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Stäbchen in the Dark

Stäbchen in the Dark

Female Karyotype 2014 Hey Paul Studios CC BY 2.0.jpg

Female Karyotype 2014 Hey Paul Studios CC BY 2.0.jpg

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The 19th century was an exciting time to be a man with a microscope (and yes, they were mostly all men). The tools and techniques for peering at the inner workings of life were advancing fast, most notably the development of brightly-coloured synthetic dyes concocted from the chemicals in coal tar. These were the glory days of cell biology, as scientists sketched the strange never-before-seen structures that appeared under their lenses.

In 1873, the German zoologist Friedrich Schneider was busying himself spying on the developing sperm in his favourite animals – a type of transparent flatworm called Mesostomum ehrenbergii– when he noticed something very strange.  

Some of the cells contained a row of curious little rod-like structures, which he called Stäbchen – German for little skewers – all lined up along the middle. Some of the more elongated cells appeared to contain not one but two sets of Stäbchen, one at each end. As far as we know, these are the first descriptions of what later came to be known as chromosomes – the long strings of DNA inside cells.

Sadly, very few people came to know about the discovery at the time. Schneider was apparently far more fond of talking than writing, eventually publishing his descriptions of the little Stäbchen in a dense paper about flatworm biology in the little-read yearbook of the Upper Hesse Society for Natural and Medical Science.

The next German microscopist in our story is Walther Flemming, who had become fascinated with the dark material inside the middle of every cell, in a structure known as the nucleus. He named it ‘chromatin’ after the Greek word for colour, in reference to the way this substance soaked up coloured stain.

Sifting through preparations of salamander cells, Flemming described how this chromatin rearranged itself into long threads as a cell got ready to divide, then appeared to be split between each new cell as they separated, so each one got an equal share.  

Flemming referred to this process as Karyomitosis, and the thin threads as ‘Mitosen’, publishing his key observations in 1882 in a hefty book entitled Zellsubstanz, Kern und Zelltheilung (that’s ‘Cell substance, nucleus and cell division’), which laid the foundations for the decades of research into cell division that were to come after him.

But while we still use the word mitosis today to describe the process of cell division, it took another German scientist, Heinrich Wilhelm Waldeyer, to come up with a catchier name for the strands of coloured chromatin, and so the word ‘chromosome’ was born. But it would take many more years for scientists to discover what these little strands were made of, and that they contained the secrets of life.

At the turn of the 20th century, biology was running along two parallel strands. On the one side were microscopists like Flemming and Schneider, carefully fixing and staining all sorts of specimens of eggs and sperm from salamanders to sea urchins to spy on the hidden mysteries inside cells. On the other were the geneticists, exemplified by William Bateson in the UK and Thomas Hunt Morgan in the US.

Inspired by Mendel’s experiments with peas, which had only just been rediscovered, they were busy breeding fruit flies, chickens and anything else they could get their hands on to work out how characteristics and traits were passed down the generations, through the actions of these new-fangled units of inheritance that had just been invented, known as genes – at the time a hypothetical device for explaining inheritance patterns, rather than any kind of molecular entity.

Being good biologists, all of them knew that babies of any species are made when mummy and daddy love each other very much, bringing together egg and sperm.

The geneticists knew that certain combinations of genes were passed on from parents to offspring in these special cells. And it was obvious to the cell biologists that correctly separating chromosomes into developing sex cells was an essential part of the process. But it was hard to figure out the connection between the two.

Eventually, American geneticist Walter Sutton and German microscopist Theodor Boveri figured it out at the same time, thousands of miles apart.

The behaviour of genes segregating from parents to offspring exactly mirrored the behaviour of chromosomes. Genes must be physical entities within the chromosomes. There are two pairs of each chromosome in every cell – one from mum and one from dad - which are segregated into eggs and sperm when they’re made, only to be reunited in new combinations at fertilisation, when mummy and daddy love each other very much.

Looking back, it seems so obvious that you might think that would be the end of it. But you’d be wrong. The Sutton-Boveri chromosome theory was hugely controversial, and the debate raged on for years.

One of the first objections was that the stringy chromosomes weren’t always present inside cells. Most of the time, the nucleus was just a blob of darkly-stained chromatin, with not a single little Stäbchen to be seen!

We now know that chromosomes only pack down into their characteristic rod shapes during cell division, coiling and supercoiling to create the structures that the early German microscope men could so clearly detect. The rest of the time, they relax and unwind, wriggling around in the nucleus like a writhing mess of biological string, loosely organised into their own particular territories.

The other objection was that one chromosome looks very much like another in some organisms, making it hard to be sure that there were specific pairs of chromosomes inside cells, which matched up and separated into new cells as they divided, rather than a more general biological pick’n’mix where random chromosomes were matched and separated.

Eventually, the confusion got sorted out. Living cells contain matching pairs of chromosomes, made of long strings of DNA, and genes are specific stretches of code within them. There are regular old autosomes, which make up most of the genome, and then there are sex chromosomes, first discovered in 1905 by Nettie Stevens.

This is a special pair of chromosomes that come in different varieties (X or Y in humans and other mammals) which are responsible for determining genetic sex. Overall, the number of chromosome pairs depends on the species, with fruit flies having just four pairs and a chicken blessed with an impressive 39.

And as we all know, humans have 23 pairs of chromosomes – 46 in total. But that wasn’t always the case, as we’ll find out in our second story…

References and further reading:

Lyons, tigers and pussycats

Lyons, tigers and pussycats

The budding lady botanist - Harriet Creighton

The budding lady botanist - Harriet Creighton