The Crystal

I

In 1804, in the back room of a pharmacy in Paderborn, a twenty-one-year-old assistant boiled opium with ammonia and obtained some white crystals that resembled nothing.

His name was Friedrich Sertürner and he was not a chemist [no degree, no laboratory, nobody to correct him]. He was the assistant, the one who weighed and ground what the pharmacist ordered, and what interested him was a question nobody considered interesting: why two batches of opium of the same weight did different things.

The answer was that opium is not a substance, it is a mixture, and that inside it there was one thing doing almost all the work. Sertürner separated it, washed it, crystallised it again and weighed it. He gave it the name of the god of sleep.

That was the first thing truly weighed in the history of medicine. Before, materials were weighed, not active principles. Until that morning bark, leaf, root and resin were administered, and the dose depended on the harvest, the soil, the year and the judgement of whoever prepared it. From that crystal on, a quantity could be written on a piece of paper and be expected to mean the same the following week.

II

In 1817, to demonstrate that the crystals carried inside them all the force of opium, he took them; and he gave them also to three boys, none older than seventeen.

He began with little and worked upwards, in three doses, in half an hour. The four of them went red, their eyes bright, and then came the nausea, the stomach pain, the drowsiness and a sensation of fainting that he described in writing with considerable precision for the state he was in.

He took fright. He drank a quarter of a bottle of strong vinegar and made them drink it too —six or eight ounces, by his own reckoning—, and the four of them vomited for hours.

The three boys were worse off than him. They were not pharmacist's assistants and they did not know what they were taking in the sense in which knowing is understood today; they were three seventeen-year-old kids in a provincial pharmacy to whom a man of thirty-four gave a new substance, miscalculating the dose.

That is in the file and there is no pretty way to tell it: the first trial of the first pure molecule in history was done on three minors who had no business being there.

What he did afterwards is what half redeems him: he published it entire, with the symptoms and with the error, and warned in writing that the substance was dangerous and that care had to be taken with it. He wrote that he considered it a duty.

Then he spent the rest of his life taking it. Both things at once, for twenty-four years: the published warning and the bottle in the drawer.

III

The box they gave me had twenty ten-milligram tablets and cost less than five euros.

It was for two broken ribs, in March, from a silly fall coming down some wet stairs. With ribs nothing can be done [they are not plastered, not operated on, they are waited out for six weeks]. It hurts to breathe, it hurts more to cough, and it hurts in a particular way when you turn over in bed, which is what wakes you at three.

The first night at home I counted. Twenty tablets, one every six hours, four a day. Five days. After those five days there was paracetamol and ibuprofen and a kindly explanation about inflammation.

Never in my life had I done arithmetic with a box of medicine. With antibiotics you count the other way, how many days you have to keep taking them; here you count how many are left.

The first tablet took forty minutes, and what it did was not take the pain away. The pain was still there, perfectly located, with its edge and its shape; what happened is that it stopped being urgent. I breathed deep on purpose, to test it. It hurt just the same [the same stab, in the same place] and I did not mind.

I slept six hours straight for the first time in five days [the pain woke me twice and both times I went back to sleep].

The rest came on its own: constipation from the second day, an odd itch in the nose that went away with scratching, and a general warmth I would not call pleasure and that is not neutral either. Desire disappeared for the five days [that is textbook and nobody mentions it in the consulting room]. On the fourth day I realised I was looking at the clock before it was due.

I finished the box on the fifth day, as planned, and did not ask for more. The prescription allowed a renewal [once, without going back to the consulting room]. The third night without tablets I slept badly, and lay awake knowing perfectly well why.

IV

Inside, the business has an oddity that has to be looked at straight on.

The molecule is rigid, five rings stuck together, fairly large for what it does. It enters the blood, crosses into the brain with difficulty —only a small part arrives— and there it wedges into locks that were already in place.

That is the strange part. The poppy did not bring the locks; the body had them from before, and it uses them with substances of its own that it makes itself when a pain has to be switched off in the middle of a run or a fight. The plant produces a key that fits a human lock, probably because it served to stop it being eaten.

What the key does is not what it seems either. The pain signal goes on leaving the broken rib and goes on climbing the spinal cord; the molecule sits at the door that signal passes through and turns the volume down, and above, in the brain, it switches off the part that turns the signal into urgency. That is why the patient says the sentence they all say: it still hurts and I do not mind.

It is not the indifference of the operating theatre or that of a room in 1952. Here what stops mattering is one single, very concrete thing, and the rest of the world stays where it was.

The body, as always, responds. If the locks are occupied all day, the cell reduces its own production and makes them less sensitive, so that the same dose does less and more is needed for the same. That begins within days. When it is withdrawn, what is left is a system with the brakes taken off and nothing to hold them for a few hours, between twelve and seventy-two, which is what people call cold turkey, and it is literally that: a body used to somebody from outside doing a job it stopped doing.

There is one exception and it is the one that gives the business away. The gut has the same locks and never gets used to them. Tolerance comes for sleep, for euphoria and for pain, and does not come for constipation, which lasts as long as the treatment lasts and does not negotiate.

V

What happened in that back room was not the discovery of a painkiller. Painkillers existed, and one of them was opium.

What happened was that for the first time a substance was separated from the plant that contained it, weighed and could be repeated.

Everything that comes after comes out of that operation. Quinine, cocaine, atropine and caffeine are isolated in the following two decades, by the same procedure and almost by the same hands. It is a method, not a series of loose findings: boil, precipitate, wash, crystallise, weigh. Pharmacy stops being a trade of mixtures and becomes an industry of quantities. The pharmacist who adjusted by eye turns into an intermediary between a factory and a prescription. The word dose, as we use it, is two hundred years old and starts there.

The same operation has the other edge, and it does not work as an unfortunate consequence; it is the same thing seen from the other side. Weighing makes it possible to give exactly enough. Weighing also makes it possible to give too much on purpose, to know how much too much is and to sell it by units.

Before 1804 nobody could die of a figure. One could die of a badly made decoction, which is another thing and cannot be industrialised.

VI

The easy piece here is the epidemic, and I am not going to write it.

Not out of delicacy, but because I do not have it in my body. What I know of that I know from statistics, and writing in the voice of a witness about a thing I have read is the vice this series tries not to have. I had a box of twenty tablets, I counted it, I finished it and I slept badly for three nights.

The only thing I can contribute at first hand is of a ridiculous size next to the matter. On the fourth day I looked at the clock before it was due. That is all I saw from inside, and it already seemed to me a fair amount of information.

VII

Of the three boys of Paderborn nothing more is known [no names, no trade, nothing of what they were told beforehand]. There are no names, no exact ages, nothing of what became of them; there are three lines in the report of a man who was describing his own poisoning.

Of him a good deal is known. He went on working, argued for years over recognition for what he had done, had chronic pain and treated it with the very thing he had isolated. He died on 20 February 1841, in Hameln, fifty-seven years after those crystals.

The era of the exact dose began with a dosing error. The man who made it possible to write ten milligrams on a piece of paper came close to killing four people for not knowing how much was too much [and three of them had not decided anything].

1804, the first crystals.

1817, the test on himself and on three seventeen-year-old boys, with a quarter of a bottle of vinegar to bring it back up.

20 February 1841.

Box of twenty ten-milligram tablets, today, in a Spanish pharmacy: less than five euros.

Five days.