch of derdiedasderendessens. Instead you could have used that time volunteering at an NGO that rescues victims of genocide, or Ebola. Or you could organize the annual staff Christmas party.
But back to the issue of obtaining an organ transplant while visiting Heidelberg. Across the bridge you need only follow the signs to the proper clinic. You should decide which of your organs is causing the most pain, and that’s the clinic you should head for. For a new heart you go to the Heart Clinic, and kidneys are stored in the Kidney Clinic. This cuts down on a lot of mistakes that might occur during transplantation surgery, those stories you hear, you know? Where they cut off somebody’s healthy arm or leg, and leave the injured one hanging there? Cutting off the wrong appendage is bad, but other mistakes are really gruesome, for example, when they sew an arm back on the wrong side. You see a person like this and realize there is something odd about his arms, but that they’ve been stuck on backwards isn’t the first thing that comes to mind. You usually only notice when you try to shake hands.
It’s easy to criticize a surgeon who makes this type of mistake, but think of the skill that is actually required. While there’s surely some difference between a right-arm socket and a left-arm socket, would an amateur notice? After all, our bodies are not designed like IKEA bookshelves. You go trying to jam a right-side arm into a left-side socket, at some point you ought to recognize that something’s wrong. You can get the sucker in there, but you have to use a lot of WD40 and then whack the arm with a hammer a few times and apply a lot of duct tape to keep the thing on.
Even worse than having one of your arms sewn on backwards is receiving the wrong arm entirely. I read of such a case recently. A man recently lost his arm out in the desert somewhere and they reattached it in a field hospital. After two months they took off the cast, and on his good left arm there were tattoos starting on the shoulder and going all the way down the arm, including tattoos across his knuckles. The sewn-on arm was a foot shorter, with nails painted bright pink and a little girl’s ring that they had tried to get off but couldn’t, at least not under his current medical plan. Later the biggest question was where they found a fresh arm like that, in the middle of the desert.
Now such mistakes rarely happen in Heidelberg; this university clinic has never put a right arm on the left side, or vice versa, respectively. There’s a good reason: long ago they decided to keep all the transplantation centers entirely separate. The kidneys are in a different building than the livers. The hearts are in a different clinic than the brains. There are different clinics for your right side and your left side: a clinic for right arms and another for left arms, more for right legs and left legs, left eyeballs and right eyeballs, etc. Unfortunately some of the clinics for the right side are on the left side of the road, or vice versa when you’re coming from the other direction, so you need to follow the signs. You’ll see, “RIGHT LEFT ARM CLINIC” on a sign that is, appropriately, shaped like an arm, pointing right, and if you’re coming the other direction you’ll see the arm from the other side, so it’s pointing left and it says “RIGHT RIGHT ARM CLINIC.” Most people head for that one. They certainly don’t want the “WRONG RIGHT ARM CLINIC,” or the “RIGHT WRONG ARM CLINIC,” which are in an entirely different part of town.
The system works wonderfully until you get to an organ such as the heart or brain, which most people only have one copy of, and then the university has the dilemma of deciding whether the clinic gets grouped with the right or left, at which point politics and special interests may come into play. Years ago the rightists jumped in to lay claim on the heart. In making the pitch, a representative said the following:
First of all, a heart is red, and red is the color of the right, as is obvious from the fact that Americans place their right hands on their hearts when Pledging Allegiance to the flag. For Americans, the heart is a sacred tradition. Their mothers had hearts, and you can’t get much more sacred than your mother, I don’t care what religion you belong to. In some cultures this affection extends to mothers-in-law, which means that a person regards his (or her) mother-in-law as more sacred than his or her wife or husband, respectively. Probably in France, for example. In France it could well be an ancient tradition to sleep with your mother-in-law. There are also cannibalistic societies that celebrate funerals by eating the heart of the person who died. I have no direct evidence of this in France, but I wouldn’t rule it out, given other things that the French are known to eat, including horseflesh, which is sold under the generic term “beef”.
In fact the administrator was misquoting celebrated French sociologist Simon Saucisson, who had first noted the overlap of the two trends in New Guinea. It could not be an accident, said Saucisson, that cannibalism and mother-in-law reverence showed such an overlapping pattern among ancient tribes. In some cases the traditions had become confused, so aboriginals began eating the hearts of their mother-in-laws, usually at the funeral, but sometimes a few minutes before. Saucisson invented the technical term “mangeurs du coeur de la belle-mère” that is now commonly used to classify these cultures in a larger social matrix.
Simon Saucisson comments: “Members of these cultures typically regard mothers-in-law as goddesses and therefore eat their hearts, so that you can develop an intimate relationship with the goddess as she passes through your digestive tract. The heart of your average mother-in-law will feed a normal-sized family, but in a tribe there aren’t that many mothers-in-law to begin with, and you go through them pretty fast. So you need to supplement your diet with other things, as well. For example, crickets.”
Since the right got the heart, the brain automatically went to the left, which explains a lot about the current political climate.
Good Science Writing 