Rage On
Recently, my eldest daughter sent me a link to a talk given at the Margaret River Readers and Writers Festival on 17 May 2024, when Andrew O’Hagan, author, essayist, and editor-at-large of the London Review of Books gave a compelling defence of literature and truth in the age of the machines (https://www.abc.net.au/listen/programs/bigideas/andrew-o-hagan-a-defence-of-literature-and-truth/103997464). It’s an outstanding talk. At the end, he quoted one of my favourite poems, Do Not Go Gentle into That Good Night, by Dylan Thomas. I won’t retreat from quoting the whole piece, especially as part of its power are poetry comes from that repeated, anguished line at the end of several stanzas:
Do not go gentle into that good night,
Old age should burn and rave at close of day;
Rage, rage against the dying of the light.
Though wise men at their end know dark is right,
Because their words had forked no lightning they
Do not go gentle into that good night.
Good men, the last wave by, crying how bright
Their frail deeds might have danced in a green bay,
Rage, rage against the dying of the light.
Wild men who caught and sang the sun in flight,
And learn, too late, they grieved it on its way,
Do not go gentle into that good night.
Grave men, near death, who see with blinding sight
Blind eyes could blaze like meteors and be gay,
Rage, rage against the dying of the light.
And you, my father, there on the sad height,
Curse, bless, me now with your fierce tears, I pray.
Do not go gentle into that good night.
Rage, rage against the dying of the light.
As far as I’m concerned, Dylan Thomas’ words address two concerns. The obvious and explicit message is that we should never feel we have finished our tasks, even as we are getting close to death. At the same time, as I read the poem I also read it as relevant to us at any stage of our lives, urging us to stay alive, awake and focussed, to abandon any sense of having done enough, to believe we have achieved what we can, and to set aside thoughts of giving up or retirement. Living in an increasingly soporific world, it is easy to allow the world to slip by, to succumb to being cocooned by social media.
As it happened, I listened to Andrew O’Hagan just after I had read an article about Hannah Arendt, and in particular her last unfinished book, The Life of the Mind (in Beyond authenticity, by Samantha Rose Hill, Aeon, July 2024). It was one of those moments when serendipity strikes. Like Dylan Thomas, Arendt was asking us to rage against the dying of the light, but her target was rather different from giving up in the face of impending death: it was asking us to abandon a fascination with the satisfaction of ‘authenticity’ and, instead, to return to the importance of acting in the world rather than turning away from engagement. A second clear call to remind us to keep doing things.
As Hill explains, “Arendt turned Heidegger on his head and argued that all thinking moves from experience in the world, not from Being. By arguing that thinking was a function of Being, Heidegger had tried to divorce thinking from the will in order to argue that it was one’s true inner Being that determined ultimately who they became in the world. But for Arendt, this was an abdication of personal responsibility and choice. It was a way of handing over one’s decision-making power. And for her, it is only the choices that we make in real time when confronted with decisions that determine who we will become, and in turn determine the kind of world that we will help to shape.” Arendt wanted us to rage, but do so throughout our lives, and to rage against the subversion of personal responsibility and choice. She wanted us to engage in ‘willing’, which she saw as is the mental activity that goes on between thinking and judgment: willing is about action, something one has to do.
Hill contrasts willing with authenticity: “unlike authenticity, there is no sense of comfort in ‘the will’. Authenticity promises certainty, whereas the will promises uncertainty. And in times of turmoil, it is all too human to prefer that which promises predictability to the unknown.” However, she notes that “for Arendt, the will was the means to our freedom, it was the promise that we can always be other than we are, and so to the world. The will is a space of tension inside the self where one actively feels the difference between where they are and where they would like to be.” Don’t allow rage to be a merely intellectual perspective but translate what you can see is needed into action; it isn’t enough to know what is at stake, you also have to do something to bring about change.
If that were not enough, serendipity struck yet another time, and alongside Dylan Thomas and Hannah Arendt, the other author whose work seemed determined to become involved in my thinking was an essay by scientist Philip Ball, writing on post-genomic biology in Aeon, on the topic We are Not Machines (July 2024). If Dylan Thomas wanted us to (maintain the) rage, and Hannah Arendt wanted us to keep focussed on bringing about change rather than slumping into lazy acceptance, Philip Ball wanted to reassure us about our capacities, disabusing us of believing we are nothing more than complex machines.
The article explains that the central idea that underpins post-genomic biology represents an approach that is recent, a rethinking of the roots of how and why we behave, and a liberation from the feeling that what we do, the very nature of life itself, is determined by our DNA. We aren’t just simple biological machines, we aren’t the passive recipients of predetermined sequences and systems.
Can you remember all the excitement when the structure of DNA, the true nature of genes and the genetic code itself were discovered in the 1960s, to be followed by the Human Genome Project, launched in 1990 and first ‘completed’ with a preliminary announcement of the entire genome sequence in 2000. Philip Ball reminded me of Bill Clinton’s comment when the draft sequence was unveiled: ‘Today we are learning the language in which God created life.’ Wow. If those words seemed prophetic, then the Human Genome Project (HGP) transformed genome sequencing, to the point today you can have your genetic information unveiled for a few hundred dollars. This data, and comparison of individual variations, has become a critical yet everyday resource for biomedicine, used to help address diseases and traits. We saw that dramatically realised in the use of sequencing to study the SARS-CoV-2 virus during the COVID-19 pandemic, and from that to identify treatments.
Where does serendipity fit into this? How does gene sequencing relate to the need to keep raging, to keep wanting to make changes? The answer Philip Ball provides is somewhat surprising: “copious genome databases haven’t yet produced the flood of new treatments and drugs that some had predicted from gene-based medicine, nor delivered on the promise of therapies tuned to our own individual genomes. Despite the COVID-19 vaccines, drug development as a whole has stagnated or even slowed over recent decades, becoming ever more costly. And most drugs are still found by old-fashioned trial and error, not by leveraging genetic data. The outcomes have been particularly disappointing for understanding and treating cancer, long thought to arise from changes (mutations) in the sequences in our DNA that are either inherited or accumulated through age and environmental wear and tear. Despite the genetic data glut, biology seems to have settled back into a long, slow slog.”
Ball explains that what he describes as the transformative advances of the post-genomic decades are revealing “nothing less than a new biology: an extraordinary and fresh picture of how life works. And ironically, those advances turn out to undermine the skewed view of life … in which the genome sequence of DNA was (in the words Watson put into Crick’s mouth) the ‘secret of life’”. Why isn’t there more discussion of this? Ball points out that science is inherently conservative: slow to change its narratives and metaphors. He suggests we do need some new stories to replace what considers “at best a partial and at worst a misleading picture”, while we remain stuck on explanations. As he puts it, a model based on the ideas of our genetic blueprint, of selfish genes, and the like have given us a narrative that’s deeply embedded in biological science today, a conventional and established narrative that is proving challenging to abandon.
I have to quote from Ball once again, as he has a way with words! “[I]t seems astonishing that, at least in biology’s public-facing image, it can seem as though nothing much has changed in the narrative of genetics since the 1960s. It is rather as if cosmologists, having discovered that all known matter makes up just 5 per cent of the Universe, being outweighed by a factor of five or so by the mysterious stuff dubbed dark matter while the remainder is the even more mysterious dark energy, were to say: ‘Nothing to see here! It’s still the same story!’” So, what is the view that is emerging?
Ball explains that it appears that we may have misunderstood genetic programming in complex organisms because of the widely held assumption that most genetic information is transacted by proteins. This is turning out not to be the case in more complex organisms, whose genomes appear to be dominated by RNA. We’re told that scientific expert Mattick explained it this way: it is RNA and not DNA that is ‘the computational engine of the cell’.
In simple, single-celled organisms, like bacteria, transcription is controlled by a process where one gene can (via its protein product) switch on another. That’s not the norm for complex organisms, and it certainly isn’t true for human gene regulation. We have layer after layer of regulatory processes, and to date we’ve little understanding how it all works together.
The emerging science is complex. “The same transcription factor can act on several different genes and can have different effects on the same gene in different types of cell, so that the result depends on some higher-level contextual information. Genes are also regulated by how the physical material of the chromosomes called chromatin – a composite of DNA with attached proteins called histones – is packaged up, which is a poorly understood matter. … We don’t understand the language of these histone modifications – why they sometimes suppress genes and sometimes activate them, say. But we do know that they matter: mutations of genes that make histone-modifying enzymes, for example, have been implicated in some diseases. What’s more, our genes tend to be regulated not by individual molecules but by whole gangs of them. Transcription factors act together with other molecules (especially that regulatory ncRNA) and with regulatory segments of DNA called enhancers, insulators and so on, in vast teams that gather into loose collectives that some call condensates, which emerge like blobs of vinegar in the oil of salad dressing. No one knows how all this works, but it looks weirdly messy and analogue – think not of the digital computer but of knobs and dials for controlling old electrical circuits – given that our health and perhaps our life depends on it working reliably and accurately.”
Ball continues “The temptation is to throw up one’s hands and conclude that, for humans at least, how life works surpasses all understanding. … But I don’t think that is so. On the contrary, it’s not hard to see why, the more complex the organism, the fuzzier its molecular mechanisms have to be. A huge machine that works only if all its countless components interlock in precisely coordinated ways is far too fragile – especially if those parts are, like molecules, constantly moving about randomly in a warm, wet environment. By the same token, if life relied on the accurate readout of innumerable genomic instructions in exactly the right order, it would be far too vulnerable to errors. It’s for these reasons that we are not machines – not, that is, like any machine humans have ever built.” It’s a far better and more robust solution to find principles that work over many hierarchical levels, with the operation at one level being not too sensitive to the fine details of the levels below. Gene regulation by rather loosely defined condensates rather than by specific molecular switches, say, means that it can still work without every molecule having to be present and correct.
He concludes that the best narratives and metaphors for thinking about how life works might come from life itself, rather than machines or computers. Some biologists now argue that we should think of all living systems, from single cells upwards, as cognitive agents, analysing and integrating information to achieve some self-determined goal. “Our biomolecules appear to make decisions not in the manner of on/off switches but in loosely defined committees that obey a combinatorial logic, comparable to the way different combinations of just a few light-sensitive cells or olfactory receptor molecules can generate countless sensations of colour or smell.” He concludes “And shouldn’t we have seen that all along? For what, after all, is extraordinary – and challenging to scientific description – about living matter is not its molecules but its aliveness, its agency. It seems odd to have to say this, but it’s time for a biology that is life-centric.”
Let me be clear. The are hundreds of thousands of people doing good work based on dated assumptions. There is excellent work being undertaken in laboratories around the world seeking ways to address diseases using what is now proving to be an inadequate model. That’s nothing new. It has always been the case that a dominant paradigm in science, and in life, can continue to provide improved understanding and outcomes. However, we need to move forward, to overthrow outdated ideas, we need paradigm change, we need to want to confront the easy acceptance of existence, and, above all, we need to ‘maintain the rage’.
We need people to rage against complacency. We need people to rage against misplaced priorities and behaviour. We need people to rage against mistaken scientific models and assumptions. While rage can be misplaced, it is only through raging at what is that we find what might be. It is raging against the dying of the light that makes us human, and the light is always dying, whether you are young or old. Andrew O’Hagan, Hannah Arendt and Philip Ball are addressing the same theme: keep pushing to change for the better. Rage on.
