LabLit.com

Fiction

It looks like a miracle

Of mice and men

Richard P. Grant 17 February 2019

www.lablit.com/article/954

Sometimes our tinkering with the mice and the chemicals and Norman’s tubes and bowls seems so worthless, so insignificant in the face of what must, God help us, be such a dark disaster

Editor's note: We are pleased to present the thirteenth installment in our series, The League of Imaginary Cats. Read more about the Series in our accompanying editorial, and use the navigation links at the top right to catch up.

Friday 24 May
 

Ethel is standing by the fireplace with her arms crossed and her lips pursed.

We are watching Norman doing his party trick, and he is managing to entrance not just the children, but also Ethel and Howard and me too. Under the blade of his penknife the wood is taking shape; there is a beak and tail feathers already. I think that’s what they are: I can’t see all that well from here, but Ethel has been unusually cool towards me, and I’m glad of the distance.

As I lean against the doorjamb there is a hand at my elbow. I turn to acknowledge Howard’s lopsided grin. He must be planning something, and that look in his eyes tells me that whatever it is, we’ll all have to go long with it. Maybe it is something to do with the experiment tomorrow.

He winks.

“Want a word with you and the boys when the kiddies are in bed. Can’t talk now, loose lips and that.”

He gives my arm a squeeze and saunters over to the fireplace. He puts his hand on Ethel’s shoulder but she moves away, just an infinitesimal distance, and I wonder if anybody else notices. Perhaps I am imagining it.

But now Norman’s eyes crinkle, and my heart gives a little squeeze as he holds out his hand towards the children.

Paquita, with all the worldly wisdom of a ten year-old, is affecting to be bored and has turned away, but Charlie is rooted to the spot, openmouthed. He stretches out his hand, extends a finger to stroke the head of the little bird that Norman has carved.

“Look mama! A robin!” he squeaks, and finally Paquita gives in and lifts the carving from Norman’s hand. As he lets her take the bird, Norman’s face is bright enough to light up the whole room.

“That’s right, Charlie. It’s a robin. You take good care of him, Paquita.”

How does he do it? It’s not just skill in carving; somehow he puts something of himself in it, some of his own, almost simple joy that can vivify the most anonymous lump of firewood.

I keep telling him he should sell the carvings, but he won’t have any of it. I’m not sure he keeps any for himself, either: I’ve seen a couple around this house, and he’s given some to students; I even have an exquisite little sparrow at home, although I keep it hidden from Denys.

Paquita slowly turns, holding out the robin in one hand while gently stroking it with the other. “It’s like magic,” she breathes, and I’m hard-pressed to disagree.

“Now then, Charlie, Paquita.” Ethel is all business and bustle as she herds the children. “Kiss your father goodnight.”

Howard bends down on one knee, holds the children tight; kisses them on the tops of their heads.

“Off you go, scamps. And say thank you to Uncle Norman!” The children turn obediently as one – Charlie forgets himself and hugs Norman tight – before Ethel sweeps them before her, out the door and up the stairs.

I detach myself from my corner and go over to where Norman is sitting. His face is still beaming, and he is carefully wiping the blade of his penknife with his handkerchief.

“You are such a sweetheart, Norman,” I say to him. “How do you it?”

He gives a little shrug.

“It’s a gift. It’d be wrong not to use it.” He looks up at Howard. “Compared to some, it’s not much.” There is a touch of awe in Norman’s voice, but I can’t blame him for it. Not if it goes well tomorrow.

Howard snorts with laughter, pats him on the shoulder.

“Ever the modest Pom, Norm! Meg, you know what his latest trick is?” To be honest, nothing that Norman can come up with would surprise me now. “Marmite! He’s mixing Marmite in with the broth! Smells like a bloody brewery down there. And it’s working, yes?”

Norman shakes his head.

“A little, maybe. The mould grows so slowly, it’s difficult to tell at first if it makes any difference.”

“But you’ve got enough for tomorrow,” Howard says. “Talking of tomorrow, where’s that useless bastard Chain got to?”

At the mention of Ernst, Norman loses his smile.

“He’s not coming, is he?”

Howard sighs.

“Don’t look so glum, Norman. You’re getting on all right now, aren’t you?”

“That’s only because you’ve fixed it, Floss, so that they never have to talk to each other when you’re not there,” I say.

Howard’s face reminds me of a puppy that’s been banished to its kennel.

Neither man speaks for a while. I hear small feet running across the floor above, followed by a slower, heavier tread. Soon there’ll be the creak of the top stair. It won’t do to let Ethel see them fall out, I think, and I’m on the verge of asking Norman more about the Marmite, when Howard breaks the silence.

“Listen, Norm. Don’t be so bloody miserable about it. It’s going to be right as rain – he hasn’t figured out our plan yet, and I’ve got a new bloke coming soon, name of Abraham. Why don’t you show him the ropes when he gets here? That’ll keep you from under Chain’s feet even more. And after tomorrow we’re all going to be too busy to worry about any funny business.”

While Howard is speaking, I see a shadow pass the window, and I slip into the hallway. I open the front door just as Ernst is raising his hand to the door knocker. I put a finger to my lips.

“The children are in bed. Quiet now.”

He clicks his heels and nods.

“Doctor Jennings. It is such a pleasure to see you again.”

“Ernst! It was only this afternoon.” We look at each other for a few seconds, and I wonder what he’s waiting for. “Oh do come in, there’s no need to stand on ceremony here!”

I help him off with his coat, and usher him into the drawing room. Howard looks up, rubs his hands together and in two strides is by the great oak dresser.

“Chain! You old malingerer. What took you so long?”

Without waiting for an answer he’s rummaging in one of the cupboards, finally appearing with a dust-covered bottle, which he lofts triumphantly.

“Here it is! I’ve been saving this. Ethel! Where the blazes are you, woman?”

He looks around, apparently momentarily disconcerted, before his eyes rest on me.

“Meg,” he points a thumb over his shoulder, “be a doll and help me with the glasses will you?”

Ernst is looking intently at the bottle, rubbing his chin.

“That is a fine wine, Howard. Do you perhaps not know there is a war on?”

“All the more reason to drink fine wine! Besides, we must remember the sacrifice,” and here he nods to me, “that dear Meg’s mice are going to make in the name of science tomorrow.”

“It is bad luck to toast before an experiment, no?” Ernst says, nonetheless relieving me of one of the glasses. “In the Times, they say Nazi armour has broken through the French lines,” he wags his finger at Howard, “and even in Belgium the Allies are now outflanked.”

“So we should drink it now, before the bastards get here and get their thieving hands on it!” Howard laughs, but it is a little too forced. We all see the papers, and it does not make for comforting reading.

It is worse for Ernst: although he rarely mentions them, he worries about his family trapped in Berlin.

I can only imagine.

**********

Later, Howard catches me looking at the clock on the mantelpiece. He comes over.

“It’s barely nine, Meg. Do you have to?”

I nod. “Denys –”

“Yes. Let me help you with your coat.”

Ernst is lecturing Ethel on some finer point of snake venom biochemistry, and neither of them notice us leave the drawing room. Norman however, standing a little way apart, raises his hand to breast height and waggles his fingers. I smile back.

In the hallway, Howard cocks his head, listening for any sounds from upstairs.

“We’re going to send them to Canada, y’know.”

“Oh Floss! How awful. Is that why Ethel is so...?”

“Cold? Yes, it could be. You know things aren’t too good don’t you? I’m hoping some time alone might put things right.”

“You poor man,” I say, trying to keep the tremor out of my voice. In my mind, I’m frantically searching for something safe to say. Safe – yes. “And they’ll be safer there, won’t they?”

“We hope so. Not much bloody point otherwise! It’s a hell of a way though.”

“They’ll be fine, Howard. Children are more resilient than we give them credit for. And it’s not as far as Australia, is it?”

At the mention of Australia, Howard brightens.

“When the war is over I thought we could take a trip over there. Especially if the experiments work out.”

I’m flabbergasted. “You mean you and me? The lab?”

“Why not?”

“What would Ethel say?”

Howard flaps his hand in the direction of the drawing room.

“She’ll be right. I’ll sort it.”

He helps me with my coat. This close, I hear his feel his breath on my neck, and I lean back slightly, sensing his reassuring bulk, wondering what it would feel like if his arms were to extend and draw back in, enveloping me.

“Meg,” he says, “I’ve been thinking about you.”

I keep my eye on the front door and hope it’s too gloomy in here for him to see the crimson rising on my cheeks.

“Floss, if this is about –”

“It’s about tomorrow. The experiment.”

“Oh! You said something earlier. I thought you’d forgotten.” I slowly turn around. Fortunately, he’s still looking up the stairs.

“Thing is, Meg, they’re your mice. Your children, I s’pose. And it’s only fair, only right, that you should do the experiment. The injections, anyway.”

“Why, Floss, I’d be delighted. But you know how Denys is –”

“Bugger Denys!” I take a step back as he turns and jabs his finger at me, remembering himself just in time and stopping before he touches me. “This is important. You know it is, Meg. Y’know, I don’t know what you see in that bloody galah.”

I could say the same about you, Floss, I think.

Howard frowns, peers at me. “Are you blushing?”

“I’m excited, Floss. I’d love to do the experiment. Yes, yes of course I’ll be there. Denys can, oh I don’t know, make his own breakfast or something.”

We both laugh, briefly, before Howard puts his finger on his lips and nods upstairs. We stand there, sharing this moment. It speaks longer, and further and deeper, than any word.

Saturday 25 May

Despite his dedication to his own work, Denys is not happy with me coming to the lab. He doesn’t like Floss, not one of “our type”. He doesn’t say it but I know he thinks it. We row. No change there.

But I get on my bicycle and by 8.30 I’m carrying it down the steps to the Dunn School basement.

Norman is already down here, tightening valves, tapping pipes, giving bedpans a shake or a stir. Occasionally he takes a thin, glass tube and draws up some liquid; peers at it with a frown, and drip-drip-drips the murky amber fluid back into the networked miles of rubber tubing and copper pipes and tortured glass that fill an entire room. There’s the remains of an upright piano at the end of the corridor, gutted for its strings I suppose. Next to it stands an iron bath, the enamel inlay cracked and browned, filled with earthenware pots and ceramic jugs and various lengths of copper pipe jutting out at unparticular angles.

The entire basement has, over the last few months, become Norman’s private workshop, and there isn’t a shelf or cupboard or spare square foot of floor he hasn’t covered with something scrounged from somewhere in Oxford or beyond in his efforts to get this dratted mould to grow. It resembles a junkyard more than a cutting-edge physiological laboratory.

And weaving and binding the mess and the junk together is the smell. The smell that works its way up the stairs into Howard’s office, into the library where we take tea; even into the clinical polish and efficiency of Ernst Chain’s laboratory. It clings to our coats, our hair, and our clothes. Denys has remarked upon it on more than one occasion. It’s difficult to describe, but it has overtones of damp, of mice and their droppings and their bedding, of sour milk and alcohol and ether, of the mould itself and yes, lately, of Marmite.

As I rest my bike against possibly the only free wall in the basement, I glance down. I fancy that some of the mould is actually growing in the grouting. Perhaps I shouldn’t tell Norman.

I stand for a while, just watching this kind and gentle man as he goes about the task of checking, tweaking and rechecking his apparatus. Eventually he straightens up and turns around, noticing me for the first time. He smiles, and waves. I walk over.

“Good morning, Norman. Are we all set?”

“Almost,” he says, cheerfully. “We’ve got just shy of ninety milligrammes. That’s enough for one experiment, with spare in case we drop some.”

I nod.

“And how many of my mice will you need?”

Norman’s face darkens. “Eight. Four controls and four experimental.” He shrugs his shoulders. “Any fewer and we won’t be able to be sure that it’s worked.”

“Yes, I understand.” Chain has been using mice almost profligately – “willy-nilly” in Norman’s words – for the toxicity tests, and neither of us are particularly happy about it. Fortunately penicillin doesn’t seem to harm them; unlike the experiment we’re planning to do today.

The bigger headache for Norman is the amount of the drug Chain gets through. There is never enough: if our experiment gives a positive result then he’s going to have to come up with something even more ingenious to make enough for human tests.

But that’s a problem for another day. We don’t even know yet if it will work in animals, even small ones. Penicillin appears to be tremendously potent against bacterial cultures, but there’s a world of difference between agar plates and a mouse.

Or a man.

“The professor’s upstairs,” Norman says, “tearing a strip off Jim.” He smiles. “That’s why I’m staying out of the way down here!”

“Oh no,” I say, “What did Jim do?”

Since he was a boy, Jim Kent has been Howard’s technician. He understands Howard’s tempers more than anybody, having been on the receiving end of that abrasive Australian tongue too many times to reckon, but still he worships him. As we all do, apparently.

“Who knows? Probably put too much sugar in his coffee or something. Anyway, would you care to look at my experimental set-up? I’d appreciate it.”

I say that of course I would, although it would be a rare day indeed that I’d be able to improve on any of Norman’s schemes.

**********

We are sitting at the bench in Howard’s personal laboratory: Howard, Norman, Jim and myself. Howard and Jim have obviously made up; to use one of Howard’s expressions, Jim’s grinning like a shot fox. The mice in their separate cages are scruffling and twitching. Norman is nervously fingering a row of syringes in a metal tray.

Howard leans towards Norman, rubs his hands together.

“Well troops. Eleven o’clock. Let’s get a wriggle on.”

Norman slides the tray towards me. He indicates the syringes.

“These contain strep cultures. Which do you want?”

I look to Howard in surprise.

“They’re your mice, Meg. You take four, and I’ll do the others.” Howard grins. “What, you didn’t think I’d make you do all eight did you?”

I open the lid of one of the cages and lift out its occupant by the tail.

A male mouse this, I notice, as I gently clamp the skin behind his shoulders between the forefinger and thumb of my left hand, securing his tail against my palm. I tip his head down and pick up the first syringe, sliding the needle into his belly. I withdraw the plunger slightly; the liquid is clear, meaning I haven’t punctured his intestines or bladder. Then, as quickly as I dare, I push the plunger all the way in, take the syringe out and put him back in the cage. As I close the lid I look up to see Howard finishing his first injection. When he’s done he looks over, nods, and opens the next cage.

Norman, dear Norman, is watching, silent, never fussing, an ever-present rock. His presence is a comfort to me, and to the others, no doubt. Where would we be without him?

Wordlessly, then, we complete our task. These syringes contain certain death – for man or mouse. One hundred thousand Streptococcus pyogenes in each little glass tube, enough to cause an infection that will kill a mouse within a day.

At the end, Norman makes a mark with his fountain pen in his notebook. Then he repeats for the benefit of the others what he has already told me:

“These four are our controls. We’ll give them normal saline, at,” he looks up at the clock on the wall, “five past twelve. These two,” and he points, “get 10 milligrammes of penicillin. The other two will get five, and then another five every two hours. Or thereabouts.”

“How many doses in total, Norman?” Howard asks.

“Five. Twenty five milligrammes each, spread over the day.”

I do a quick calculation.

“That means we have to keep working until midnight!”

Norman nods soberly.

“I’m meeting some friends this evening. I’ll come back and finish off after.”

“Ripper,” Howard says. “Let’s get some coffee.”

**********

At the stroke of noon we file back into the laboratory. This time we are on a mission of mercy; at least for some of the mice. Norman hands me a syringe, and I quickly open a cage, lift out the occupant, and inject her in the skin behind her head. I’m about to open the second cage when there’s a knock on the door.

“Doctor Jennings?” It’s Mary, one of the office girls. “I’ve got, um, Doctor Jennings on the telephone.”

“Hell’s bells!” Howard slams the bench with his hand. “What does that drongo want now?”

I peel off my surgical gloves and walk towards the door. “It’s all right, Howard. He’s probably just crying for his lunch.”

“Well, can’t he make it himself? I need you here!”

Howard catches up with me in the corridor, puts his hand on my arm.

“Margaret. Meg. Why do you run after him?”

“He needs me, Floss. I’m sorry.”

“The devil he needs you. He’s using you, can’t you see that? You threaten him! A Sheila, doing a bloke’s job? He hates it.”

I stop, turn around to face him. Calm.

“Do you think this is a man’s job? Do you think I should be at home in the kitchen?”

“No, yer mug. You know I don’t. That’s what he thinks. He’s got his bloody Lancet paper and now he thinks he’s the big nob and you should know your place. He doesn’t even do any teaching!”

Howard is so outraged on my behalf I can’t help but love him. I rest a finger on his shoulder, move it slowly down his jacket sleeve.

“Floss. Let me go. Jim can finish the experiment; he’s dying to, you know? Call me tomorrow, let me know how it goes.”

Sunday 26 May

I am back from church, listening to the wireless. Denys doesn’t come with me anymore: he just sits in that tiny room, writing, writing. I’d hoped it would change once he got his big paper published, that we’d have more time for us, that we could go back to how we were. But that seems now more impossible than ever, and to my growing horror I find that part of me welcomes the thought.

Mr Churchill has just been on the wireless, describing the situation in the Low Countries. Two weeks ago he promised us nothing but blood, toil, tears and sweat.

I’ll say this for the man: he keeps his promises.

Now Cosmo Lang is praying for "our soldiers in dire peril". There is talk of hard and heavy tidings.

Sometimes our tinkering with the mice and the chemicals and Norman’s tubes and bowls seems so worthless, so insignificant in the face of what must, God help us, be such a dark disaster. I think, although Howard never says it, we are trying to save lives. But sometimes, when the night is still and I can’t sleep, I wonder why we are messing around in the Dunn School basement when there might not be a future left to save.

The phone is ringing. Denys is yelling at me to answer it. He needn’t fret so: I’ve been waiting for this all morning.

I take a deep breath, and hold the receiver close to my ear.

“Oxford three oh seven six.”

“Meg? It’s Howard.”

“Floss! What’s happening?”

“Listen, I think we’ve got something. Jim and Norman stayed with me until dinner yesterday. The control mice looked right crook, poor bastards. We gave the first two another booster dose, and I sent Jim home. Then I came back about 10, gave them another boost. I met Norman coming in as I left, told him what was going on, and to keep an eye on them.”

I grip the receiver tightly, hardly daring to breathe.

“Norm was here till near four this morning. I looked in his notebook. All the controls were dead by half three.”

“That’s not a scientific breakthrough, Floss.”

I hear him smother a laugh.

“Yeah, fair go. The other mice, the four that got penicillin…”

He pauses. Ten seconds, perhaps a minute, passes. There is a strange calm, disturbed only by the crackling on the line.

In my mind’s eye I can see thousands of soldiers, tired and dirty and hungry, crowding onto the Belgian beaches. Over the horizon, still out of sight but closing in, Nazi tanks are pulling the trap shut. Is there really no hope left for them, for us?

“They made it.”

Howard’s voice brings me back to the here of now. I look at the phone in my hand, trying to make sense of the message it brings.

“What are you telling me, Floss?”

“It looks like a miracle, Meg. They’re still alive.”


Flawed heroes

The hero of the penicillin story is Norman Heatley.

It was he who figured out how to grow the eponymous mould in sufficient quantities to enable its purification; he who realized the deceptively simple chemical trick that would allow it to be purified: to let Ernst Chain and Edward Abraham propose its structure (to be confirmed by Dorothy Hodgkin with crystallography in 1945); to enable the first experiment with purified antibiotic in mice to be performed in 1940; to treat policeman Albert Alexander a year later; to, eventually, facilitate the industrial-scale production of penicillin.

And yet his name, let alone his contribution to the extraction, purification and subsequent production of penicillin, is largely unknown.

His kind, gentle and humble nature belied his contribution to arguably the greatest medical advance of the twentieth century. Even into his 80s he could be seen prowling the Sir William Dunn School of Pathology in Oxford, where he and Howard Florey and Chain performed their seminal work so many years previously, looking for things to fix with his penknife – and being called upon to sort out the flagpole when it wouldn’t work.

The doings of science are the same as any other human endeavour.

The agents involved are flawed, brilliant, selfish, generous, idiosyncratic men and women. Chain and Heatley could not stand one another. Florey’s marriage – to Ethel Reed, an accomplished medic in her own right – was not a happy one. Margaret Jennings, who looked after the animals with which Florey and his team worked, divorced from her husband in 1946 – due in no small part, no doubt, to her ongoing relationship with Florey himself.

Despite the state of their marriage, Florey refused to divorce Reed. But after she died in 1966 he married Jennings seven short months later. Their marriage was by all accounts a happy one; sadly he died only a year later.

For most people, the key experiment in the penicillin story is the treatment of Albert Alexander, a policeman who had been scratched by a rose thorn and developed septicaemia. In March of 1941 he was treated with all the penicillin that was then available, and started to recover. Unfortunately the mould from which penicillin was then extracted grew very slowly, and supplies soon ran out. In desperation, Florey and colleagues attempted to extract the drug from the constable’s urine, but even that wasn’t enough, and he died soon after.

But the real test had come almost an entire year earlier, in May of 1940. Two days before the evacuation of Dunkirk, Florey’s team assembled in the lab to test the minute quantities of penicillin they had been able to extract and purify – on some of Margaret Jennings’ mice. They had previously checked that the new drug wasn’t toxic in the animals, but this was the first time they were to deliberately infect some with bacteria... and try to cure them.

Eight mice were to be injected with a lethal dose of bacteria. Four would receive differing doses of penicillin; the other four, the controls, would get saline placebo – in effect, they’d be left to die.

None of the team knew whether the new drug would work. They had no idea whether the dose was enough, or even if the extracted, purified penicillin would be active in the body of a mammal.

In the event, the four control mice had died by half past three in the morning the next day – while all the mice that received penicillin survived. Heatley recorded it all in his notebook, and even wrote in his diary that, in the darkness and with the excitement of the experiment, he had put his underpants on back to front.

His personal note on the experiment read simply,

"It really looks as if penicillin may be of practical importance."

On the other hand, Florey called Jennings in the morning and told her,

"It looks like a miracle".

In reality it was Florey’s technician, Jim Kent, who assisted with this critical experiment. I have told the story however through the eyes of Margaret Jennings, as it strikes me that, they being ‘her’ mice, it is more fitting that she should be the one taking responsibility for their fate.