This Keto Life: All Up In Your Science (Confirmation Bias)

Scientists are not immune to confirmation bias – no one is. That is, to a large extent, why we have peer review: because otherwise we could publish any old shit that we thought was convincing and not ever have anyone point out “Yes, but you would find that convincing. Have you thought instead that your data could mean something quite different?” or even “Yes, but you failed to account for this confounding factor,” or “Your analysis includes several underlying assumptions that are not met, and thus it is invalid.”

I am reading a few more books about the ketogenic diet (and yes, I am seeking out criticisms online to see if they are valid for me. I already did this before I decided to go low-carb, but I continue to do it. I think it’s important to stay on top of these arguments).

It’s become clear to me that nutrition is a minefield of confirmation bias, much of which is dangerously close to woo, and that if I’d read the wrong books first, I would not necessarily be convinced.

The first books that I read and found convincing were, firstly, The Art and Science of Low Carbohydrate Living and The Art and Science of Low Carbohydrate Performance by Drs Phinney and Volek. Here are the reasons I found their work convincing:

  • they are qualified researchers with expertise in the field about which they are writing (you wouldn’t think that would be hard to find, but I’ll say more about this below)
  • they go into exhaustive detail about the studies they have done, how they set them up, and how they have drawn the conclusions they did
  • they go into similarly exhaustive detail when they critique other studies (which they do in a calm and consistent fashion)
  • they let you follow the dots

Now, the first of these books does get a bit technical – only slightly, but it might be enough to scramble one’s head a bit. This is because the initial intended audience included healthcare providers. There are a couple of chapters, particularly regarding saturated, polyunsaturated and monounsaturated fats and the mobilisation of these in muscle tissues and muscle membranes that I am going to have to re-read, because that information did not stay in my head.

Before I read these books, I read a few posts from the blog of Dr Peter Attia, who likewise goes into clear and precise detail about a number of key concepts. He writes as I like scientists to write: he provides a few basic definitions, diagrams where appropriate, and proceeds from there.

In the last couple of days, I downloaded Keto Clarity and Cholesterol Clarity by Jimmy Moore. I’d read a few posts on his blog, and they seemed to make reasonable sense, but were a bit more simplified. The books were reasonably cheap and I like the word “clarity” in the titles. I thought they might be a good shortcut to get my head around some important metabolic concepts.

And I hate to say it – no disrespect to the man intended – but I have not found these books (I have not finished the latter, to be fair) nearly as convincing.

Moore does a good job of making it clear that his experience is only his experience, and you should not over-extrapolate from it; I like that. He describes his personal experiments as “n=1”, and I like that too. He also says things like, “At this point, you may be wondering why the hell you should listen to anything I have to say, as I have no qualifications. That’s excellent! You should question people! My job is to convince you!”

I really like that. I think it’s a good position to have, and since Moore has no qualifications in science or nutrition other than researching heavily (like I have no qualifications in nutrition apart from that sort of researh), it’s a very responsible position. What he has done is tried to get a large body of research and a large body of opinions from other experts and distill it down into more digestible (ha, see what I did there?) material for the layperson.

I think he has done a reasonably good job, but for two problems.

Firstly, I do not like his choice of experts.

Don’t get me wrong, a lot of them do tick the box for me. His co-author, Dr Eric Westman, mostly explains things well (although he has a couple of metaphors which are just plain silly and trying a bit too hard to communicate to the common folk, what is the word on the street, yo). There are a large number of medical doctors, qualified nutritionists and biomedical researchers in his arsenal of consulted experts. There are cardiologists. There are lipidologists. There are diabetes specialists. These are the people you want to back you up when you make the case for a ketogenic lifestyle or the role of cholesterol (or lack thereof) in heart disease.

However, there are also food bloggers. There are personal trainers (I trust a qualified personal trainer to understand anatomy and sports science and how I should move in order to maximise efficient muscle development, flexibility, coordination and aerobic efficiency barring medical hurdles. That is about as far as it goes).

There are- and I honestly find this quite damning- people who are highly qualified academics in computer science or astrophysics. These people are no more qualified than I am to offer advice (which is one reason I mostly restrict these posts to my own experience and any advice I give has been heavily, heavily validated elsewhere, i.e., salt), except that they may have spent longer doing their own amateur research. I was entirely dismayed to see in the list the name of a person who has been associated with the worst kind of sneakily published, pay-to-publish-in-an-inappropriate-journal junk science listed as an expert (by pure coincedence, I’d read a write-up of this junk science the very day before I bought the book. I stared at the photo in the bio in genuine horror).

As scientists, are they well equipped to deal with the primary literature? Yes, of course, better than most people. That’s the value of scientific training (to a lesser extent, research training in general teaches you to evaluate claims and evidence). Are they probably, in many cases, correct in what they are saying? Yes, mostly, in the context I’d give them the benefit of doubt. Are they people whose blogs I would read and find interesting? Perhaps. Blogging expertise is a low bar (I posit myself as Exhibit A); anyone can have an opinion and make an argument, but to do that well is a skill I admire.

But are they people who should be being quoted by a health blogger in his book as experts in the field? No, they are not; and I think that by including them as experts in his book Moore makes a terrible error in judgment, reducing the credibility of his case and his own credibility by association.

Perhaps he is playing a numbers game. He has clearly met all these people and respects them highly, and is thinking, “Wow, all these intelligent and respectable people are in my corner here, I should list them all and quote them all!” but in my opinion he would have done better to thin the herd, cut a good number of his “Moment of Clarity” quotes and not been so determined to quote all his mates (to be fair, it was his first book).

The second problem I have with his book is a big one: in spite of his apparent determination to do so, he does not always back up his claims.

This doesn’t make me want to drop keto, because I’ve already read Phinney and Volek and Attia, and they make many of the same claims and they do back them up with references and well-designed studies; but if Moore was the first book I had read, I would doubt some of the claims he makes. He backs some of them up well, but others he just leaves sitting there or – and this ties in with my first nitpick – he relies on his stable of experts to back them up for him.

Which would be fine if all his experts were experts, but some, as I said, are not necessarily deserving of the title.

I have been convinced that the ketogenic diet is one that leads to a healthier metabolic situation for people who are either insulin resistant or heading in that direction. The evidence is very good that a monitored ketogenic diet is extremely helpful for Type 2 Diabetes, and that it maybe be helpful for Type 1 Diabetics; however, in the latter case it must be medically monitored. Type 1 Diabetics are the only effective risk group for ketoacidosis – i.e., where blood ketones get too high, in the order of 10mM or so. Nutritional ketosis shouldn’t get much past 5mM for most people because we will produce insulin to reduce it when it gets too high, but deliberately provoking ketosis in a system that does not produce insulin can be a wee bit problematic.

I have been effectively convinced that the ketogenic diet, by swapping one’s fuel specialisation from sugar-burning to fat-burning, increases one’s energy levels after adaptation, because we can store a twenty times more fat than we can glycogen. I’m finally feeling fully adapted, and it is amazing how awake and functional I am all day (as long as I avoid sugars). It’s unprecedented for me.

I have also been convinced that the ketogenic diet will reduce inflammation (as expressed by C-reactive protein) and improve lipid profiles. I haven’t been convinced by personal experience because I can’t test those myself; rather I have been convinced by a number of extensive studies, literature reviews and meta-analyses that have been published in reputable journals. Inflammation is important to me because my body is prone to sit around having an inflammatory response for no good reason, and then I end up having an HS flare (hidradenitis suppurativa, which I’ve mentioned before. Don’t Google it, please, it’s pretty gross). Inflammation is also implicated in a couple of other minor conditions to which my body is prone – and, I think not coincidentally, those conditions are correlated with Type 2 Diabetes and insulin resistance, suggesting that if perhaps you react badly to certain glucose situations, you end up with a lot of inflammation happening, and there might be shared causes there. I am therefore hoping that a ketogenic diet really is anti-inflammatory, and while I don’t expect my HS to disappear entirely, I am hoping that the incidence of attacks will decline. I did notice that attacks declined significantly after I quit eating wheat regularly in 2009 (my own “n=1” observation).

My plan of attack here is to get a thorough lipid profile (and inflammation blood work) done when I have been doing keto for six months.

Why am I listing all these things?

Because I have not been convinced that the ketogenic diet is anti-carcinogenic. The only people making this claim are people who are not actually qualified experts in health – those people usually know better than to make wild anti-carcinogenic claims. The people making these claims are also the people making claims about the “paleo” diet (more on that another time, I promise, but a quick summary on my view is that people can choose whatever labels they want, and if that makes them happy, fine, but it doesn’t make it scientifically accurate), and the evils of processed foods (which can be evil, sure, but are not necessarily carcinogenic. That is a big damn claim and you need to back that up).

People who have terminal cancer are in many cases desperate and upset, which makes perfect sense. It’s hard for most people to hold onto rationality and skepticism under these circumstances. Many do so, but it’s not necessarily easy. I feel that it is grossly unethical to promote a particular way of eating that focuses on that desperation without any evidence to back it up. Promote it because of the documented positive effects on inflammation, heart health and metabolic processes – that’s fine. A cancer sufferer might find that makes them feel better for other reasons, and the improved health (if they are a person who will benefit from keto; not everybody will) might turn the tide; but honestly, keto-adaptation in a cancer patient is also going to make a very sick person feel even worse (at least temporarily), and whether it’s worth it or not will vary from person to person.

That claim really rubbed me the wrong way.

In summary, confirmation bias is a sneaky thing. It’s not that I don’t want to believe these claims, but the minute any lifestyle change is purported to solve everything, cure everything, change everything, I get skeptical. I can’t help it. It sounds like snake oil. There is no magic cure for everything because life is complicated, and biology is complicated. Frankly, if I hadn’t seen these studies for myself, I’d be thinking even the well-supported claims made concerning the keto diet were a bit dodgy, just because there are so many of them.

Wanting to believe something is very, very dangerous, and this is why I will keep reading criticisms of keto as well as defenses and explanations.

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You are not stupid. Please stop saying that you are.

A personal tale of stereotype threat

One of our collection managers was showing me how to use the digital camera. We’re not talking a point-and-click here; this was some sort of Nikon, with a herd, maybe even a plethora, of lenses; this was shades and remote flashes set up in the photography room for the purpose of documenting specimens.

I’d been shown how to use the setup a few years previously, but since I hadn’t used it in the intervening time, my memory of the appropriate settings and icons had faded somewhat, and I’d asked Dave to take me through the basics again. He kindly found time to do so.

I felt guilty, since the collection managers are always busy, and I dislike interrupting people, especially very busy people. So I babbled. Like an idiot.

“Sorry about this,” I babbled, “I’m just really stupid with cameras.”

Dave just smiled and shook his head, and after he’d left the room I stared at my tray of specimens and I had a moment. A capitalised Moment. A goddamn epiphany.

What. The. Fuck. Kate. I snapped at myself. What the fuck did you just say?

I did a media production subject in undergrad. I’ve developed black and white film. Silver nitrate and I have hung out like buddies, if one of those buddies can permanently stain the skin of the other. I didn’t pursue media production (although it did play an indirect role in me switching from Creative Arts to Science, but that’s another story). I didn’t reveal a heretofore unknown talent for the captured image like a beautiful photographer butterfly emerging from a wannabe novelist coccoon.

But I know how a camera works. I’m not stupid with cameras. Apertures, exposure time, depth of field – all those concepts make perfect sense to me. It’s just that I don’t remember what the icons on the dial represent relative to the kind of photos I would like to take, and that’s an issue of memory, not an issue of stupidity.

In fact, even if I hadn’t previously been taught about those concepts, that would be a case of ignorance, not stupidity.

This wasn’t the first time I’d had such a moment, but it was the first time I’d really, really noticed myself doing it.

I’ve noticed other women doing it.

I did my PhD in a university lab that, during my time there, was comprised entirely of women. Apart from some teething issues with a bullying R.A., it was a great work environment, and I still consider them close friends and some of the best people I have ever worked with.

Let us be clear. These are all highly intelligent women. They were all doing PhDs in science. They were all capable in a laboratory environment.

There was so much apology, so much self-deprecation in regards to their abilities, that it was no wonder a bully found fertile ground to play with it all in those early days.

I’m finding it a little hard to write about real people without making generalisations and naming names, so understand that the following stories are broad strokes.

I used to think I was dreadfully stupid at chemistry. I managed to scrape an H1 in the last required chemistry subject for my degree, so clearly this wasn’t a logical position. It took four months of work as an analytical chemist at CSL Pharmaceuticals (I was temping between finishing my Honours project and starting my PhD) to realise that the chemistry I was doing was just some basic maths and measurements, and once I realised that, suddenly it got easy. Chemistry is – or can be – an extremely complex discipline, but I wasn’t doing it at that level. My first year undergrad was actually sufficient to get by for the tests I was running.

This meant that by the time I started my PhD, making basic stock solutions held no fear for me. It took the uncertainty in the eyes of a colleague to remind me that, prior to working at CSL, I would have been really nervous even about putting together TE buffer (dead easy to make), let alone the phenol-chloroform-isoamyl mix (even easier to make, technically speaking, but with a significantly higher chance of burning and fuming and generally doing oneself harm).

It was really common for my colleagues to constantly put themselves down and second guess what they were doing – but they knew how to do these things. They never actually screwed it up. It’s one thing to get confused about picomoles vs nanomoles (10,000 pmol is the same as 10 nmol, but given the price of the fluorescently labelled primers and how rarely I use units with “pico” and “nano” in front of them, I do double-check), when tired after a couple of twelve hour work days. It’s another thing to panic and decide that you can’t deal with it, when demonstrably you can.

Since the branch of genetics that I work in is heavier on analysis than it is on lab work, we would spend some time over coffee musing over analytical options and approaches. There was often a chorus of, “I have no idea about some of that stuff,” and for the first year or so I was just as guilty as everyone else. And yet, a few sips into the first cappucino, we’d be tossing alternative approaches and limitations back and forth like pros. Which we were. Pros. And then I got some confidence. I looked around me, and realised that I actually seemed to know what I was talking about a good portion of the time, and I stopped apologising. I was willing to be corrected on analytical questions, but I stopped apologising for not knowing everything, and I stopped acting as though I knew less than I did.

I bought a textbook at a conference a few years ago: Wakeley’s Coalescent Theory. I understand the basics of coalescence, but I wanted to really get my head around the nuances of it. I got through about a chapter and a half and gave up, since one summary integration formula followed by pages of “As you can see from this summary formula” made me feel stupid and miserable.

It wasn’t until last year that an expert in this field mentioned the book, and said that, as an introduction for biologists, it wasn’t one, and really it was something to read through after you’d gone through this other book. I just didn’t have the background skills to get through Wakeley, and since the blurb raved about what a wonderful introduction it was to the subject, I decided I must be stupid.

Why is that the first option? Why isn’t the first option that perhaps you lack the background knowledge – or even that you have the background knowledge, and you actually know what you’re doing, but that society has told you for so long that women don’t do maths and chemistry, and the moment you hit a wall, your determination falters for a moment, because what if you really are trying to fit the round peg in a square hole, what if you really shouldn’t be doing this?

And even if you know better – you know that there’s really no gender in how this is done, and honestly, you get furious at feeling this way, because you know what you know, but the minute there’s someone in the room who might stereotype you, you start to falter and panic – because you’ve heard how some men talk about the women they work with, and you know how easy it is for you to end up in a box for one slip-up, one mistake, one faulty assertion – and you panic, and now you’re more likely to make those mistakes.

It’s called stereotype threat.

I am demonstrably not stupid. I actually have a pile of evidence, on hand, that I can supply to prove my lack of stupidity. I have no idea how intelligent other people will be, and I can’t make any assumptions as to where I fit relatively speaking when I meet someone (and it’s best not to do that sort of thing anyway), but having that evidence there reminds me that I am actually not stupid.

None of the women that I worked with were stupid. Most of them, at some point, said that they were. I ranted about the issue one time over coffee with one friend. She went quiet and thoughtful. The next time I saw her, she said, “I’ve been paying attention. I do that all the time.”

Do what?

Apologise. Tell yourself you’re stupid. Tell yourself you don’t understand those things anyway. Because it’s perhaps easier to lower all expectations – within a conversation, or within yourself – than to try, and have some trouble, and then feel like everyone who told you that you couldn’t do science because you were a girl was right.

And it’s not just the scientists that I’ve worked with in the lab. It’s the older women, family and friends of the family, that I know, who back away and say, “You’re so smart. I could never understand all that stuff.”

Yes. Yes, you could. Stop selling yourself short. You are more than this.

But how do you fight a message that someone’s been getting their whole lives? You can’t. You just have to wait, and watch until they challenge themselves. Watch that delight as they realise, in some shock, that they are actually not stupid. Sure, it would have been nice to realise that forty years ago, but better late than never.

 

 

What do you do, Doctor Kate?

When one has donned the floppy hat of the PhD graduation (your local campus regalia may differ, but my university follows the pompous and hilarious Oxford dress, which I enjoyed a great deal), one receives certain conversational responses.

First there are the congratulations – much appreciated, thank you, why yes, it has been a long time, hasn’t it? Stop asking when I started, I don’t want you to do the basic arithmetic… Yes, alright, it was shortly before the Earth cooled…

Then there is the question: “So, what are you going to do now?”

I think that people in many walks of life are a bit taken aback at questions like this. They always smack of what is your PLAN for your LIFE, they feel like a demand for you to have a plan (and let’s be honest: most people’s life plans are vague at best; pushing for clarity just makes people anxious), and they tend to come at pivotal moments of change when people are already unsettled, like:

…finishing high school.

…quitting a job or a university course.

…switching careers.

…ending a relationship.

…getting pregnant.

…getting back from a gap year or a backpacking tour of south-east Asia.

It often seems to come attached to questions like “When are you getting married/buying a house/having children/inventing cold fusion?” (maybe not that last one)

I’m sure there are many more times when this question ambushes people; I just pulled some out of thin air and the various experiences of my nearest and dearest. To be fair, people usually ask these questions out of interest and, depending on other circumstances, concern – I know I do, and it’s often not until I’ve spotted the combination of impatience and hysteria flashing out of someone’s eyes that I realise: I might just be making conversation (particularly if I’m asking this question of someone I barely know), but they are just over this question and everything that follows on from it.

I’ve now seen a few people ranging from close friends to acquaintances achieve their PhDs, mostly in the sciences, and here’s the list of things that tend to happen after getting a PhD, in no particular order, and the circumstances that tend to lead to it:

1)    a complete change of career

Life in research can be horrific. Often a PhD is finished solely through sheer force of will, teeth gritted to such an extent that your dentist will either weep in sympathy or celebrate, depending on whether the yacht is paid off (apologies to dentists without yachts). Even if you love what you do, it’s easy to feel burnt out after it all, and that’s under the best of circumstances. Under the worst of circumstances – incompetent or downright malicious supervisors, an unsupportive or completely non-functional lab environment, a lack of publications – a recent doctorate can feel entirely justified of washing their hands of the whole disaster. Who wants to spend their life begging for money, just to be allowed to do their job? Who wants to butt heads constantly with the sorts of egos that lurk in the back corridors of academia, where there is often a mentality that being a complete arse is somehow necessary for appropriate scientific critique (note: it isn’t. You can critique sensibly without being a tool. It’s really not difficult)? Who wants to try to compete in an environment where your own hard work can be deemed instantaneously meaningless by someone else’s errors? Who wants the long hours, the low pay, the pressure to publish… the list goes on.

I still love science. I’m still in it, for now; but I’ve heard the arguments for getting out and they are compelling. A not-insignificant number of PhD scientists just turn right around and head straight back to uni to do something else.

2) …frequently, teaching.

I know a truly staggeringnumber of teachers, when the number is taken as a ratio of friends in my age group. Admittedly, only about five or six either pursued or achieved a PhD prior to entering teaching. Either they started a PhD, noticed what it was doing to them psychologically, and decided “Hell, no…”, or they got to the end of a PhD, and have no papers, or one paper only. This places one at something of a disadvantage when applying for postdocs. Funding is scarce. Jobs in one’s field are often like hen’s teeth, and not in the plausible, palaeontological sense of a missing link between birds and reptiles. Furthermore, while the first year out teaching can be exhausting (having seen so many friends go through it, I can confirm that the long hours and limited sleep do take a toll on people. I’m sure they didn’t have those bags under their eyes at the start of the year), you do get the opportunity to be excited about science again, and mostly you’re being excited at teenagers who, while they can be difficult, are much more likely to catch your excitement and run with it.

Being excited and exhausted beats being jaded and exhausted any goddamn day of the week.

3)    a postdoc… somewhere else.

Remember how jobs in one’s field are like hen’s teeth? Job’s in one’s field where you actually live are like diamond-encrusted hen’s teeth. Say people get to the end of a PhD, and they have a reasonable shot at a postdoc. In most cases they have to be ready to pack up their lives and head interstate – if not overseas – just to get a look-in. It’s the nature of the game. PhDs are best off if they don’t have permanent commitments like, oh, say, pets… relationships… mortgages… friends… especially children…

I don’t mean to make this sound like a necessarily terrible thing – it’s not. Often the overseas postdoc, while stressful, is an exciting adventure, a horizon-broadening, challenging experience that most would not trade for anything. For those of us, however, who acquired the inadvisable relationships, pets and mortgages prior to finishing a PhD, it’s just not an option.

4)    a technical job, and what PhD?

If you decide you’re not up for research, but you still want to do lab work and use your technical skills, suddenly a PhD becomes a hindrance. You’re overqualified. You’re going to need more pay. You’re not a good long-term bet because any day you could get offered a more lucrative postdoctoral position and abandon your current job (even if you have no intention of doing this, employers can see it as a risk). People have been known to remove the PhD from their CV and come up with other ways to legitimately explain their work over the past three to six years.

5)    Technical equipment sales rep.

This is actually not a bad option. It pays well, often by commission, and you get to use your technical know-how and familiarity with laboratory situations, but you do also have to schmooze people and convince them to give you money, so in some ways it’s not unlike a career in research. If you’ve got the personality to pull this off, it’s worth giving it a whirl. I think I am probably too blunt.

6) other industrial or policy science applications. I haven’t seen this happen too often among my own people, but it does happen, and it can be beneficial to have the old PhD on hand.

7)    a postdoc, on your home turf.

The bee’s knees, and what I personally aspire to, but it’s not straightforward and I’m not applying at the moment. My story comes in just a moment.

Not a single one of these is mutually exclusive. Often “complete change of career” comes along after one or two postdocs, or a year or so of job-hunting.

So what are you doing now, Doctor Kate?

At the moment I do two days a week of paid contract taxonomy work at the museum. I have a couple of client institutions over in Western Australia, and when they get a batch of crinoids from local surveying, they send them to me, and I unpack them and do my best to put species names on them (or set them aside, with “sp. nov.?” written on the jar, which happens more often than you might expect) (erm, “sp. nov.” means new species). While I do that, I take tissue from everything I identify (presuming it’s big enough to do this without destroying the specimen), in case I one day have funding to do molecular work. I have permission to do this, and crinoids are an excellent group to take tissue from because they have heaps of repeated anatomical structures and they fall apart as soon as you look at them cross-eyed anyway.

It pays reasonably well (by my standards, and depending on who I talk to my standards are either phenomenally high or phenomenally low…), and at the moment there is plenty of work because there are ongoing surveys. For the greater part of my professional life, I’m not expecting there to be a great deal of taxonomic work available.

The other three days a week are ostensibly for writing papers.

(I say “ostensibly” because “writing papers” can very often become “going to the gym”, “running errands”, “taking the dogs out for training and playing”, “catching up on housework/yardwork” or any other number of necessary pursuits that enrich and enable a smooth life)

I have a bucketload of data in my PhD that, due to various circumstances, could not be published during the process of doing the actual PhD. That’s the problem with a comparative project – you don’t have all the data until you get to the end. Looking back, I see ways it could have been done, but hindsight is always 20:20, and I have to make the best of the situation. I have one first author paper from my Honours year and one fourth-author paper from some data I got for the PhD and didn’t use and ended up giving to my supervisor (I also wrote some methods and so on).

I’ve got one paper at the “Accepted, let’s start proofing” stage (yay!) and another at the “Just submitted major revisions, waiting to hear back from reviewers” stage. Hopefully in the not-too-distant future, I can claim two more first-author papers.

I have another first-author paper from my PhD data at the first-draft stage, and some “probably third or fourth author” analytical work to do on another collaborative project (on bats. The great thing about molecular work is you’re not always restricted to your personal specialisation, in my case marine biology). There are plenty more papers I can write from my PhD. I have an extraordinary wealth of data, which is not something one usually complains about, but there are downsides to wading through it all and pulling out useful, informative narratives for publication. It’s hard to leave any of it aside as too incomplete for publication, but sometimes that is what happens.

I’m lucky that we’ve got enough money for me to be able to do this, and I’m lucky that I’ve got a niche skill and support from the museum to be able to do the contract work and still be the master of my own time.

I’m actually considering swapping one of my paper-writing days for another work-in-the-lab day, since there is also some paid molecular work I can do on two other projects, which just increases the amount of juggling I’m doing, but which could be very satisfying.

The plan – yes, the PLAN for LIFE – is to get enough publications over the next few months that I can reasonably start applying for grants. That’s right: grants. Husband has an excellent, non-mobile job. We have a house and mortgage, two elderly cats, two large dogs and a very settled life. I’m not going to be doing that postdoc in Norway like I originally planned – I just couldn’t leave that many aspects of my life on hold for that much longer.

And the odds of a job coming up that plays to my skill set may vaguely resemble the odds around me discovering the aforementioned diamond-encrusted hen’s teeth. So, rather than a job coming up, I’m going to have to try to make one for myself.

Wish me luck, amigos.

When do you Science?

[I am now working out this blogging thing. What I’ve determined is that if something needs references and images, it gets delayed – so my new policy is that, for every post that needs references and images, I’ll put up a few that are just basically mental screeds on things I care about. That speeds things up. –KN]

Nearly a year ago now, I was at a conference dinner,  discussing the fact that some scientists appear to have a bit of a cognitive disconnect. Scientists, I lamented in that post-one-or-two-glasses-of-wine sort of way, are so often only scientists from nine to five. Then they go home and stop being rational.

The woman sitting next to me looked taken aback. You can’t be rational all the time, she pointed out. That would be awful.

Since then, I’ve decided that what we are stuck on is our use of the word rational. Take it to mean sensible. Take it to mean, essentially, that most advertising should be taken with a grain of salt, that media rhetoric should be dissected to find the underlying message and to assess whether or not it is supported, that herbal foot baths are not going to remove “toxins” from your bloodstream and that fish oil probably isn’t going to boost your kids’ brainpower.

Don’t take my use of the word rational to mean “unemotional” or “robotic.” That seems to be a common misunderstanding. You can be passionately rational. Being rational – sensible – isn’t at odds with being passionate, or loving, or miserable, or creative. It isn’t at odds with expression or the exploration of ideas and symbolism. It isn’t at odds with artistic or cultural pursuits or loving your children.

To be confessional about my own sins in this regard: I have a guilty irrational pleasure (well, one that I know about, anyways). It’s skincare. I like having soft skin that smells nice. It’s part of a physical indulgence for me. At the same time, I am well aware that stimulating the production of collagen is probably not what is going to happen in response to the use of eye cream. I don’t believe that, every five minutes, someone discovers a new soothing flower oil that magically dissolves wrinkles, clears pores, tightens skin and – how convenient! – doesn’t smell like a horse’s arse (although I appear to be one of the few people in the entire world who hates the smell of both jasmine and lavender, so that’s a qualified feature right there).

I like massages and facials, but I let my eyes glaze over when they start talking about toxins and so forth. There are some truisms in skincare (“sorbolene is an excellent moisturiser”, “barrier creams help stop your skin drying out when you have to wash your hands fifty times a day because you work in a lab” and “antibiotic skin treatments do seem to reduce acne for sensible and obvious reasons”) and it appears to be true that you can make oily skin less oily, dry skin less dry, and neither-oily-nor-dry-skin stay neither-oily-nor-dry. Other than that, I’m not game to commit. I’m not a dermatologist. The only time a dermatologist recommended I use a particular skin product, it was in the well-over-$50-per-jar range which was way out of my budget (if anyone’s curious, it was all that alpha-hydroxy-acid stuff. This was after I finished a course of Roaccutane and my face was feeling rather traumatised).

It’s worth mentioning that when many serums and so forth say “supported by clinical trials!” the actual data is something like “Ten out of ten respondents reported that their skin felt better.” This doesn’t distinguish it from a placebo effect. I pretty much use skincare as a placebo effect, for the most part, unless I have some environmental exposure I need to guard against (i.e. the aforementioned lab work, or SCUBA diving. Diving wrecks my skin. You have no idea), and yes, I am aware that this means I drizzle away money when I do this.

A friend suggested I should use a product on half my face for a while and use that as a test, but I admitted I was too vain to do that. If it was going to work, I wanted it to work, and if it didn’t, well, then it didn’t, and either way I wasn’t willing to look like Harvey Two-Face.

Image

In the end I decided (based on some before and after selfies) that it had a decent effect, but not enough to justify the expenditure, and I moved on to slightly cheaper pastures.

Skincare is just one example. We can stand around in a lab in our seasonally-inappropriate closed-toed shoes, and still someone might recommend homeopathy, or multi-vitamins, or reiki, or one of any number of things that don’t do you any good at all outside of a placebo effect (although the placebo effect can be very powerful, and for reiki and homeopaths in particular, being in an environment where you get to sit down or lie down and relax, where someone is going to actually have the time to listen to your problems, really is a recipe for feeling better. It won’t cure illnesses, but it could definitely reduce stress, and, alright, if stress is causing your illness…) (and having said that, I have no patience with homeopaths. At. All).

The fact is that, sometimes, being rational can be exhausting. Unless it comes from a trusted source with access to solid facts, you can’t take anything on faith. You constantly question your assumptions. You spend most of your time living inside an interrogative framework (when you’re not just mechanically pipetting samples and reagents from one place to another place, which is how I spent half my day yesterday). Does this work? Why does it work? How do I know that this is why it works? Is there a loophole in this reasoning?

I try to do the same thing with my dogs. As any half-decent dog owner knows, you do have to be rational with dogs. You have to remember what you are expecting from them, what signals you are giving them and, crucially, that dogs don’t speak English and don’t necessarily know that the vague fluffy hand signal you’re giving them now means the same as the decisive hand signal you gave them this morning. They don’t necessarily know that the same word, in a different tone of voice, means the same thing (that is a hard one for English speaking humans to learn). They don’t know that the same gesture or command in a different situation means the same thing – or perhaps something different (which is why, in our house, “Down” means “get off the damn couch”, “No jumping!” means exactly that, and the command to lie down is “drop”. If I used “Down” to mean both “drop” and “get off the damn couch”, I have no right to tell off or correct my dogs if they get confused).

It can get messy. Sometimes someone will say something that you know is not supported by the evidence, and you have to choose whether to simply say “Hmmm,” or nod and smile,” or to bite the bullet and say, “Well, actually, there have been a few studies on that…”

Everyone can get butthurt when you challenge them on their use of the word “holistic” or the phrase “Western medicine” no matter how gentle and tactful you are about it. The alternative is to let people muddle on and make inaccurate and potentially harmful decisions based on crappy information.

Now, I was under the (mistaken, naïve, egotistical) impression that scientists would be less butthurt if they were challenged on misunderstandings, instead open to the possibility of “Oh? Really? I didn’t know that. I should look into it!” as a response, since that is what we have to do all day. It turns out even someone who is rigorous and consistent within their area of research and work can start to sulk if you suggest that perhaps homeopathic vaccines are not going to do them any good.

To be fair (and this is important), people don’t necessarily go to work to debate their lifestyle and medical choices, so I can see how it would be confronting regardless of your scientific training.

I don’t have an answer to this issue. It’s not just scientists who need to be rational outside of working hours, of course: everyone does. Irrational decisions lead to, at best, wasted time and money (homeopathy, erm… expensive skincare products) and, at worst, death and suffering (vaccine refusal, terrorist activities). In spite of what I just said, you can’t really expect yourself to be rational all the time – you’re human. You have a number of built-in cognitive biases that actively work to prevent you from being rational, from seeing the big picture, from breaking things down into useful statistical blocks. Humans as a group are bad at risk assessment, bad at probability and statistics, and absolute slaves to confirmation bias (i.e. placing more weight on arguments that support what they already believe rather than the opposite, instead of evaluating the merits of those arguments).

As a take-home message, it would obviously be beneficial for people to think more about some of their decisions as they make them, and try to be more honest about whether they’re rationalising or not. This includes me, looking down upon everyone from my lofty perch on the couch, in my pyjamas. We have to go easy on ourselves (see the aforementioned cognitive biases), but we really should give it a go.

I mostly mentioned the pyjamas because no matter how I edit it, this post sounds a little sanctimonious. I just get frustrated sometimes.

Also, they’re cute pyjamas.

Taxonomy Part 1: reproductive isolation, biodiversity, and why it matters what Latin name you put on a species

[Note: I am aware that I came, I saw, I posted four times, and I disappeared into the dread abyss of non-posting. It occurs to me now that perhaps October was not the most sensible month to embark on my blogging adventures. November is National Novel Writing Month, and I signed up for it this year for the first time in four years. This means I am attempting to ensure I write 1667 words of my planned novel per day, to complete 50,000 words by the end of the month. Now, the reason I could do that this year is that I finally submitted my PhD thesis back in June. Irony of ironies, my examination results came back at the end of October, and now I have to make minor amendments to that thesis, while trying to write a novel. At the same time my current paper is – and I quote – “so close!” to being submission ready that I can’t really put that down either. Between the novel, the thesis, and the paper, I’ve had quite enough writing projects. But I am determined to share my love of taxonomy so here is my – somewhat lengthy – prodigal return post. -KN]

“I’m having trouble,” I told my friend at the bar. “I’ve tried six times to write a post about taxonomy. Normally I don’t have any trouble conveying my enthusiasm or making things interesting, but every time I start it ends up somewhere… else.”

She gave me a puzzled look. “You look at dead animals trying to work out which Latin name to put on them.”

“Well, there’s more to it than that…”

Perhaps that is the problem: the public perception of taxonomy is very much about putting the appropriate name (Latin, Greek, or otherwise derived) on critters, plants, fungi, microbes, what have you; one pictures crotchety old men with magnifying glasses and ancient sea shells, far disconnected from the environment in which they were found – less a cataloguing of biodiversity than a process of formalin-soaked stamp collection. I have seen my share of such scenes, although to be fair taxonomists vary in age and gender, and they are only very occasionally crotchety.

To be honest, it’s not just the public perception of taxonomy that suffers from that image; other biologists and environmental scientists also appear to have this notion.

Taxonomist is one my many Science Hats, and is the reason for my recent short jaunt to the Land of the Long White Cloud (New Zealand, although I have yet to see the cloud in question) – which, incidentally, is why there was zero blog action for a few days.

I had to visit Dunedin, New Zealand, because I’m revising a genus (what does that mean?) of feather stars (of what?) and I had to examine a type specimen at the Otago Museum (what the hell is a type specimen?) to make sure it was the same as the species of the same name we have in Australia (why does that matter?).

You can see how quickly the whole thing becomes quite muddled. I’m actually going to leave feather stars/crinoids for another day (although I will provide a link at the bottom for the curious), because they are gorgeous and marvellous and deserve a post all of their own.

Taxonomy is an exercise in categorisation, and since the natural world works the way it does, it is inherently an attempt to impose order upon chaos. At no point does the multitudinous swarming life among which we live feel any justification to make things easy for us. The best example of this is probably the species concept.

In fact, the very best example of that is the fact that I am going to set aside plants, fungi and microbes in my discussion of the species concept; they all interbreed and hybridise; plants have a tendency to randomly multiple their chromosome number (ploidy level) for (as near as I can tell) shits and giggles; microbes just swap in and out bits and pieces that they seem to find useful; and I don’t even want to know what the fungi are doing. It’s hard enough to work out what comprises an individual organism in a fungus, let alone an entire species.

Animals – for the most part – make things a little bit easier. The most common species concept is based on the notion of reproductive isolation, i.e., can the animals that look like this produce viable offspring with animals that look like that?

I have made up some critters to illustrate this. We shall call them “Bongs” and Bings”, because then the hybrid of these two can be called “Boings” and that appeals to my sense of the ridiculous (which is, let us be honest, all that matters).

Reproductive isolation takes two basic forms: prezygotic and postzygotic.

Prezygotic isolation involves the case where ne’er shall egg and sperm meet. There are a host of plausible mechanisms here. Maybe Bings and Bongs live on different continents (but does that make them different species?). Perhaps Bings are fertile in summer and Bongs are only fertile in winter. Perhaps Bings produce eggs that float up onto the surface of the water and Bongs produce sperm that sink to the sea floor. Perhaps the mating call of the female Bing, an irresistable siren song to the randy male Bing, is simply quite uninteresting to the randy male Bong. The same could apply to mating dances, plumage, pheromones, or any other behavioural cue. At the absolute farthest edge of what we can safely call “prezygotic”, perhaps male Bong sperm (you may giggle any time. I shall not judge you) cannot penetrate the envelope of the female Bing egg, due to a lack of protein recognition.

But wait! Reproductive isolation can be asymmetrical, meaning that perhaps a female Bong and a male Bing can get busy and experience a successful breeding season together, but a male Bong and a female Bing are utterly uninterested in one another. Due to the behavioural and chemical complexities of sexual reproduction, this is more likely than not.

Postzygotic isolation involves the case where a delightful Boing zygote is produced. Perhaps it doesn’t develop past a certain point. There is a spectrum here on which a hybrid offspring might be considered inviable – even if it survives to maturity, it may not produce useful gametes and thus it won’t be able to breed a second generation.

Unfortunately, while that seems simple, the definition of “viable” is somewhat fungible (see what I did there?). Imagine our Boing reaches adulthood and sexual maturity, and is entirely capable of producing worthwhile eggs and/or sperm which will be enable it to produce offspring with other Bings, other Bongs, or both.

But maybe those offspring are not quite as good. Maybe they are a bit less fertile than they should be, or a bit smaller and less competitive for food or mates, or perhaps a bit prone to disease, and over several generations they are eclipsed and outcompeted by purebred Bings and Bongs.

That’s called outbreeding depression, and it makes the species concept a bit more of a grey area than we would generally prefer.

The problem taxonomists face is that reproductive isolation is often not something that is easy to test. When someone throws you a dead animal (note: do not throw), you don’t have the opportunity to drop it into a tank with a similar looking animal and wait for them to get busy – or rather, if you do, all that will happen is you’ll end up listening to Barry White for a while and staring at a dead animal in a tank.

What I do, as a molecular biologist, is to look at DNA samples from a large number of animals from various groups and to work out whether they are swapping genes around. If you look at enough different genes (one is not enough, but that’s another story), you can get a very good idea of whether the Bings and Bongs living under the same rock are able to successfully get busy (because, as a general rule, if they can, they will).

Even then, however, you have to assume that

1)   you have access to enough fresh tissue for DNA analysis (DNA can be extracted and used from very old specimens, but it’s extremely fiddly and expensive)

and

2)   you have the money to embark on DNA analysis (even though whole genome sequencing, or WGS, is becoming a great deal cheaper and more accessible, molecular biology as a whole is another entire world of expense on top of just collecting the animal)

Often, this is not the case, and this is illustrated my most recent adventure to New Zealand. In that case, all you have to go on is morphology (what the animal looks like, often specifically what it looks like when preserved in formalin or ethanol), and working out what key feature (a.k.a. “diagnostic character”) separates one species from another can be tricky.

I was trying to explain the species concept to some friends of friends at a party. They brought up dog breeds, and there was some confusion about the term “breed” versus “species”.

Dog breeds can, obviously, interbreed (although there are some mechanical difficulties if you try to breed a Great Dane to, say, a chihuahua). They are the same species, and yet they look stupendously different from one another. Dogs are not a great example, since we deliberately bred them to look different and it can hardly be called natural selection, but it is a useful illustration nonetheless.

When it comes to a lot of the animals that I look at, many of them look almost identical to one another; and yet their DNA is telling me that not only do they not interbreed, but they probably haven’t shared a common ancestor for a few million years.

Morphology is an essential piece of the puzzle – without it, field surveys would be almost impossible (or prohibitively expensive); we wouldn’t know what animals are living where; and we wouldn’t be able to look at interesting things like the evolution of various features. At the same time, it’s important to realise that there is often no apparent relationship between the degree of morphological difference and how distant something might be genetically. Species that diverged at least six million years ago might be nearly impossible to distinguish, while humans of various different ethnicities who are all quite clearly the same species (but who, to our eyes, can look quite different) probably first diverged only a paltry few thousand years ago.

Of course, this brings us to a problem (you may have spotted it already). If a species has natural variation within it (and they all do), how do you at any point confidently describe what a species actually looks like, such that it can’t be confused with another species?

Enter – the type specimen.

How much does a gram weigh? How long is a metre? They’re not rhetorical questions; to avoid variation over time, these things are measured against a universal standard. We do the same thing with species.

When you find a new species, you pick one of the specimens you have (hopefully you have more than one, but that is not always the case) and you declare, “This is the type specimen! This is what Doorbellius bingius looks like! It has all the requisite bits and pieces for us to know what it is.” Then you take photos and make drawings and describe it in excruciating, tedious detail and publish it so that everyone knows your species exists and where to find the type specimen. That way, when they are handed a box of specimens, they will be able to see that one might actually be D. bingius instead of actually being D. bongius (I am enjoying that far more than I should).

That standard is called the holotype. If you’re fortunate enough to have a reasonable number of specimens and you are sure they are the same species as the holotype, you can pick a number of them and declare them to be paratypes. This is so they can capture the natural variation. You might choose a Bing with curly fur, for example, because the holotype has straight fur and you want to make it clear that the fur of a Bing can be straight or curly. You might choose a big one and a little one, because maybe they look different when they are different sizes (a very common problem in taxonomy, particularly invertebrate taxonomy, is that juveniles have different features from adults).

Although I have at most recent count eleven species to describe as a result of my PhD work (eleven!), I have only at this stage described one species. We thought they were all the same species, but some of the animals we had were different. Then it turned out that they produced different larvae, and they were very differentin their DNA, and when it came right down to it and after complicated multi-dimensional scaling analyses yes, alright, alright, they were different colours.

I designated a holotype and a paratype and they live at the museum where I do my taxonomic work, and no doubt I shall repeat that process another eleven times.

But what does it matter, Kate? you may ask. Why does it matter that the species are different?

It matters for a lot of reasons. Some of it, I suppose, comes down to a philosophy of valuing biodiversity that I hold dear; and I don’t know how we can value something properly if we don’t know that we have it. A great deal of it is related to our understanding of the natural world, how species form, how they persist and change over time, and how that process will continue into the future – these are good and important things to know.

For me, personally, it comes down to conservation. If we are going to take care of our environment, we are going to have to keep an eye on it. In order to effectively monitor our environment, we need to be able to recognise what’s in it. That species I described was a cute little biscuit star (yes, I think starfish are cute. Sue me) that produced unusual larvae that could not swim. If the larvae can’t disperse, that means that all the different populations of that star are relatively isolated from one another, and in turn that means that if one population is wiped out due to a natural disaster or pollution event, it is less likely to recover.

Before I described it, no-one knew it existed. They all thought it was the same as the other biscuit star that mostly occurred in exactly the same environments. It could have suffered a silent extinction, and no-one would ever have noticed because the other species was still there. Perhaps it performed an interesting ecosystem function, like preying on an invasive sponge, and its disappearance would have a knock-on effect. These kinds of questions are bread and butter for ecologists, and once they have the taxonomic information they can ask some truly marvellous questions about the natural world.

But in summary, if people think that Bings and Bongs are the same species, and think they are all Bings, then they won’t notice the decline of the Bongs and the loss of biodiversity.

I am not saying that my description of one little biscuit star (no matter how awesome I think the animal is and no matter how cheered I am by seeing it on a dive) is particularly momentous. It’s not. There are numerous taxonomists who describe tens of species a year. It is incremental work. Our estimates of biodiversity, particularly in Australia, are turning out to be very short of the actual value.

As to how all this resulted in my recent trip to New Zealand, and what happened with the specimens there, that is a tale for another time. 

Animal breeding, genetics abuse, and Powerpoint pedigrees

I’m about to tell a little story, here, and be aware that there are far worse and far more egregious cases of what I’m going to call “genetics abuse” than the situation I am about to describe.

After dog training the other day, as we were walking Amos (our purebred Rottweiler, for those who don’t know) back to our car, a woman stepped out of our car and went “Oh, he’s beautiful!” (thank you, we know our dog is gorgeous).

“What line is he from?”

This question, well-intentioned as it is, makes me twitch. While we did glance at Amos’s pedigree (in my case, and as I’ll explain below, it was to calculate his inbreeding coefficient) and look at his parents’ records for eye examinations and elbow and hip scores, we don’t care what line he is from. We’re not breeders. We won’t breed Amos for a number of reasons. We got Amos from Oscelly because his parents were healthy and good-natured, and the breeders were supportive.

“Oscelly,” Husband replied politely. “In Kyneton.”

“I used to breed Rottweilers, in Queensland,” the woman explained. “But I can’t have another one since my last one died.”

I flooded with sympathy. “Oh, that’s awful,” I said.

“Yes, and there was no sign! I line-bred him as close as I could-”

At this point the conflict between “It’s so sad to lose a dog” and “you fucking idiot” caused a blood vessel to pop somewhere in the tact-zone of my brain. I actually inhaled my own spit when I went, “Ah… ha?”

“-and I’d been wrestling with him the night before, and he was fine, and I went out to the garage in the morning and he was dead. He was only seven.”

A healthy Rottweiler has a good chance of making it to ten years old and beyond. Quietly I observed, “Sounds like a heart problem?”

“Yes, I thought so.”

Then she admired Amos some more while he wriggled in sociable happiness, particularly his beautifully shaped head (he does have a nice head), and we parted ways. As in all truly frustrating situations, it actually took a few hours for me to get angry enough to start composing this post in my head.

Let Auntie Kate explain line-breeding to you, as well as some basic genetics, and let’s get cracking on what happened to this poor dog and his owner.

Line breeding is where a particular breeder/stud decides that they want their dogs (or horses, or cats, or alpacas) to have a particular look and tendency. They basically want a genetic stamp that says “These are our dogs. You have a dog from Stud X!” They also want all the traits that will allow them to win more dog shows, which will get them more stud fees. In order to achieve that, they try to concentrate the particular desired traits in their dogs.

They do this by inbreeding. Let’s be clear here: line breeding is just another way of saying “inbreeding.” There is no fucking around. It is the same thing, and it is very, very bad for any population to have this happen.

I know a good deal about population genetics (the thesis is coming along nicely) and next to nothing about animal husbandry. All that I know about animal husbandry is based on breeders of any kind of animal delivering bone-headed pronouncements that make me want to smack them upside the head with a population genetics text book (heavy enough to concuss). Having said that, animal husbandry is one of the long arms of human agriculture. Humanity has been breeding animals to conform to their specifications for millennia, and we’ve become pretty good at it. Without an understanding of DNA, or complex inheritance patterns, we managed to work out that breeding too close was a bad idea.

We worked this out from a number of signs: deformed offspring is one obvious sign. Less obvious signs are infertility or reduced fertility. If, for example, you want to buy a puppy from a breeder, and they announce that the bitch only had one pup in that litter, do not buy that pup. That pup has a good chance of breaking your heart. If you do cave, and buy the pup that almost certainly carries a number of recessive defects, do not breed the pup. Ever. If you do, you’re part of the problem.

So some animal husbandry has limits as to how close they are willing to breed their animals. They draw these limits far, far closer than they should, and then cite some pretty random research to say that this is okay. This research does not say what they think it says, and I’m going to explain why.

In every cell of your body*, you have two copies of your master genome** – the 23 (usually) chromosomes that are tightly wound strings of DNA. You have one copy from your biological mother, and one from your biological father. In the simplest scenario, when you produce gametes (eggs and sperm), each gamete contains only one copy. They might have your paternal copy, or your maternal copy (they might have a slight mix of the two as your chromosomes cross over and recombine, which is how new combinations arise). The successful gamete will pass that copy on to the next generation. Odds of having a mostly paternal versus a mostly maternal copy are 50:50.

So we have two copies of every gene and every gene region. When these copies are different in any way, we refer to the different versions as “alleles”. For example, I have red hair. Red hair is what we call a recessive trait, which means that I have to have inherited alleles relating to red hair from both my mother and my father (hair colour is actually a polygenic trait, so it’s not that simple, but both parents have to be involved for my hair colour to express the way it does). This also means that, since I have two copies of the relevant alleles, I am guaranteed to pass on one redhead allele copy to any kidlets I one day have.

So we’ve got the background for simple recessive inheritance. Now we get to the scary part.

YOU ARE A FILTHY MUTANT.

No, really, you are. DNA is self-replicating, and it even has proofreading systems to make sure it copies everything perfectly. It still screws up, and leads to mutations. We all have these mutations, every single one of us. Most of them are probably relatively benign on their own – after all, you’re reading this, right? – but in many cases if you had two copies, the result would be lethal. In fact, most of the time, if you have two copies that were flawed in the same way, you wouldn’t develop all the way to viability. You would be miscarried, maybe as a zygote, or an embryo, or a fetus.

Here’s the thing: because these mutations are so sparsely distributed throughout the genome, and so individual, and because there is so much diversity in the human genome (we have what is called a large effective population size, more on that later), it’s astoundingly rare that you will get two copies of a flawed allele (with the exception of some named recessive disorders that have persisted in the population – and there are some nasty ones out there).

Of course, if you’re closely related to someone, it’s much more likely that you both have that allele. I am now going to illustrate why cousins shouldn’t marry and have kids****, only in my example, they are DOG cousins.

(****early footnote to prevent offense also pasted in here: Of course, cousins are perfectly allowed to marry. It’s their right and their choice. It’s just that most of them seek genetic counselling to make sure that they are not going to pass on some deleterious recessive trait. In most cases, it’s perfectly fine.)

We begin with a basic pedigree.

Slide1

Meet Lord Doggington and Princess Jemima. They are both perfectly healthy, show line dogs of the breed I just made up called Zimbabwean Slothhounds. They win awards for how amazingly pretty they look. Depending on the breeder, they may also be valued for their robust strength and good nature, or the breeder might just be interested in appearance. Let’s give them the benefit of the doubt: they are, after all, particularly good at chasing down sloths.

Like all dogs – and all DNA-bearing organisms – Lord Doggington is carrying a nasty secret in his genome. It’s okay, because it arose with him due to a point mutation in one of his parents’ gametes, so it doesn’t exist anywhere else in the Zimbabwean Slothhound population. We should be safe from anyone ending up with two copies of this allele.

Alas, Lord Doggington’s owners think he is super awesome, and they want their whole stud to be like him. They want to concentrate his traits.

Lord Doggington and Lady Jemima have a bunch of puppies (ideally around eight). The stud sells six, and keeps two, Daisy and Fido, whom they like the look of. Daisy and Fido each have a 50% chance of inheriting Lord Doggington’s crap-arse allele. However, they will only ever have one copy, because Princess Jemima does not have the crap-arse allele. She probably has her own deleterious alleles, but we’ll focus on the other one here.

Slide2

Let’s imagine that both Daisy and Fido inherit the crap-arse allele. There is a 25% chance that this will happen (0.5 x 0.5 = 0.25, for those who forgot probability as soon as they graduated high school). Daisy and Fido are each bred to outstanding Slothhounds from other studs, and produce, respectively, Butcho and Miss Dogface, who are adorable puppies.

Slide3

There is a further 50% chance each that Miss Dogface and Butcho respectively will inherit the crap-arse allele from Fido and Daisy. If we know that Fido and Daisy have each inherited the allele, then, again, there is a 25% chance that both Miss Dogface and Butcho will as well. If we don’t know the status of Fido and Daisy – i.e., we’re just guessing, which is the fun part of recessive trait pedigrees – then there is a 25% chance that each pup will have the allele, and a 6.25% chance that both of them will. That’s a more than 1 in 20 chance; it’s actually quite high.

Let’s say that this untoward event happens, and the breeders decide to breed Dogface to Butcho (some breeders won’t do this. Some will. It varies) to create the pure strain of awesome that descended from Lord Doggington, thus elevating the Zimbabwean Slothhound from relative obscurity as a breed to glorious renown.

If we know that Dogface and Butcho have the crap-arse allele, there’s a 50% chance that their pup will have one copy, a 25% chance that they will have no copies, and a whopping remaining 25% chance the pup will have two copies. If it is still unknown – if, in fact, all we know is that Lord Doggington is on both sides of the pedigree and that Butcho and Dogface are first cousins – then we have a 1.56% chance that their offspring will have two copies of any allele from Lord Doggington. This is what we call the probability of identity by descent (IBD).*****

Slide4

In this last figure, I’ve now changed the colour to indicate that this unlikely event has happened, and we can see the carriers of the allele. The offspring of Miss Dogface and Butcho inherits both copies (something that is a 1.56% chance from the word go), and either aborts, or is born with a severe defect that may even require euthanasia. This is why you want to avoid dogs with tiny litter sizes – unless they’ve been bred for reduced ovulation, small litter sizes generally represent resorbed pups that did not develop or even useless gametes.

Lest you think 1.56% is vanishingly small, in a population-level analysis, it is huge. It is a matter of some concern, and this shit happens all the time. In livestock animals, offspring may often be bred back to their parents – now that you’ve got the basics, I’ll leave you to draw out the pedigree of all the shit that comes out of that.

When Amos’s breeder showed me his pedigree, he brought out a photo of his very own Lord Doggington, explained how fantastic that dog was, and that he was on both sides of Amos’s pedigree. This was stated to me as a good thing, and if I were not a geneticist, I would have been convinced by his superior knowledge. That is why I am writing this post and using too much bold typeface.

I gently pointed out that I was a population geneticist doing a PhD and that this was of some concern to me. The breeder told me about some research some fellow in the UK had done on plants where he experimented and showed that inbreeding wasn’t so bad.

I haven’t managed to find whatever research he was quoting, but here’s the question I want to ask: what sort of plant? Was it a native population? Because this, I think, is where animal husbandry and population geneticists part ways. Animal breeders know what I’ve just been explaining. These are not stupid people – they have a science all of their own. They’re just not updating it, and they are missing a crucial piece of the puzzle: the piece that comes from population genetics.

They are missing effective population size.

Effective population size is basically a way of describing the background genetic diversity in the population and what is passed on to the next generation. For example, you might have an enormous population of corals on a reef, but if the millions are all reproducing by cloning themselves, and if they are all descended from the same clone, the corals will have a very, very small population size (i.e.: 1). However, since they are clonal, they already have their two genome copies, and we already know that they are functional. There are advantages to clonality.

You might have a very large herd of deer, but if all the young males keep getting their arses handed to them by the boss male, he’s going to do all the mating. Because you have a large number of different females, the effective population size will be larger than 1, but it’s not going to be enormous. There’s going to be a lot of deer wandering around with that paternal genome copy.

The basic message is this: when you breed to concentrate physical traits in a population, you are removing variation from the genome, because you are not breeding the animals that don’t fit your requirements. These animals do not contribute to the next generation; therefore they are not included in your effective population size. You are concentrating the physical traits you desire, but you are also concentrating the invisible, deleterious alleles. You are increasing the likelihood that matings will result in double copies of the same rare, lethal allele. You are reducing your effective population size.

You are drying up your gene pool #nerdpun.

So inbreeding is tolerable and manageable when you have a large effective population size, although it is itself reducing your population diversity. It is a horrible thing to do when you have a small effective population size.

This just in: purebred dogs have a very small effective population size. We’re not talking clonal corals, but we’re definitely not talking human-grade levels either. It’s a closed system; generally they only breed purebreds of a breed to others. That’s the whole point. I decided to get a purebred dog despite knowing all this, because I grew up with and love the breed, and also because this way there is a measure of predictability regarding temperament (I like large dogs. Temperament is important) and disease (I want to know what to look for).

I decided to look at Amos’s pedigree myself. All up, his probability of any allele being identical by descent was less than 0.06%. Since I’d been told that the odds of finding a breeder who does not practice line breeding are slim to none, I decided that was an acceptable risk. Amos has an undershot jaw, so it would be irresponsible to breed him (it’s not a huge deal for him personally), but otherwise he is perfectly healthy.

I think. I’m not sure, because here’s the rub: Rottweilers became very fashionable at some point in the 1980s. Before that, they were known for the elbow and hip problems, and possibly the minor eye issues – and that was it. These are also common to many breeds of dog.

When a dog breed becomes fashionable, you get a lot of what is termed “backyard breeding” – people either breeding out of ignorance (because they like puppies), or greed (because purebred dogs are worth squagloads) or both. This means people didn’t necessarily check that their dogs were healthy before they bred them.

Rottweilers are now known for heart problems. This is a new thing. I now have to worry about my dog’s heart, because even though he has a 0.06% chance of identity by descent, the odds of these crappy heart alleles floating around are much higher (there’s also cancer. Don’t get me started).

And this woman I met in the parking lot – to come back to the point after a long and circuitous journey – line-bred her dog as close as she could, and she did it because she honestly believed that it would produce a healthier dog. She believed this because all the dogs she bred were outwardly healthy, with no consideration for or knowledge of what was hanging around unexpressed in their DNA. This is the problem. Because they don’t consider effective population size, because they don’t consider recessive traits, and because they do not acknowledge how common these mutations are, they only breed from the appearance and behaviour of the animal, i.e., from the phenotype, not the genotype (this is not universal: a number of recessive traits are very well understood and bred for, but this doesn’t connect with effective population size).

It’s possible that if she outbred her dogs with other studs – and you could even do this and keep a dog purebred – the resulting pup wouldn’t have had a congenital heart defect.

It’s just possible she wouldn’t have gone out to the garage and found her best mate dead on the floor at seven years old.

So, even in purebreeding systems, you can outbreed. Do that. Avoid genetic abuse. Reduce animal suffering. Avoid getting your heart broken.

*Except red blood cells. They need extra room for hauling around oxygen, so they don’t have a nucleus.

** We’re not talking about the mitochondrial genome. While that is important in its own way, it is only maternally inherited, it doesn’t recombine, and because cellular respiration is so crucial and you only have one copy rather than two, deleterious mutations don’t tend to survive.***

***Having said that, there are rare cases of species or individuals where a mitochondrion may be bi-parentally inherited and/or undergo recombination, and there are rare human diseases that are caused by mitochondrial mutations.

****Of course, cousins are perfectly allowed to marry. It’s their right and their choice. It’s just that most of them seek genetic counselling to make sure that they are not going to pass on some deleterious recessive trait. In most cases, it’s perfectly fine.

*****IBD! Identity by descent! Not to be confused with Isolation By Distance, or any other number of concepts for which IBD is an acronym…

(Backdated entry: Originally put together November 2012)