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What’s In Your DNA, Friedrich Miescher?

Double helix - by Kirsty Martin

The second in series of posts from Kirsty Martin on "Whose Shoulders Are These Anyway?" takes a close-up look at DNA and the work of scientist, Friedrich Miescher.

Recently, I've been thinking about DNA.

To be honest, this is not that unusual; I find myself manipulating the stuff every other week in the lab. Even in everyday life, we are used to the idea that we all carry an inherited code that makes us unique (except identical twins of course!) This idea permeates our popular culture: we see it in CSI, X-Men, Jurassic World, to name but a few.

It even makes its way into social media: last month a story about ‘London’s DNA trail’ popped up in my facebook page. The associated image showed a forest of colourful, twisted sculptures: the shape is inspired by the structure of DNA (published by Crick and Watson in 1952) and the colouring reflects each artist’s interpretation of the question ‘What’s in your DNA?’ We understand that question to mean 'What makes you who you are?' : expressing this on a double helix is an interesting idea – so I gave it a go (picture below).

Double Helix by Kirsty Martin

Photography and original ‘art’ by Kirsty Martin!

Of course, here is also a literal, scientific answer to the question ‘What’s in your DNA?’: carbon, oxygen, nitrogen, hydrogen and phosphorous. But how do we know that? The truth is, we have known what DNA is made up from for more than 100 years – since, in fact, 1869!

And so we come to this month’s set of shoulders. Meet Freidrich Meischer, a man whose story, like any good tale, includes a castle (below) and… buckets full of pus filled bandages?

Okay, so it’s not your typical fairy tale; more like a Gothic horror story!

„Sinner-Tübingen-Neckarfront und Uhlandstraße um 1873“ von Paul Sinner - Götz Adriani und Andreas Feldkeller (Hrsg.): Tübingen Kulturdenkmale. Katalog der Tübinger Kulturdenkmale Tübinger Fotografien von Paul Sinner. Kunsthalle Tübingen, Tübingen 1984 (unveränderter Nachdruck der Ausgabe 1978). Lizenziert unter Gemeinfrei über Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Sinner-T%C3%BCbingen-Neckarfront_und_Uhlandstra%C3%9Fe_um_1873.jpg#/media/File:Sinner-T%C3%BCbingen-Neckarfront_und_Uhlandstra%C3%9Fe_um_1873.jpg

Photography by Paul Sinner

Friedrich Miescher was probably always destined to be a scientist. Both his father and uncle held senior academic positions at the University of Basel, Switzerland, and the young Miescher grew up in a home full of scientific debate. As a result Fritz, as he was known in the family, kept his parents updated on his research later in his life; so some of the first written records concerning DNA can be found in a 25 year old's letters to his Mum.

Yes, Miescher was only 25 when he made the breakthrough that was to influence the direction of biochemistry over next century.

After finishing his studies in anatomy and physiology in Basel, Miescher was considered qualified to work as a physician. But his uncle, and mentor, Wilhelm His encouraged him to pursue his true passion, which was physiological research. So he spread his wings and moved from his hometown of Basel to Tübingen in Germany.

The laboratory in the former kitchen of the castle in Tübingen.

Photography by Paul Sinner, Tübingen

The attraction of Tübingen was not its resources: he was moving to a minimally equipped laboratory located in the defunct kitchen of a mountain castle (pictured above). This lab, however, was run but a professor called Felix Hoppe-Seyler. Hoppe, as Miescher came to know him, was a pioneer of the field he termed physiological chemistry, which we now know as biochemistry. Whose own workspace was in the laundry room.

Hoppe-Seyler's work chimed well with Miescher's ambition to understand the chemistry of living cells; this stemmed from his beloved uncle's conviction that 'the ultimate solution of the problem of tissue development will be found in chemistry'. They wanted to start by chemically identifying all the compounds that make up cells. The professor himself was working on red blood cells. It was the new boy, Fritz Miescher, who had the pleasure of collecting used bandages from the local hospital and extracting white blood cells from the pus that had collected in them!

The work seemed to go smoothly enough, until he reached the nucleus - a problem that Hoppe did not have to contend with in his red blood cells. Since the detailed description of nuclei by Scottish botanist Robert Brown in 1831 there had been been continuing debate as to whether microscopy data such as his could really help develop an understanding of life; many of his and Miescher's contemporaries dismissed the structures as unimportant.

But it was there, and it was Miescher's job to characterise all the components of these cells. So he set about isolating the nuclei - a slow process that took weeks - in the draft basement kitchen of that castle in Tubingen.

In winter.

Before he had obtained the material, both Miescher and Hoppe-Seyler assumed it would be protein. As it turned out, the cotton-wool like substance had entirely different properties to any previously analysed cellular compound! Hoppe-Seyler, very much a protein man, appears too have been sceptical of this result.

But Miescher stuck to his guns. He purified enough of this nuclear material, which he called nuclein, to apply established chemical approaches and identify the elements making it up. These kinds of analyses involved burning the material, isolating and weighing the products, and then calculating what had been there to begin with. It was a painstaking, protracted process, but he showed that nuclein had to much phosphorus in it to be protein.Through the dedicated work of one year, Miescher was convinced that he had identified an entirely new molecule that was somehow involved in life. And he was only 26! He moved on to a new lab, writing up his results and submitting them for publication to his supervisor Hoppe-Seyler. Who said no.

Hoppe-Seyler insisted on repeating all the experiments himself - something that I'm grateful is not a standard part of peer reviews, given that it took him twice as long as Miescher's original work!

It wasn't a complete shock to Miescher. He had expressed some doubt as to Hoppe's openness to his data in a letter to his parents in December 1869. But finally, in 1871, Miescher's paper describing the chemical composition of the nucleus was published.

This work formed the basis of the experiments that led, step by tiny step to Rosalind Franklin's DNA crystals, and that iconic structure, which can been seen around London for the next two months. And if you would like to make your own DNA sculpture, why not pop over to the Glasgow Science Centre website; I used their DNA origami activity and it is great fun!

 

Kirsty Martin graduated in biochemistry from the University of Glasgow in 2006, moved to Dundee to pursue her PhD in cell signalling at the MRC Unit there. She continued her scientific tour of Scotland with a post-doc in advanced imaging techniques at the newly founded IB3 institute at Heriot Watt University before returning to Glasgow where she's currently combining these skill sets working at the Beatson Institute for Cancer Research.

Outside of the lab Kirsty's an avid reader of classic, historical and fantasy literature; she enjoys puzzle and adventure games; and her geek status is cemented by a love of fibrecrafts, particularly knitting and crochet. She's always excited to find things that combine these varied professional and personal interests!

You can read the first blog in this series of "Whose Shoulders Are These Anyway" posts from Kirsty on 'Living Liebig’s laboratory legacy' here. And look out for more from Kirsty in the months ahead.

Think you could blog for Glasgow City of Science? Get in touch!


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