The ghosts in the human genome machine

The purpose of the Human Genome Project was to map all the individual bases that make up our DNA. There are four types of these bases, adenine, thymine, cytosine, and guanine, and they combine to form genes.

Now that the project has achieved its main goal and finished the sequencing, the next step is to identify the actual genes as distinct from the majority of the material, the so-called ‘junk DNA’. (Only a tiny proportion of the overall DNA actually consists of genes.)

Humans share 99.9% of their genes, and so the information discovered through the HGP is relevant to all of us. As we have about 20,000-25,000 genes, only a handful are unique to any one of us. But whose DNA was actually sequenced? The project used samples from anonymous donors. Neither the scientists nor the donors know whose samples actually ended up being sequenced, but it is clear that more than one person’s was used, i.e. the information we have is an amalgamation from different donors. Because the ‘map’ created by the HGP is actually linear – a sequence of letters corresponding to the order of bases, at any one point in the sequence, the information we have corresponds to just one unknown donor, but we don’t know who.

This deliberate uncertainty interests me. Scientists (whatever their discipline) spend so much time battling uncertainty, trying to quantify or eliminate it from their work. Much of this uncertainty is caused by random fluctuations or systematic biases in what they are trying to measure. Both need to be understood and accounted for, if you’re trying to make sense of your external world. And more fundamental uncertainties exist in quantum physics, which are not simply due to errors or limitations in the way that we measure things.

So it seems counter-intuitive to increase the amount of uncertainty in this major experiment. But clearly it has several purposes. Uncertainty about knowledge of the donors can protect them from the consequences of having their genome sequenced. For example, subsequent identification of genes relating to disease can’t be attributed back to a particular donor. Also, by banishing information on the particular donors, the experiment is able to interest everyone. It encourages us all to feel that that map has a direct relevance to each and every one of us. As a result, the project is allowed to gain a certain amount of authority.

But you could just as easily say that the project is relevant to no one. What does it mean to sequence a genome of a person that doesn’t actually exist?

This partial information is an excellent example of synecdoche, a type of metaphor in which part of a thing is used to stand in for its entirety. We don’t yet have DNA sequences for all humans, and we don’t yet know which parts of the sequence we do have are shared by all humans. So ‘The Human Genome Project’ is a misnomer.

Perhaps I shouldn’t be too harsh. In practice, it’s actually impossible to communicate without using synecdoche. Fiction writers know that they can’t get across the entirety of their fictional characters. They write about aspects of these characters, and the reader uses these a bit like dried milk, to reconstitute them and make up their own pictures.

Or you can say ‘there is nothing outside the text’, and therefore the human genome is just a sequence of bases, and we are free to give it as much or as little significance as we wish.

Invention versus discovery.

Fiction invents, science discovers – right?
But fiction can make you see the real world differently, through examining how humans react to it. For example, Hamlet is torn between two impossible choices, and cannot act because he sees the disadvantages in both. He analyses and rejects the modes of behaviour that his peers would have chosen (as articulated in other Elizabethan revenge tragedies). As a result, we cannot look at how humans think of themselves and their place in the world, without thinking of Hamlet. The play extended humans’ self-consciousness by showing the limitations of actions and the consequential inevitability of self-analysis.

More practically, a fictional depiction of real-life social issues can profoundly affect the way we react to those issues. When the film ‘Cathy Come Home’ was first shown in the Sixties, it exposed the way that homeless people were treated by the authorities and started a national debate. The charity Shelter was formed as a result, and homeless people now have legal rights to housing.
Fictional depictions are sometimes the only way that we can ‘see’ big problems. Poverty in India can seem vast and overwhelming, until the novels of Rohinton Mistry bring it within our understanding, and our empathy. Similarly ‘Half of a Yellow Sun’ by Chimamanda Ngozi Adichie probably works as a better introduction to the Biafran war than many factual texts, because it uses interesting and sympathetic characters (including a child soldier who is forced to take part in a mass rape) through which the reader can see the effects of that war.
A recent academic paper (http://www.bwpi.manchester.ac.uk/resources/Working-Papers/bwpi-wp-2008.pdf) examines the use of fact and fiction in understanding developmental issues and argues that fiction is a credible way of spreading knowledge. It can reach a wider audience than more factual approaches, and provide a richer illustration of how people react to their surroundings, because it’s at liberty to investigate the inner lives of those people in a way that factual narratives are simply not able to do.

Conversely, discovery is not just a passive intake of external data. It’s also a framework to put the data into, in order to make sense of it. Constructing this framework necessarily involves invention. When you carry out an experiment, and measure some variables, you have to have an idea of what these variables are; you have to conceptualise them. For example, if you decide to measure the temperature of a box of gas, you have to have an idea of what temperature actually is, and how it might be related to the gas’s energy. How is the gas’s confinement to a box going to affect the result? What if you pump in more gas and increase its pressure? Or heat it up? Which of the variables are important and will affect the results? And which can be ignored? Will the colour or shape of the box holding the gas affect the results?
Straightaway the process of doing experiments becomes recursive; you carry out an experiment to get a better understanding of the external world, but you already need some sort of narrative of it in order to do the experiment in the first place.
Sometimes this narrative is drawn from places outside science. The importance of Galileo’s observations of four moons orbiting around Jupiter stems partly from the religious dogma which stated that everything orbited the Earth.
Modern science likes to think it makes its models exclusively from within science and that nothing else taints it. But models are made from language, and this can give the lie to this belief of purity. For example, in the fifties James Watson came up with ‘the central dogma of biology’ to express the idea that the flow of information from DNA to RNA and then onto proteins is one-way. (This excludes Lamarckian models of evolution in which DNA can be changed by changes to the proteins during the lifetime of the host organism.) He confessed afterwards that he didn’t really know what dogma meant, but he wanted a word to stress the importance of the idea. There’s no doubt that it’s important, but calling it a dogma implies that any criticism of it is heretical. Maybe Watson was being tongue-in-cheek when he used this word, but it’s hardly an incitement to open debate.

Time takes a cigarette...

The concept of time in science is problematic. It’s everywhere, yet elusive. The one-way flow of time from the ‘past’ (i.e. what we remember), to the ‘future’ (what we cannot yet recall) is the ghost in the machinery of physics. Newton’s laws on motion, quantum mechanics, general relativity; all these theories are symmetrical with respect to time. They don’t invoke or explain its passage. As is well known, the only equation in physics that does directly invoke the passage of time is the second law of thermodynamics, which says that things tend from an ordered state (low entropy) to a disordered state (high entropy). One way of explaining time’s flow from past to future is to say that the universe started off in a very low state of entropy, which is subsequently increasing.
So, does biology fare any better? DNA can work as a natural ‘clock’ in the way that it accumulates mutations. We can compare DNA from different organisms and estimate when these organisms diverged. I suppose this is similar to using the decay of carbon 14 to date organic matter.
This gives the study of DNA a natural rhythm, perhaps.

Time flows naturally in fiction. I can’t think of any novel that is set in one ‘present’ moment. There are novels that are set in the present but that present does move on. Perhaps by their very length, novels preclude the examination of the single moment, in a way that short poetry or short stories can. But novels (or epic poetry such as the Iliad) can play with time, make it double back on itself, even run backwards (e.g. Time’s Arrow by Martin Amis), and examine moments in time over and over again from different perspectives. Plays can do this too; Michael Frayn’s play, ‘Copenhagen’ consists of conversations between Bohr, his wife, Margrethe, and Heisenberg[1]. Within each conversation, time flows ordinarily, but the whole play is set in the afterlife, and all three characters are dead. As such they are unable to move or develop, they are curiously static in time, and the play itself does not move forward. It succeeds, brilliantly, because it takes a single point in time (the real-life conversation between Bohr and Heisenberg) and unfolds it to expose all the complexities that exist in that moment, like hidden extra dimensions suggested in string theory.
But what do we mean by the ‘present’? The moment that we exist in is always hemmed in by the past and the future. We walk a knife-edge between what we remember and what we anticipate. Is it just a trick of the consciousness, that we think we ‘are’ at any given point in time?
A novel, poem or short story is a system of words that relies on relationships between them to function. And yet they are always read sequentially. We are taught to read by moving from one word to the next in an ordered way. We can possibly read a short sentence at once by glancing at it, but no more than that. So our ‘present’ corresponds to a short block of text, and poets can explicitly take advantage of this in the way they present their work on the page. Is a line of poetry equivalent to a present moment? And how does this relate to breathing? And music? When we listen to music we hear a phrase, the aural equivalent to a line of poetry. The phrase is there in our head, but it continuously gets superseded. If our perception of the present were any different, e.g. if it were shorter than it is, would poetry or music ‘work’ in the same way?
The sequential nature of literature and music has a nice analogy in the structure of DNA, with its rows of neatly ordered bases. And yet, like literature or music, there is something in the ‘wholeness’ of DNA that is not present in its parts. Different genes may be responsible for different functions in the parent organism, but they affect each other, they don’t work independently of each other. A novel is like that too. Whilst we can only retain in our short term memory a small proportion of what we are reading when we read a novel, we also retain an overall structure. The sentences we read accumulate in our memory to create an impression of the overall work.
[1] I’ve referred to this play before, see my third blog. It’s being performed at the Edinburgh Royal Lyceum this April.

Naming things...

Why do we love words so much? Is there a gene responsible for the love of language?

There’s a lot of commentary on genes which seems to conflate the four bases with the alphabetic symbols used to describe them; A, C, G, and T. For example, I’ve read that ‘genes are made up of sequences of these four letters’. But at the risk of stating the obvious, bases are not letters, they’re acids. So are we confusing the thing with its symbol?

The statement ‘DNA behaves like a written instruction’ is a powerful analogy. But not everything is language. DNA is not a written instruction, and to say it is muddles the distinction between a thing and its name. Perhaps this is a hangover from the belief in magic, the power of the spell and the perception that to know a thing’s true or secret name was to have some power over that thing.

I think there is a related confusion over the reporting of a new gene being discovered and its role. Often we are presented with information on the name of a new gene with the implication that there is now an understanding of what that gene does. The naming of chemical elements, living organisms and genes allows us to structure and order our external world. But it does not necessarily explain it.

And I love the fact that there appears to be no order or structure in the way that genes are named. It seems that anarchy rules, and there are no naming conventions. By contrast, in astronomy only solar system objects get names, and now everything else just gets a rather prosaic mixture of letters and numbers, usually based on their coordinates and the catalogue in which they are listed. This wasn’t always so. Stars which are visible to the naked eye, and which therefore were identified and named before the invention of the telescope kickstarted astronomy in the West, tend to show the influence of medieval Arabic civilisations. There is a sort of palimpsest on the night sky, we look through a web of names and their associated civilisations when we look up at the stars.

So in the future, people will look at genes’ names and get a sense of the civilisation that produced them. They may ask themselves what on earth was meant by ‘radical fringe’, ‘mindbomb’, or ‘zinc finger’. They may try and infer something about the processes which produced these names. They may suggest that geneticists in the 21^st century were using these names to convey secret messages to one another, to rebel against the authoritarian times in which they lived, or to provide an amusing counterpoint to the way that science was normally described at that time. I wonder what they’ll think…

I've started work at the Genomics Forum

I’ve been at the Genomics Forum for a couple of weeks now, and I’ve spent some of that time trying to figure out what happens here. That may sound rude, but it’s not. According to its website, the Forum has been set up to ‘integrate the diverse strands of social science research…, develop links between social scientists and scientists working across the entire range of genomic science and technology, and connect research in this area to policy makers, the media and civil society in the UK and abroad.’

That’s a long shopping list, and I want to understand how the people here actually do join up all this… stuff. But first I need to figure out what the ‘stuff’ is. What is the science and what is the social science? Is the latter a sort of commentary on the former, to analyse its impact upon society etc?

Before I make any headway on that, I need to find out more about the science. I’m a scientist by training, but I know nothing about biology or genetics. I also know that I don’t want to read too much commentary on this science without first having a basic understanding of the science itself.

So I’ve been reading a dummy’s guide to genetics. For some reason I picture the twin strands of DNA as a zipper that is capable of being unzipped and zipped. I know that this is not a very good analogy, as all the teeth of a zipper are identical whereas it seems that the four types of “teeth” on a strand of DNA can only be matched so that A meshes with T and C with G. Perhaps I can come up with a more scientifically accurate and yet also nicely ‘literary’ analogy in the future.

And how do I think that the Forum will impact on my writing? I’m excited about working here because much of my writing looks at the same issues that people here are interested in. For example, I’m writing a series of short stories about people who migrate from one country to another. I want to explore how this experience changes them, their children and subsequent generations. How does someone ‘become’ British? Is it a consciously learned process? How do people adapt their behaviour? How is our identity affected by our genes? My family is Jewish and I’ve learnt that some ‘groupings’ of Jews (such as the Cohens) are more likely to share genes than others, and non-Jews. But there’s no straightforward link between being Jewish and one’s genetic make-up.

More generally, I’m keen to see if fiction can convey not only information about science itself, but also open up the process of doing science. There’s such a tension between the way that end results of (successful) science are portrayed, and the often messy and problematic route taken there.

For example (I chose this because it’s just been dramatised on TV with David Tennant), in 1915 Einstein published the general theory of relativity which immediately transformed our understanding of gravity and superseded Newtonian physics. But it was a theory, not proven. Sir Arthur Eddington was very keen to ‘prove’ that Einstein’s theory was ‘correct’, not only because of the aesthetics of this theory, but also because Einstein was German. Eddington, who was a Quaker and a pacifist, could see how this could be used to build bridges with Germany during and after the First World War.

He set up an experiment to distinguish between Einstein’s and Newton’s theories. But this was an extraordinarily difficult experiment to carry out, and much of the data are not convincing. Eddington discarded the data which corroborated Newton, managed to persuade the rest of the scientific community that the experiment was a success and proved Einstein correct.

But would the outcome of this experiment have been different if Eddington had not been a pacifist? Would it even have been carried out at all? It’s not clear how a strictly ‘scientific’ analysis of the problem could admit the influence of Eddington’s beliefs. But a fictional telling of the story could explore them.