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.

Free will with every packet of cornflakes

Yesterday I spent all day writing. What I produced was rubbish, all 2000 words of it. The words were flat and lifeless with no energy at all. In contrast, last week I was working on short story and the words zinged across the screen. I didn’t know where those words came from, I hadn’t planned them in advance. They just appeared.

Every fiction writer knows the excitement of setting up a situation and then being surprised at what happens next. Your characters can behave in ways that surprise you. Are they exhibiting free will? Even when you consciously plot out your characters’ stories, you have to be sensitive to what feels right and what doesn’t. If you force your characters to do something for the sake of the overall story, they may turn into puppets. They lose their ‘divine spark’ and the story can feel over-engineered. (Interestingly, this may only be true in literature. In Kleist’s famous essay on marionettes, he pointed out that they can be more graceful and more likely to achieve ‘perfection’ in their movements than humans, precisely because they lack human’s self-consciousness which, according to him, inhibits a complete understanding of the universe.)

Nowadays, free will is elusive. It suffered a fatal blow in the seventeenth century from Newton’s discovery of universal physical laws. The corresponding vision of a wholly predictable and mechanistic universe which only needs to be set going before it simply carries on for ever, doesn’t seem to need free will.

A universe that allows time travel (ours doesn’t appear to rule it out) must also impinge upon free will in some way, if only to prevent logical paradoxes (think of ‘Back to the Future’).

Is there any space for free will in quantum physics? After all, it (re)introduces uncertainty into physical systems, albeit on atomic scales. But this uncertainty (in the ability to know simultaneously an object’s position and momentum) is random. And when we exhibit free will, we don’t think we behave randomly.

Geneticists don’t have much time for free will, either. We’re creatures ruled by genes and all our behaviour can be explained by those genes’ desire to replicate themselves. Even apparent altruism to other people only seems to exist because we share practically all of our genetic material (99.9%).

So perhaps we enjoy reading about characters in novels who appear to exercise choice because that choice is a mirage in our real lives. Do our fictional characters have more free will than we do?

In thee (author) I trust?

I’m currently reading a historical novel, Quicksilver by Neal Stephenson, which tells the story of the machinations of the Royal Society in the late seventeenth century and the row between Newton and Leibniz over who first invented the calculus. The book is a mixture of real and imaginary characters and it’s narrated by the latter. I think it’s these imaginary characters that move this book firmly into the realm of fiction, without them the reader would be more likely to wonder if what we were being told about Newton, Hooke, Leibniz, Charles II et al. were ‘real’. The addition of the fictional makes us feel secure that to a large extent all the interactions, even those between the real characters, are made up. (To that extent they’re not real characters at all).

The relationship between the reader and the author needs trust on several levels, overtly in the case of scientific narratives, less so for fiction. The most general trust requirement that the reader has, is that what they are about to read is interesting and worth spending their time (and perhaps money) on. In fiction, the reader needs to trust the author to invent a coherent universe, one that operates according to some specific laws (even if the author is the only one that knows those laws). If something happens in the story that seems to violate its fabric, then the reader stops trusting or caring. (See John Gardner’s excellent book ‘The Art of Fiction for a more detailed discussion of this point).

Of course, you don’t need to trust the narrator who may be unreliable and whose vision of events may be completely skewed. For example, Pip in ‘Great Expectations’ assumes that his mysterious benefactor is Miss Havisham and initially there is no reason to doubt this. The interest in the novel partly lies in exploring how this error affects Pip’s development. Barbara in ‘Notes on a Scandal’ tells us she only has Sheba’s best interests at heart. By the end of the novel, this is patently untrue.

Part of the fun in reading novels with unreliable narrators is working out the reasons for this unreliability. And even here, I think there needs to be some initial trust in the narrator. Someone, who from the very first page is clearly lying, is going to have to be incredibly engaging to keep the reader involved, because it will be so much more hard work just to figure out how this universe works.

Novels with unreliable narrators tend to be written in the first person, so are all first person narrators inherently unreliable due to their necessarily restricted and partial outlook?

Trust in scientific papers operates at various levels, some of them more explicit than others. Most obviously, the reader has to trust the authors’ integrity and believe that what is reported in the work actually happened. If this is violated it can have a huge far-reaching impact on the science. For example, one infamous case of scientific fraud is that of Paul Kammerer and the midwife toads in the twenties. Kammerer said he’d shown that the Lamarckian version of evolution was correct, in that an organism’s environment can directly affect how it develops and the attributes that it passes onto offspring (in violation of Darwinian natural selection which holds that genes mutate randomly and those organisms which are better adapted to their environment – by chance – are more likely to survive and mate and produce offspring, thereby ensuring that their genes are passed on.)

Male toads, from toad species which mate in water, have nuptial pads on their feet to enable them to hold onto their females. Toad species which mate on land don’t need, and therefore don’t have these pads. Kammerer claimed that by forcing the landlubbers to mate in water, he’d got them to develop nuptial pads in only a couple of generations. This caused a furore until it was shown that the nuptial pads on one of his specimens had been faked, and were caused by injections of ink. Kammerer committed suicide shortly afterwards.

This discredited Lamarckian ideas. And yet, how can a fake result be used to disprove a theory? Just because it doesn’t disprove Darwinian ideas, it doesn’t mean that the alternative is wrong. But this is what happened – bad science has been used to discredit Lamarckianism. (Alongside good science which favours Darwin, of course).

Fraud is (presumably) rarer than inadvertent mistakes. Science is difficult to do, mistakes happen. So how does the reader know whether to trust that the author hasn’t messed up?
Popper argued that science should be falsifiable i.e. you should be able to refute a theory if you get an experimental result that disagrees with it. In practice because of the possibility of mistakes there is more caution than this implies, and scientists are unlikely to chuck away an entire framework on the basis of a single result, simply because that result could be wrong.

More insidiously, scientists can be skewed towards a specific reading of their results based on their prejudices. So, trust is required to assume that the author has been open-minded and considered all options.

Of course another factor that influences the reading of a scientific paper is the authors’ reputations. If you know the authors, and accept their previous work, you are more likely to believe their current work. Is this true in fiction? Are you more likely to read a book based on the author’s reputation? Can the book ever stand alone?

You also have to trust what you are not being told. In fiction, much of the art lies not in writing but in editing, the cutting out of extraneous words to leave only the essentials. You have to trust that what has been left out is inessential. In science this is more problematic. Many experiments go unreported, because they don’t give interesting results. This is a particular problem in medicine with the testing of new drugs. If the results are inconclusive or unfavourable, they are more likely to go unreported than if they appear to support the hypothesis that the drug ‘works’.

From A to B

Writing fiction presents the writer with a near-infinite list of choices, not only on the subject matter, but also on the style and the process. For example, most stories are written in the past tense, but not all. Sometimes, I find that when I write in the present tense, my writing becomes more immediate and more fluid. I can ‘see’ my characters better as I can understand what they are doing right now. I don’t have to interpret their past actions for my readers.

However, this sort of writing can go badly wrong, and you can tell when it does because the characters in the story get stuck in a sort of realisation of Zeno’s paradox, in which an infinite number of steps are needed to get anywhere. The characters stop being able to do anything, because every single action occupies all of the present. When you’re concentrating on the present and not the future or the past, the present can seem like eternity. The writer chops the present down into finer and finer slices until time stops completely. This is probably a good thing if you’re meditating. It’s not a good thing if you want to write interesting fiction.

Of course, the antidote is to know which of the present moments are the important ones and leap from one to the next, leaving out all the others. A story never really flows continuously and smoothly from one moment to the next, and consequently the space-time in the story becomes rather lumpy and quantised. If the writer is good, the reader doesn’t notice these invisible joins.
The use of the past tense in literature is a method of telling the reader that the narrator has seen these events happen in the past and is relaying them to the reader. Using the present tense does away with this artifice, and replaces it with another. The reader is now ‘watching’ the events unfold before his or her eyes; this is the literary equivalent of watching a film. Was this method of writing influenced by the rise of film in the early twentieth century?

In scientific narratives (i.e. papers published in scientific journals), there is also a subtle editing of time and space. In these sorts of writings, you never read about the nights spent at the telescope waiting for the cloud to go away and the cabin fever brought on by spending two weeks alone at 10,000 feet observing the same star night after night. You never usually read about the things that go wrong, the wrong star observed, the wrong chemicals mixed, the endless debugging of the computer program. These things are not supposed to be relevant to the experiment.

The actual work reported in scientific papers is summarised in the past tense, although the results are reported in the present. So the work occupies a specific moment in time, but its outcome should stand for all eternity, even after the invisible narrator is long gone. And the passive voice is always used, to indicate that the presence of the author did not impact on the results. In fact, the scientist is the ghost in the machine. Events unfold with a certain inevitability, the stars were observed, the gases were mixed, the temperature was taken, the theory was developed, but who did all this?

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.

Where do you stay?

I’ve already mentioned in a previous posting the complexities around the links between genes and Jewishness. Sharing an ethnicity does not mean sharing an exclusive genepool. There can be more variation within shared ethnicities than between them. And the link between genes and nationalities is even more complex, although perhaps less so in a small country like Scotland which has had relatively little immigration. Perhaps nationalities are (becoming) more memetic than genetic – one can learn to be a different nationality through subconsciously, or consciously, adopting the mores of the people around you.

For example, when I was a child we drank coffee. We hardly ever drank tea. Although my parents were both born in England, one grew up in America and the other was the child of German and Austrian immigrants, and neither had a history of drinking tea. Even as a child I drank coffee for breakfast. Now (perhaps as a result of living in Yorkshire for several years and having a partner from there) I drink tea all the time, and so does my father. Has he learnt it from me?

But sometimes you can get stuck in the middle – for example, I never know what to reply when someone asks me where I ‘stay’. Scottish people use the word as a synonym for ‘live’ or ‘reside’. If I reply ‘I stay at…’ it feels artificial, as if I’m appropriating someone else’s language. But if I reply ‘I live at…’ it implies I’ve thought about using the word ‘stay’, have rejected it as being too Scottish for me, and have retreated to ‘standard’ English. Either alternative makes me feel self-conscious.

Perhaps I should make up my own word.

I’ve learnt that genes are influenced by their envronment, too. They get turned on, or ‘expressed’, by influences surrounding them. This environment stretches all the way from the neighbouring genes, through the rest of the cell, the host organism, and the wider environment. So, genes are not little bullet entities that whistle unperturbed through their host organisms, only randomly mutating. (This concept of ‘random mutations’ sounded so dangerous when I first read about it and I couldn’t figure out why until I realised that it’s a reminder of radioactivity.)

This adaptation to your surroundings can be reflected in laws on nationality. Different countries have different attitudes and laws on the conferring of nationality is conferred. Some use ‘blood’ (e.g. Germany before 2000) through which you can confer your nationality to your offspring even when they’re born outwith the country, others use ‘territory’(e.g. USA) through which your offspring automatically achieve that nationality by virtue of being born there. Those that use territory – do they place more emphasis on learning behaviours and attitudes, such as the desire to aspire to ‘American’ ideals? Because there are no genetic links to rely on to hold society together?

Notice that I used the Scots word ‘outwith’ in the previous paragraph. Perhaps I’m adapting my language after all.