Reading Strunk & White

I don’t remember who, but someone wrote that people who hand out the advice to read Strunk & White’s Elements of Style probably haven’t read it—the implication being that it’s not as good as its reputation. The names of famous works and authors often work as metonymies for common wisdom more than as references to their content, not just Strunk & White, but Machiavelli, The Modern Synthesis etc. The journal GENETICS, where I recently sent a couple of papers, have Strunk & White as part of the guidelines for authors, so I decided to read Strunk & White.

This is from the part that the GENETICS guidelines refer to, namely the famous ”Omit needless words” section:

Vigorous writing is concise. A sentence should contain no unnecessary words, a paragraph no unnecessary sentences, for the same reason that a drawing should have no unnecessary lines and a machine no unnecessary parts. This requires not that the writer make all sentences short, or avoid all detail and treat subjects only in outline, but that every word tell.

This is some good advice that is apt for scientific writing. All the rules that deal with vigorousness and conciseness would make life easier for all us readers of scientific papers:

15. Put statements in positive form.
16. Use definite, specific, concrete language.
17. Omit needless words.
18. Avoid a succession of loose sentences.
19. Express coordinate ideas in similar form.
20. Keep related words together.

Scientific writing is often too roundabout and guarded. I think that happens not because we’re trying to worm our way out of criticism, but because we have misguided notions about style that we get from reading heaps of badly written papers, and can’t shake without effort.

But there is also a ton of advice that is tedious and arbitrary. A problem with learning from authorities is that we end up reifying their pet peeves. The Elements of Style is full of them. There’s this thing you do when you state your opinion: You try to express it forcefully (forcibly, I guess, according to Strunk), but you are not Kantian about it. You don’t expect it to be elevated to a universal law. If it were, especially without the conditions that applied to those opinions, you might be unhappy with the results. Yes, we should omit unnecessary words, but for some authors, it may be more pressing to look for words to add, to elaborate, explain, and exemplify.

The same is true for graph-making (where should the y-axis end? what is the best way to show proportions?), the proper way to email university teachers as a student, the placement of figures in manuscripts to be reviewed, … In the absence of evidence, we substitute opinion, loudly spoken.

‘All domestic animals and plants are genetically modified already’

There is an argument among people who, like yours truly, support (or at least are not in principle against) applications of genetic modification in plant and animal breeding that ‘all domestic animals and plants are genetically modified already’ because of domestication and breeding. See for example Food Evolution or this little video from Sonal Katyal.

This is true in one sense, but it’s not very helpful, for two reasons.

First, it makes it look as if the safety and efficacy of genome editing turns on a definition. I don’t know what the people who pull out this idea in discussion expect that the response will be — that the people who worry about genetic modification as some kind of threat will go ‘oh, that was a clever turn of phrase; I guess it’s no problem then’. Again, I think the honest thing to say is that genetic modification (be it mutagenesis, transgenetics, or genome editing) is a different thing than classic breeding, but that it’s still okay.

Second, I also fear that it promotes the misunderstanding that selective breeding is somehow outdated and unimportant. This video is an example (and I don’t mean to bash on the video; I think what’s said in it is true, but not the whole story). Yes, genome editing allows us to introduce certain genetic changes precisely and independently of the surrounding region. This is as opposed to introducing a certain variant by crossing, when other undesired genetic variants will follow along. However, we need to know what to edit and what to put instead, so until knowledge of causative variants is near perfect (spoiler: never), selection will still play a role.

Genome editing in EU law

The European Court of Justice recently produced a judgement (Case C-528/16) that means that genome edited organisms will be regarded as genetically modified and subject to the EU directive 2001/18 about genetically modified organisms, which is bad news for anyone who wants to use genome editing to do anything with plant or animal breeding in Europe.

The judgement is in legalese, but I actually found it more clear and readable than the press coverage about it. The court does not seem conceptually confused: it knows what genome editing is, and makes reasonable distinctions. It’s just that it’s bound by the 2001 directive, and if we want genome editing to be useful, we need something better than that.

First, let’s talk about what ‘genetic modification’, ‘transgenics’, ‘mutagenesis’, and ‘genome editing’ are. This is how I understand the terms.

  • A genetically modified organism, the directive says, is ‘an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination’. The directive goes on to clarify with some examples that count as genetic modification, and some that don’t, including in vitro fertilisation as well as bacterial and viral processes of horizontal gene transfer. As far as I can tell, this is sensible. The definition isn’t unassailable, of course, because a lot hinges on what counts as a natural process, but no definition in biology ever is.
  • Transgenics are organisms that have had new DNA sequences introduced into them for example from a different species. As such, their DNA is different in a way that is very unlikely to happen by spontaneous mutation. For technical reasons, this kind of genetic modification, even if it may seem more dramatic than changing a few basepairs, is easier to achieve than genome editing. This the old, ‘classic’, genetic modification that the directive was written to deal with.
  • Mutagenesis is when you do something to an organism to change the rate of spontaneous mutation, e.g. treat it with some mutagenic chemical or radiation. With mutagenesis, you don’t control what change will happen (but you may be able to affect the probability of causing a certain type of mutation, because mutagens have different properties).
  • Finally, genome editing means changing a genetic variant into another. These are changes that could probably be introduced by mutagenesis or crossing, but they can be made more quickly and precisely with editing techniques. This is what people often envisage when we talk about using Crispr/Cas9 in breeding or medicine.

On these definitions, the Crispr/Cas9 (and related systems) can be used to do either transgenics, mutagenesis or editing. You could use it for mutagenesis to generate targeted cuts, and let the cell repair by non-homologous end joining, which introduces deletions or rearrangements. This is how Crispr/Cas9 is used in a lot of molecular biology research, to knock out genes by directing disruptive mutations to them. You could also use it to make transgenics by introducing a foreign DNA sequence. For example, this is what happens when Crispr/Cas9 is used to create artificial gene drive systems. Or, you could edit by replacing alleles with other naturally occurring alleles.

Looking back at what is in the directive, it defines genetically modified organisms, and then it goes on to make a few exceptions — means of genetic modification that are exempted from the directive because they’re considered safe and accepted. The top one is mutagenesis, which was already old hat in 2001. And that takes us to the main question that the judgment answers: Should genome editing methods be slotted in there, with chemical and radiation mutagenesis, which are exempt from the directive even if they’re actually a kind of genetic modification, or should they be subject to the full regulatory weight of the directive, like transgenics? Unfortunately, the court found the latter. They write:

[T]he precautionary principle was taken into account in the drafting of the directive and must also be taken into account in its implementation. … In those circumstances, Article 3(1) of Directive 2001/18, read in conjunction with point 1 of Annex I B to that directive [these passages are where the exemption happens — MJ], cannot be interpreted as excluding, from the scope of the directive, organisms obtained by means of new techniques/methods of mutagenesis which have appeared or have been mostly developed since Directive 2001/18 was adopted. Such an interpretation would fail to have regard to the intention of the EU legislature … to exclude from the scope of the directive only organisms obtained by means of techniques/methods which have conventionally been used in a number of applications and have a long safety record.

My opinion is this: Crispr/Cas9, whether used for genome editing, targeted mutagenesis, or even to make transgenics is genetic modification, but genetic modification can be just as safe as old mutagenesis methods. So what do we need instead of the current genetic modification directive?

First, one could include genome edited and targeted mutagenesis products among the exclusions to the directive. There is no reason to think they’d be any less safe than varieties developed by traditional mutagenesis or by crossing. In fact, the new techniques will give you fewer unexpected other variants as side effects. However, EU law does not seem to acknowledge that kind of argument. There would need to be a new law that isn’t based on the precautionary principle.

Second, one could reform the entire directive to something less draconian. It’s not obvious how to do that, though. On the one hand, the directive is based on perceived risks to human health and the environment of genetic modification itself that have little basis in fact. Maybe starting from the precautionary principle was a reasonable position when the directive was written, but now we know that transgenic organisms in themselves are not a threat to human health, and there is no reason to demand each product be individually evaluated to establish that. On the other hand, one can see the need for some risk assessment of transgenic systems. Say for instance that synthetic gene drives become a reality. We really would want to see some kind of environmental risk assessment before they were used outside of the lab.

Skype a scientist

Skype a scientist is a programme that connects classrooms to scientists for question and answer sessions. I have done it a few times now, and from the scientist’s perspective, it has a lot of reward for not that much work.

It works like this: the Skype a scientist team makes matches based on what kind of scientist the teacher asks for; the scientist writes a letter (or it could be a video or something else) about what they work on; the students prepare questions; and the scientist tries to answer.

One thing I like about the format is how it is driven by student questions, turning the conversation to things students actually want to know, and not just what the the scientist (me) believes there’s a need to ‘explain’ (scare quotes used to imply scepticism). Of course, the framing as a classroom exercise, the priming by the letter, and the fact that the questions pass through the teacher influence the content, but still. I also like how some students ask questions that I suspect are not entirely serious, but that still turn out to be interesting. Something I like less is how each session still is kind of a monologue with little interactivity.

I think it has gone reasonably well. I hope my answers will get more polished with time. Another thing I need to get better at is extracting useful feedback from the teachers to improve what I do. They’ve all said positive things (of course, how else could they respond?), but I’m sure there are all kinds of things I could improve.

Here, enjoy some of the questions I’ve gotten! I won’t answer them here; you will have to sign up your classroom for that. I have organised them into categories that I think reflect the most common types of questions.

Pig and chicken genetics

What are some mutations in pigs that you see?

Have you ever encountered a chicken that had something about it that surprised you?

What kinds of chickens live the longest?

What is significant about the DNA of pigs and chickens?

What is the most pervasive genetic disorders in pigs and chickens?

Which genes have the highest demand from industry?

Evolution

If certain traits are dominant and humans have been around for 6 million years, how do we not have all those dominant traits?

What came first, the chicken or the egg?

Does the DNA of chickens and pigs have any similarity to humans — if so, what percent is common?

When were pigs domesticated and what were they domesticated from?

Hard questions

Are science and religion compatible?

Can genetic engineering lead to the creation of a super-race?

Do you think that, if extra-terrestrial life was found, a breeding program between humans and aliens could exist to create hybrids?

Do you think you could genetically modify pigs to create the perfect bacon?

Can you genetically modify an organism to make it more clever?

Will we be able to genetically modify humans with features from other organisms such as gills, not just single gene traits?

What do you think is the next big genetically modified breakthrough on the horizon?

How far away are we from being able to clone a human (like Dolly)?

Have you researched genes designed to protect chickens or pigs from super bacteria resistant to antibiotics?

Personal stuff

Do you ever get to dissect anything?

What is the most exciting part of your job?

What is your favourite complex trait?

Have you always been interested in science?

What makes your job so important that you are willing to move countries?

Why did you choose to study genetics?

Do you prefer group or solo work?

Are you under intense pressure in your job?

What are you looking forward to working on in the future?

The practice of science

What materials do you use in your research?

Who decides what you research?

How do you use computers to research genes and DNA?

What kind of technology/equipment do you use?

Why do you research pigs and chickens?

Different ways to cite papers

The journals Genetics and Nature Genetics seem to take opposite views on citations. See first this editorial from Nature Genetics: ”Neutral citation is poor scholarship”. It is strongly worded in a way that is surprising and entertaining:

The journal deplores and will decline to consider manuscripts that fail to identify the key findings of published articles and that—deliberately or inadvertently—omit the reason the prior work is cited.

(All the emphasis in all the quotes was added by me.)

The passage that suggests a difference in citation policy occurs at the end:

Authors are of course free to select the literature that is relevant to their current work and to cite in their arguments only those publications that meet their standards of evidence and quality.

Genetics, on the other hand, says this in the instructions for preparing a manuscript:

Authors are encouraged to:

  • cite the supporting literature completely rather than select a subset of citations;
  • provide important background citations, including relevant review papers (to help orient the non-specialist reader);
  • to cite similar work in other organisms.

I’m sure the editors of Genetics also don’t support scattershot citation of tangentially related papers (as in ”This field exists [1-20]”), but they seem to take a different stance on how to choose what to cite.

I wonder what the writers of the respective recommendations would make of these, in my opinion delightful, opening sentences (from Yun & Agrawal 2014). Note the absence of hundreds of citations.

Inbreeding depression has been estimated hundreds of times in a wide variety of taxa. From this body [of] work, it is clear that inbreeding depression is common but also that it is highly variable in magnitude.

På dna-dagen: dna-metaforer

Det finns olika metaforer för deoxyribonukleinsyran och vad den betyder för oss. Dna kan vara en ritning, ett recept, ett program eller skrift.

Det är nästan omöjligt att säga något om molekylärgenetik utan metaforer. Med kvantitativ genetik går det lite lättare, i all fall tills de statistiska modellerna och beräkningarna kommer fram. Kvantitativ genetik handlar om saker som alla kan se i vardagen, som familjelikhet och släktskap. Molekylärgenetik handlar om saker som, i och för sig finns i det allmäna medvetandet, men inte syns omkring oss.

Men metaforer kan vara ohjälpsamma och leda tanken fel. Bilden av dna som en ritning av organismen kan verka för enkel och leda tanken till genetisk determinism. Nu vet jag, trots att jag ska föreställa ingenjör, inte mycket om ritningar. På flera sätt är det inte så tokigt: en ritning representerar det som ska byggas med ett specialiserat bildspråk i en lägre dimension. Ett hus är i 3D, men en ritning i 2D. Proteiner är tredimensionella; den genetiska koden beskriver dem i en dimension. Men det kanske är sant att ordet ”ritning” (eller ”blåkopia”) för tanken till något som är för exakt och för avbildande.

Ett alternativ är att dna är ett recept (det är många som föreslagit det; bland annat Richard Dawkins i The Blind Watchmaker, 1986). Receptet har den fördelen att det beskriver en process med både ingredienser och instruktioner. Det är lite som organismens utveckling från ett befruktat ägg till en vuxen. ”Tillsätt maternell bicoid i ena änden och nanos i andra änden; låt proteinerna blandas fritt”, och så vidare (Gilbert 2000). En annan fördel är att det naturligt påminner om att dna inte är allt. Samma recept med lokala skillnader i ingredienser och improvisationer från den som lagar blir olika anrättningar. Å andra sidan överdriver receptet vad som finns i dna. Vilka gener som uttrycks var och när är ett samspel av dna och de proteiner och rna som redan finns i en cell vid en viss tidpunkt.

Eller så är dna ett program. Program är också instruktioner, så det har samma fördelar och nackdelar som receptet på den punkten. Å andra sidan är program abstrakta och fria från konkreta ingredienser och associationer till matlagning. Lite som en ritning låter det mekaniskt och exakt. Det spelar tydligt också roll vad dna skulle vara en ritning av eller ett recept på. Det är viss skillnad att kalla dna en ritning av proteiner än ett recept på en organism.

Till sist finns det metaforer inskrivna i själva terminologin. När genetiker pratar om dna, hur det förs vidare och används, pratar vi om det som ett skriftspråk. Det kallas kopiering när dna reproduceras när celler ska dela sig. Det kallas transkription, alltså kopiering men med en ton av överföring till en annan form eller ett annat medium, när rna produceras från dna. Det kallas translation, översättning, när rna i sin tur fungerar som mall för proteinsyntes. Till råga på allt skriver vi dna med ett alfabet på fyra bokstäver: A, C, T, G. Det är en bild som är så passande att den nästan är sann.

(Den 25 april 1953 publicerades artiklarna som presenterade dna-molekylens struktur. Därav dna-dagen. Gamla dna-dagsposter: Genetik utan dna (2016), Gener, orsak och verkan (2015), På dna-dagen (2014))

Clearly, obviously

This is my kind of letter to Nature:

This is a friendly suggestion to colleagues across all scientific disciplines to think twice about ever again using the words ‘obviously’ and ‘clearly’ in scientific and technical writing. These words are largely unhelpful, particularly to students, who may be counterproductively discouraged if what is described is not in fact obvious or clear to them.

Clearly, this is easier said than done. It is common writers’ advice to remove adverbs, and to a lesser extent adjectives. These words may be pointless filler words, and when they’re not, there is a risk of telling the reader what to think in a manner that seems impolite. But they also do some work to make the text flow, and prose without them can seem sterile and disconnected.

If we could also get rid of ”surprisingly”, I would be happy.