It’s About Time

What then is time? If no one asks me, I know what it is. If I wish to explain it to him who asks, I do not know.’ So wrote Saint Augustine, bishop of Hippo in North Africa, more than fifteen hundred years ago. And we’re still confused… Okay, I’m confused.

When considered philosophically, you’d think it would be a relatively simple concept: I exist right now: the Present; I remember what happened to me: the Past; I don’t know what will happen to me: the Future. That is Time. It is divided into separate Magisteria like scenes through the window of a moving train. And yet… and yet the divisions seem so arbitrary. So evanescent. It’s almost as if Time were merely an all-purpose synonym for Change. A generic label.

But things happen in time, our bodies being no exceptions, so it’s difficult to ignore. We have come to prioritize those happenings as constituting Time. The intervals between events have gradually become divested of significance, although whether it is the interval, or the event that is prime could be argued -much as whether the placement of a comma in a sentence contributes almost as much to the meaning to be conveyed as the words themselves. And yet, is it really all contingent…?

Are habits -those things we do almost without thought- or the endless train of happenings the commas? Is it actually in the intervals between things where we live? Do we inhabit the interstices, and merely mark their boundaries by events -rely on things that happen in order to count? Do we live between the nodes or does reality only exist for me when stuff happens, when I am aware of what I am doing? And if so, then what about when I’m not aware? What happens to Time then? Do you see why I am confused?

And, at the risk of sounding too Cartesian, is the reality my body inhabits different from the awareness my mind tells me about? Bodily existence seems to have been issued with different rules because it is far more contingent than my mind. Too needy. Too ad hoc, and less spontaneous. It seems overly pulled by evolution and ontogeny, unable to explore new things. It straddles the intervals like a bridge. It is a scaffolded entity, constantly in a state of repair.

No, Time, for a body at least, was always thought to be continuous. Contiguity of events allows restoration and medicine discovered this. It started on its quest to heal the body, even if the mind was not always in synchrony and did not understand. But it assumed that mind was only a by-product of body. It is… isn’t it…?

At any rate, something that has often puzzled me is the difference in prescription instructions for various medications. Of course some drugs are relatively short-acting, and need to be taken frequently, say, Q6H (every six hours), or perhaps they are more potent and require a smaller, but spaced out administration, say, Q8H. That seems fairly obvious, so instructions as to how much and how frequently to take them would therefore make sense.

But suppose the directions are to take them QID (four times per day) or even TID (three times per day)? By comparison, that seems almost sloppy, doesn’t it? I mean, what is the difference…? And how much variation is permissible between the timing of every eight hours, and three times per day? What impact would, for example, a two hour difference -or even more- have on the medication efficacy? This is not meant as a criticism, but merely an exploration of time in the administration of a treatment.

And yet, even a more precise prescription of the interval does not usually state a specific time for its consumption like, say, 8 PM. Given that our bodies (and hence probably our metabolism) are subject to a circadian rhythm, I’ve often wondered whether that might make a difference in a medication’s effectiveness. An article in Nature that I ran across addresses that very issue: https://www.nature.com/articles/d41586-018-04600-8?utm

‘The circadian clock is a remarkable system. A central timekeeper in the hypothalamus orchestrates a network of peripheral clocks in nearly every organ and tissue of the body, turning on and off a bevy of genes including some that encode the molecular targets for drugs and the enzymes that break drugs down. These clock genes are particularly important in cancer because they govern cell cycles, cell proliferation, cell death and DNA damage repair — all processes that can go haywire in cancer.’

Until recently, technology was unable to determine the genes involved, let alone the timing of their activation, and so chronotherapy remained on the fringe. But, ‘More than four decades of studies describe how accounting for the body’s cycle of daily rhythms — its circadian clock — can influence responses to medications and procedures for everything from asthma to epileptic seizures. Research suggests that the majority of today’s best-selling drugs, including heartburn medications and treatments for erectile dysfunction, work better when taken at specific times of day.’

Steroid levels, for example, ‘naturally cycle with the circadian clock. In the late 1960s, scientists found that the synthetic corticosteroid methylprednisolone is safer for treating arthritis and asthma if taken in the morning rather than at other times of the day. This is because the feedback loop in the hypothalamus, which controls the release of cortisol, is least vulnerable to inhibition in the morning.’ Other factors such as age and gender also seem to be important in circadicity. So is the inconvenience of the times when the appropriate genes might best be manipulated. Not only that, but ‘practical biomarkers are needed to help clinicians identify optimal times for treatment.’

There are many variables to account for, but clearly there is a growing appreciation of Time in understanding the body’s underlying physiology. There is a need to adjust not only the treatment, but also its provision in harmony with individually derived schedules that are often by no means intuitive or convenient. As if, by finding each body’s unique variations on the theme of circadian rhythm, we discover the hidden melody playing deep within.

Maybe Rabindranath Tagore, the Bengali polymath who won the Nobel prize in Literature in 1913, was not so far afield after all: Let your life lightly dance on the edges of Time like dew on the tip of a leaf.

I’d like to think we all dance in Time…

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The best laid schemes o’ Mice an’ Men Gang aft agley

Two steps forward and one step back –isn’t that  always the way with progress? Reward coupled with unintended consequences? The Industrial Revolution with worker exploitation? Nuclear power with the Bomb. Nothing, it seems, comes without a price. Even religion, the great leveller, once established brooks no rivals. Life itself, is a succession of survivors outcompeting the other contenders.

But simply to focus on the successes is to miss the important lessons to be learned from the failures. In biology the difference between winning and losing might hinge on a single change in a single gene, or more instructively, on an adaptation of an existing organ for another, more useful function in a different environment –an exaptation. Arms and hands for wings, in the case of bats, or for fins, in the cases of aquatic mammals like whales and dolphins.

In the early days after the discovery of X-rays, their ability to see through things was thought to be miraculous, and many possible uses were suggested. It was not until much later, after countless reports of cancers, burns, hair loss and worse, that the dangers of its careless use were acknowledged. Then, Phoenix-like, from the ashes of its many unwanted side-effects, grew carefully investigated treatments like irradiation for tumours, CT scans for internal visualizations, or fluoroscopy for placement of medical kit like stents, anti-embolism balloons, etc.

Unfortunately, even nowadays, the sundry complications of progress are often inadequately predicted in advance, probably because most things are multifaceted and changing one parameter has a knock-on effect on the others. Clearing forests for agriculture changes the animals that can survive in the changed ecosystem; monoculture to maximize demand for a particular variety of crop, say, increases the likelihood that the plants –previously diverse- may not be able to withstand the onslaught of a disease or infestation that would otherwise have only affected a small portion of their number. Evolution would normally have winnowed out the susceptibles, leaving only the resistant plants to reproduce. But all of this is Grade 9 biology, isn’t it?

What led me to think about this was an article in the Smithsonian Magazine discussing the effects of making friction matches on the women and children involved in their manufacture: https://www.smithsonianmag.com/smart-news/friction-matches-were-boon-those-lighting-firesnot-so-much-matchmakers-180967318/ – 6ZQ6WshMH2Ghpoys.03

‘Like many other poorly paid and tedious factory jobs in the nineteenth and twentieth centuries, match makers were predominantly women and children, writes Killgrove [in an article for Mental Floss]. “Half the employees in this industry were kids who hadn’t even reached their teens. While working long hours indoors in a cramped, dark factory put these children at risk of contracting tuberculosis and getting rickets, matchstick making held a specific risk: phossy jaw.” This gruesome and debilitating condition was caused by inhaling white phosphorus fumes during those long hours at the factory. “Approximately 11 percent of those exposed to phosphorus fumes developed ‘phossy jaw’ about five years after initial exposure, on average”. The condition causes the bone in the jaw to die and teeth to decay, resulting in extreme suffering and sometimes the loss of the jaw. Although phossy jaw was far from the only side-effect of prolonged white phosphorus exposure, it became a visible symbol of the suffering caused by industrial chemicals in match plants.’
So much so, that by 1892, newspapers were investigating the problem. ‘“Historical records often compare sufferers of phossy jaw to people with leprosy because of their obvious physical disfigurement and the condition’s social stigma,” Killgrove writes. Eventually match makers stopped using white phosphorus in matches, and it was outlawed in the United States in 1910.’

Civilization is the steady accumulation of successes over failures. Trials and errors –mistakes which perhaps seem to have been largely anticipatable in retrospect- summate to useable compromises. It’s how a child learns; it’s how evolution learns.

But the point of this essay is not so much to highlight the exploitation of workers in the past as to suggest that there can be sociological as well as biological evolution. After all, the etymological root of the word is the Latin evolvere –to unfold.

Occupational Safety and Health -as a distinct discipline, at least- is a relatively recent development stemming from labour movements and their concern about worker safety in the wake of the Industrial Revolution. As Wikipedia explains it: ‘The Industrial Revolution was the transition to new manufacturing processes in the period from about 1760 to sometime between 1820 and 1840. This transition included going from hand production methods to machines, new chemical manufacturing and iron production processes, the increasing use of steam power, the development of machine tools and the rise of the factory system.’

Although this provided jobs and undoubtedly improved many aspects of living standards, the driving force was production, and in its early stages, had little regard for worker safety or health. Enter the labour movements in the early 19th century, along with great resistance to their demands. In many instances they were seen as antithetical to progress –antithetical to Capitalism, for that matter. And yet, in the fullness of time, the benefits of a healthy workforce to economic success evolved from an initial, grudging pretense of acceptance in some countries to a legal framework of protection in others.

There is certainly a long way to go along this path to be sure, and exploitation still seems a default that is all too easy to overlook. Especially since it is the poor and vulnerable who are usually the victims –people with little voice of their own, and even less power to resist.

But are things actually changing? Does knowledge of exploitation make a difference? We know slavery is still practiced; we know that refugees are still being brutalized and abused in places like Libya; women are still being kidnapped and sold into prostitution despite the best intentions of agencies like the World Health Organization.

So, do the gains experienced in some areas, offset the tragedies in others? We cannot appreciate the broad sweep of History in the few years we are allotted, and evolution –even social evolution- can be deceptive and disheartening. But remember the words of Khalil Gibran:

You are good when you walk to your goal firmly and with bold steps.
Yet you are not evil when you go thither limping.
Even those who limp go not backward.

I have to hope he saw something that I missed along the way…

The Feminist Egg

Once upon a time, I suppose that one of the characteristics of Age was its hubris. After a certain age, it was easy to dismiss most new things as mere variations on time-tested themes –additions, clever perhaps, intriguing even, but still accretions. Ecclesiastes lived in old minds: The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun. And yet nowadays, even the quickest peek over the shoulder calls that into question. Maybe it always did, but without the publicity it now entertains.

New things –truly new things- are often the hardest to accept, especially if they fly in the  face of cherished beliefs sufficiently entrenched as to be regarded as not merely true, but obviously true -common sense, in fact. It took generations to accept evolution –and now it seems only sensible that the random acquisition of those traits that help survival will be the ones selected for in the next generation. It was not an upwardly purposeful spiral that inevitably led to homo sapiens; evolution doesn’t change cows to humans –it just eventually creates cows better able to survive in whatever milieu they find themselves. And randomly –the unfit are still granted existence, but if they are not suited, they pass on little benefit to their progeny.

It’s true that animals –mammals, especially- do attempt to influence desirable traits in their offspring by choosing healthy partners exhibiting those characteristics. Hence various mating rituals and dominance contests amongst the males; hence elaborate male bird plumage, presumably a proxy, recognizable by a receptive female, as indicative of a primus inter pares. And yet it was probably regarded as curious in premodern societies that a female would be accorded any important choice, let alone that of selecting what she wanted in a partner. Although there has always been a cadre of women who have made their marks throughout recorded history, the examples are sadly limited –curtailed no doubt, because it was usually men writing about what they felt was important to document.

Fortunately, times are changing, as is the realization that each side of the gender divide is equipotent. Just how fluid the roles are is a constant source of wonder to me. Even in these days of Darwin, I am amazed at the still unsuspected porosity of the envelope. And while it no longer seems unusual or unlikely that an information-processing organism like, say, a bird might be able to select an appropriately endowed mate based on observable clues, it is still surprising –to me, at least- that selection duties might be conferred on a more microscopic scale: on an egg, for example.

I first encountered this idea in an article from Quanta Magazine: https://www.quantamagazine.org/choosy-eggs-may-pick-sperm-for-their-genes-defying-mendels-law-20171115/  I have to say it reminded me of Hamlet’s rejoinder to the sceptical Horatio on seeing Hamlet’s father’s ghost: ‘There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy.’

The competition in sexual selection was thought to be pre-copulatory –‘After mating, the female had made her choice, and the only competition was among the sperm swimming to the egg. This male-oriented view of female reproductive biology as largely acquiescent was pervasive, argued Emily Martin, an anthropologist at New York University, in a 1991 paper. “The egg is seen as large and passive. It does not move or journey but passively ‘is transported’…along the fallopian tube. In utter contrast, sperm are small, ‘streamlined’ and invariably active,” she wrote.

‘Beginning in the 1970s, however, the science began to undermine that stereotype. William Eberhard, now a behavioural ecologist at the Smithsonian Tropical Research Institute, documented all the ways that females can affect which males fertilize their eggs even after mating.’ For example, ‘Internal fertilizers have their own methods of what Eberhard dubbed “cryptic female choice.” Some female reproductive tracts are labyrinthine, complete with false starts and dead ends that can stymie all but the strongest sperm. Some females, including many species of reptiles, fish, birds and amphibians, that copulate with more than one male (which biologists estimate are a vast majority of species) can store sperm for months, even years, altering the storage environment to stack the odds to favor one male over another. Many female birds, including domestic chickens, can eject sperm after mating , which lets them bias fertilization in favor of the best male.’

The plot thickens. These strategies seem only to select whose sperm to allow access to the precious as-yet unfertilized eggs. But even sperm from the same individual can vary. So, are things just left to chance? Are we still talking Darwin here? And are the combination probabilities proposed by Mendel that depend on randomness still in the picture?

It would seem that the egg itself may have a say in which sperm it uses, and that unlike the voting system in many democracies, it may not be just the ‘first past the post’ -the marathon winner- who gets the prize.

The article presents several theories as to how the egg may be able to ‘choose’, but as yet there seems to be no clear indication as to whether it always happens, or whether it is just able to weed out some potentially damaging or clearly unsuitable ones by the signals they emit –or fail to emit… Sometimes, anyway. Mistakes clearly occur; abnormal genes do manage to slip through, leading to abnormal embryos –some of which are unable to develop enough to survive.

But that there may be yet another layer of protection built into the system –another unsuspected surveillance system- is what intrigues me. And that, once again, it seems to invest the power of a truly critical decision with the female is a cautionary tale for those who cling to the shredding coattails of androcentrism. It is simply another piece of evidence, if more were needed, that Life and all that it enables, is not a zero sum game. It is not a contest between genders, but a journey together. Still…

Let there be spaces in your togetherness.                                                                                      And let the winds of heaven dance between you.
Love one another, but make not a bond of love.
Let it rather be a moving sea between the shores of your souls.
Fill each other’s cup but drink not from one cup.
Give one another of your bread but eat not from the same loaf.
Sing and dance together and be joyous, but each one of you be
alone – even as the strings of a lute are alone though the quiver
with the same music.
Give your hearts, but not in each other’s keeping.
For only the hand of Life can contain your hearts.
And stand together yet not too near together:
For the pillars of the temple stand apart,
And the oak tree and the Cyprus grow not in each other’s shadows. –Kahlil Gibran –

I couldn’t resist.

 

 

 

 

 

Life’s Like That

Why is Life so hard to define? When I was in school, it was easy –as mentioned in a BBC article on the topic: http://www.bbc.com/earth/story/20170101-there-are-over-100-definitions-for-life-and-all-are-wrong -Life was MRS GREN (Metabolism, Reproduction, Sensitivity, Growth, Respiration, Excretion, and Nutrition). That’s all you needed for the exam –although I’m glad they never asked for an explanation of Sensitivity. But times change, and as do definitions, so by the time I was in university, I was confused. Every faculty had its own perspective –chemists defined in terms of chemicals, biologist preferred DNA, and physicists were partial to the dynamics of molecular properties that bypassed structural components in favour of information transfer.

Me? I wandered around a fair amount in my undergraduate years before I ended up in Medicine so, already rainbow-hued, I opted for a just-right-baby-bear definition -not too much of anything. By then, I understood that Life was an amalgam –but the product and not the recipe. The final taste, and not the way the ingredients are cooked. Telos, I suppose, rather than methodos– words sufficiently nebulous as to dissolve in most of the more erudite proposals. To me, Life is a story – scilicet, a spirit-  and one whose progress is tied to the outcome. We humans are requisite classifiers and groupers –itself a story- and we thereby miss the uniqueness of entity, the magic of identity; for us, something is either alive or not. Black or white. It’s an important distinction to be sure, but as I said, it misses the pungency of the flavour. The excitement of the effect. The Proustian Phenomenon of the madeleine biscuit soaked in tea… My route explains nothing, I’ll concede, and yet somehow, it’s what makes it Life, and not something else.

But I was always hopeless at philosophy, and despite my zeal for it, perhaps wisely accepted parental advice and wandered off into Medicine and eventually a career as an obstetrician/gynaecologist. I suspect they were concerned that otherwise I might end up living with them at home.

From time to time, however, I am still tempted to wax lyrical on Life with the occasional patient who seems to require some additional prodding with regard to their own. I can’t say I’ve achieved any truly publishable results, but the process is nonetheless enjoyable for me on those otherwise interminably complaint-ridden days that crop up from time to time.

It usually requires a stimulus –an opportunity when my input would not be construed as an imposition on their time with me.

Janet, for example. She was a forty-one year old woman who had pursued her own career as a lawyer at the apparent expense of a stable relationship. Intelligent, and attractive, she had finally ‘decided to accede to an intimacy request’ from an acquaintance –that’s how she put it- and when she had first made the appointment had wanted some advice as to how to avoid pregnancy. Her would-be partner was an older man who had not felt comfortable using condoms however. So he hadn’t. And she was. Not only that, but she was confused about it.

“Doctor, I’m almost forty-two years old, and despite the occasional ‘dalliance’ I’ve never been able to become pregnant…” She stared at me like I was somehow to blame for the vagaries and vicissitudes that had befallen her.

I could almost see the quote marks around her word ‘dalliance’. “You said ‘able to become pregnant’, Janet. Were you trying?”

She shook her head almost before my question reached her, but I could tell by her expression that she wasn’t sure. “Life is such a precious thing… I’d want to be sure about everything…”

“Like…?”

“Like whether I could care for it. Whether I would regret whatever decision I made about a pregnancy I hadn’t planned.” She didn’t even mention what effect the father might have on the process. “So…” she thought about it for a second. “…So I suppose I’m happy I didn’t have to make that decision before…”

“And now…?”

She shrugged and sent her eyes, like beggars, to ask my face for something –wisdom, maybe; suggestions, at least. “I mean, what are my chances, doctor?”

“Chances?”

“You know, that I won’t miscarry anyway. Remember, I’m forty-one now… And there’s also a risk of genetic malfeasance, isn’t there?”

Even though I have many lawyers as patients, I’d never heard the risks of pregnancy in an older mother put quite like that… I’m definitely in the pro-choice camp, as she well knew, so I realized she wouldn’t think I was trying to sway her ultimate decision no matter what I said. But still… “We can do the usual prenatal testing to identify any genetic problems beforehand, Janet. And yes, miscarriages are more common with pregnancies in older mothers…”

Her eyes grasped at the hems of mine like supplicants. “And if I were your daughter…?” I knew I had to be careful then -she was asking for an opinion, albeit framed as a personal one.

I sighed and sat back in my  chair. “A new life is a new story, Janet –a bit of yours, a bit of the father’s- but at this stage, most of it is still an idea somewhere. It doesn’t have to get written to qualify –we all have ideas inside when we stop and think about them. We write down some of them, I suppose but sometimes even then, we just can’t get the wording right. Or the idea, once on paper, doesn’t seem what we thought. Remember, a story is no less a story for not being completed, and no less a creation for not being read… But sometimes, you just have to take the chance that you’re on to something.”

Her eyes flew away and settled on her lap for a moment. “You’d make a great lawyer, doctor,” she said, with a mischievous smile, her eyes back on mine once more. “Obfuscation is something they just can’t teach…”

I’m not sure she followed my argument so I risked a little smile. “Isn’t it what you do when there really is no case to be made beyond a reasonable doubt?”

She rolled her eyes and chuckled. “I don’t take cases like that anymore.”

I suspected she hadn’t this time, either.

 

 

 

As I Age

As I age, it becomes increasingly clear to me that Life is far more complicated than I could ever have suspected. It is like a stew where I keep finding new ingredients –some to my liking, and some… Well, let’s just characterize them as unexpected -mysterious strangers that surface from time to time, wreak havoc, then disappear again like shadows on a moonless night.

Social movements are often like that –or, rather, social solutions. Society changes over time and it has been the fashion of late, to see this as an evolutionary adaptation to underlying conditions –the slow but steady metamorphosis of caterpillar into butterfly. And yet, sometimes the change is more abrupt -a mutation- and we are forced to deal with the consequences. When things around us change, we attempt to keep up –or at least, like the Red Queen in Carroll’s Through the Looking-Glass, find ourselves running faster and faster to stay in the same place.

And one manifestation of this is the need to preserve a thin weft of values as a template during the inchoate and often thread-bare interregnum. I’m thinking, of course, about the age-old philosophical conundrum of whether we should tolerate the intolerant –and if so, then how? And at what price the compromise? One example from many: the need to establish special female-only transportation in the city of Zhengzhou in eastern China to help women feel safe from sexual harassment. To guard them. http://www.bbc.com/news/blogs-news-from-elsewhere-36169029  Of course, the problem is by no means unique to China -other countries have discovered the same need and arrived at similar solutions.

But it seems to me that the issue is far more complex than these solutions might suggest. This gender issue, in some ways is not dissimilar to the racial problems that surfaced so violently in the last century in America. To think that having different buses for people of colour would salve the problem was proven to be naïve, and in itself discriminatory.

It comes down to the difference between toleration and acceptance: putting up with something that might not actually be approved of –enduring it: ‘toleration is directed by an agent toward something perceived as negative. It would be odd to say, for example, that someone has a high tolerance for pleasure’; versus  Acceptance: acknowledging and welcoming something as itself; permission versus approval. A power struggle either deferred, or shared.

To equivocate for a moment, should we tolerate mere tolerance, or accept it…? As an interim solution, of course. In other words, is it better to have the segregated buses for women, say, than groping and intimidation on more inclusive public transit? To say that there should not be sexual harassment is all well and good, but it ignores the present reality –there is, and to ignore it would therefore be akin to tolerating it. So are we  trapped in a never-ending game of chase-your-tail, forever condemned to wander the Mobius strip looking for an exit?

Perhaps it might be helpful to distinguish the component parts of the issue (I have adapted some principles from the peer-reviewed Internet Encyclopedia of Philosophy: http://www.iep.utm.edu/tolerati/#SH4a).  It seems to me that there is a difference between the more superficial and emotional response to whatever is being tolerated (Let’s call this the Reactive Stage) –the need to separate the aggrieved from the aggressor, for example- and the Rational Stage: the more dispassionate and reasoned analysis of the problem –if indeed such an analysis is feasible, or could even be rationally justified. In other words, on what grounds does the prejudice in question continue to exist? Is it remediable, or inevitable? Should we be forced to retreat behind our own societal boundaries and accept the relativistic excuses proffered that we simply can’t superimpose our own values on those who are not like us? That we, in fact, do not understand –nor likely ever will, since we are other?

Or, closer to home, can we ever hope to change attitudes such as disrespect and insensitivity to aspects of personal autonomy that have been entrenched –and indeed accepted- for countless unquestioning generations -that, until recently, were not even considered problems requiring solutions?

Well, societies do alter as time and members change; I’m not sure we could characterize the alterations as necessarily evolutionary, or teleologically driven, but certainly the initial reactive and then the more rational stages can often be discerned. The societal attitudes towards Gay rights, for example, have undergone major shifts within the past few years –even the initial toleration, which was rare in past decades, is now remodelling itself as acceptance.

So what -if anything- has Age taught me? What has the passage of years and the successive unfolding of events disclosed? Well, it has become clear that in the long run, our enemies become our friends; that we seek and find compromises satisfactory to each –bargains that in due course cease to be seen as concessions by either party, but rather as amicable balance; that Force only suppresses while it is being applied; and that discussion is inevitable and infinitely preferable to confrontation. We may not be able to evince our much-touted rationality in all things, but we are all eventually susceptible –amenable even- to accommodation.

Omnia vincit amor, I suppose.