Four Rounds

I

On 20 August 2015, in Atlanta, a ninety-year-old man sat down in front of the cameras to explain what they had found in him.

Two weeks earlier a small mass had been taken out of his liver in a scheduled operation [at the start of the month, without it being announced], and the mass was a melanoma. The scan done afterwards found four spots in the brain, of about two millimetres each.

His name was Jimmy Carter and he had been president of the United States. He said in front of the journalists that on hearing it he had assumed he had a few weeks left, and he said it without drama and with the following month's diary on the table.

That same afternoon he received the first session of radiation aimed at the four spots. And he began receiving, every three weeks, an antibody approved eleven months earlier.

On 6 December 2015, in the Sunday school class he taught at a church in Plains [Georgia, six hundred and eighty inhabitants], he said the latest scan showed nothing. Neither the four spots nor any new one.

He had been given at least four rounds. He went on being given them.

II

Carter was not the first body; he was the body that made it public, and the difference is documented with dates.

The first went in in December 2011, in a phase one trial that began the way they all do. Three patients at one milligram per kilo of weight, three more at three, three more at ten, going up until you find where it poisons. That first body has no public name and its dose is in a table [one milligram per kilo, the bottom step].

What happened afterwards never happens. The trial went on widening as it ran, cohort after cohort, because people were responding. It ended with more than one thousand two hundred patients inside it and became the largest phase one trial in the history of oncology.

A phase one trial serves to find the toxic dose in a few dozen people. This one turned into an efficacy trial without stopping the machine, and the United States agency approved it by the “accelerated” route on 4 September 2014 with those data.

The design broke by working. Eleven months later, Carter was given the first bag.

III

I have been photographed entire for eighty euros.

It is a mole mapping. You go in your underwear into a booth with a platform marked with two footprints —they are put there so that everybody comes out in the same posture—, the apparatus goes round, shoots from several angles and composes a figure with all the marks numbered. Then a dermatologist looks at the ones the program has flagged and passes a magnifying lens over three or four.

It took twelve minutes [nine of them taking my clothes off and putting them on]. The report arrived in an email with an attachment of fifty-two megabytes.

It says there are no findings of interest and to come back in twelve months.

That is what I can buy. What Carter was given costs eleven thousand seven hundred and ninety-five dollars a bag at the manufacturer's rate, and is given every three weeks until it is no longer needed or until it stops working.

Mine is detection; detection is always cheap, and that is why it is the only thing offered at the counter on the street.

IV

The lymphocyte that knows how to recognise that melanoma is already inside the tumour.

That is the part that is hard to believe. Nothing has to be made and nobody has to be taught anything: the cell that could eat the tumour went in, touched it, recognised it and switched off right there.

It switched off because it has a brake, and the brake is there for a good reason. When you go through an infection, the army that fights it has to demobilise at the end, and if it does not demobilise it starts eating your own. For that there is a socket on the surface of the lymphocyte which, when it receives the right signal, orders a halt.

The tumour learns to give that signal. It makes the piece that fits the socket and puts it out like a flag, so that every lymphocyte that approaches it receives the order to withdraw at the moment of touching it.

The antibody sits on top of the socket. Nothing more. This family is called “checkpoint inhibitors”, and the checkpoint is the brake.

It does not grab the tumour, does not puncture it, does not cut off its supply and does not enter any cancerous cell; in this whole series it is the first drug that does not get as far as touching the disease it treats. What it does is cover the place an order was arriving by, and the army that was already there, halted, sets off again.

The body responds to that with what you would expect from an army whose ceasefire order is lifted. Between five and ten per cent of patients develop a serious inflammation in some organ of their own: the thyroid, the gut, the pituitary, the skin, the liver. Some of those faults are switched off with corticosteroids and others stay for life [a burnt-out thyroid does not come back; nor does a diabetes of this kind].

Of Carter's radiation something is suspected that was not demonstrated in him. When tumour cells are burst by radiation, recognisable pieces are left floating, and an immune system with no brake suddenly has far more to read.

V

Every drug in this series puts something in. A molecule that can be weighed, a piece that fits somewhere, a sequence the body runs.

This one takes away.

What is administered is the suppression of an order the body was giving itself, and the whole treatment consists of the patient ceasing to obey themselves. The target is not the tumour or a protein of the tumour; the target is the patient's prudence.

That is why the price is charged in the same currency. Whoever lifts the brake is left without the guarantee that the army will distinguish between the melanoma and their own thyroid, and that guarantee is what one was paying for with the disease.

VI

Against me: Carter's case is the worst possible evidence.

He is one patient [one], ninety years old, famous, irradiated at the same time in the four lesions that afterwards disappeared. There is no way of sharing out the credit between the radiation and the bag, and no committee would accept that file as evidence of anything. It did more for the drug's reputation than the trial of one thousand two hundred that approved it, and it did so for reasons that have nothing to do with pharmacology.

Besides, most do not respond. In the five-year follow-up of that enormous trial, thirty-four per cent of the patients with advanced melanoma were still alive; of those who had already received other treatments beforehand, fewer. Two out of every three died with the best drug of their generation in them.

Before 2011, with melanoma in the brain, median survival was about four months.

VII

I come back to the Sunday school class.

A gentleman of ninety-one tells a group of neighbours sitting on folding chairs that the scan came back clean, and he tells it in the same tone in which in August he had told the other thing. There is nothing in that scene a doctor can use. It is an old man speaking in a carpeted room —there is no white coat and no hospital anywhere in the scene— and in the photographs you can see the mark of the tape on the back of his left hand.

He lived nine more years. He died on 29 December 2024, at a hundred [he had been born on 1 October 1924], and the obituaries carried the drug's trade name.

Four lesions of two millimetres, one session of targeted radiation and at least four rounds between August and December.

First patient of the trial, December 2011, with no public name.

Final size of that phase one trial: more than one thousand two hundred patients. Approval, 4 September 2014.

Five-year survival in advanced melanoma: thirty-four out of every hundred.

Serious inflammation of an organ of one's own, between five and ten out of every hundred.

List price of a two-hundred-milligram bag: eleven thousand seven hundred and ninety-five dollars. Per year, above two hundred thousand.

Worldwide sales of the product in 2024: twenty-nine thousand five hundred million dollars, the best-selling drug in the world.

My mole mapping: eighty euros, and come back in twelve months.