Tag Archives: unintended consequences

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Scrambled Eggs

Great! Test tube mothers now, is it? Not enough to eliminate the Fallopian tube, or the on-egg dating site where potential sperm candidates meet, are scrutinized, profiles scanned and competition held for first across the zona (pellucida, that is) … Oh no, now we have to eliminate the entire coffee shop. What is happening out there… or do I mean in there? It’s so confusing.

There was a time when it was simple. Well, maybe it wasn’t, but at least we were used to it. You met somebody and expectations and hormones took over. No need to put in a special request for stem cells, or people in white lab coats and masks. No need to take out a loan –although flowers and dinners aren’t that cheap anymore, either. But it was the excitement of the chase, the hunt –searching for clues about the other person that weren’t all tied to their DNA; picking them because they were funny and considerate, cute and snuggly. They had histories. Stories. Isn’t that why we get together? Wasn’t it? http://www.bbc.com/news/health-37337215

Okay, I’m leap-frogging here. We’re not there yet –I mean they are not there yet; I suspect that, despite the occasional slip-up, most of us are still going to prefer to stick to the traditional court-and-impregnate model that has served us so far. I mean, fun is fun, eh? And to be fair, there’s a lot to deal with if you want to bypass natural stuff -ingredients, for example. Right now, you need a minimum of two things to make babies: a sperm and a receptive egg (sperm always seem to be in the mood…). Yes, and you need a place for them to meet and grow together, but there are any number of uteri out of work at any given time, so, with the rise of things like Airbnb, I suspect they won’t be a problem.

And everything that is alive has DNA and its instruction manuals closeted away somewhere… Do you see the opportunities I’m suggesting? Trick some skin cell, or whatever, into thinking it’s a sperm or an egg, and poof –reproduction-lite. Better still, why not hoodwink that ordinary cell into thinking it’s pregnant? I mean, it’s got all the necessary assembly instructions squirrelled away, hasn’t it? Your argument just has to be convincing. Persuasive. It doesn’t necessarily need to be, well, necessary. You could just be doing it for fun. A prank. Or to prove that you can, I guess. Isn’t that why a lot of stuff gets done? When you tire of trying to justify something that would fly in the face of current needs and desires, you simply create a niche product. Create a want. Wants usually evolve into needs –mutate into needs, at any rate. Look at Selfies and their requirement for sticks. Or bell-bottomed trousers –no, wait, that was a while ago…

My point, I think, is that gender may be rendered redundant not by increasing social awareness of its variations, but rather because of its dispensability. Why keep something you don’t really need? History will decide, of course, but hindsight tends to come down hard on things that outlive their time. Consider phlogiston. It was the postulated fire element that was contained by combustible things and was released when they caught fire. Of course! But who, apart from old people, have even heard of it? Or want to?

And then, in keeping with the air theme, there is the Miasma Theory which just assumed that disease was caused by ‘bad air’. Simple. Elegant. No need to bring in a lot of accessory stuff like animalcules and other things you couldn’t see anyway. Germs, let alone viruses prions and the like, were simply unnecessary and unduly complicated. Why dump many unknowns into an equation that could be solved by one charming known? Why mess with E = mc 2 when it isn’t a theory of everything, especially if it needs Quantum? Explanation isn’t everything, either…

Okay, so I’ve non sequitured again, but hopefully you see my concern. Obsolescence is one thing –we often persist past our best-before dates- but unplanned obsolescence is another creature entirely. It smacks of blundering about in dark corners hoping there are no unpleasant surprises -nothing that will sting in retrospect.

I am as excited as the next person about the prospects for the future, but experience teaches caution. The principle of unintended consequences is a favourite historical topic –almost as seductive as the ‘what if’s’ so popularized in historical fiction nowadays. Maybe there is nothing enchanted about that first introduction between egg and sperm. Nothing magical. Nothing necessary. Maybe life will carry on much as before and procreation will still scratch out a living between the sheets. And maybe it’s always good to have options -choices freely made and understood. Even needed, occasionally. We have always been condemned to live in interesting times –the Past was never an Eden.

And yet…

 

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Biding the Pelting of this Pitiless Storm

Hubris –the extreme arrogance that was so offensive to the old Greek gods that they reacted with punishment and an exile from grace- is that what this is? I’m not sure anymore… It’s not, perhaps, so obvious as the vaulting ambitions of a Macbeth or the arrogance of a Caesar, nor even the overweening pride of an Oedipus in the Sophoclean plays, and yet… And yet, viewed from a distance, it’s hard not to notice the similarities that inhere in the attitude that End justifies Means, that intentions trump consequences, that methodology is the servant of results –however narrowly beneficent we define them. And it’s important that we not be so blinded by those touted benefits that we ignore other, perhaps less harmful routes, to achieve them.

And what, you may reasonably ask, prompted this jeremiad? It was a study reported in the New England Journal of Medicine (NEJM) on the addition of a second and possibly more powerful prophylactic antibiotic during non-elective Caesarian Sections to reduce post-operative infection rates: http://www.nejm.org/doi/full/10.1056/NEJMe1610010?query=gynecology-obstetrics -certainly a worthy aim, to be sure. Who could possibly take issue with that? Well, in this era of increasing antibiotic resistance, and the unfortunate dearth of replacement antibiotics in the wings, I think not only the study, but also the idea demands more than a cursory analysis. This is not to criticize the intent, so much as to explore alternative roads to the same destination.

Few would argue that antibiotics, when they are deemed necessary, should be used according to the infecting bacterial sensitivities if they are available –or considered expectations as to sensitivities if they are not. It’s why we can no longer use penicillin for everything –not all infections would respond. Surgical prophylaxis (where there is not yet an infection) is one of the few exceptions, and even there, the antibiotics are chosen in anticipation of the type of bacteria that might reasonably be expected in the surgical field (although there are some who believe that their effect is merely that of decreasing the total bacterial load in the area whether or not the expected ones have been targeted). But, nevertheless, we toy with resistance at our peril.

I’ve chosen to link the editorial rather than the study itself because of the insights it offers. The full-length study to which it refers can be accessed via a link in that editorial, however.

As I mentioned, the study by Tita and colleagues, in a randomized trial, attempted to reduce post-operative infections by adding another broad-spectrum antibiotic (Azithromycin) to the usual antibiotic (cefazolin) in non-elective Caesarian sections (i.e. there was some condition in mother or baby that required urgent delivery) where the current infection rate was 12% -and it worked! Compared to the usual group that just received the cefazolin alone, they dropped the infection rate to 6.1% -not zero, but at least an improvement. And, ‘Neonatal outcomes, which were tracked up to 3 months, were similar in the two trial groups.’

But on closer analysis, 73% of the population in the study was obese -and that, plus the fact that the Caesarians were unplanned, certainly added to their risk of infections. So far, so good.

But, as the editorialist wonders, could the fact that these women were obese have meant that the usual dose of cefazolin was inadequate: ‘[…] should the potential pharmacologic benefit of higher doses of cefazolin alone be evaluated further before the addition of a second agent?’

Another consideration leading to the study of adding azithromycin to the regimen, was that it may be useful for eliminating a potentially  infective organism in the vagina –ureaplasma– that cefazolin doesn’t touch. Unfortunately, there are no prospectively adequate data for the contention that the organism was even present in the studied women.

And finally, the azithromycin was more beneficial in those women whose incisions were closed with staples, and there seems to be evidence that staples, themselves, may increase the post-operative infection rate.

So why, you may ask, have I chosen to comment on this rather obscure study –especially since it seems to have demonstrated the benefits it expected? First of all, I think we have to be careful that we don’t lose sight of the forest as we wend our way through the undergrowth. There do seem to be other options that could be explored before the addition of yet another antibiotic –and indeed should be anyway, given the non-zero infection rate even with the addition of azithromycin. Such things as more ‘stringent adherence to infection-control protocols’, avoiding the use of staples in this high-risk population, or even re-calculating the dose of the standard prophylaxis (cefazolin) to account for differing patient weights before deciding to add the new antibiotic.

I don’t mean to be the new Cassandra, issuing thundering prophesies of doom that will not be heeded anyway, or aspersing well-intentioned attempts to improve our lot… And yet we must not forget that consequences follow actions, not precede them. To be fair, we do try our best to anticipate and thereby avoid, or at least minimize them, but history is riddled with examples of unintended outcomes. The road to disaster is paved with should’ves –only seen with clarity, after arrival.

It seems to me that, wherever possible, we should be exploring options that reduce the likelihood of incurring bacterial resistance. And the answer may not lie in the reliance on new antibiotics -new guns for our on-going war with the microscopic world. It’s a battle in which we cannot hope for more than a temporary truce while we search for peace. Without that, as the map makers of old were said to write on unexplored regions, Here be dragons.

 

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An Obstetrical Edition

Miscarriages –early pregnancy losses- have long been the subjects of research. They are unfortunately all too common, and until very recently, we were only aware of those that occurred after a noticeable menstrual delay –the tip of the iceberg, in other words.

Some progress has been made in understanding why they occur, of course –random genetic mistakes either from development, or from abnormalities in the sperm or egg DNA that happened to be involved, for example. But this type of knowledge is often after the fact -insufficient to predict or prevent the problem, although with in vitro fertilization (IVF) there are often techniques available to detect genetic flaws and guide the choice of fertilized egg to be implanted. This does little to address the issue in the much larger population attempting pregnancy in the more traditional, unaided fashion, however.

I was therefore intrigued by an article in the BBC news: http://www.bbc.com/news/health-35301238 that outlined a proposal to genetically modify some human embryos (not for implantation, be aware) to ‘…understand the genes needed for a human embryo to develop successfully into a healthy baby.’

I realize that, at first glance at any rate, this proposal seems to cross a boundary that has been hitherto sacrosanct: experimenting with human embryos. It seems to trespass on at least two traditional shibboleths. The first one –the more problematic and dogmatically based one- is that from the moment of conception, the embryo –or morula, once the fertilized egg has divided into 16 cells- is a person, or at least entitled to all the respect and privileges of a human being. This is more of a belief, a religious or moral tenet, than a demonstrable attribute of the embryo at this stage, though, and a more neutral consideration of its personhood would have to rely on either arguments from potential or its ability to survive outside of the uterus, should that be required.

The other, and maybe less religiously coloured objection, is the issue of unintended (or even intended) consequences: that to interfere with human DNA is to interfere with humanity itself and perhaps even the reason we are as we find ourselves –evolutionary adaptations that are the solutions to myriad problems of which we may be only dimly aware, if at all; and that we don’t really understand what we’re doing –or how to do it safely –i.e. without inadvertently affecting other things, even if we did. Like any ecosystem, everything is interdependent in one way or another: solve one problem and perhaps create another that you might not have even suspected was being modulated by the initial problem.

This, of course, is the thrust of the UK proposal. One can reasonably study animal models –mice, for example- only if they have comparable genes for early embryologic development. And as Dr Niakan, from the Francis Crick Institute, said: “Many of the genes which become active in the week after fertilisation are unique to humans, so they cannot be studied in animal experiments.” Initially, the study could have more benefits in IVF work – ‘Of 100 fertilised eggs, fewer than 50 reach the blastocyst stage, 25 implant into the womb and only 13 develop beyond three months…’ “We believe that this research could really lead to improvements in infertility treatment and ultimately provide us with a deeper understanding of the earliest stages of human life.”

Convinced? It’s a difficult one, isn’t it? Clearly, we need to understand how things work (as the study proposes) long before we attempt to modify them in any way. And if gene editing on a human embryo can be done, it is inevitable that it will be done by someone, somewhere, but perhaps with less stringent rules and guidelines to constrain it. So, should we just bite our collective tongues, and bow to progress? And is there really a choice?

I’m not sure where I stand on the issue of genome editing; I don’t think there is a one-size -fits-all solution, but I do think there is un bel compromis. The issue must be kept open for discussion, made public, in other words, so that at the very least it is not perceived as being done in secrecy and without identifiable or appropriate input. The pros and cons must be aired and in terms that all can understand. And the opinions of all of the various interest groups -both religious and secular- should be publicly and repetitively solicited. The left hand must know what the right hand is doing.

No, there is unlikely to be consensus; people will divide along predictable lines as I have suggested, but at least there will be a chance for an airing of the arguments, and an assessment of their merits or deficiencies that is available to all who care –a public catharsis. A mitigation…

But in the end, I think we must always be mindful of the dangers that Shakespeare intimated in his Much Ado About Nothing: ‘O, what men dare do! What men may do! What men daily do, not knowing what they do!’

 

 

 

 

 

 

 

 

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Stereotypes in Medicine

I suppose we are all, at times, seduced by stereotypes. They are, after all, a simplified way of processing the other world –underlining how they are different from us. Even the etymology of the word, derived from Greek, seems as if it would be helpful: stereos –firm, or solid; typos –impression. But unfortunately it has wandered from its first use in the printing field as something that would reliably duplicate what was engraved on the master plate, to its use in 1922 in a book entitled Public Opinion that suggested a ‘preconceived and oversimplified notion of characteristics typical of a person or group’.  It has grown and metastasized, cancer-like, from there. Now, any attribution is suspect. Any observation, coloured. What was once felt to be useful is now recognized as impossibly simplistic. Naïve.

We are far too complex to fit into labelled baskets that purport to describe our essence or predict our opinions. Indeed, to stereotype a group is to consider it different –perhaps not unreasonable as an observation, but also dangerously close to slipping into an us/them perspective with its risk of discrimination and prejudice. As Wikipedia (sorry!) summarizes it: ‘Stereotypes, prejudice, and discrimination are understood as related but different concepts. Stereotypes are regarded as the most cognitive component and often occurs without conscious awareness, whereas prejudice is the affective component of stereotyping and discrimination is one of the behavioral components of prejudicial reactions. In this tripartite view of intergroup attitudes, stereotypes reflect expectations and beliefs about the characteristics of members of groups perceived as different from one’s own, prejudice represents the emotional response, and discrimination refers to actions.’

So, the stereotyping of an individual, or worse, the group to which she presumably belongs, can have consequences well beyond the initial encounter –‘unintended consequences’, as we are so fond of saying in retrospect- and yet we still seem genuinely surprised that things would turn out like that. I am always heartened, therefore, when I read about those who are able to pierce the curtain and see what lives outside the window: http://www.bbc.co.uk/news/technology-34359936

I like to tell myself that all my years in practice have dissolved the last dregs of stereotypes from my psyche, and yet my guilt, my terror of succumbing, is still alive and well –if tucked away. But, if stereotyping can occur without conscious awareness, the very act of trying to avoid it suggests that there is something there in the first place…

Manipulation always reminds me of the danger. Not my manipulation, you understand (and besides, I don’t call it that); no, my patients’ attempts at beguiling me. My mother was a masterful manipulator and I’ve always noticed similar attempts by others. Perhaps the very labelling of their actions as manipulations is itself a stereotype, but I’m getting ahead of myself.

I still remember a time, several years ago now, when I was discussing the pros and cons of vaccination against HPV, the sexually transmitted virus responsible for cancer of the uterine cervix. The woman, a well-educated software engineer at a local start-up company, had asked me what I thought of her daughter being vaccinated in school.

“She’s only in grade six, doctor -11 years old! She hasn’t even thought about…” Loretta hesitated briefly as she sorted through her vocabulary. Clearly, even the thought of her daughter as a sexually active individual was uncomfortable for her. “…being intimate.” She immediately blushed at the word.

It’s a delicate topic for parents and I nodded sympathetically. “Not intimate yet, I’m sure,” I said and smiled to diffuse her embarrassment. “But when she gets older, it would be nice to know she will be protected against the virus, don’t you think?”

Loretta’s face hardened at the thought –or maybe at the fact that I needed to bring it to her attention. Her expression was adamant: her daughter was not like that. She studied my face for a moment, her eyes made short angry excursions onto it, then, finding nowhere to roost, hurried back to safety. “I think I will decide when she is older and more able to understand.”

I tried to disguise a sigh. “Sometimes our children understand a lot more than we suspect, Loretta…”

I could see her stiffen in her chair. “I know my daughter. You may be a parent…” She paused to run her eyes up and down what she could see of me from where she sat, obviously trying to decide whether even that was possible. “But you are not a woman, doctor; you couldn’t possibly understand the mother/daughter bond!”

My only possible response was a smile, so I parried with the best one I could muster under attack. “You did ask for my opinion, Loretta,” I managed to reply in an even voice.

She unleashed her eyes on my face again, this time as birds of prey, and as they circled for the kill, she managed to answer in a polite monotone. “You health practitioners are all the same, aren’t you? You think you have all the answers. You, my GP, the school doctor –even the school nurse- prattling on about anticipated behaviours and how you want to deal with them as if you were all decanting untasted wine from the same expensive bottle.”

My smile broadened at her use of the simile but my reaction only seemed to fluster her more. I shook my head slowly. “Most of us certainly don’t think we have all the answers, Loretta.” Her eyelids fluttered as if I were a politician trying to convince a wary population. “But I suppose we do try to prevent problems when we see them coming. Cancer of the cervix used to be a major problem until we recognized it was caused by a common sexually transmitted virus. The obvious next step was to see if we could develop a vaccine to protect against it like we did with small pox –or polio…” I shrugged as if I had just made an irrefutable point.

She stared out the window for a moment, undecided, and then I could see her body language change. Soften. Her eyes were sparrows again –finches, maybe: curious, but playful. “I just stereotyped you didn’t I?” I hadn’t thought of it that way, I have to admit; the accusation usually comes from the opposite direction. I nodded in pleasant agreement. “But it’s a two way street isn’t it?” she added with an impish smile, obviously unwilling to let me off unscathed. “I saw you rolling your eyes at the mother-daughter bond thing.” She could hardly talk for her smile. “Over-protective mother meets omniscient doctor, right?” She settled back more comfortably in her chair. “Both of us using our unique and non-reciprocable roles to pull rank. To manipulate each other –ad hominem stuff…” she added and then chuckled.

Suddenly she became serious and I could sense she needed an answer. “Tell me, doctor,” she said, carefully choosing her words, “If I were your daughter, would you advise me to have your granddaughter vaccinated?”

A serious question; a personal question -and I didn’t hesitate to respond. I nodded my head immediately.

She relaxed again. “Then I have my answer, don’t I?” she said and started to put on her coat. She stopped at the door and turned to me with a little smile waving for attention on her face. “Did I just get swept up in another stereotype?”

I had to shrug. I’m just not sure anymore.