Tag Archives: bacteria

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To hold, as it were, a mirror up to Nature

Who am I? No, really -where do I stop and something else begins? That’s not really as silly a question as it may first appear. Consider, for example, my need to remember something -an address, say. One method is to internalize it -encode it somehow in my brain, I suppose- but another, no less effective, is to write it down. So, if I choose the latter, is my pen (or keyboard, for that matter) now in some sense a functional part of me? Is it an extension of my brain? The result is the same: the address is available whenever I need it.

Ever since my university days, when I discovered the writings of the philosopher Alan Watts, I have been intrigued by his view of boundaries, and whether to consider them as things designed to separate, or to join. Skin, was one example that I remember he discussed -does it define my limits, and enclose the me inside, or is it actually my link with the outside world? I hadn’t really thought much about it until then, but in the intervening years it has remained an idea that continues to fascinate me.

Clearly Watts was not alone in his interest about what constitutes an individual, nor in his speculations about the meaning of whatever identities individuals think they possess by virtue of their boundaries. There was an insightful article in Aeon by Derek Skillings, a biologist and philosopher of science at the University of Pennsylvania entitled ‘Life is not easily bounded’: https://aeon.co/essays/what-constitutes-an-individual-organism-in-biology

‘Most of the time the living world appears to us as manageable chunks,’ he writes, ‘We know if we have one dog or two.’ Why then, is ‘the meaning of individuality … one of the oldest and most vexing problems in biology? …  Different accounts of individuality pick out different boundaries, like an overlapping Venn diagram drawn on top of a network of biotic interactions. This isn’t because of uncertainty or a lack of information; rather, the living world just exists in such a way that we need more than one account of individuality to understand it.’ But really, ‘the problem of individuality is (ironically enough) actually composed of two problems: identity and individuation. The problem of identity asks: ‘What does it mean for a thing to remain the same thing if it changes over time?’ The problem of individuation asks: ‘How do we tell things apart?’ Identity is fundamentally about the nature of sameness and continuity; individuation is about differences and breaks.’ So, ‘To pick something out in the world you need to know both what makes it one thing, and also what makes it different than other things – identity and individuation, sameness and difference.’

What about a forest -surely it is a crowd of individual trees?  Well, one way of differentiating amongst individuals is to think about growth -a tree that is growing (in other words, continuing as more of the same)- and contrasting it with producing something new: as in reproduction. And yet even here, there is a difficulty. It’s difficult to determine the individual identities of any trees that also grew from the original roots -for example from a ‘nurse’ tree lying on the ground with shoots and saplings sprouting from it.’

But it’s not only plants that confuse the issue. If reproduction -i.e. producing something new– counts as a different entity, then what about entities like bacteria? ‘These organisms tend to reproduce [albeit] by asexual division, dividing in half to produce two clones… and, failing mutation and sub-population differentiation, an entire population of bacteria would be considered a single individual.’ -whatever ‘individual’ might therefore mean.

And what about us, then? Surely we have boundaries, surely we are individuals created as unique entities by means of sexual reproduction. Surely we have identities. And yet, what of those other entities we carry with us through our lives -entities that not only act as symbiotes, but are also integrated so thoroughly into our metabolism that they contribute to such intimate functions as our immune systems, our weight and health, and even function as precursors for our neurotransmitters and hence our moods? I refer, of course, to the micro-organisms inhabiting our bowels -our microbiome. Clearly ‘other’ and yet essential to the functioning person I regard as ‘me’.

And yet, our gut bacteria are mostly acquired from the environment -including the bacteria colonizing our mother’s vagina and probably her breast milk- and so are not evolutionarily prescribed, nor thereby hereditarily transmitted. So, am I merely a we –picking up friends along the way? Well, consider mitochondria -the powerhouse of our cells. They were once free-living bacteria that adapted so well inside our cells that they, too, are integral to cell functioning but have lost the ability to survive separately; they are transmitted from generation to generation. So they are me, right…?

Again I have to ask just who is me? Or is the question essentially meaningless put like that? Given that I am a multitude, and more like a city than a single house, shouldn’t the question be who are we? The fact that all of us, at least in Western cultures, consider ourselves to be distinct entities -separate individuals with unique identities- makes me wonder, about our evolutionary history.

Was there a time when we didn’t make the distinctions we do nowadays? A time when we thought of ourselves more as members of a group than as individuals? When, perhaps sensing that we were constantly interacting with things outside and inside us, the boundaries were less important? Is that how animals would say they see the world if they were able to tell us?

Does our very ability to communicate with each other with more sophistication, create the critical difference? Is that what created hubris? In Greek tragedy, remember, hubris -excess pride and self-confidence- led inexorably to Nemesis, retributive justice. Were poets in that faraway time, trying to tell people something they had forgotten? Is that what this is all about?

I wonder if Shakespeare, as about so many things, was also aware of our ignorance: ‘pride hath no other glass to show itself but pride, for supple knees feed arrogance and are the proud man’s fees.’

Plus ça change, eh?

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Zealandia?

Sometimes things are not as they seem and we see, as the biblical Paul wrote, ‘through a glass darkly’. Sometimes there is more than meets the eye; it is what makes the world so interesting. Maybe it’s why we wrap gifts –or give them, for that matter. They are such stuff as dreams are made on…

I have always loved New Zealand; to me, it is a gift, and so is what I’ve recently learned about its origins. To think that Aotearoa –the land of the long white cloud- is more than the ribbon I can see today, more than the Maori seafarers could see even a thousand years ago when they first arrived, is astonishing, and not a little intriguing. An article in the Guardian (https://www.theguardian.com/world/2017/feb/17/zealandia-pieces-finally-falling-together-for-long-overlooked-continent?CMP=Share_iOSApp_Other) reports on a paper published in GSA Today -the journal of the Geological Society of America: ‘Zealandia covers nearly 5m square km, of which 94% is under water, and encompasses not only New Zealand but also New Caledonia, Norfolk Island, the Lord Howe Island group and Elizabeth and Middleton reefs. The area, about the same size as the Indian subcontinent, is believed to have broken away from Gondwana – the immense landmass that once encompassed Australia – and sank between 60m and 85m years ago.’

Of course, even with satellite-derived bathymetric data, it’s hard to appreciate. And the skeptics, largely silent in their apathy, still sit in the shadows wondering what difference knowing  this  makes. After all, it’s almost all underwater, some of it way underwater –one edge of it ‘can be placed where the oceanic abyssal plains meet the base of the continental slope, at water depths between 2500 and 4000 m below sea level.’ http://www.geosociety.org/gsatoday/archive/27/3/article/GSATG321A.1.htm Would we be any the worse, the unimpressed might argue, if this remained undetected? Would the ignorance handicap us in some way? Any way…?

In the conclusion to the paper, the authors assert that: ‘As well as being the seventh largest geological continent Zealandia is the youngest, thinnest, and most submerged. The scientific value of classifying Zealandia as a continent is much more than just an extra name on a list. That a continent can be so submerged yet unfragmented makes it a useful and thought-provoking geodynamic end member in exploring the cohesion and breakup of continental crust.’ But it seems to me that questioning the value of this discovery misses the point entirely. Misses, perhaps, the point of gifts and the wrapping in which they are concealed.

Although I am now retired, I am reminded of something that happened late in my career as a gynaecologist and which continues to intrigue me. It makes me wonder just how many other assumptions limit our vision…

Sometimes in medicine, we feel the need to step back from the fray, to attempt an objectivity denied to those whom we treat. It allows us, we explain, to adopt another, more reasoned perspective -one which is unadulterated by their pain and emotion. ‘A thought which, quarter’d, hath but one part wisdom’ as Hamlet said.

And yet, looking out from the forest of my age, I realize that sometimes people don’t want to be treated as patients, but as people. Fellow travelers. What they want is a knowledgeable friend, not a textbook to which they can turn. One has to learn to gauge the needs…

Jean was not a new patient, but her visits were erratic and unpredictable. Sometimes it was for a pap smear, but more frequently it was for what she would only characterize as an ‘infection’ –“The usual one,” she would inevitably add with an embarrassed laugh. But neither I, nor any of the other doctors she had seen were ever able to find the infection, so it had become a sort of standing challenge as to who would find it first.

Jean was a very fit woman then in her early fifties, who taught both English and drama at a nearby high school. Meticulous about her appearance, I would see her in the waiting room sitting bolt upright, shoulders back, head perched on her shoulders like it was suspended on fine wires to keep it from despoiling the immaculately dressed body below. Her hair was brown and short with each strand assigned an immoveable location lest it be chastened with the brush she kept on her lap in a little purse.

That day, however, I noticed she had added another weapon to the arsenal on her lap –a little pump action plastic bottle, the content of which she would surreptitiously spray on her hands from time to time, followed by a vigorous rubbing as if she had just applied some soothing lotion.

She smiled when she saw me and extended a just-sprayed hand in greeting. “I think I’ve solved my problem, doctor,” she said as soon as we were settled in my office. “I just wanted you to check and see if there was any difference –you know, down…” She blushed before she could finish her sentence. She immediately produced the little bottle and sprayed her hands again. “No infection,” she added, regaining her composure after the little entr’acte.

“And the little bottle?” I had to ask.

“Sanitizer,” she answered proudly. “It’s antibacterial,” she added, and dived into the purse to read the label to me. “It contains triclosan… For some reason it’s really  hard to get nowadays.” Her face suggested that puzzled her. “I mean it kills bacteria doesn’t it? And they’re the troublemakers…”

I suppressed a sigh and sat back in my chair. “It also encourages bacterial resistance, Jean. And it doesn’t seem to be any more effective at cleaning than good old soap and water.”

She blinked, but whether in surprise, or disbelief I couldn’t tell. “But…” She gathered her thoughts before continuing. “We pick up bacteria from our environment and dirty hands are how we transmit a lot of diseases. We have to keep them clean… Bacteria” –she said it as if the word itself were dirty- “Bacteria are everywhere.” She pointed to an alcohol-based hand sanitizer I kept on my desk. “And I see you don’t take any chances either. ”She relaxed in her chair as if she’d proved her point.

I allowed myself the sigh I had avoided earlier. “An interesting dichotomy, isn’t it?” She raised an eyebrow. “That we live in a world jam-packed with so many bacteria that they are virtually ubiquitous…” I continued, “…and yet so few cause us trouble.”

“But…” She leaned forward on her seat.

“But we seem to want to malign them all; we act as if they were all our enemies. And yet, our own microbiome –the bacteria living in our intestines- are absolutely essential for our health in ways we are just discovering. And apparently the number of bacteria normally living in and on a healthy human body outnumber our own cells by ten to one.” I stopped and smiled at her incredulous expression. “We –our cells- are only the tip of the iceberg.”

I suppose I thought I’d just be reminding her of something she already knew, but her eyes were saucers. “Zealandia,” she said after a moment’s reflection.

“Pardon me?” I’d never heard the word, and wondered whether she was referring to the title of some obscure novel she was teaching at school.

“Zealandia,” she repeated as if she were surprised I didn’t recognize the term. “You know, doctor, the continental landmass of which New Zealand is a part? It’s 95% underwater so you can’t see it and therefore don’t appreciate it’s importance. We usually only judge what we can see, don’t we…?” she added with a wink and a big winning smile.

We all have our blind spots.

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Probiosis

Bacteria, by and large, have received a bum rap (pardon the pun). Ever since they were discovered, there was a sense they were up to no good. Why were they always hanging around sick people, it was asked? And why did foul smelling things –the miasma (you gotta love these words)- always have bacteria skulking about in the background? There must have been some reason why -since the beginning of time, we have instinctively avoided rotting meat or putrescent items… Could it be the bacteria?

Of course, this eventually caused people –okay, Scientists– to wonder why our intestines are full of these malevolent creatures –and therefore why we weren’t all dead, or at least always ill on their account. The further paradox was when it became murkily clear that if this same intestinal effluvium were mixed with drinking water, we would be –very ill, that is.

So, how can you have your cake and eat it, too? Could it be that there was some sort of balance of good guys and bad guys in our guts that kind of neutralized each other in there? And maybe the balance wasn’t the same in the water near the sewage pipe?

And for that matter, because there were so many of them inside us, maybe it was for a reason? Even thinking like that seemed anathema to doctors –and companies- who had made their fortunes out of fighting them. And then, slowly, as the moon slipped quietly behind some clouds on the horizon, came the dawn. The paradigm shifted and it became acceptable to speculate that at least some bacteria might be on our side in Tennyson’s ‘Nature, red in tooth and claw’. Helpful bacteria living in secret bowel-caves, like traitors imbedded behind the enemy lines, were diligently hunted. And myriad uses were ascribed to their families. I even wrote about this a couple of years ago:

https://musingsonwomenshealth.wordpress.com/2014/05/15/the-human-microbiome/

So it was only a matter of time until those who had hitherto persecuted all microbes, were persuaded to alliances -marriages of mutual convenience. Helpers of helpers were proffered: probiotics.

Probiotic –even the word has come to inspire hope. And its etymology: pro –on behalf of- and bios –life, nails it, don’t you think? I’ve touched on the subject before in my essays, as well:

https://musingsonwomenshealth.wordpress.com/2015/09/27/miasmatics/

But I’m not trying to reinvent the wheel here, nor seduce you into re-reading my old essays. I am, however, still interested in the subject and was therefore somewhat disappointed in an article in the BBC News that seemed, at first, to denigrate the concept of probiosis: https://www.theguardian.com/science/2016/may/10/probiotic-goods-a-waste-of-money-for-healthy-adults-research-suggests There is a link in the article to the original meta-analysis paper in Genome Medicine.

I suppose it captured my attention the way any attack on my Confirmation Bias might: once I have been converted to a point of view, I take umbrage at any attempts to desecrate it… No, actually, that’s not true –I pay attention to the detail of the contention and see whether it could be refuted -what Carl Popper believed must be an essential component of all good Science.

This paper –a review of seven randomized, controlled trials (admittedly small numbers in each) of probiotics in healthy adults- concluded that there was ‘a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults’. Fair enough, but contrary to the headline that might have attracted people to the article (Probiotic Goods a ‘waste of money’ for healthy adults, research suggests), buried near the end of the piece is the admission that ‘the real impact of the probiotics may have been masked by small sample sizes and the use of different strains of bacteria and variations in participants’ diets, among other factors’.

And the author of the Danish study, Oluf Pedersen, admitted: ‘“To explore the potential of probiotics to contribute to disease prevention in healthy people there is a major need for much larger, carefully designed and carefully conducted clinical trials.

“These should include ideal composition and dosage of known and newly developed probiotics combined with specified dietary advice, optimal trial duration and relevant monitoring of host health status.”’

So I think the final word on probiotics is still to come. It would make sense that one might not notice much of a change in fecal microbiota composition in those who are healthy and presumably already in possession of what Goldilocks described as ‘Just right baby bear’ stuff. But whether it could be further improved is the point at issue. There seems to be some evidence that it can be improved in those who need improvement –but at this stage, even that claim is contentious.

But it’s early yet, and as Robert Frost observed when he stopped by woods on a snowy evening: The woods are lovely, dark and deep, But I have promises to keep, And miles to go before I sleep… And so do we.

 

 

 

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The Colour of my Baby

What a great idea: a bandage that tells you when what it is hiding, is itself hiding something –an infection.  http://www.bbc.com/news/health-34808273

I suppose it was an idea looking for a platform. When bacteria are growing, they often invent ways to keep doing just that. Sometimes they overwhelm by sheer numbers to defeat the body’s defences, at other times it’s toxins that break down tissues and help them invade. The body, for it’s part, has its own bag of tricks. In the end, infections are often simply a kind of parry and thrust contest –a fencing match, if you will.

Most bodies are not unduly challenged by wounds, however –keep them clean and cover them with some sort of dressing, and they heal. Antibiotics are seldom required. The problem, of course, is that sometimes the foes are not evenly matched. People on immune suppressants (transplant patients), or those with already compromised immune systems –whether from disease or immaturity (babies, for example)- may not be able to mount a suitable response to bacteria in a wound and are at risk of severe infections. These are the ones in whom a timely and appropriate antibiotic would be prudent.

Sometimes, though, antibiotics are used like soap: if it looks dirty, or if it might turn out to be dirty, why not use an antibiotic? Just in case. Well, the simple answer is that the body is usually pretty good at dealing with bacteria. After all, we are all exposed to bacteria from day zero. It starts with the journey down the obviously non-sterile birth canal, and progresses to crawling along things, tasting things… none of which could be said to be free of bacteria of some sort or other. Bacteria are what we do, where we live… Bacteria live in our mouths, in our bowels, on our skin. There are more bacteria in our intestines than cells in our bodies; we simply cannot get rid of them all.

Nor should we. I’ve written before about the benefit of these usually commensal creatures and the benefits they provide both for continuing health and development: https://musingsonwomenshealth.wordpress.com/2014/05/15/the-human-microbiome/

But let’s not be naïve about bacteria –they don’t give a fig about us -they are amoral. A bacterium prefers to live with others –family. They grow and prosper with no regard for boundaries or house rules. Without suitable checks and balances they would take over. Like pouring water in a cup -too much and it merely overflows the constraints and moves on. That’s an infection. That’s when the body may need some help.

The trick is obviously intervening when it is necessary, but monitoring when it is not. Why? Well, treating every wound, say, with an antibiotic might get rid of the truly sensitive bacteria, but leave behind those that don’t respond quite as easily or quickly. The result of the treatment may therefore be to select for those bacteria that don’t mind the antibiotic –the resistant organisms. That’s how it happens.

So in those people who may not be able to deal with bacteria efficiently, it would be helpful to know when –or if– to intervene. That’s where the bandage that changes colour when bacteria in wounds begin to proliferate and infect would be helpful. There are other ways, of course: the old Latin aphorism I was taught in medical school, for example: Tumor, Dolor, Rubor, Calor – Swelling, Pain, Redness (inflammation), Warmth (infection). But sometimes it’s nice to have another tool in the kit that may detect a problem earlier -before these signs are present. Or, in the case of a body incapable of even producing the signs- when an infection would be catastrophic.

Clearly a lot of work needs to be done to detect the mischief of different types of bacteria –they don’t all produce toxins, and even if they did, there would likely be differences in their structures that would have to be accounted for in the detection mechanism. But this may be the bandage of the future –a Facebook band aid that is constantly posting. Almost like refrigerators that tell you what you need, or coffee pots that turn on when they hear the toilet flush in the morning. A brave new world.

It is ‘a hit’, as Osric, a courtier, says of Hamlet’s thrust as he is dueling with Laertes, ‘a very palpable hit.’ Let us hope so.

 

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The Human Microbiome

 

 

I have always been excited by a new paradigm. Captivated by its novelty. Intrigued by the realization that what we had previously considered to be self evident and true was not sacrosanct. Immutable. Of course I have to confess that it is often the perspective that interests me: that it sometimes okay to question the consensual adherence to a theory -to question what we have all come to believe is correct. To re-interpret the data.  Consensus establishes nothing; it only demonstrates that that we have been swayed by it. It merely lionizes a viewpoint; it does not validate it. And yet that’s Science: always open to refutation, reassessment. Change. According to Karl Popper -the great philosopher of science- a theory should only be considered scientific if it allows the possibility of being proven false.

I’ve just read a fascinating new book on the microbiome (microbiological contents) of the gut and its influence on our health (Missing Microbes, by Dr. Martin Blaser). Admittedly it’s a topic that is all the rage nowadays, but its previous neglect seems, in retrospect, to defy belief. Of course, since the Germ Theory was proposed in the mid sixteenth century, and since microbes were first observed by Anton Van Leeuwenhoek through his primitive microscope the following century, we have been at odds with them, to say the least. They seemed to be hostile to us. Alien. Their presence caused diseases, suffering, and death. We called them germs. That they could be other than enemies was inconceivable. The only good germ was a dead germ; it was obviously in our best interest to eliminate them. All of them…

And yet if they are so menacing, so evil,  why do our bodies tolerate such a large number of them? Seventy to ninety percent of all the cells in our bodies are not ours -an estimated 100 trillion enemy soldiers hidden in a Trojan horse. And inside our gates… If microbes are bad, why is our large bowel packed with them? Why would we carry around our own sources of disease? How could evolution be so stupid?

It seems blindingly obvious, in retrospect, that they must help us in some fashion. And indeed, the bowel micro-organisms are now being increasingly recognized as extremely useful; so useful in fact that one might be well advised to consider them to be another organ –as important for our health as the liver or the kidneys. It’s becoming clear that they seem to serve as co-directors of many bodily processes – immune functions most importantly perhaps, but also for digestion and production of important nutrients, suppressors of other less-friendly bacterial and viral invaders, and even regulators of energy resources -changes in gut flora may be important in obesity and diabetes, for example. We’re only beginning to understand what role they play in our health, and how altering them can alter us.

But I’m an obstetrician, un accoucheur; I deliver babies; I take care of moms and their foetuses through their pregnancies. I lay no claim to much bacteriological expertise, let alone a privileged view of its cutting edges. But as I mentioned, I was absolutely fascinated by Dr. Blaser’s book -especially the chapters about how we get the first dose of bacteria in our bowels, and how the method of delivery might alter that for good or ill. Obviously at this stage, much of this is speculation -interesting, but as yet largely unproven. But think about it: foetuses in the womb are pretty well bacteria free before they are born. They acquire bacteria only after (or during) birth. On their way down their mother’s vagina they acquire their first micro-organisms: they swallow the lactobacilli which dominate the vaginal bacteria. This helps the baby to break down lactose -the major sugar in its mother’s milk. And given the proximity of the vagina to the anus, the baby also gets its first dose of bowel bacteria -the area is not clean no matter how hard we pretend.

So what happens to the baby’s bowel flora if it never passes through the vagina and is delivered instead by Caesarian Section? Is it different? Is it deficient? And if so, does this have any long lasting effects -either good or bad? I mean, the babies seem to turn out okay…

And what about the customary prophylactic dose of antibiotics that are given preoperatively to prevent maternal infection, or the penicillin (or other antibiotic substitute) that is given to mothers who are intending to have a normal vaginal birth but are positive for Group B Streptococcus (GBS) and in labour? Some of this enters the baby, too; does it alter their bowel bacteria? Is this bad, or do the bacteria recover eventually? Does the interim bacterial alteration, come at a crucial time in the immature but rapidly developing immune system just as the baby is learning to adapt to life and its challenges outside the womb?

The difference is obviously an area that needs more study, but some of the early data are truly intriguing. Researchers have even wondered whether the mode of delivery may alter conditions in the growing child -but later (and so less easily attributable to method of delivery). Things such as asthma, or allergies are exaggerated immune responses -maybe ones not dampened by early modulation by the microbiome. And inflammatory bowel disease, autoimmune dysfunction, and even diabetes may be types of genetic epiphenomena -existing genes turned on or off, dimmed or augmented- altered from an early age and possibly -maybe probably- influenced by the bacteria in the gut …

So, am I recommending we stop doing Caesarian Sections? Stop giving antibiotics? Stop wiping off babies to dry them and help their thermoregulation but also -almost a bonus- to clean them after delivery? Should we abandon all that we’ve accomplished, all that we’ve learned in the last 50 years? No, of course not. But sometimes there are options. Choices. If nothing else, it behooves us to discuss these issues with our patients  -early in their pregnancies, preferably, so that rational conversations, untainted by fear and stress, can provoke dialogue and exploration. There are consequences to every decision. So if an elective Caesarian section is chosen for reasons other than absolute necessity we -patient and doctor- must be apprised of the risks -even the potential, unproven risks of suboptimal microbiomal acquisition…

We are naturally engrossed in the prevailing paradigms -they have served us well and reduced mortality rates; we no longer fear death each time we fall ill. But we have entered an age when an increasing cohort of bacteria are becoming resistant to even the most powerful antibiotics. We need a different appreciation of micro-organisms -a paradigm shift- one that acknowledges that not all of them are malevolent; one that appreciates that they probably do more for us than they do to us. An approach that acknowledges there are far more of them than us and so we should try to use their strength to our advantage. It seems to me that, as members of the current paradigm flock, we’ve almost exhausted the meadow where we’ve successfully grazed for such a long time; we have been so happy with the pasture, so complacently wandering with the herd that we didn’t even notice a gate in the fence to an area where the grass is truly greener and more abundant.

We progress incrementally, but only when our minds are open to new ideas. New perspectives. Truth, it seems, is ever changing, and not always what we want it to be. It can be messy and unbelievable at first -uncomfortable even. But as Einstein once remarked: If you are out to describe the truth, leave elegance to the tailor.