Unfinished Business

I’ve reached that age where my eye is drawn to the obituary column every time I open the newspaper. It hasn’t been a conscious move but, having arrived at my fiftieth year, I am increasingly aware of the hopes of youth shedding and floating away, like leaves from a tree, and find myself more often looking back over the road now travelled than peering into the future at the way ahead. I have a vague sense that there has to be an accommodation — some kind of reckoning — but I’m not sure how to achieve that. I’ve not been this way before, and I suppose that might explain my interest in the report cards of those who have.

Thinking on the beach

Youth is such a beguiling fantasy, provided of course you are lucky enough to be born into the relative comfort and safety of a developed existence and a supportive family. As you grow up and learn more of the possibilities that life has to offer, a world of potential fulfilment unfurls before you: places to visit, people to meet, books to read, ideas to wrestle with, disciplines to master, the chance to become someone, to make something of yourself.

I have travelled that road and worked hard along the way. School, university and a PhD, followed by stints in labs in France, England and America that took me to my early thirties. From there I gained a foothold as a junior lecturer at a university where, a dozen years later I became a professor of structural biology, a position I hold today. I have published over eighty scientific papers, and lectured to my peers on three continents. I would appear to have attained my academic acme; to outsiders it must seem like the completion of a magnificent destiny.

The only trouble is, it is nothing of the sort. I have little sense of being the finished article. What I am and what I know is incomplete.

To some it may seem odd for a fully-fledged professor to make such an admission but there it is. I am not insensible of my scientific achievements, such as they are, but when I look at the whole, it is the holes that stand out. I was probably not helped by having relocated to biochemistry early in my research career after first training in physics; a certain inter-disciplinarity is no bad thing but the move has also left me feeling not quite at home in either field. I suspect in any case the sense of mastery would not have been much improved by sticking to one area of research; most scientists enclose only small plots of expertise and are wary of straying outside.

As a consequence, impostor syndrome looms large and brings with it moments of disabling dejection. Most days it’s OK. It helps that the phenomenon has a name and is widely shared. That knowledge, and the experience that comes with over a quarter of a century of scientific work and learning — failure punctuated by enough triumphs to keep the show on the road — go some way to providing the resilience to live with the never-ending feeling of never ending.

This should come as no great surprise since we cannot perceive the world except incompletely, though we may sometimes be taken in by the astonishing rate of scientific progress. As a scientist myself, I might be equipped with one of the most powerful modes of inquiry developed by humankind but am nevertheless all too aware of its limitations. Consider as an example the work involved in X-ray crystallography, the main technique that I use in my research to reveal the structure of protein molecules at a level of detail that is normally hidden from sight. It is the work of weeks or months or sometimes years to conjure crystals from our samples so that we might illuminate their innards with X-rays. The crystal splits the beam into myriad rays that are captured and recombined in the sophisticated, knowing embrace of mathematics to reveal the protein structure within. These long projects ultimately yield an object of dazzling complexity, a rich, three-dimensional representation of a molecule on a minuscule scale. Such power: we see essentially every part. The atomic construction is revealed and that enables us to understand the chemistry of its function.

And yet, seeing everything is not the whole story — one eventually learns not be taken in by the flush of excitement that accompanies a new result. The view remains partial, illusory, problematic in so many ways.

In spite of the power of the technique, we cannot see all of the structure. The image is an average of information summed over the billions of molecules in the crystal so that parts that are moving or that differ slightly in conformation between individual molecules remain blurred and invisible, like hands waving in a dimly-lit photograph.

Moreover, the method only reveals a single structure, the particular conformation locked into place by the inter-molecular forces that hold the crystal together. This captured state, an experimental convenience, is just one that the protein might adopt as its polypeptide chain flexes and writhes in its natural state in a living organism.

And that is not all. Crystallography may be powerful but it is also an exacting technique. Typically, only samples that are extremely pure are likely to yield crystals suitable for X-ray diffraction experiments, which means that you can often only examine one molecule or fragment at a time (though occasionally you might be able to crystallise two or three that cluster together naturally to see how they interact). The purifying isolation that is the secret of success in crystallography is therefore also one of its severest shortcomings, since it is rare to be able to examine all the interactions that proteins make while playing their part in the cellular dance of life. There is a kind of uncertainty principle in operation, above and beyond the quantum scale puzzled over by Heisenberg: the harder you try to pin something down for examination, the more the world in which it operates is expelled from the experiment.

And so, though replete with information, we are forced to realise that the big picture is mostly empty. We might have coloured in one isolated patch with our analysis but spent so long working out the shading, focusing on each atom as the glorious structure was gradually revealed, that only when we step back do we realise that the molecule that had loomed so large in our mind’s eye is but a speck on a gigantic canvas of white. Disappointment hacks into the sense of achievement. Sometimes the easiest escape is to move on, to distract yourself with the next experiment, the next structure.

Of course sometimes a story emerges, piece by piece, which is more satisfying; one experiment leads to a new insight, to another experiment or line of inquiry that connects parts of the world and makes sense of it in ways that could not be seen before.

But there are only so many stories, or in my case, molecules, than can be worked on in a lifetime. Like most scientists, I don’t have a grand achievement I can call my own, though I have had smaller moments of satisfaction. I think of work in the 1990’s that uncovered a role for the arcanely named 135S particle in the pathway of poliovirus infection; of a decade of experiments to probe how the serum albumin in our blood plays catch and release to shepherd all manner of molecules, from drugs to fats, around the body; or of our ongoing examination of the protease from foot-and-mouth disease virus that cuts and shapes viral proteins in each round of infection, and might yet be exploited in the fight against this alarming pathogen. Following the threads of these investigations from one clue to the next has certainly been gratifying but I have never had that sense of reaching a conclusion. Some of these stories have ended for me but only because I moved labs or ran out of funds or arrived at a question that was beyond the reach of current techniques, not because the investigation was complete.

The scientist’s lot is partial, incomplete. The answer is never the end and the puzzle at hand has to be enough. There is consolation in the notion that our published work confers some level of recognition and even perhaps a deceptive hint of immortality. My papers are doing reasonable business at the moment — people are reading and citing them — but most (all?) will eventually fade as the tides of time wash in new observations and ideas to divert attention elsewhere. Who knows when the stories that I joined for a time will be finished?

Cloudy sky and shining sea 2 (BW)

Of course, none of this is exclusive to my particular branch of science or even to scientists. A sense of incompleteness surely affects us all, to greater or lesser extents, though the noisy colour of life blinds us for much of the time to the empty spaces in our comprehension of this world.

How can we truly know where we are when our knowledge of the world is so incomplete? And what we are supposed to make of our lives? In the midst of so many unknowns, it is easy to lose your bearings; or rather, it can be difficult to find them in the first place. These are obvious problems of course — they are the very stuff of philosophy and religion and have been tackled by many finer minds throughout human history. I think of Socrates (’The unexamined life is not worth living.’), of Montaigne (‘Rejoice in the things that are present; all else is beyond thee.’), of Camus (‘One must imagine Sisyphys happy.’) and even of Pirsig’s musings on motorcycle maintenance. My own meandering reflections here were prompted by a review of Oppenheimer’s biography, which suggested that, for all his extraordinary learning and accomplishments, he ‘never figured himself out’. Has anyone?

Questions of meaning and purpose are obscured early in life by the certainties and norms passed on to us by parents and teachers and other cultural authorities. Through our early years we are immersed in ‘the ways of the world’ and will accept them until we learn to think for ourselves. Even then, the problem of incompleteness can easily be deferred by the optimism (or is it the arrogance?) of youth, which imagines itself to be only starting out on the learning curve of life and to have all the time in the world.

But I now know that I won’t meet all the people, read all the books or discover all the ways of thinking that I thought I would get around to in the span of a normal life. (That word ’normal’ — such a charlatan.) And I sense that even close examination will not succeed in all its hopes, for no experiment tells the whole story, however hard you try. How, therefore, to live in a world that we understand but little? Through force of habit and in the companionship of family and friends, I do well enough most days but then I open the paper and another obituary calls me to account.

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30 Responses to Unfinished Business

  1. Oh crumbs, you are only 49! I’m 77 so should I be doing one of these too?

  2. Stephen says:

    Hah — that’s entirely up to you. I meant I have completed my fiftieth year so I am at the big five-oh. Maybe it’s just a phase I’m going through.

  3. Steve Caplan says:

    I am set to enter my own 50th year next month, and I think you have summed up in incredibly erudite terms many of the thoughts that have been passing through my brain. It’s astonishing how decades of research can be broken down to a few bullet points to sum up most our our existence as scientists…

  4. Maybe it gets easier after 50 because you KNOW there is too little time and anyhow health starts to catch up with youth. You can stop being reflective again and just enjoy what you can. At least that’s how it has taken me (I think I went through your phase at around 45 thinking ‘is this all there is’). Now, a decade older than you, I just relish each new challenge knowing that I don’t know enough about it but I should seize it while I can – and share what I can too. Here’s to you feeling introspection job done and you can move on nd enjoy life again. (When I read obituaries the first thing I do is check what year they were born in!)

    • stephenemoss says:

      Growing up in Maine, a young Stephen King used to read the obituaries/death notices in his local newspaper, and then cross out the names in the telephone directory.

    • Stephen says:

      I’m hoping it does (!) (and have read elsewhere about older people being happier with their lot by letting go of unattainable hopes). These thoughts have been rattling around in my head for a while but 50 did seem like a bit of a landmark that needed acknowledging.

  5. Heather says:

    Thanks first, for that comment, Dr. Moss!

    My initial reaction to the post was, “Et tu?” But I think there’s truth in Athene’s observation, that there are phases to life, and we’ll get past this one, as most do.

    Like most scientists, I don’t have a grand achievement I can call my own, though I have had smaller moments of satisfaction.

    Let’s be grateful for those, at least. When I had to compile my “habilitation à diriger les recherches” a couple of years ago (requisite link), I was glad of the opportunity to revive some out-of-print book chapters and never-cited research findings and give them a second, archival life as such. But it’s so much graffiti, really. In particular, Athene might resonate with this, the never-cited research has some parallels with blog posts that never received a comment.

    As far as purpose is concerned, I have decided that mine is to do what I can, in a local and minute way, to realize where possible the hopes of those people I respect and love, who have already invested in me. To serve the next generation in my unique manner, and to remember consciously to enjoy the present moment.

    When you’ve reached your own existential conclusion – but a never-ending one, truly, just as no novel truly ends until all the protagonists and the narrator are all dead, and the novel is no longer opened – please do share it.

  6. Jim Woodgett says:

    Lovely writing Stephen. Most of us amble through life thinking we are in some form of control of our destiny but we typically steer only part of the direction. We’re like a canoeist navigating stiff currents and trying to make our opportunities count. Those who appear driven or who claim clear intent in their lives (and whom we think must be so because they are successful) are largely the product of incredible luck mixed with circumstance (there are many talented actors who never break through).

    But you hinted at something that is very insightful which is that we actually only have time to do so many thinks. I’ve never thought of structural biology in this way. You only have 50 or so structures in you (or whatever), a very finite number. You’d like to be sure those you work on are the most interesting. Yet, each needs dedication. You cannot simply leave one grossly unfinished because another looks to be much more interesting. Otherwise, nothing would be done, just hopping to ever (apparently) greener grasses. In other words, we cannot look for perfection and second guess every decision. We take our best guesses and run with them. Sometimes this works out wonderfully, other times we find we’ve given birth to an ugly duckling (that maybe someone will nurture into another type of beauty).

    As you note, introspection is important, as is review and perspective. But don’t judge yourself against false milestones; instead lean harder into your own paddle.

  7. Jen D says:

    Wonderful writing.

  8. Brigitte says:

    For those who have not seen this tweet. Essential musical accompaniment to this post!!

    @drugmonkeyblog: For @stephen_curry – Pete Seeger – Get up and go http://youtu.be/OdNQt4a6f7g

  9. stephenemoss says:

    Stephen, this is a wonderful post and judging by the vintage of several of the commenters, one that clearly resonates with that age group of which I am part. I negotiated the tricky ‘big five-oh’ (or Hawaii) several years ago, but I don’t recall feeling ‘the hopes of youth shedding and floating away, like leaves from a tree’. For me this is too much wistfulness and melancholy, and I strongly recommend a regular fortifying glass to keep such thoughts at bay.

    However, I suppose we all take stock from time to time, and while crystallographers evidently take an ultrastructural look at life, we cell biologists indulge in our own form of total internal reflection.

    At 50 I believed that time had only modestly diminished the possibilities that lay ahead, notwithstanding the need to keep mind and body in reasonable working order. With regard to the latter I did have to come through open-heart surgery four years ago, but having done so I decided to substantially change the direction of my scientific research. This was not a strictly Damascene conversion, it was rather forced on me as a consequence of the changes in science funding away from basic/fundamental to more applied/translational research.

    For 25 years I had been investigating a fairly obscure family of proteins called the annexins and I was generally satisfied with work we had done to elucidate the functions of several of these proteins. However, I abruptly ceased activity in this area when a grant application that scored the highest possible ratings from the reviewers was rejected by the panel. I realised I was either going to spend the next 15 years scraping along on odd bits of funding or I would have to do something else, in other words, adapt to survive.

    For me the change was not radical, I am not nearly brave enough to quit my job in order to raise rare-breed pigs on a croft in the Outer Hebrides, just giving up the familiarity of my niche research area was tough enough. But the switch has been rejuvenating, and this year if my plans to start a spin-out company come to fruition, I can look forward to another new and exciting challenge. At 50 you still have many years, perhaps decades, in which to take on new challenges, and if some of those take you into unfamiliar territory then so much the better.

    • Stephen says:

      Thanks Stephen. I suspect the post may come across as more downcast than I intended; it was left to mature for some weeks after I had the initial idea but even so I struggled to get the right tone. So thank you for your encouragement and for sharing your own story. I’m not shutting up shop just yet (!). Like you, while I am more mindful of the finite number of years remaining, I still have enough life left in the tank to seek out some new things to do. Indeed one of the advantages of a certain maturity is the devil-may-care freedom that comes with having banked a certain amount of achievement. I don’t see myself at the helm of a new spin-out company any time soon but I’m sure something interesting will turn up.

  10. I can recommend a complete change of field even when slightly, oh all right quite a bit, older than you. Yes there’s the problem of imposter syndrome and tactfully trying to gain credibility, and I’m unlikely to develop a world reputation in this discipline, but it feels forward-looking (irony, since it’s history) and it’s very liberating.

  11. Cromercrox says:

    As a consequence, impostor syndrome looms large and brings with it moments of disabling dejection.

    As you’ll know (because you read my blog on OT) my 50th birthday was passed in a slough of depression, brought on, in part, by doing far too many things, and trying to make a mark at one of them.

    We see ourselves quite differently from the way others see us. Inside the typical over-achiever (that’s you, me, Athene and all the other commenters here) is someone who is deeply insecure. What the world sees, of course, is the distinguished professor, science writer, pillar of the academic community, whatever – in any case, someone that the person at the eye of the storm fails to recognise as themselves.

    It’s taken me a lot of hard introspection, the support of family and colleagues (and, oh yes, the drugs) to accept that I don’t keep having to engage in various Sisyphean tasks in order to prove myself – as I have proven myself many times over.

    As my boss explained to me the other day, I must learn to realise that the science editor, science writer, scribbler of novels and short stories, commentator, husband, father, blogger and weekend rock star are ALL THE SAME PERSON, so it’s not surprising that one get’s exhausted, especially as one is now >50.

    One way to combat the urge to look at the past is to get down with the kids and look at the future. Through Crox Minor and Crox Minima I have discovered all sorts of things (films, books, music, social trends) I’d never have found on my own, some of which I quite enjoy and therefore can share with them.

    • Stephen says:

      Many thanks for the comment Henry. I totally agree that children, even though exhausting when young, can be quite a tonic for old bones.

  12. Rhodri Ceredig says:

    I attach one of my mother’s unpublished poems entitled “Bound to fall” which I think is appropriate. My father was a physical chemist…I am now a research biologist aged 63…..

    Bound to Fall
    Like the bad scholar whose exams
    Loom low and heavy, I
    (See now the approaching end)
    Have failed to note
    The abundance of the world;
    The sheer, unstinted bounty.
    Winter came
    And covered our misdeeds with snow,
    To sow, to seek
    And find, and reap.
    The pear tree came alight….

    I did not see or feel
    The wond’rous awful ecstasies of life.
    My own heart’s beat
    Until it falter
    I will take for granted.

    Why I did this, do that
    Stays, midst my so muddled past,
    My cluttered papers:
    Long experiments
    Those ultimate results
    No one will know.
    I saw the green leaf stiffen
    And the young thrusting shoot
    Take heart and open
    Year after year; and now
    The year will come
    When that for me will be the last,
    The very last of times.

    And I know nothing,
    Nothing of it all.

  13. Frank says:

    56 and counting here. I think that changing fields, or pushing out into new fields regularly, is a good ruse for justifying one’s impostor syndrome. If I dabble in an unfamiliar field, well then it’s OK to feel a bit out of my depth.

    I never used to like obituaries but I do now. I used to think they were all about death and so avoided them. But of course they are (in most cases) actually about lives well-lived, and are usually far from morose.

    I think our individual experience of being a particular age is just that, individual. The confluence of home life, work life, world events, and one’s health status, can combine in interesting ways. Sometimes they cancel each other out, sometimes they make a pincer movement with painful results. Just keeping on walking through the years may be all that’s needed, as Athene suggests, in order to find a new plateau of contentment. Fingers crossed.

  14. Stephen says:

    Thanks Frank — and to all the wise old heads who have chimed in.

  15. ian says:

    Probably I am midway now between birth and death, turning 40 this year. I am distant from my youth, I am astonished at my memories. I am again unrecognisable to myself. If I look closer I am almost unrecognisable to who I was but not a week ago. How can I live in this world? How can I persist in it? There is darkness in there, there is shame. How can anyone bear it? For me I am a recovering lifeaholic. Without asking I am imbued with it, this life. I take a step, another one. I am walking, I keep on walking, the ground unfolds before me. All I see is the next step, and after it another one. I’ll keep walking. For now that seems right.

  16. I have little to add, other than to congratulate you on a beautifully wistful piece of writing. Bravo!

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  18. Freya Morris says:

    What a post! Beautifully put. You’ve summed up how I feel most of the time. Although I have ‘youth’ on my side (not time, because who knows, how long), that acute awareness of ones mortality and desire to accomplish (and never enough time) is magnified at some points in our lives more than others (or in some personality types). It reminds me of TS Eliot’s The love song of J Alfred Prufrock. That pressure of ‘time’ and the eternal footman who sniggers.

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