Chain reaction: 30 years of PCR

CHAIN REACTION 30 years of PCR: Art, Science, History

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CHAIN REACTION 22nd November – 21st December 2013

What is Chain Reaction?

Chain Reaction is an attempt to combine science and art in a way that embodies approaches taken by historians of science.

On a simple level, it celebrates a simple piece of experimental procedure, the Polymerase Chain Reaction (PCR), which is 30 years old in 2013. This process is carried out in the lab by automated machines, thermocyclers (or PCR machines). By rapidly multiplying fragments of DNA into the kind of quantities necessary for experiment, the PCR machine has made possible all of the genetic science of the past generation.

And yet the PCR machine is an incredibly humble and simple piece of kit, essentially a heater with a cycling thermostat. As such, PCR challenges many common assumptions about science. Science is not all about fancy ideas or extraordinary outcomes; simple and basic graft is a vital part – the biggest part – of it. This, then, is a show not about the products, but about the processes of science.

One way in which historians of science think about the processes of science is to open up its ‘black boxes’. Popularised by the sociologist of science Bruno Latour, a black box is any piece of technology where everyone agrees that the input reliably leads to output, and no-one questions this process even when things go wrong. For 4

example, imagine if I’ve received a letter from my boss saying that my contract will not be renewed; I won’t wonder whether perhaps his printer has inserted the word ‘not’ into that sentence. I assume (alas) that the printer reliably outputs whatever was sent to it.

One can productively broaden the notion of the black box beyond material technologies. We could think, for example, of the journal Nature as a kind of black box; we assume that any paper published in it has been put through a reliable system of checking by qualified peer reviewers. Only in extreme circumstances do black boxes get reopened. Historians of science, on the other hand, like to open black boxes all the time, to discover how they were put together. They like to see how and why a piece of science has come to be trusted, which is to say how and why certain human/ mechanical processes come to be relied upon.

Chain Reaction aims to open at least three black boxes.

First, of course, there is the box that is the PCR machine itself. OK, it’s beige or cream, not black, but in other respects it’s a classic black box. No one questions that what

goes in and comes out of the PCR machine – except in extreme cases like in court, where DNA evidence may be challenged on the grounds that the scientists sneezed into the test tube. Annie Halliday’s work opens this box up for us, showing us the components of the machine and visualising the process of exponential replication that occurs within it. And yet despite the machine’s apparent reliability, there is still room for doubt and superstition, as in the case of the lucky rabbit, explored by Stig Evans in his work on ritual.

Secondly, the laboratory is also a box: a room full of people who know what they are supposed to do and how they are supposed to behave. They move around and do things, and out of the room comes scientific knowledge. But for the general public, its workings are as mysterious as the inside of a computer. What goes into the box, and how does it work, to output things like the ancestry of humankind, or the identity of a father? Three of our artists engage with such themes. Andy Birtwistle’s film both reveals and re-enchants the generally unseen spaces of the laboratory, showing them to the public for the first time yet in such a way that they are defamiliarised for their usual occupants. Sarah Craske’s lab practice over the project has immersed her in the culture and workings of a lab,

and, curiously, her product has come out as self-contained and apparently sui generis as a piece of science – rendering the processes of its production almost invisible. Meanwhile, Katy Price’s cut-up art problematises the many steps between lab and public, over the course of which data becomes ‘science’.

Finally, the human mind is a black box too: we learn things, have experiences (including experiments), and out come ideas and conclusions. But what goes on inside? Does it work the same for artists and scientists? These days we tend to assume that scientists’ minds are tidier and more rational places than artists’, but that’s a historically local assumption. At other times, creativity and romanticism have been highly rated in scientists. Tony Stallard’s piece interrogates these thought processes, provoking us to wonder what will be the future relations between creativity and science.

Let the chain reaction begin!

CHARLOTTE SLEIGH

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Chain Reaction

PCR: A beginner’s guide to the science Sometimes the best ideas are the simplest.

Why did nobody else think of putting a strip of adhesive on the back of yellow notepaper before Art Fry did so with the Post-It note?

Beautiful in its simplicity, enormous in its impact, PCR has become a fundamental cornerstone of modern biology. It is hard to think of any significant development within biology in the last 30 years where PCR has not played its part somewhere.

PCR is a process of copying DNA, amplifying specific sequences of As, Cs, Gs and Ts – the chemical alphabet that makes up the genetic code. It does so by making millions of identical copies of the original ‘template’ sequence. It allows the detection and analysis of vanishingly small quantities of DNA, and in combination with a vast array of add-on technologies it is a central part of biomedical research. Applications are endless - forensic detection, disease diagnosis, food safety testing, therapeutic protein production, biotechnology, to name only a few.

PCR performs the process of DNA replication – the copying of the genetic code, which is essential for all life – in a test tube. At its most basic, it requires a ‘template’ sequence to copy, along with the building blocks of DNA, called nucleotides, 6

which when arranged in sequence make up the genetic code. PCR also needs an enzyme called DNA polymerase which, during PCR, sticks these building blocks together in the order determined by the template. Primers – short sequences of nucleotides that are designed to bind to specific regions of the DNA template – define the start and end point of the region to be copied, and are also necessary for the DNA copying process to start.

But in the absence of some of the cellular machinery required for DNA replication in organisms such as bacteria, copying DNA in a tube needs additional, external influences.

PCR initiates and sustains the copying process in the tube simply by heating and cooling the mixture it contains. It is first heated – almost boiled – until the two strands of the DNA double helix separate.

The mixture is then cooled to allow the short primers to bind to each of the strands.

Once these are in place, the temperature rises slightly to allow the DNA polymerase to string the sequence together, using the original DNA strand as a template. In this way, the original DNA sample comprising two strands has ‘doubled’. Repeat that temperature cycle again, and the samples double again. Repeat over 30 cycles and you begin to see how, in principle, PCR leads to massive amplification of a specific

sequence. This amplification permits further analysis of the sequence and a development of a ‘PCR product’ that would not be possible without that amplification.

Further developments in PCR, beyond the original idea, cemented its role in modern biology. The heat-stable polymerases used in PCR today are unusual proteins, because they withstand repeated exposure to high temperatures. This means that they don’t need to be replaced after each copying cycle, and in turn this means that the repeating process could be automated, without the need for human intervention between each cycle. Thus PCR thermocyclers (colloquially, PCR machines) have been created – machines that control the heating and cooling. In turn, this automation has ensured that this powerful technology has, in the years since the first experiment, become an essential part of any biological laboratory environment.

DAN LLOYD

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The scientist and the lucky rabbit Chain Reaction’s project manager encounters superstition and ritual in PCR When PCR machines landed on the benches of molecular biology laboratories, they supposedly brought objectivity and rationalisation to bench practice. However, even thirty years after the PCR was invented there are some strange rituals, and apparently irrational beliefs, lurking within laboratory culture …

Asked to explain the benefits of PCR machines, bioscientists will talk about how they reduce the chances of error, because they drastically diminish the number of human manipulations in an experiment.

Most of the process is delegated to the machine; human operators simply have to fill small tubes with set quantities of liquids. This is a relatively simple operation which, on the face of it, only requires good pipetting skills.

But sometimes PCR does not work. Either the reaction does not happen in the tubes, or something unexpected occurs instead.

This latter case is not the kind of serendipity that leads to unexpected discoveries. It tends rather to be something irritating, such as the reaction apparently occurring in purified water where nothing ought to happen. The results are meaningless, unusable, setting in train a tedious and frustrating chain of troubleshooting and 8

preventing the next stage of research. In most cases, such failures can be ascribed to human error when preparing the reactions.

But sometime the causes are mysterious and escape simple explanation.

In order to protect themselves from such vagaries some bioscientists will resort to what can look like bizarre rituals, ranging from common sense intervention to more desperate means. One scientist might obsessively always use the same machine, and always fill in the tubes in the same order. Another, repeatedly confronted with a reluctant PCR reaction, might dress up in gown, gloves, mask – the full paraphernalia of laboratory work. She will scrupulously decontaminate an area of the bench, separated from the rest of the laboratory, and keep to this place to prepare her successive reactions. There is a level of logic in this rather theatrical preparation, which attempts to eliminate contamination from the tiny amounts of DNA on skin, bench, breath and clothing. On some occasions, however, even these carefully-performed rituals are not enough. Lab people then turn to more drastic measures, as I myself discovered.

A molecular biologist invited me to come and watch whilst she was setting up a PCR

to amplify a fragment of DNA, (F). After just under an hour all the tubes had been filled with the required blend of DNA, enzyme, and water, and loaded into the machine.

Once the PCR had amplified fragment (F), the biologist would introduce it into a population of bacteria. She would spread the bacteria in Petri dishes containing a substance that would selectively let bacteria grow on it if they had successfully incorporated (F). In this way F would be in a biologically useful form for future experiments. I was invited to come the following morning to watch that next stage.

However, when I arrived the next morning, the biologist was instead preparing a new PCR. She showed me Petri dishes: they had too many bacteria in them. The PCR had not worked and she did not know why.

As a result she had to perform a new PCR. ‘But’, she said, ‘I know this time it will work, because this morning I saw the Cloning Rabbit!’

Pressed for an explanation she revealed that, in the small wood growing near the laboratory, there lives a rabbit. It’s just your average bunny, but each time you see this rabbit, she says, the PCR is successful.

And she’d seen it on her way to work that morning, so she had no doubts this time her PCR would work. Of course there must be several rabbits living in that wood, and the one she saw this morning probably wasn’t the same one she saw last time. But she’s not alone. Other scientists in the lab ‘believe’ in the lucky Cloning Rabbit. They know it is irrational, but it doesn’t stop them.

researcher whose PCR was consistently failing. When the giraffe sat on the machine, it delivered the expected outcome, a nicely amplified sequence. So the older member of the lab, whose giraffe it was, gave it to her permanently so that she would not to lose faith in her capacity to get good results.

For that matter some people in the lab are lucky too. Labs very often have somebody who is uncannily better than others at obtaining successful PCRs. It’s generally a woman, a technician, or an oldie, but rarely a senior male scientist. These individuals have shaman-like respect within their labs.

You can turn it every which way you like, check each parameter: sometimes PCR just doesn’t work and nobody can tell you why.

When something is beyond our control we search for strings to pull, reasons, gods to placate. Because the machine sometimes resists rational explanation, adding your own bit of irrationality makes it easier to deal with the feeling of powerlessness.

And the best part of it is that eventually these shamans and animals always make things work. When the science comes good, the rabbit must be responsible. Right?

Sometimes PCR is a dark art.

JEAN-BAPTISTE GOUYON

There are other animals in the laboratory’s irrational bestiary. There’s a giraffe – a gummy one – which was loaned to a new 9

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Chain Reaction

Annie Halliday ‘Sum of the Parts’ 2013 I decided to explore the key concepts of ‘doubling’ and ‘copying’ implicit in PCR, to develop artwork that makes doubling and copying tangible in space and time, and so to reveal the contents of the ‘black box’ of the machine itself.

The huge numbers generated in exponential doubling inspired me to search for a three-dimensional equivalent, finally resulting in the large scale chain-crochet installation ‘Exponential’. The stop-frame animations for ‘Copy.copy’ are collaborative works, exploring ways of copying an image, like ‘Chinese Whispers’, incorporating inherent errors and mutations. The large photogram ‘Sum of the Parts’ traces the components of a PCR machine, as a full-size homage portrait.

From an earlier career in Bioscience, it’s been a wonderful revelation to return to the lab as an artist, and to discover the dramatic advances in bench techniques and equipment. Parallels can be drawn between the scientist’s laboratory and the artist’s workshop as places of research, and of the exploration of exciting ideas for success or abandonment. Scientists and artists alike have constraints: the scientist is limited by research tools and equipment, and the need to produce testable results; the artist 10

is limited by materials, formats, and the commissioned brief. Both rely on intuition, creativity, and the rational assessment of outcomes. And both use schemata in their work, for the required degree of accuracy or expression: conceptual imagery which is common to written language, the scientific diagram, and visual artwork.

Annie Halliday is a multimedia artist. Her specialisms are experimental photomedia and digital collage, often evolving into 3D formats. She is currently extending her practice into animation and sculptural installation.

Annie has exhibited extensively in galleries and museums and has engaged in artist residencies and commissions. She has designed and facilitated workshops, and been involved in arts management.

She brings to her practice earlier career experience in environmental science, journalism, PR and advertising, drama, puppetry, and establishing a vineyard. anniehalliday.com/

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Sarah Craske ‘Echo of Narcissus’ 2013

In nova fert animus mutatas dicere formas corpora I intend to speak of forms changed into new entities Ovid, Metamorphoses, Book One, Lines 1-2.

Metamorphosis has inspired artists and scientists for thousands of years. From Ovid to Kafka, literature has explored transformation and mutation governed by both unknown and deific influence. The concept of metamorphosis itself passed through a shifting scientific taxonomy, not least through Goethe’s idealist opinions on transformation, Lamarck and his Transmutation of Species to Darwin, which in turn led to evolutionary theory. It was at this point that its previously expansive meaning was reduced to a specific biological term.

Scientific discoveries and research in the field of genetics have significantly increased tensions between the scientific and religious communities. As scientists learn more about genetic inheritance, evolutionary theory, mutation and genomics, criticism has been felt by the ‘Intelligent Design’ communities which include those who don’t accept evolutionary theory and those who are opposed to genetic experimentation.

As scientists instead of deities now create new life through synthetic biology and bio engineering, I reflect on how over 2000 years the agent of change has been subverted from celestial to the corporeal.

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In laboratories across the world, the replication of genetic material is so frequently done, that it is now taken for granted. In DNA amplification one strand of DNA is copied thousands of times.

During this Polymerase Chain Reaction, copying errors can occur. What fascinated me is that these copying errors, which can be controlled or minimised by the scientist, are in fact mutations; the PCR machine mimics the evolutionary process. I felt that ‘metamorphosis’ could be subverted further, by allowing the machine to be the agent of change; harnessing the creativity of the PCR thermocycler and its components to alter a specified genetic sequence.

Revisiting Ovid’s Metamorphoses I was reminded of the story of Narcissus and Echo. Echo’s own expression was restricted

by Juno and with that I drew parallels with scientists restricting the PCR machine’s results by selecting out the ‘copying errors’.

Echo in turn copies Narcissus, though only in part in an attempt to communicate her love for him. The allegorical nature of Echo and Narcissus’ relationship and the relationship that the PCR machine has with DNA, led me to conduct PCR-based

random mutagenesis on a gene from a daffodil.

The Echo of Narcissus is imaged using that mutated DNA. The daffodil becomes an icon of change over 2000 years, from an ancient Rome poolside to a paddy field in the Philippines, where you will now find a daffodil gene in a genetically modified crop called ‘Golden Rice’.

Through mixed media and performance, Sarah Craske creates work that discusses the cultural relationship between art and science. She is currently a Honorary Research Fellow in the School of History at the University of Kent whilst regularly working with scientists within the School of Biosciences at both the University of Surrey and the University of Kent. Her interest and belief in interdisciplinarity means that she is consciously ambiguous about her practice within artistic terms, however sometimes describes herself as a ‘bioartist working at the intersection of art and science’. Her work ranges from research, writing, installations, performances to sculpture using a range of media including bacteria, fungi , DNA and collected specimens.

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Sarah Craske StudioLab documentation of The Echo Of Narcissus

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Kary Mullis’s own goal A contradiction at the heart of PCR Science is complicated. Not in the way you might think – equations and molecules and whatnot – but complicated by the people who do it. It is a profoundly human enterprise, no more or less reliable than the collected agreement of the people who do it. Scientists can achieve great results in one sphere but remain completely irrational in other respects.

a dangerous to assume that science is a general cloud of rationality that extends to all areas of life. Stephen Hawking, for instance, is undeniably brilliant, but undeniably bonkers in his proposal that the colonisation of space is the best means to save us from the environmental crisis. (Or, for that matter, in his claim that ‘women are a mystery’…)

PCR illustrates this perfectly. This machine has, amongst things, vastly sped up the speed, cost and convenience of testing for the HIV virus. It has been a huge benefit to diagnosis and treatment of those who have, or may develop, AIDS.

Unfortunately, one of our favourite stories about science is that of the maverick figure who faces persecution but is later vindicated – exactly the Galileo myth that Mullis reaches for. This view of the genius scientist leaves us poorly equipped to judge mavericks when they come along.

Andrew Wakefield, for example, with his theory of MMR-caused autism, chimed with a lot of people who thought that the very condemnation he attracted was a sign of his legitimacy. Similarly, climate change deniers find the very consensus of the world’s scientific community a sign of conspiracy rather than settled science.

What does the inventor of the PCR machine, Kary Mullis, have to say about this?

In his autobiography, Mullis writes:

“Years from now, people looking back at us will find our acceptance of the HIV theory of AIDS as silly as we find the leaders who excommunicated Galileo.”

Kary Mullis, Dancing Naked in the Mind Field [Vintage, 2000], p. 180.

He doesn’t believe that HIV causes AIDS. He thinks that people are wasting their time using his machines testing for HIV. It is a colossal irony. Something has gone terribly wrong with science. Well no, not quite. It’s 16

PCR is a testament to the mixed rationality and ineradicable humanity of science.

CHARLOTTE SLEIGH

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Katy Price P R I M E R 2013 Cork boards, pins, primer, Nature, books, paper, type, glue.

Primers are vital to the PCR process: they are custom designed to pinpoint segments of DNA for replication, and they aid the copying process by starting off the chains of letters in copied material. P R I M E R brings the PCR meaning of ‘primer’ into contact with the old fashioned meaning of the word – a book to teach us from the beginning.

Words and pictures from Mother Goose Primer are used to mark out sections from Nature reports of a confusing story about the first known AIDS patient. These reports do not give us any clarity about whether David Carr was HIV positive or whether the samples analysed even came from his body. Fragments from the science journal are combined with cutouts from Mother Goose Primer published in the year of his birth, to create visual poems exploring the unknown story of David. The process of PCR with its ingredients, selections, copying and false moves has a lot in common with the processes of writing and publication, something that David Carr was physically involved with in his trade as a printer.

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Visitors are invited to select words and place them in the small tubes which are used to assemble ingredients when performing a PCR experiment. Words from the tubes will be gathered and used to write new poems specially for the Chain Reaction! exhibition.

Katy Price is a poet and performer working with twentieth-century technology. Previous works include ‘Kippered (Edison) Herring’, a poem in two voices recorded on wax cylinder by Aleksander Kolkowski for Phonographies (2010), and Bookmachine (2010), a performance with voice, mutilated books and computer speech.

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PCR and the mechanical view of nature How PCR turns machines into bacteria and bacteria into machines The sociologist of science, Bruno Latour, suggests that we should understand the world in terms of ‘assemblages’. Objects, animals and people become assembled into stable groupings that then act in powerful ways; they are a whole that is greater than the sum of their parts. Thus, for example, a man holding a gun is different from a man; and a gun being held by a man is different from a gun on its own.

PCR machines are caught up in an assemblage that includes humans, bacteria and machines. Just as in the man/gun example, so having the machine, people and organisms work together in PCR transforms each part of the assemblage.

Scientists studying genes use the PCR machine with micro-organisms, especially bacteria. The machine is designed to work like all living cells do – a tool that imitates nature. But it also changes how we think about bacteria. As the machine is a kind of mechanical organism, so, since its adoption, micro-organisms have increasingly come to be understood as ‘bio-machines’.

One of the project’s scientists observed in passing that ‘bacteria are like PCR machines’. This is an interesting shift of perspective; the machine was designed 20

to mimic a natural organism, but the end result is that the organism is thought of as mimicking the machine. The advent of machines in labs has led lab practitioners to think of organisms in a more mechanical way than before. Some older scientists see this trend of mechanisation and lament its side effect – a loss of contact with, and understanding of, living organisms. One of our scientist participants noted that some younger colleagues now have such an impoverished view of micro-organisms that they do not really know anymore, in practice, how to differentiate a bacterium from a yeast.

The Nobel-winning scientist Barbara McClintock (1902-1992) provides a sharp contrast with such mechanical perspectives.

McClintock worked on a type of genetics (cytogenetics) that went beyond DNA and the nucleus (the usual focus of genetics over the past 25 years) to look at how genetics actually works out in the cell. It was more of a holistic perspective; she refused to see life as a mechanical process, or to engage in reductivist thought: ‘Every component of the organism is as much of an organism as every other part.’

This resulted in, or was inspired by, her sheer delight in nature: ‘I start with the seedling, and I don’t want to leave it. I don’t feel I really know the story if I don’t watch the plant all the way along. So I know every plant in the field. I know them intimately, and I find it a real pleasure to know them.’

perhaps harmful (or even fatal) – but once in a million times it may be advantageous: the creative driver of evolution.

PCR is a brilliant tool for science, but there is a challenge not to let nature, or ourselves, be drawn into its mechanical assemblage.

CHARLOTTE SLEIGH

McClintock went to the opposite extreme to mechanisation, treating the cell as if it were a person: ‘The ability of a cell to sense these broken ends, to direct them towards each other, and then to unite them so that the union of the two DNA strands is correctly oriented, is a particularly revealing example of the sensitivity of cells to all that is going on within them. They make wise decisions and act on them.’

The concept of mutation drives a wedge between ‘natural’ and ‘mechanical’ views of DNA replication. One of the project artists picked up on a scientist who mentioned ‘copying errors’ in PCR. ‘Why is it an error?’, she questioned. In the laboratory, a copying error is a glitch in PCR, a problem in the experiment. But in life, it is a mutation: most likely irrelevant to the organism, 21

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Tony Stallard 2013 With the help of University of Kent scientists Anthony Baines and Ian Brown the work ‘Mutation’ evolved through discussions as to the nature of mutation both in genetic diversity and as a random variable.

Ideas emerged gradually as to what mutation might mean both in science and from my own perspective. They originated through discussions and Chain Reaction workshops and experiments.

They developed further through the use of microscopes: a laser-scanning, confocal microscope, and an electron microscope.

I was fascinated by the notion that mutation is beneficial in the long term of evolution, whilst at the same time being detrimental or even lethal in an individual.

Through these notions the work evolved into an exploration of the consequences of random change and adaptation, and what these might mean for a species.

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Stig Evans Gene Amp 2700 The starting point for ‘Gene Amp 2700’ was the marks found on the inside lid of the eponymous de-commissioned PCR Machine that the University of Kent lent me.

The marks are made by the tops of the little reaction tubes that rub and move against the PCR lid during the heating and cooling process. I was very interested in the rituals and practices in the lab. But how to embody these in an ‘abstract’ painting? I felt that these marks related visually to my ‘meme’ paintings and were a good way to represent the rituals and practices that scientists apply within the Laboratory, on macro and micro levels, within the gene replication process. The painting went through many different stages and colours (and rituals). I finally decided on a more monochromatic painting that resembled a b/w photocopy, a poorly taken photomicrograph or a badly reproduced diagram that I often saw in articles and abstracts when I was studying conservation science and physics.

Stig Evans is a painter and paintings conservator. His work as a restorer informs his artistic practice and vica versa. He is particularly fascinated by colour, how we perceive it, respond to it, and represent it, by its historical, chemical and physical provenance. His work intersects between Science and Art often using the analytical processes in conservation as a means of exploring the moral and ethical issues in making and conserving Artworks.

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Memes, genes, codes, habits  rituals, customs  cutting, copying, repeating and amplifying  re-occurring cycles and sequences  surviving existing  building blocks for life  building blocks for paintings  engineering mutation  staining dyeing  manipulation control  God religion faith belief  studio ritual laboratory custom  memes constructing genes  scientific codes - artist’s codes  God manipulation  cutting building  habit cycles and sequences  amplifying blocks for engineering rituals  building blocks for life belief  custom copying  faith paintings  painting life genes and memes  faith controlling memes  reoccurring  constructing God manipulation  chromatogram meme  building customs  cycles and block sequences  engineering amplifying religion  block building life  belief habits controlling rituals  faith genes controlling memes  science meme construction  cutting manipulation and amplifying  cycles and sequences re-occurring  building blocks for engineering life  building blocks for belief  rituals habits copying  belief paintings.

Stig  Evans  2013

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All shall have prizes?

What PCR tells us about real science vs. Nobel science Science-making is more like rugby than tennis. It is a collective enterprise, in which ideas would account for very little without the environment to debate them and the practical skills to bring them into being.

Nobel Prizes, by contrast are awarded to just one person. Sometimes they are awarded to two or three, but even then they have rarely worked together. The prizes give the impression that discoveries are the outcome of single individuals struck by sparks of genius. In reality, science involves lots of people, lots of communication, and lots of negotiations in order to reach a consensus. It involves collective work and collaborative thinking, often across time, space, and disciplines. It involves innovative laboratory techniques, technicians and machines. But if the Nobels rewarded this more realistic process, who would come and collect the medal?

PCR is a story that cuts to the heart of real vs. Nobel science. Any standard account will mention Kary B. Mullis as the inventor of PCR, who received the 1993 Nobel Prize in chemistry for it. According to the legend – mostly propagated by Mullis himself – it all started on the road, on a moonlit April night in 1983. Mullis says he was driving along a mountain road in northern California when the idea suddenly struck him. In the 26

months that followed, Mullis says he tested his hypothesis, corrected mistakes and progressively refined the technique. By spring 1984 he was ready to present his idea at the annual scientific meeting of Cetus, the biotech company that employed him.

PCR’s simplicity and self-evidence led to a communal forehead slapping by the other scientists. How could they not have thought before of such a simple technique? The technique’s impact on molecular biology is described as revolutionary because it has enabled scientists to explore DNA in ways which were previously impossible. The Nobel Prize was a well-deserved reward for the lonely father of this revolution. Or at least, that’s the story.

But slightly changing the focus – looking at the laboratory and its activities, rather than the inventor and his ideas – yields a different story. A chemist by training, Mullis had been hired by Cetus in 1979 to work in the company’s DNA synthesis group. He became head of this group in 1981, with the mission of increasing the lab-produced quantity of artificial DNA fragments – also called oligonucleotides – and their quality.

Oligonucleotides were essential to a variety of emerging DNA-centred technologies such as diagnostic gene sequencing, and cloning, in which they were used to locate

specific sequences on the molecule.

This appointment enabled Mullis the chemist to acquire a working knowledge of DNA. It also allowed him to explore different parameters associated with DNA synthesis, in particular the effect of temperature variations on the separation of the two strands of the molecule, and their recombination. This knowledge would prove crucial in the development of PCR, because temperature variation and control is key to the technique. As a University of Kent molecular biologist remarks, a PCR machine, ultimately, is nothing more than a heating and cooling block, whose efficiency depends on its precision in terms of temperature as well as the speed at which it can heat and cool down over a series of repeated cycles...

However, about a year after that fateful moonlit drive, few at Cetus believed in the PCR idea, and they mostly perceived it as a technique no one really needed. At this stage, though, although he had his concept right, Mullis could not show any kind of experimental evidence that his idea worked. Additionally, to the few believers in the PCR idea – even Mullis himself – the technique did not appear to promise much more than large quantities of artificial fragments of DNA. And in 1984 (a year

after the supposed lightbulb-moment), these were still seen as of limited utility.

The experimental evidence, as well as the demonstration of PCR’s usefulness besides the synthesis of fragments of DNA came in fact from another lab at Cetus, one devoted to the development of DNA diagnostics.

There, two technicians with skills Mullis did not possess, spent several painstaking months trying to demonstrate the validity of the initial concept, and eventually performed the first successful reaction.

So the story is not so straightforward.

The ‘idea’ was intended to solve another problem altogether, and a commercial one at that. It was a chemist’s cookery, not a leap of molecular biology. Other people were vital to the development. And it took effort to convince scientists that it would work, and that it was useful. Making the PCR was a collective enterprise from start to finish.

JEAN-BAPTISTE GOUYON

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Andy Birtwistle Laboratory Film 2013 This project develops out of my interest in cinematic time – in particular how, as spectators, we experience duration, and how cinema is able to represent simultaneity. In recent years I have been working on a series of ‘empty’ films in which content is drained out – or at least reduced – so that the viewer’s attention can be focused on those forms, styles and qualities of cinema that are hard to perceive in content-driven work. In Laboratory Film I wanted to make duration tangible – to make a film in which time is not simply an idea, or an ‘invisible’ container for a series of things that happen, but rather a film in which time itself it attains a certain density and weight.

PCR takes time. It can take several hours for a PCR machine to amplify a DNA sequence.

Laboratory Film was thus conceived as a piece that would echo or mimic or mirror the temporal duration of a PCR experiment.

The film also explores the idea that multiple events and multiple spaces coexist, even though we are rarely aware of this multiplicity. When we leave a space – particularly the everyday spaces of the workplace or the home – we tend to forget about them as our attention engages with the changing environment around us, and moves to other tasks, other objects. But of course, those spaces continue to contain 28

objects and continue to host events despite our absence. In Laboratory Film I wanted to explore the space of the lab after the scientist (Maryam Sadraie) has left the PCR machine to run through its programme. But why stop there? So once the camera has explored the ‘empty’ lab, it continues to move through a succession of other spaces while the PCR machine performs its series of cycles and the scientist goes about her daily business.

The lab – workplace of the scientist – is an institutional space, and one that has its own style and particular beauty: a beauty that is often overlooked because institutional spaces become so familiar to us. In Laboratory Film the camera turns its attention on these familiar institutional spaces, carving out a piece of time for each of the objects and spaces it examines, and offering duration as a taste of time itself.

Andy Birtwistle is Reader in Film and Sound in the Department of Media, Art and Design at Canterbury Christ Church University. He is also a filmmaker and sound artist whose work has been broadcast and exhibited internationally.

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