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: ‘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 ( 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…