Mary B. Mitchell and Gene Conversion

George W. Beadle in 1949, with an unnamed assistant who could plausibly be Mitchell but might not be.

I was reading up on gene conversion this week, and vaguely recalled that a woman discovered it, so I looked her up for the Zuskateer Party Calendar of women scientists' birthdays. Although I found her name easily enough - Mary B. Mitchell - and the 1955 paper in which she presented her results was available online, I found no birthday, no photo, and no biographical details except that her birth name was Houlahan. There wasn't even a description of her discovery on any blogs. Unto the breach! You can count this as an early entry for Ada Lovelace Day.

It may surprise you how good an understanding of genes scientists managed to achieve before they had any clue what exactly genes were. These days, if you choose your organism right, you can practically treat genes like Lego bricks, and break'em apart and stick'em back together how you please. But in the first half of the twentieth century, scientists worked out a lot about the nature of heredity, genetic variation, and the organisation and transmission of genetic information, largely by Counting Things.


22,747 mutants, ah ah ah. Mitchell counted over 100,000 spores for her gene conversion paper.

Fly-counters like Morgan are probably more famous, but one could argue that foost-counters like Beadle made even greater contributions. Mitchell worked in Beadle's lab, and she noticed something odd.


Photo by N. B. Raju, nicked from here.

This is the bread mould Neurospora, the fungus Mitchell worked on, under the microscope. Those things that look like strings of beads are groups of spores that have all come from one parent cell. Spores are made by meiosis - the same process that makes egg or sperm cells in people - and usefully, they're all held together so you can see which cell made what spores. Mendel's laws state that if the parent cell has two kinds of a gene, they should be doled out evenly to the spores. That's what's happening in the picture above: each set of eight spores is made up of four that are green and four that aren't.

Except it wasn't always true. Very occasionally there were six of one and and two of the other. It seemed Mendel's laws had some kind of loophole.


There were attempts to explain away this observation. Most blamed experimenter error, or insisted that two genes rather than one were involved, which would allow for a six to two split (if you're a biologist and can't see how, you should scribble your Punnett Squares right now and work it out). Mitchell's paper shot these doubts down: her experiments are meticulously controlled and double-checked at every stage to refute possible counterarguments. In her fungi, rarely but surely, a gene would sometimes change to match another one.

"Blimey," I hear you exclaim sarcastically, "how riveting. And how extremely surprising that a monk in 1850 knew a bit less than a professional geneticist in 1950." Sark ye not! Mitchell's results really did matter and they still do.
First, the findings lit the way to a better molecular understanding of the way in which genes are dealt out into sperm or eggs (or spores) and shuffled from generation to generation. Mitchell's discussion says: It might even be supposed that the event which gives rise to crossing-over took place in each case... but that this event results in an actual exchange in, statistically, only half the cases. This was startlingly prescient; explaining why is a whole 'nother post which I might write if there is general clamour for it, i.e. someone asks nicely.

Secondly, gene conversion has evolutionary implications that are still being argued over. It might affect the evolution of whole sets of similar genes, or the repetitive bits of our DNA (which is nearly all of it).

My third reason is more nebulous, and more tenuous, but I think it holds some water. Mitchell and the other founding mothers of non-Mendelian inheritance (Ruth Sager and Barbara McClintock - and maybe we can count Nettie Stevens) started people thinking about why genes are inherited the way they are, and what might happen if genes didn't play by the usual rules. They provided illustrative examples, conceptual frameworks, and probably a bit of inspiration, to the evolutionary biologists of the following few decades who were developing theories that centred on conflicts between selfish genes. So I'm particularly saddened that we don't know her birthday. I'd certainly celebrate it lavishly: I suspect she helped to kick-start my own field.

Amiable Cookies with Mean Choc Chips

Cromagnon made these by accident when he used a bar of intense fuck-off 85% cocoa solids cooking chocolate instead of the normal stuff meant for eating. It was an adaptive mutation and we've been making them this way ever since. The cookie dough should be as mild and all-American as possible to contrast with the dark, bitter chocolate.
They're freezer cookies, so you make a vast batch of dough, freeze it in a cylinder shape, and slice off a few cookies at a time for baking. I defy the Breakfast Police and eat them for weekday breakfasts with orange juice and an espresso. Oh yes.
Makes about 100 cookies but not necessarily all at once.

Recipe
To make the dough, beat 175g caster sugar and 110g brown soft sugar with 225g butter (at room temperature), then beat in 2 eggs and 1 tsp vanilla extract.
Next, sift 450g plain flour with 1/2 tsp salt, 1 tsp baking powder and 1/2 tsp bicarbonate of soda, and mix all that in. Finally stir 55ml milk and 100g very dark chocolate chunks through the dough. (Green & Black, Lindt and Cote d'Or all make 100g bars with 85-90% cocoa solids which you can chop up into little bits). Chill the mixture for an hour or so in the fridge if you have time.
Then tip it out onto a floured board and squish it into two sausage shapes about 5cm across and 30cm long. Wrap them in baking parchment and shove them in the freezer until needed. They keep for a good few weeks.

When you want cookies, preheat the oven to 200 deg C. Cut off 5mm slices of dough like slicing a salami, and put them on a baking sheet lined with baking parchment (or just well greased). Leave room between them so they can spread out a bit. Bake them for 7 minutes. Let them cool slightly before trying to remove them from the tray, as they're still very soft when they leave the oven.

Compare and Contrast

Here are some edited highlights of a BBC news story published yesterday, about some medical research that only looked at female subjects:

Women... Women... Women... women... women... The women... the study did not include men, the authors believe the findings may not apply to men. The women... men who drink might not do this... the way men and women break down alcohol in their liver may differ, which help might explain why women... you... people should be wary... women... women.

Here are some edited highlights of a BBC news story published today, about some medical research that only looked at male subjects:

you... you... your body... us... we... we... our mood... we... People... we... volunteers... people... volunteers... volunteers... patients... patients.

Book review: The Immortal Life of Henrietta Lacks

My copy, on campus at the University of Thighmarcester. I couldn't wait for the UK version to come out so I ordered the US one for a princely sum, and the VERY NEXT DAY someone offered me a review copy for free. Gah.

Are you a scientist? If you're not, I recommend that you read Rebecca Skloot’s The Immortal Life of Henrietta Lacks because it's a jolly decent popular science book.

But if you are, I urge you to read it, because it is not really a popular science book at all. It has yer standard pop-sci format – human interest, historical background, there's the eccentric genius, here comes the science bit, concentrate… but at heart it's a human story, albeit one that stirs up questions of politics, race relations, and medical ethics. What's inspired about it is that Skloot has inverted the usual "framing" of pop-sci, where personal narratives are a means to inspire the lay reader's interest, and instead uses scientific content to draw nerds like me into caring about a family history.

The family in question is that of Henrietta Lacks, who had eleventy squillion and six offspring: four sons, two daughters, and an immortal cell line cultured from the cancer that killed her in 1951. HeLa cells, as they were labelled, have thrived in laboratories across the world ever since: they’ve been to space, they’ve caught AIDS and Ebola, they’ve tested innumerable drugs, and they’ve caused an international scientific scandal. They’ve even been classed by Van Valen* as a new species of unicellular mammal, a distinction they share only with two transmissible cancers.

Henrietta's eldest daughter, Deborah Lacks, spent twenty years unaware of her mother's legacy, and when – by coincidence – she did find out, she was haunted for as long again by worries about the pain and distress her mother must be feeling as the subject of such horrific experimentation. If at this point you're tempted to snigger at Deborah’s ignorance, as I was when I heard a garbled version of this story thirteen years ago, you just exposed your own. The medical and scientific establishment made no attempt to inform the Lacks family about the situation - unless you count sending a postdoc who spoke little English to sample their blood and talk over their heads about adrenergic receptor genotypes - and the shadow of the Tuskegee syphilis study alone would have justified almost any level of paranoia. In fact, Deborah’s grace and forgiveness, her eagerness to understand her mother's contribution to science, and the extraordinary manner in which she comes to interpret it, lift the mood of a book that could otherwise have been a relentlessly miserable piece of Improving Literature.

The Immortal Life is thought-provoking, challenging, and downright harrowing at times. I hesitate to say you ought to read it because nobody likes a chore, but thankfully it's well-paced, suspenseful and inherently fascinating, so I only need to say you ought to start reading it and you'll finish it in no time (keep tissues handy if you have a soul - I cried). It's due out in the UK on the 10th of June, so get your pre-order in now so's you can smugly lend it to your friends after it wins a bunch of prizes.

*I will consider myself grown up when I can read the name of this distinguished evolutionary theorist with no accompanying urge to play air guitar.