Cycling in a Dish

Where do they get this stuff? Menses in a dish –or, to be more academically abstruse, ‘A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle’?

It has a pedantic ring to it, even though it doesn’t exactly roll off the tongue, but I have to ask a simple, quasi-lay interrogative: why? Critical Thinking 101 –at least as they used to teach it- would demand to know why it is important that we make this model. If the answer is vague, or even unnecessarily complicated,  then one begins to suspect academic foppery.

The model is unique –I’ll give them that –let me refer to a succinct description of the model from a BBC News article: http://www.bbc.com/news/health-39421396 ‘The 3D model is made up of a series of cubes that each represent the different parts of the female reproductive system.

‘Each cube contains collections of living cells from the respective bits of this system – fallopian tubes, uterus, cervix and vagina (all human cells), and the ovaries (taken from mice).

‘The cubes are connected together with small tubes, which allow special fluid to flow through the entire system, much like blood.

‘This also means the “mini organs” can communicate with each other using hormones, mimicking what happens in a woman’s body during a “typical” 28-day human menstrual cycle.

‘Tests suggested that the tissues in the system responded to the cyclical ebb and flow of hormones, in a similar way to those of the female body.’

At first, I have to admit, I was skeptical of the need for the model –and yes, I was inclined to see it as foppery. But when I actually read the paper (http://www.nature.com/articles/ncomms14584) I was impressed. Why not just obtain the same cells from, say, hysterectomy specimens, grow them, and subject them to whatever hormones or chemicals you pick to study? It quickly became evident that there are two types of scientists: clinical, and laboratory –as a practicing doctor, I’m afraid I fall squarely into the clinical end, and never the twain shall meet… The reason became all too clear as I continued to read.

First of all, as they explain in the introduction, ‘Preclinical studies often begin with individual cells, separated from cellular and physical contacts that are important for biological function. These dispersed cells must be propagated through weekly reduction divisions and maintained on flat plastic; however, these cells are missing the cell physicochemical microenvironment, three-dimensional (3D) tissue-specific architecture, and blood flow perfusion found in natural tissues.’ In other words, they take a long time to grow and aren’t subject to the same environment they would have in the body (i.e. in vivo).

Secondly, what is used to perfuse them may not have the same effect as the blood circulation they would receive in vivo: ‘typical media composition is based on basal nutrients, bovine serum and a few specialized factors that are placed in a static setting with random mixing. As a consequence, cell–cell and tissue-level cytokine and endocrine signals are not integrated into signalling pathways.’

So not only can delicate organs be assessed as if they were still in the body (like the rhythmic beating of the hair cells that line the Fallopian tubes –cilia), but the effects of different pharmaceuticals could be safely tested in the model before expensive clinical trials were undertaken. ‘Despite large investments in research funding, only ∼8% of drugs for which Investigational New Drug applications have been filed will be approved by the FDA.’

I have to say that I am intrigued, and not a little embarrassed that I was put off by the title of the article. Perhaps to expiate that guilt a little, I mentioned it to Ted, a –I hesitate to say ‘older’- colleague of mine that I met for lunch the other day.

We are both retired now so, apart from our similar past histories, talk heads more towards hobbies and bowels, than to scientific literature. I’m not even sure how it came up, except that his niece was trying –unsuccessfully, it seems- to conceive and his sister had phoned him for advice. She had mentioned several chemicals she’d discovered in an online search –both as potential therapies, as well as putative endocrine disruptors. She wanted to know what Ted thought.

“So what do you think?” he asked me as he carefully cut his hamburger in quarters so he could manage the entry problems. “You retired a couple of years after me…” he added, as if that meant that I was a couple of years smarter than him –or at least a bit more up to date.

“Ted, you know as well as I do that it’s dangerous to speculate on the effects of chemicals on human pregnancies. There are too many variables, too many potential effects that may not show up till birth, or even later…”

He nodded. “I remember DES for threatened first term miscarriages and the later damage to reproductive anatomy -not to mention the clear-cell cancers of the vagina that didn’t show up till years later…”

“Or thalidomide for morning sickness in pregnancies…” I added solemnly.

He nodded thoughtfully and after carefully picking out shreds of lettuce that were hiding under the bun, attempted to cram a freshly-cut piece of the hamburger into his waiting mouth, but it leaked somewhere south of his lips. “They can’t even design a portable hamburger,” he said, unsure whether to laugh or blush. He wiped his face, picked up the meat, and then searched for more hidden pieces of lettuce and placed them on his plate.

When he noticed me watching his lettuce hunt, he shrugged. “I’ve always hated lettuce,” he explained. “So does my niece for that matter. Probably hereditary,” he mumbled and then licked his fingers, contritely. “I mean, look,” he said with a crooked smile on his face, “I solved this problem using in vitro techniques.” And he held up his now-clean fingers and licked his lips in embarrassed satisfaction. “There’s gotta be a way to test these drugs without endangering a pregnancy. Mice and rats are not humans and you can’t safely extrapolate the results to us.”

“Amen,” I said, shaking my head sadly. We’d had similar discussions over the years, so I suspect he was merely venting his frustrations again.

We sat in silence for a moment while he tried to improve his in vitro technique, as he insisted on calling it.

“You know, Ted,” I said after it looked as if his practice runs at the lettuce were failing, “I did read about an in vitro way being developed for safely testing things in women. It was in the journal Nature and entitled something like ‘Microfluidic culture model of the human reproductive tract’. I’m not sure they could adapt it to pregnancies, but maybe it might be helpful in seeing what effects drugs or other chemicals could have on reproductive cells in the events leading up to a pregnancy…” I tried to remember more. “And it seems to me they were even able to replicate a 28 day menstrual cycle…”

His eyebrows shot up, and then one stayed elevated, as if scotch-taped to his forehead. “Micro fluidic what…? My god, is your retirement that bad?”

I think I blushed –he made it sound as if I’d been caught downloading porn. “Uhmm, it’s called ‘body on a chip’, or something –or at least this part is…”

He suddenly turned his attention to the chips still languishing on his plate and smiled. “Thanks for the excuse,” he said. Obviously his wife or maybe Chrissie, his sister, had warned him not to order them, let alone eat them.

“Yeah, I gather that the idea, eventually, is to be able to take cells from somebody who needs a particular treatment and test those cells in the model with various chemicals to see what happens.” It seemed quite exciting to me.

“Mmmh,’ he said, polishing off the last of his fries, while the puzzled lettuceal remnants stared at him from the plate. “I don’t think I can tell Chrissie about it, though.”

I looked up from my napkin and cocked my head. “Why not, Ted? Wouldn’t she find it interesting?”

He rested his head on his hands and peered at me as if he were looking over a pair of bifocals like a professor with a sleepy student. “She’d be on Craigslist trying to buy one as soon as she got off the phone… In fact she’d probably try for a matching set –a male one as well as a female one,” he added when I stared at him.

I must have still looked puzzled, because he smiled and picked up a piece of lettuce. “Chrissie’s a dietician and she thinks her daughter has a terrible diet… and she certainly remembers mine,” he explained, shaking his head. “She’d be trying to feed this to the model to prove her point.” He sighed. “I’d never hear the end of it…”

I suddenly realized I’d not thought about it that deeply. He’s right, maybe the ‘body on a chip’ thing needs a bit more work before they advertise it on Facebook…

Unregarded Age in Corners Thrown

I worry too much; I didn’t used to, but it kind of crept up on me along with my aches and pains over the years. Age is something that has always been fraught with tensions as we stumble through the calendar first wanting more, then less and then, I suppose, trying to forget about it altogether -ignore it when it clearly needs to be addressed. Demands recognition.

Age –especially old age- is one of those concepts that is very much contextually driven. Age-driven, in fact: where one sits on the spectrum very much influences age perception. An elder would live many fewer years if it is a teenager, rather than a senior who is canvassed.

But a good case can be made that age is not a mono-dimensional concept. Chronology does not come in one flavour; not all eighty year olds, say, are tied to the same constraints. Age might better be considered as a quartet with the other members consisting of Biological –we all age differently, Psychological –some aged people retain their faculties better than others, and Social –some elderly people, whether by fiat, or necessity, no longer work outside their homes and are no longer as connected to social networks. Indeed, in times past, ‘old’ might well have been related to usefulness rather than chronology.

http://www.bbc.com/news/magazine-34465190

So there we have it: usefulness. Purpose! Self-worth. All contingent concepts to be sure. And retirement, despite the positive connotations that Society has tried to foist upon it, is still a denouement –however it is rationalized. However many cosmetics are applied. Wallpaper may fool strangers, but it is still wallpaper…

So, you see why I worry. It is not that there might not be new opportunities available in retirement -new venues- but simply the realization that it is a final chapter of a thoroughly read book. An epilogue.

But I digress. It is something of a fool’s errand to attempt to encapsulate Retirement under one banner. It is a chapter as yet unprinted, and at best only sketchily conceived. There are also portions of it written, even if unwittingly, by someone else.

There is a store I visit every so often to buy dog food. It is a large and perhaps corporately criticized chain, but my dog is fussy and became addicted when she was only a puppy to a brand only they seem to offer. To tell the truth, I enjoy the store; I enjoy wandering the aisles and feeling -what? – pride at resisting things I do not need and casting a cold eye on those I do not want. It is a juvenile thing, I suppose, but maybe that’s the point: a recapitulation of past temptations seen through different eyes. Different years…

But on my way in, I saw a face that seemed familiar. It wore the uniform of the store and yet it seemed out of place somehow. A bush growing in a patch of vegetables –or more aptly, perhaps, a tree standing all alone in the middle of a field of wheat. Staid and stolid, watching, bemused, the tender stalks waving frenetically around her feet.

It was not so much her age that separated her from those around her as her composure, her calmness in the Storm of Store. In the eye of the hurricane of shoppers intent on their own missions, her smile was like a shrine erected at the doorway, a refuge offered, but seldom taken. Seldom noticed: the store was not a temple –just another place to visit when the need arose, a series of shelves to inspect. There were no sacred places here, no altars, no need to reflect on the meaning of it all. The store fulfilled a function, not a curb-side meditation.

I have to admit, the face was so unexpected, so completely out of context that I passed it by with barely a thought, although I did stop halfway down a nameless aisle and wonder why. And it was there that it –she– caught up with me.

“Doctor?” she asked tentatively, clearly uncertain from behind at least, that it was me. And when I turned to face the voice I remembered somewhat shakily from the past, she smiled broadly. I could see it was all she could do to refrain from hugging me; instead, she proffered a bony hand, its skin replete with veins and the brown patches of age.

“Doris!” I somehow managed to retrieve the name from a long closed memory drawer -although not without an awkward pause because it was not the Doris I remembered, but an older, frailer model. Doris had been well into her seventies when I had last seen her in consultation but this face, this figure, was a worn and crumpled copy of that older woman I had once filed away.

Her smile looked painful it was so wide and welcoming, but it was her eyes that immediately captivated me. Like delicate pale blue figurines trapped behind the glass of an old cabinet, they begged for release, and when she opened their cages they flew to my face and rested there. “It’s so nice to see you again, doctor,” she said with her joy so evident I was almost taken aback.

Her frailty dissolved as I watched, and the younger Doris emerged as if it had been hiding all the while. I remembered her now as the vibrant woman who had quoted poetry to me when I was trying to take her history. Who had dismissed the referral from her GP as ‘misguided over-concern’ from a young doctor uncomfortable in dealing with a patient older than his grandmother. And as a result she had brokered the compromise of seeing an older specialist. When I also agreed that she really had no cause for concern, she’d bonded with me and even showed up at the office the next week with flowers. I suppose we all like our judgements to be validated.

But on that occasion it had led to a discussion of age, and whether or not to succumb. Whether, as Dylan Thomas had written, to go gentle into that good night. Or to… Rage against the dying of the light. She most emphatically was with Thomas, whereas I, in an uncharacteristic disclosure, had expressed uncertainty as to whether with identity obscured and purpose thwarted, I would be forced to go gentle into whatever the good night hid in retirement.

“Nonsense!” I still remembered her saying that, her face fierce, her eyes locked on mine. “Is ‘Doctor’ your last name? Age and function do not change who you are –just what you do…” Then her expression softened and her eyes unlocked from me and twinkled when they had returned to her face. She got up from her chair with an enigmatic smile and turned to me as she was walking out of the room. “Do not become what Shakespeare called Unregarded age in corners thrown. I would be very disappointed.”

I took a long hard look at her, standing in the aisle with her uniform proudly displayed and I smiled. “You’ve certainly taken your own advice, Doris. Not too many people your age would have chosen your path. You look happy.”

“Have you ever read any Robert Frost?” she asked after observing me quietly for a moment.

I nodded, suspecting what was to come.

She closed her eyes and a beatific expression emerged as if she were about to pray.

“Two roads diverged in a wood, and I— I took the one less traveled by, And that has made all the difference.”

There are forks in every road. Maybe she was praying -praying for me…