A Week in April

I

On 21 September 1948, at the Mayo Clinic, a twenty-nine-year-old woman with rheumatoid arthritis received a hundred milligrams of a compound the laboratory called, by alphabetical order of isolation, substance E.

In the papers she appears as “Mrs G.” She had had the disease for five years, her joints were deformed and she arrived at the hospital unable to move by herself —she had come in in a chair—.

On the fourth day she got up and walked [alone, down the corridor, in front of the doctors].

Within a week she left the hospital and went shopping in the city. That detail, which sounds like a serial, is in the doctors' notes and in a film shot there to document the effect [fourteen patients, in black and white, moving for the camera].

She said she had never in her life felt better.

What came afterwards, and which she did not know, is that the effect did not hold. On withdrawing the compound the symptoms came back within days, and on maintaining it other problems appeared. The spectacular improvement of the first week turned out to be the beginning of a long negotiation [and in 1948 nobody knew it was going to be long].

II

It has to be said where that compound came from, because it explains why it took so long.

Substance E was a hormone of the cortex of the adrenal gland, and in 1948 the only way of obtaining it was to extract it from cattle viscera in absurd quantities: tonnes of glands were needed to get a few grams [tens of thousands of cattle per kilo]. During the war there was a programme to manufacture it in series, fed by a rumour —German pilots flew at great altitude thanks to adrenal extracts— that was never verified.

The rumour was false. The programme existed all the same and left the chemistry set up.

When Philip Hench asked for the compound to try it on his patient, they sent him a bottle with what there was: there was no more in the world.

III

I had cortisone injected into my right shoulder two years ago.

It was a rotator cuff tendinitis, of the kind that begins with not being able to sleep on the bad side and ends with not being able to hang a shirt on a hanger. Six weeks of anti-inflammatories and exercises had done nothing.

The injection takes two minutes; the whole consultation, twelve. The unpleasant part is not the needle, which is fine; it is the sensation of pressure when the liquid enters a place that has no space for anything. It hurts during the jab itself and then it hurts more for twenty-four hours, which is what nobody tells you.

By the third day nothing hurt. Nothing at all.

I raised my arm over my head for the first time in two months, in the hallway at home, and stood there a moment with my hand up, like an idiot, checking it.

Eighty euros at a private practice, with an ultrasound scanner [with the needle on the screen, going in]. The orthopaedist told me, without my asking, three a year at most and that each one deteriorates the tendon a little.

That last part is the whole summary of this molecule.

There is a sentence from that day that stayed with me, because it describes the whole business without meaning to. I asked why three and not four, and he answered that because by the fourth it starts costing more than it fixes. That is the drug: a sum with its break-even point, different for each joint and for each person.

IV

Inside, cortisone does not do one thing: it switches off a department.

Almost every cell in the body has, floating inside it, a receptor waiting for this class of hormone. It is a large apparatus that is inactive until the molecule wedges into it; then it changes shape, goes into the nucleus and sticks directly to the genetic material.

There is the difference from the rest of the series. The other drugs occupy locks, block channels, weld enzymes. This one goes into the control room and changes which genes are read and which are not.

The result is that dozens of processes are readjusted at once. The signals that summon the cells of inflammation stop being made, the ones already there leave, and the vessels stop letting fluid through; the swelling goes down. The pain follows after.

It cures nothing. The disease is still where it was [intact, advancing]; what disappears is the body's response to the disease, which was what hurt.

Since the control that has been touched governs many things, the price appears everywhere: blood sugar rises, calcium is lost from bone, the skin thins, the mood is altered, sleeping infections wake up. The gland itself, seeing that there is already hormone to spare, stops making its own.

That last point is the most treacherous. After weeks of treatment, taking it away abruptly leaves the body without its own hormone and without the one from outside, and that can kill. It has to be lowered slowly, like somebody waking a sleeper.

V

In 1949 Hench presented the results and the film at a congress, and the effect was that of a bomb.

Within a few months the press was talking of a miracle. In 1950 the Nobel went to him and to the two chemists, less than two years after the first injection. It is among the fastest prizes in the history of medicine.

The clinic showed that film for years as a triumph, which it was. What was not screened with the same frequency were the clinical records of afterwards.

Then came the hangover, which lasted decades. It was prescribed for everything, in high doses and for months, and there appeared the swollen faces, the hip fractures, the provoked diabetes and the opportunistic infections. The word cortisone came to mean two opposite things at once [miracle and harm], and still means them.

What this case teaches, then, is not the miracle. It is the shape of the curve: an immediate and spectacular relief, a cost that appears late and somewhere else, and an interval of several years between the two in which nobody connects one thing with the other.

VI

Against me. I have written four paragraphs on the risks of the treatment and I had my shoulder injected without hesitating, and if it hurts again I will do it again.

There is something still more honest. Mrs G. received the compound in its crudest form and at the highest dose, and within a few years, when the effects of prolonged use became known, many of those people paid for having been the first. I benefit from seventy years of learning in other people's bodies what the quantity is, how often and for how long.

My two-minute injection is the summary of that learning.

VII

Of Mrs G. almost nothing more is known. Not her full name, nor what became of her. In the film she is seen moving about a room, in a light gown, turning her body to show the camera that she can.

She is among the first bodies of this series preserved in images and among those least recorded in writing; she is seen, and she is not named.

That film was screened at congresses for years and convinced more doctors than any table. A woman raising her arms in front of a camera did for cortisone what twenty papers would not have done, and in passing fixed the way of presenting a new drug that is still used today, which consists of showing somebody doing something they could not do before.

21 September 1948, a hundred milligrams of substance E.

Four days until getting up; seven until going out shopping.

Tonnes of cattle glands for a few grams.

1950, the Nobel, less than two years after the first injection.

Shoulder injection, today, at a private practice: eighty euros.

Three a year at most.