The Four Kilometres

I

On 19 April 1943, at twenty past four in the afternoon, a thirty-seven-year-old Swiss chemist took in his laboratory two hundred and fifty millionths of a gram of a substance he had synthesised five years earlier and left forgotten on a shelf.

His name was Albert Hofmann. He wrote down the hour and the quantity in his notebook before taking it; that is what distinguishes an experiment from a piece of foolishness.

Everything that comes from that afternoon comes out of that notebook and of the report he wrote the following day for his boss. Not out of his memoirs, which are from forty years later and are already contaminated by everything that happened in between.

He had chosen that quantity because it seemed ridiculously small to him; he wanted to rule an effect out, not to find one. With any other known compound, two hundred and fifty micrograms would have done absolutely nothing.

By five he could not go on writing. He asked an assistant to accompany him home and they went by bicycle —it was 1943, there was a war and there were no cars and no petrol for such things—.

It was four kilometres.

During the journey, as he noted afterwards, the road moved, time came apart for him and he was convinced he had poisoned himself and was dying. At home they called the doctor, who examined him and found nothing abnormal except enormous pupils: pulse fine, breathing fine, blood pressure fine.

At six hours it began to pass; by ten at night he could speak normally. The next day he got up with a sensation of clarity he described as though the world had been freshly washed, and went to work.

II

What makes this first dose singular is not the experience. It is the figure.

Two hundred and fifty micrograms is a quantity that cannot be seen. A grain of salt weighs some sixty micrograms [more or less, depending on the grain], so that this was four grains of salt spread through a body of seventy kilos.

Nothing known at the time did anything at that scale. Drugs were measured in milligrams and often in grams [an aspirin is five hundred], and this substance was a thousand times more potent than anything in the cupboard.

That, by itself, forced an idea to change. If so enormous an effect is produced with so little matter, it is because it is not acting as a poison or as a solvent; it is fitting into something very specific and very scarce.

The figure was the discovery. Everything else, including all the culture that came afterwards, is consequence.

That is why the finding of that afternoon belongs not to the history of drugs but to that of pharmacology. If something acts at that scale, it has to be fitting into a particular piece of the brain, and that piece has to exist for some reason that has nothing to do with the substance. Looking for it took years and changed what was known about how a brain works inside.

III

I have not taken it and I am not going to pretend I have.

What I did was the other thing: I took a bicycle and rode four kilometres at the same hour, on a Wednesday in April, to see how much that is in a normal body.

It takes fourteen minutes going slowly [I timed it twice, just in case]. It is a short distance, of the kind you cover without thinking to get anywhere, and the route I chose had a gentle rise at the start and a straight avenue afterwards. It was thirteen degrees —April in a northern city— and I arrived without sweating.

Fourteen minutes.

In those fourteen minutes, a man who knew perfectly well what he had taken and how much was convinced he was dying, and went on pedalling, and wrote it down on arrival.

There is no honest way for me to tell the other thing. I can tell the bicycle, the hour, the thirteen degrees and what a municipal hire bike costs [thirty cents the half hour]. That is what I have.

What I can say is that the distance, covered in an ordinary body, is humiliatingly small.

There is one more thing I took from that Wednesday and did not expect. I was watching the traffic, a long set of lights and a kerb, and in fourteen minutes I took a good few small decisions without noticing any of them [brake, turn, wait]. He did all that too, with the road moving and convinced he was dying. He arrived whole, parked the bicycle and went up to his flat [the rest of the afternoon he spent on the sofa, with the assistant beside him and a glass of milk].

IV

Inside, the key is in that disproportion between how little there is and how much happens.

The molecule is rigid and has a shape fairly like serotonin, that signal which in the brain regulates mood, sleep and also, in some places, the way the cortex filters what reaches it. There are locks made for serotonin spread through the whole nervous system, and one of them, very abundant in the outer layer of the brain, is the one that matters here.

LSD gets into that lock and stays. Here is the detail discovered only a few years ago and that explains the hours. The molecule goes in, and a part of the protein itself folds over the top like a lid [a lid that was not foreseen for anybody], so that it is left trapped inside. It cannot get out until the cell swallows the whole receptor.

That is why it lasts so long with so little. It is not that there is much substance; it is that the little there is does not leave.

What changes then is not raw perception. The eyes go on seeing the same thing. What is altered is the work of filtering: the brain devotes an enormous part of its activity to predicting what it is going to perceive and to discarding what does not fit, and it is that discarding system that comes loose.

Things come in that normally do not get past the filter. Zones connect that normally speak to each other little. The sensation that one is a thing separate from the rest, which the brain also manufactures and which costs energy to sustain, weakens.

The body, meanwhile, hardly notices: blood pressure and temperature rise a little, the pupils dilate, and that is it. The lethal dose is so far from the active one that there are almost no documented cases of death from the substance itself [the dead there are come from what people do, not from what the molecule does].

V

Out of that afternoon came two stories that do not get on well.

One is the scientific one, and it did not last. During the fifties and sixties hundreds of studies were published and it was tried in alcoholism, in the anxiety of terminal patients and in psychotherapy, with methodologies that today would pass no filter but with results that could not be entirely dismissed.

The other is the cultural one, and it ran the first one over. At the end of the sixties the substance became a banner, politics entered the business and within a few years it was banned almost everywhere; with the ban, clinical research also closed down for forty years; the files were put away and the substances stayed in the fridges.

What I want to leave stated is the mechanism, not the nostalgia. A molecule can become impossible to study less for what it does in a body than for what it means in a public argument. When that happens, what is lost is not the drug, which goes on circulating just the same: what is lost are the trials.

VI

Against me: I have written one thousand three hundred words about a substance I have not tried, from somebody else's notebooks and a bicycle outing.

That is exactly what I criticise in other places in this work.

I stand by it for one reason and it is a matter of method: here the body in the archive is better documented than mine. Hofmann noted the hour, the dose, the symptoms and the duration, in a laboratory, with a medical witness, and did it again afterwards with smaller quantities. It is one of the few self-experiments in history that meets the requirements we would demand of a trial today, except the most important one, which is not being the only subject.

VII

Hofmann worked forty more years in the same laboratory, isolated the active compounds of the Mexican mushrooms, retired, wrote and died in 2008, at a hundred and two.

To the end he maintained two things at once: that the thing had medical value and that its uncontrolled mass diffusion had been a disaster. He called his compound “my problem child”.

19 April 1943, twenty past four in the afternoon, two hundred and fifty micrograms.

Four grains of salt.

Four kilometres by bicycle, fourteen minutes in a normal body.

Six hours of effect.

Forty years of interrupted clinical research.

Municipal hire bicycle: thirty cents the half hour.