Tag Archives: unintended consequences

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He’s mad that trusts in the tameness of a wolf

I am an obstetrician, and not a neuropsychiatrist, but I feel a definite uneasiness with the idea of messing with brains –especially from the inside. Talking at it, sure –maybe even tweaking it with medications- but it seems to me there is something… sacrosanct about its boundaries. Something akin to black-boxhood -or pregnant-wombhood, if you will– where we have a knowledge of its inputs and outputs, but the internal mechanisms still too complex and interdependent to be other than interrogated from without.

I suppose I have a fear of the unintended consequences that seem to dog science like afternoon shadows -a glut of caution born of reading about well-meaning enthusiasms in my own field. And yet, although I do not even pretend to such arcane knowledge as might tempt me to meddle with the innards of a clock let alone the complexities of a head, I do watch from afar, albeit through a glass darkly. And I am troubled.

My concern bubbled to the surface with a November 2017 article from Nature that I stumbled upon: https://www.nature.com/news/ai-controlled-brain-implants-for-mood-disorders-tested-in-people-1.23031 I recognize that the report is dated, and merely scratches the surface, but it hinted at things to come. The involvement of DARPA (the Defense Advanced Research Projects Agency of the U.S. military) did little to calm my fears, either –they had apparently ‘begun preliminary trials of ‘closed-loop’ brain implants that use algorithms to detect patterns associated with mood disorders. These devices can shock the brain back to a healthy state without input from a physician.’

‘The general approach —using a brain implant to deliver electric pulses that alter neural activity— is known as deep-brain stimulation. It is used to treat movement disorders such as Parkinson’s disease, but has been less successful when tested against mood disorders… The scientists behind the DARPA-funded projects say that their work might succeed where earlier attempts failed, because they have designed their brain implants specifically to treat mental illness — and to switch on only when needed.’

And how could the device know when to switch on and off? How could it even recognize the complex neural activity in mental illnesses? Well, apparently, an ‘electrical engineer Omid Sani of the University of Southern California in Los Angeles — who is working with Chang’s team [a neuroscientist at UCSF] — showed the first map of how mood is encoded in the brain over time. He and his colleagues worked with six people with epilepsy who had implanted electrodes, tracking their brain activity and moods in detail over the course of one to three weeks. By comparing the two types of information, the researchers could create an algorithm to ‘decode’ that person’s changing moods from their brain activity. Some broad patterns emerged, particularly in brain areas that have previously been associated with mood.’

Perhaps this might be the time to wonder if ‘broad patterns’ can adequately capture the complexities of any mood, let alone a dysphoric one. Another group, this time in Boston, is taking a slightly different approach: ‘Rather than detecting a particular mood or mental illness, they want to map the brain activity associated with behaviours that are present in multiple disorders — such as difficulties with concentration and empathy.’ If anything, that sounds even broader -more unlikely to specifically hit the neural bullseye. But, I know, I know –it’s early yet. The work is just beginning… And yet, if there ever was a methodology more susceptible to causing collateral damage, and unintended, unforeseeable consequences, or one that might fall more afoul of a hospital’s ethics committee, I can’t think of it.

For example, ‘One challenge with stimulating areas of the brain associated with mood … is the possibility of overcorrecting emotions to create extreme happiness that overwhelms all other feelings. Other ethical considerations arise from the fact that the algorithms used in closed-loop stimulation can tell the researchers about the person’s mood, beyond what may be visible from behaviour or facial expressions. While researchers won’t be able to read people’s minds, “we will have access to activity that encodes their feelings,” says  Alik Widge, a neuroengineer and psychiatrist at Harvard University in Cambridge, Massachusetts, and engineering director of the MGH [Massachusetts General Hospital] team.’ Great! I assume they’ve read Orwell, for some tips.

It’s one of the great conundrums of Science, though, isn’t it? When one stretches societal orthodoxy, and approaches the edge of the reigning ethical paradigm, how should one proceed? I don’t believe merely assuming that someone else, somewhere else, and sometime else will undoubtedly forge ahead with the same knowledge, is a sufficient reason to proceed. It seems to me that in the current climate of public scientific skepticism, it would be best to tread carefully. Science succeeds best when it is funded, fêted, and understood, not obscured by clouds of suspicion or plagued by doubt -not to mention mistrust. Just look at how genetically modified foods are regarded in many countries. Or vaccinations. Or climate change…

Of course, the rewards of successful and innovative procedures are great, but so is the damage if they fail. A promise broken is more noteworthy, more disconcerting, than a promise never made.

Time for a thought experiment. Suppose I’ve advertised myself as an expert in computer hardware and you come to me with particularly vexing problem that nobody else seemed to be able to fix. You tell me there is a semi-autobiographical novel about your life that you’d been writing in your spare time for years, stored somewhere inside your laptop that you can no longer access. Nothing was backed up elsewhere –you never thought it would be necessary- and now, of course, it’s too late for that. The computer won’t even work, and you’re desperate.

I have a cursory look at the model and the year, and assure you that I know enough about the mechanisms in the computer to get it working again.

So you come back in a couple of weeks to pick it up. “Were you able to fix it?” is the first thing you say when you come in the door.

I smile and nod my head slowly. Sagely. “It was tougher than I thought,” I say. “But I was finally able to get it running again.”

“Yes, but does it work? What about the contents? What about my novel…?”

I try to keep my expression neutral as befits an expert talking to someone who knows nothing about how complex the circuitry in a computer can be. “Well,” I explain, “It was really damaged, you know. I don’t know what you did to it… but a lot of it was beyond repair.”

“But…”

“But I managed to salvage quite a bit of the function. The word processor works now –you can continue writing your novel.”

You look at me with a puzzled expression. “I thought you said you could fix it -the area where my novel is…”

I smile and hand you back the computer. “I did fix it. You can write again -just like before.”

“All that information… all those stories… They’re gone?”

I nod pleasantly, the smile on my face broadening. “But without my work you wouldn’t have had them either, remember. I’ve given you the opportunity to write some more.”

“But… But I was stored in there,” you say, pointing at the laptop in front of you on the counter. “How do I know who I am now?”

“You’re the person who has been given the chance to start again.”

Sometimes that’s enough, I suppose…

 

 

 

 

 

 

 

 

 

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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…

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What’s Past is Prologue

Sometimes it’s hard to get things right; sometimes it’s hard to get things even sort of right. We pride ourselves on foresight, on our ability to anticipate the future results of our decisions, but it’s often more hubris than skill. Unintended consequences have a way of interpolating themselves like bushes in a forest while we, so focussed on the trees, see only empty spaces –shadows- in between.

Examples are not hard to find. Just think of the well-intentioned introduction of cane toads to Australia from Hawaii in 1935 to control the cane beetles. Unfortunately, the toads contain a toxin that is deadly to many animals so they have escaped effective predation and their numbers have skyrocketed.

But unexpected problems can also arise at work with employers’ attempts to adapt to the domestic problems that occur from time to time in employees with families. Things like needing to take a child to the doctor, or having to pick her up from day care don’t often happen with childless singles in the office.

I have to say that I would have assumed that thoughtfulness of this sort would have few major adverse repercussions for the employer –workers able to balance job and family equitably might well be better, more satisfied employees. After all, a reward given, is a debt owed. So, I was surprised to discover another side to this family-friendly benevolence as outlined in a BBC news item: http://www.bbc.com/capital/story/20170814-how-to-say-no-at-work-when-you-dont-have-kids?

‘Colleagues with children were […] prioritised when it came to taking their preferred vacation dates, […] while fellow single or childless workers struggled to get time off to care for elderly relatives or were asked to go on more frequent business trips.’ It’s obviously a challenge to separate envy –or resentment- from genuine favouritism and ‘While it’s tricky to nail down concrete statistics that prove how much singles might be being indirectly penalized in the workplace, a recent UK study of 25,000 workers found that two thirds of childless women aged 28 to 40 felt that they were expected to work longer hours.’

‘During research for his book Going Solo, Eric Klinenberg, a professor of sociology at New York University interviewed hundreds of single people in Europe and America and discovered “there was widespread perception that singles became the workhorses in corporate offices”’

‘Bella DePaulo, a professor of psychology at the University of California, Santa Barbara, explores the phenomenon in her books and studies, and coined the word “singlism” to pin down the stigmatisation, negative stereotyping and discrimination against singles that she believes is widespread in the workplace and society at large. She argues that many many employers are missing a trick when it comes to single employees, who, far from being lonely and isolated, are actually more likely to be actively engaged in their communities and have strong relationships with friends who “feel like family, even if they are not family in the traditional sense”’.

Unfortunately, the issue is hydra-headed. ‘“There’s a difference in perspective between people who are parents and people who aren’t. If you aren’t a parent, you really can’t see how that changes your life and your priorities,” says Jonas Almeling, a former entrepreneur turned Head of Innovation for a Sweden’s export and trade agency, who is a father-of-one. “I would definitely not have the same flexibility for someone saying ‘oh sorry I am off kayaking’ compared to someone doing a pick-up from kindergarten,” he argues.’

And yet, both parents and singles can be tempted to abuse the kindness –or naïveté- of a forgiving boss. Many years ago, when I was in my salad days and green in judgement, I started my obstetrical specialty practice and hired a young single mother as secretary on the recommendation of a friend. We got along well, and she proved a reassuring presence for my freshling patients. But she seemed to get a lot of ‘colds’ and migraines, however, and often I would only know about when I found a strange woman, a friend of hers usually, standing somewhat befuddled behind the front desk and wondering just who I was when I walked through the door.

I have to say in Martha’s defense, she certainly had nice friends and they all did admirable fill-ins, but I spent as much time coaching them on their duties as I did with the patients. I knew from my training that new mothers had a lot to cope with and, I supposed, especially single parents, so I would usually just shrug, smile at the new receptionist, and introduce myself. After a while, I got to know some of the replacements, and the office got easier. In fact, when change is common, it no longer surprises, and to tell the truth, I normalized it in my mind.

But one of my new obstetrical patients didn’t, and because of some early pregnancy problems she ended up seeing me weekly for a while.

Normally bubbly and talkative, one day Janice was unusually quiet as I led her down the corridor from the waiting area to my office, and before she sat down, she carefully closed the door behind her. “Who is it this time?” she said, and promptly placed a fake smile on her face.

I didn’t understand the question at first and merely raised an eyebrow in response.

“It was Helen last week, and Brava the week before… Come to think of it, I think I saw this one a few weeks ago…” Her eyes hovered over my face for a moment before landing.

“Martha, is supposed to be my fulltime secretary,” I explained. “She seems to call in sick a lot… Single mother, stuff, I think.”

A sardonic smile replaced the fake one. “Have I met her yet?”

I tried to remember, but couldn’t. “She has short, blond hair, and often wears a blue ribbon around her neck, I think…”

Her eyes slid down my face and stopped at my lips –to see if I was serious, I suppose. “I’m a single mother, doctor,” she said and shook her head slowly. “Well, I will be at any rate, I hope…” She sighed and glanced out the window behind me for a second or two. “And even with all the vomiting, I manage to go to work most days.”

I smiled and shrugged. “Martha shows up a lot…” But Janice could see I was struggling with the defence.

She glanced at a picture on the wall. “How old is her child?”

I shrugged again, this time to cover for the fact that I couldn’t remember. But I think Janice understood. “Uhmm, somewhere around 3 or 4 I think…”

“And does she live alone?”

I did remember that –her roommate sometimes filled in for her. “No, she shares a condo with a friend…”

Janice’s eyebrows both crept upward and her eyes twinkled mischievously. “Ever phone to find out how she’s doing?” She blinked as she suppressed a word that I could see being pulled back into her mouth in the nick of time.

I shook my head. “You almost asked ‘to find out what she’s doing’, didn’t you…? No, I trust her.”

Janice laughed. “Sometimes an employer phones because he’s concerned about his staff. Trust has nothing to do with it.” Her face brightened even more. “And by the way, I’m feeling a lot better nowadays. Maybe I can go back to monthly visits, eh?” she added. “I’ve been missing too much work lately.” And then she winked at me playfully. “Phone her, eh?”

But I didn’t, you know. I think I was too embarrassed; I liked Martha, and I suppose I didn’t want to catch her in a lie. Anyway, she resigned a few weeks later, and sent me a little potted areca palm for my desk to thank me for my patience with her.

The next month, when Janice saw it on my desk, she asked about it.

“Present from Martha –my former secretary,” I figured I’d better explain ‘former’. “She sent it as a thank you present when she resigned.”

Janice was quiet for a moment. “You didn’t phone her, did you?” Her eyes interrogated me briefly – but they knew…

I shook my head.

Then she sighed, and the slightest wisp of a smile surfaced for a second beneath those wise, experienced eyes.

 

 

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When Thou Liest Howling

There are some things we just don’t want to acknowledge aren’t there? Some things that we would rather not hear, not so much because we don’t think they’re important, but because they embarrass us… Or maybe offend us. Sexually transmitted diseases are prime examples.

For some reason, many of us find them difficult to talk about. Admittedly they require rather special venues, and the very subject casts long shadows on the interlocutors no matter how discreetly it is introduced. Rather than appearing as an intimate trust issue, the very fact of its being raised in the first place tends to arouse suspicion -accusations by proxy.

At first, I wondered if this attitude might be a generational thing. I was raised in an era when the most feared unintended consequence of premarital sex (as we called it then), was assumed to be pregnancy; VD -another time-specific term for sexually-acquired disease- was confined to clearly recognizable and therefore potentially avoidable people. This naïveté, of course, didn’t prepare us for the inevitable consequences of our wide-eyed ignorance and even nowadays, those of us still around could yet be dragged, aged and surprised, into the vortex as I outlined in an essay elsewhere:  https://musingsonretirementblog.com/2016/10/16/too-good-to-be-true/

The initial solace of antibiotic treatment also proved too good to be true. Throughout history, sexually transmitted infections were a scourge –the wages of sin as they were considered then. But with the advent of effective treatments, those debts were forgotten –although clearly not forgiven.

Syphilis, gonorrhea, and the more recently characterized chlamydia exacted a terrible toll on fertility and long term health, but until recently, all were fairly amenable to antibiotic therapy –albeit a necessarily changing one. Gonorrhea, however, seems to be particularly adept at developing resistance to the various antibiotics thrown at it.

There are various mechanisms by which a bacterium can become antibiotic-resistant but a common and easily appreciated reason is inadequate initial treatment. Even if an antibiotic is effective, there will usually be some bacteria that are less sensitive to it for whatever reason, and hence require longer antibiotic exposure for it to affect them. People tend to continue treatment only until they feel well –in other words, until the number of bacteria infecting them has fallen below whatever level was required to cause the symptoms. Unfortunately, the few bacteria that remain, are the less sensitive ones that weren’t so easily killed off at the beginning.

Physical barriers to the acquisition of sexually transmitted infections –condoms, for example- are certainly helpful, but men don’t tend to wear them with oral sex, the World Health Organization (WHO) has warned:  http://www.bbc.com/news/health-40520125  This has led to an increasing problem with throat infections according to the BBC News article. ‘Gonorrhoea can infect the genitals, rectum and throat, but it is the last of these that is most concerning health officials.

‘Dr Wi [from the WHO] said antibiotics could lead to bacteria in the back of the throat, including relatives of gonorrhoea, developing resistance. She said: “When you use antibiotics to treat infections like a normal sore throat, this mixes with the Neisseria species in your throat and this results in resistance.” Thrusting gonorrhoea bacteria into this environment through oral sex can lead to super-gonorrhoea.’

The problem is that a throat infection with gonorrhea may be relatively asymptomatic and hence more likely to be inadvertently transmitted to someone else. And ‘It’s hard to say if more people around the world are having more oral sex than they used to, as there isn’t much reliable global data available. Data from the UK and US show it’s very common, and has been for years, including among teenagers.

‘The UK’s first National Survey of Sexual Attitudes and Lifestyles, carried out in 1990-1991, found 69.7% of men and 65.6% of women had given oral sex to, or received it from, a partner of the opposite sex in the previous year. By the time of the second survey during 1999-2001, this had increased to 77.9% for men and 76.8% for women, but hasn’t changed much since.

‘A national survey in the US, meanwhile, has found about two-thirds of 15-24 year olds have ever had oral sex. Dr Mark Lawton from the British Association for Sexual Health and HIV said people with gonorrhoea in the throat would be unlikely to realise it and thus be more likely to pass it on via oral sex.’

And apparently there are only ‘three drug candidates in the entire drug [development] pipeline and no guarantee any will make it out.

‘Prof Richard Stabler, from the London School of Hygiene & Tropical Medicine, said: “Ever since the introduction of penicillin, hailed as a reliable and quick cure, gonorrhoea has developed resistance to all therapeutic antibiotics. In the past 15 years therapy has had to change three times following increasing rates of resistance worldwide. We are now at a point where we are using the drugs of last resort, but there are worrying signs as treatment failure due to resistant strains has been documented.”’

So, we’ve got a potentially untreatable, possibly asymptomatic, and very definitely prevalent infection out there, and a societal reluctance to talk about it… Perhaps it’s time for another approach. Fortunately there is an active search for a gonorrhea vaccine –and a serendipitous observation may have suggested a possible route –although, in retrospect, it seemed an obvious place to start. http://www.bbc.com/news/health-40555702

‘The vaccine, originally developed to stop an outbreak of meningitis B, was given to about a million adolescents in New Zealand between 2004 and 2006. Researchers at the University of Auckland analysed data from sexual health clinics and found gonorrhoea cases had fallen 31% in those vaccinated.

‘The bacterium that causes meningitis, Neisseria meningitidis, is a very close relative of the species that causes gonorrhoea – Neisseria gonorrhoeae. It appears the Men B jab was giving “cross-protection” against gonorrhea.’ This is very early in the work, however, and it seemed only to be effective in a third of those vaccinated. But it is certainly encouraging.

Be that as it may, however, I can’t help but worry that if there is development of an effective vaccine against gonorrhea, it will once again fool us into forgetting about the other diseases potentially transmissible by oral sex, including viruses such as hepatitis, herpes, and HPV (for which, thank god, there is also an effective vaccine), not to mention the bacterially-caused ones like syphilis, chlamydia, and many others that don’t make for salacious headlines.

But I’m not advocating for the formation of a Temperance League to combat a practice that is likely as old as humanity, nor do I have any religious or ideological objections to its persistence in our society, but I do believe that the Past informs the Future. I think that it would be prudent to ensure that all participants –newcomers to the field, as well as those who have already passed through and are merely nibbling at memories- have a working knowledge of those risks that should not be placed, as Shakespeare put it, on the windy side of care…

I just wonder if those who are entrusted with sexual education nowadays would put it so beautifully.

 

 

 

 

 

 

 

 

 

 

 

 

http://www.bbc.com/news/health-40555702

 

 

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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!’