Welcome to the Genomics Forum blog


Based at The University of Edinburgh, the ESRC Genomics Policy and Research Forum is part of the ESRC Genomics Network and pioneers new ways to promote and communicate social research on the contemporary life sciences.

Wednesday, 29 February 2012

Tick-tock goes the clock: Laboratory modes of anticipation

by Karen Jent
The world of science can seem remote to those of us outside the lab. So what is it like to be a scientist? I am a social anthropologist and am interested in understanding how everyday science works. I have spent the last six months in a stem cell research laboratory, observing what the researchers do day-to-day. It turns out that unexpected objects such as the laboratory timer play an important role.

“Drug quest to help elderly fight disease,” reads a Scotland on Sunday newspaper headline from an article reporting the award of a £600,000 grant to scientists at the University of Edinburgh for research on the regeneration of the thymus. The article is an example of a common public attitude towards biomedical research: the anticipation that a broad range of diseases may be ‘cured’ as a result of a single research project. In the case of regeneration of the thymus, no less than cures for cancer, improvements in bone marrow transplants and changes to the process of ageing itself, are mentioned.

The human thymus sits behind the breastbone and is involved in making T-cells, a type of white blood cell that is a key part of our immune system. The thymus is also one of the first organs to degenerate as the body ages, for reasons not entirely clear. As we grow older we steadily lose the ability to produce T-cells and therefore become more vulnerable to new infections such as different strains of flu. If we could find a way to regenerate the aging thymus, the body could make more new T-cells to protect us against infection. In the long term, this is what the group around Professor Clare Blackburn at the Centre for Regenerative Medicine at the University of Edinburgh is trying to achieve.


The human thymus: The thymus sits behind the breast bone and is involved in making cells of the immune system

Shadowing science
For the past six months, I have been visiting Professor Blackburn’s group and observing their routine laboratory practices. I am studying social anthropology at the University of Zurich, but I’m currently based in Edinburgh, dividing my time between the Blackburn laboratory and the ESRC Genomics Forum of the University of Edinburgh. During my stay, I am trying to capture what happens in the science laboratory. In particular, I want to explore how it operates as a physical space. How are the daily routines within this very specific environment linked to the rules and values of society? Does the political and social climate impact on practical laboratory work? And does the anticipation of future benefits from research – often fuelled by large funding awards – manifest itself in laboratory practices?

Tick-tock routine
Sadly, the everyday life of a researcher is not usually so much about ground-breaking achievements. It is about routine and meticulous regimes of manual and technical work, building evidence to help answer biological questions one small step at a time. The Blackburn team is not on a daily ‘drug quest’ – it is working to piece together an understanding of how the thymus develops in the first place, how it is maintained in the healthy body and how it degenerates.

One of the essential steps in this process is to understand the thymus’ development at the level of the genes inside the cells. All the cells in your body have the same genes, but not all the cells are the same, e.g. heart cells are different from thymic cells. This is because genes can be turned off or on, or made more or less active. This leads to a distinct pattern of ‘gene expression’ in a specific cell type. Which kinds of genes are expressed (turned on) to make functional thymic cells? Which genes are expressed when the thymus starts decaying? Scientists hope the answers to these questions will give them an idea of how to influence the cells and tissues of the thymus in a controlled way. This kind of control might then lead to new therapies for cancer, improvements in bone marrow transplants and new ways of tackling aging. Generally speaking, an understanding of the natural functioning of the thymus is key for influencing and controlling it.

"Entering the laboratory is an experience for all the senses."

Entering the laboratory is an experience for all the senses. There is a particular smell, a combination of chemicals and odours involved in the process of autoclaving (a technique used to sterilise equipment). There are areas of dazzling light, others of shadowy gloom, as well as zones of artful darkness for biological material that needs to be made visible in low light. There are hundreds of objects such as lab coats, row upon row of test tubes in every conceivable size on massive benches, arrays of chemicals and pipettes, fridges and freezers, colourful boxes and several categories of waste bins. Attached to the main laboratory is a labyrinth of offices and rooms. These rooms contain different machines and bits of apparatus, each with their own buzzing noises and humming sounds. Pervading it all is the sound of the laboratory timer ringing to announce the next step of an experiment.

In this colourful, noisy and very busy setting, the research team is taking steps towards identifying the genes expressed in the thymus. If these fundamental mechanisms are understood – like which genes are expressed when the thymus starts decaying – then scientists hope to understand how to influence the thymic tissues in a controlled way, potentially leading to therapeutic applications. The first step towards examining the active genes inside thymus cells is to break up the compact thymus into its single-cell components. The procedure starts manually: the researcher uses scissors to chop up the thymic tissue. Then refrigerated enzymes from small tubes are added to digest different parts of the tissue. This stage involves a lot of pipetting, centrifuging, calculating the exact amount of enzymes needed, mixing, heating to make the enzymes work, labelling test tubes, washing and waiting for the enzymes to do their job. The whole process is disrupted, and yet held together, by the shrill sound of the laboratory timer – the central tool used to organise the course of these events.

Eventually a small amount of material broken up into single cells from the thymus is secured. The next step is to pick out the particular types of cells that are of interest, using different tags that each bind to one of the many cell types of the thymus. This is done using a set of fluorescent tags that attach to particular types of cells in the mixture, labelling them with different fluorescent colours. Adding the tags to the cells once again involves pipetting, washing, mixing, centrifuging, calculating, labelling tubes, and waiting for the tags to bind to the cells. Again the various steps and different stages of the process are organised by the ever-present laboratory timer.

Once the timer rings to announce that the tags have bonded to the cells, living cells are sorted into different tubes according to their colour code. With their cells selected, the researchers move to extract their RNA (ribonucleic acid), a chemical a bit like DNA that is made in the cell when a gene is expressed, or ‘switched on’. So its back to pipetting, adding more enzymes, mixing, heating, washing, centrifuging, labelling tubes, filtering, waiting. And in its own understated manner, the timer organises everything.

The nature of findings
At the end of a long day’s work, the scientists are left with nanograms of extracted RNA specific to a certain type of cell. And they are now ready to start on the part of the procedure that could yield important results as they compare this extracted RNA with that obtained from samples with known genetic conditions. This means repeating the whole procedure again and again with lots of different samples to make sure the findings really show something important about the cells, and not just an accidental outcome of the laboratory procedures. So only after many months of laboratory work will the researchers be closer to establishing how the gene expression in the thymic cells of one mouse is different from the gene expression in the thymus of another mouse.

"As some of the scientists say, solving puzzles is the most interesting as well as the most challenging part of their work."

Even if the team finds a difference between the gene expression in the different cells, they still do not have a clear-cut result; a lot of testing and further work is needed to establish that these results are significant. And once a genetic cause for the decaying of the thymus is eventually established, it may not be obvious how it works or whether findings in mice are directly transferable to humans.

As some of the scientists say, solving puzzles is the most interesting as well as the most challenging part of their work: looking for creative ideas to make sense of different, sometimes contradictory findings, to pull small parts of knowledge together and work them into a broader picture. Research using nature’s samples is very slow; it is shaped by a lot of routine techniques such as pipetting and most of the time it is a long way from ground-breaking findings, and yet it is held together through the mind of the researcher and organised by the ticking of the laboratory timer.

Anticipating the future
From my anthropological perspective it is not only ground-breaking results of this biological research that are fascinating, but the seemingly unimportant and simple tools like the laboratory timer. On the one hand, the timer symbolises the repetitive everyday routine of the laboratory. On the other hand, in the standardised procedures of laboratory research, time is the organising principle that holds together the different steps of an experiment, and therefore the timer is a very important tool. When experiments are set up and biological processes are expected to happen, researchers leave the lab carrying their timer with them and go to work in their offices. The timer has an authority to it: its piercing sound has the power to introduce the next step of the experiment. The constant and continuous ticking of the clock symbolises the anticipation of the laboratory; with every tick the experiment is coming closer to its next move, to its subsequent action, to its next result.

As the article in Scotland on Sunday demonstrates, public expectations and research funders have their own kind of anticipation: namely that every further step in an experiment might bring science closer to cures for diseases. The anticipation of the everyday laboratory organised with its timer, and the anticipation embodied in research funding grants are thus very similar in one key regard: they are both highly oriented towards the future.

Further information

Tuesday, 14 February 2012

Sharing with Bright Ideas Fellow Alessandro Delfanti


by Alessandro Delfanti - Genomics Forum Bright Ideas Fellow
Contract Professor, University of Milan
Research Fellow, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Italy

Here I am, back in Italy after a wonderful month spent at the Forum as a Bright Ideas Fellow. It has been a very productive and interesting experience.

First of all, I had the time and space to work on my book – I seem more likely to be able to meet the deadline and turn the manuscript in, now. And what a space, a lovely office with a view on Edinburgh's Salisbury Crags.

I read and studied a lot, away from my daily routines and in the quiet environment of Edinburgh and its beautiful university. I even finished and submitted a paper that had been waiting for... how much? Two years perhaps!

And then, the Forum helped me organise a workshop on one of my favourite topics: sharing.

We invited eight people from the UK and the US to discuss how genomes circulate today. The focus was on the balance between stricts intellectual property rights and open source modes of managing data, and we had a very diverse set of people to attend it: social scientists, biologists, open access advocates, and policy experts.

It was great to finally meet in person some people I had only worked with online before, and to debate those issues with such an interesting group of scholars, and hopefully I will borrow some of the ideas that emerged during the workshop and use them in my book. After all, open source means that one can take, remix and reuse knowledge, right?

So I am grateful to everybody at the Forum: the two Steves (Yearley and Sturdy), who invited me, Matthias who helped me organise the workshop and Margaret, who put up with my demands. Actually, everybody has been supportive and kind, for example helping me settle, showing me the best pubs around and inviting me to Peter's theatre play. I have been back to business in Milan only for a day, and I miss Edinburgh already. But then I also know I will soon have more chances to enjoy Edinburgh and the Forum's intellectual environment. Can't wait!

Circulating genomes: sharing in the life sciences sector Workshop
My book
My personal homepage

Monday, 13 February 2012

ab-originals

http://www.openculture.com/2012/02/frankenstein_the_first_film_adaptation_1910.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+OpenCulture+%28Open+Culture%29

I'm exploring origins today...Reading Erwin Schrodinger's seminal text from 1944 "What is Life?", which seems, reading it at the end of my residency, eerily prescient of the genomic view of life...including the downgrading of the idea of "genes" in favour of a more holistic, four dimensional "thing in itself" version of that molecule of heriditary which can have existerd no more than theoretically for his audience in 1944...and harvesting quotations therefrom fro my March 29th event at the Traverse...

but I also came accross the above link to the very first Body/SciFi movie, J Searle Dawley's 12 minute long adaptation of Frankenstein from 1910. Well worth a look...particularly at the "creation sequence" about four minutes in. Frankenstein doesn't re-animate a corpse here, he grows a body from scratch...or rather, soup...and the phenotype self assembles behins a closed door...in a pot.

Oddly, that's roughly how we might actually do it.

PS...you'll need to copy and paste the link rather than just click on it...

Wednesday, 1 February 2012

Coolest Global Warming Ever

Just a quick one...a link to a wonderful site I've just, to my shame, come accross. A detailed graphic imagining of a globally warmed world (called Dubia, after George Dubya...)along with a bit of biological speculation by Chris Wayan.

Here is the link.

http://www.worlddreambank.org/D/DUBIA.HTM

And here, as a taster, is Europe...looks great, huh? This is what the world outside the library looks like, no question...



Peter Arnott is Resident Playwright at the Traverse Theatre Edinburgh, Peter will be hosting a number of public engagements as he explores ideas and seeks inspiration for a genomics related play.

Tuesday, 31 January 2012

Beginning with M

http://www.ed.ac.uk/about/video/lecture-series/changing-world/stem-cells

A while ago I blogged about thinking of genomics in terms of things beginning with "M". Memory was in there...so was machine...so was "mastery". The above link is to a lecture given at Edinburgh University by Professors Siddharthan Chandran and Charles ffrench-Constant on Tuesday 9 November 2010.

These guys have just hit the news in a big way. Using the same kind of adult pluriopotent stem cells that gave us Dolly the Sheep - (that was breast tissue used to create a whole clone...breast...Dolly...Dolly Parton...breast...get it? Scientists are such BOYS!!!) - but, HUMAN adult pluripotent stem cells derived from human skin...and they've made human brain cells. Yup. Brain cells.

The medical potential of regenerating healthy brain tissue is literally mind blowing...many of the most devastating brain disorders from stroke injury to motor neurone disease and multiple sclerosis are based on damage to particular cell locations or cell types. This technology could be targeted to address these problems with only the most minor surgery. The same is of course true of every other organ, muscle...

Now...they haven't made a brain, Dr Frankenstein...yet...But we do have to add an M to our list. "Miracle." Honest.

Check out the lecture above.

Meanwhile, on the "memory" front, news from Australia that it took 24 million generations for something the size of a mouse (which was the size of the common ancestors of all today's mammals before the dinosaurs pegged out) to evolve into something the size of an elephant...once the dinos were out of the way. This is being published in the Proceedings of the National Academy in the US...and when there's a link available I'll paste it.

http://medicalxpress.com/news/2012-01-health-inequalities-imprinted-dna.html

And mastery...or destiny, anyway...research in Glasgow describing the epigenetic poverty trap. Apparently the level of methylation of DNA in poor people means that poverty really does kill you, your children and your children's children.

Put all this together - all these things beginning with M - and what do you get? No. I'm really asking.

Peter Arnott is Resident Playwright at the Traverse Theatre Edinburgh, Peter will be hosting a number of public engagements as he explores ideas and seeks inspiration for a genomics related play.

Tuesday, 24 January 2012

The Fact of Totality

In the play I'm going to write, which is going to be called "The Fly Room", the characters are the inhabitants of a total library. Like in the legendary Library of Alexandria (of which this is a 19th Century German engraving of an imagining thereof), all the wisdom of the ages, including all the genetic information, is stored in one place, curated and researched by a genetically dedicated team, whose universe this library is.

Years ago, something happened. A power outrage...a war...they don't know. What they do know is that they have had no contact with the outside world for hundreds of years, and that, in the disruption, the total information the library held was scrambled...not destroyed, but differentially encoded. Now, at last, they've found the code...and are beginning to re-assemble and reinterpret the material of their world. The ideational underpinning of this sci fi scenario comes from my own experience of texts...and libraries. I was writer in residence at the National Library of Scotland before coming here...

As to texts, if 1859's Origin of Species was the Ur-text of evolutionary thought, then Erwin Schrodinger's "What is Life?" from 1944 was the founding text of what one might call the genomic view of life. The great quantum physicist applied what he had come to understand about matter to the special form of matter that "lives"...and his text was a direct inspiration to the generation of physicists turned biologists...Crick, Gamow, Szilard, Urey etc etc etc...who took his intuitions about the mechanism of inheritance and turned it to evidence and then an industry in the seventies and eighties...an industry that pulled clumsily, expensively and not always happily together to accomplish biology's equivalent to the Apollo missions to the Moon : the sequencing of the total human genome.

That text...the genome...is now itself a foundation and a map for a dizzying array of ideas and explorations, and, most crucially, mechanisms...life has in FACT as well as idea, become a machine. But the logic of all this still comes down the question Schrodinger asked in his introduction :

How can events in space and time which take place within a living organism be accounted for?

Accounted for, that is, within the materialist viewpoint of physics and chemistry, rather than a teleology - divine or otherwise. From the point of view of the physicist, what is strange about "life" is how orderly it is. Life is an island of anti-entropy. James Lovelock noticed the same thing...it's the basis of his Gaia hypothesis, where all life on earth needs must be considered as a single self regulating entity...jut like the individual organisms that make it up.

Now, I'm agnostic on Gaia. This is partly because I'm instinctively attracted to arguments that start by treating the familiar as anomalous. Hence I'm loath to dismiss it as easily as most right thinking materialists have.

(My theatrical master, Bertolt Brecht, said that the playwright must always treat what his or her society sees as self-evident as surprising!)

It's also because I have yet to come across the argument that would convince me that it is any more weird to regard life-in-total as "impelled by the survival imperative" than it is to regard individual cows, fruitflys or mushrooms as "impelled" to live and survive and reproduce...and self regulate. Genomics has demonstrated self-regulation, switching...choices being made by molecules in four dimensions at every level of natural selection from genes to populations...and at every stage in embryonic development into adulthood and beyond. So why is that impossible for "life" in the world? All of it? Real question.

Anyway, my librarians exist to be tortured by the certainty that they have access to all the information any conceivable civilisation could ever need...but that none of it is reliable. They only have their own inherited flaws and capabilities to go on and to judge with. What they are hoping to discover first is who has put them here and why. For they know that a library cannot, surely, have arisen by chance...I mean...if you found a watch lying by the roadside, could you not deduce a watchmaker?

Oh...there is a fab cartoon set about Schrodinger's famous dead-and-alive cat at: http://abstrusegoose.com/secret-archives/in-a-parallel-world

Peter Arnott is Resident Playwright at the Traverse Theatre Edinburgh, Peter will be hosting a number of public engagements as he explores ideas and seeks inspiration for a genomics related play.

Wednesday, 18 January 2012

purposeful dreaming

To continue the thought from the last post a little, it may be that what was hyped as the revolution was actually a sideshow. Just as it was the technologies arising from the EFFORT of the Apollo moon shots rather than the moon shots themselves that ended up changing the world (principally through developments in computing, semi conductors etc etc) it may be that it is the ethos and methods that went into the effort to sequence the human genome rather than the headline sequencing itself that is the real change.

Thomas Kuhn's definition of "paradigm shift" is centred on changes to the daily practice of science, rather than its ideology or "meaning".

Horizon, the BBC's flagship science show had a huge impact on me in the 70s, partly because I'm the right age for the properly childish excitement of the moonshots and Viking and Voyager and all that...to have hit me between the eyes growing up.

Take a look at this recent episode, if you missed it the other night. The excitement has become complicated by unease.

http://www.bbc.co.uk/i/b01b45zh/

In the show, the rendering of genetic material and the proteins to which genes code...that is, the making of machines out of living material...is surveyed by Adam Rutherford, who, like me, is a bit staggered and disoriented...by putting silk-making genes from spiders into goats in Utah...and then getting silk from the milk...(seriously!)...by feeding sugar to yeast and getting diesel...(no, really) in California. And in a community centre based bio-tech lab with open source access for all...and six year olds transferring luminous genes from jellyfish into E Coli...all at the touch of a mouse...(oh, and the mouse with its brain wired to a light source so that it gets dopamine hits by pushing a button...I couldn't watch that at all)

The shift is in what people DO...every day...what we think about what they do comes after, and not nearly fast enough to keep up.

The hardest shift in my work is to go from research (which feels like work) to purposeful day-dreaming...which is how you actually get to create things, but makes you feel guilty. (or me, anyway)...and maybe a bit of my, and Adam Rutherford's discomfort at what is happening in synthetic biology all the way from the mega-corporations buying up rainforest so they can feed sugar cane to microbes and get a substitute for petrol to the folks in their garages building lego monsters out of biobricks is that it feels like all this has passed me by...and I was looking out for it...

Out of control? World gone wrong? I'm too old? There are times I wake up a Tory.