Eighty-Two

I

What there is instead of a name is a registration number.

The Japanese trial appears as NCT00280397, registered in January 2006, with twenty-seven patients of median age fifty-three, thirteen milligrams twice a day in cycles of two weeks on and one off. Almost at the same time another ran in Europe with eighty-two patients, spread over steps that went from two tenths of a milligram to thirty-two [the first dose of an escalation is ridiculous on purpose].

The escalation stopped at thirty-two because protein started coming out in the urine of somebody on that step. The kidney filters through tufts of extremely fine vessels; when those vessels stop holding up, the protein in the blood slips through. That fact fixed the ceiling at twenty-five milligrams.

Of the person it happened to, there is a record of the sex, the age, the tumour they had, the dose, the day of the cycle on which the problem appeared and the grade of the toxicity on a scale of one to five [three means it has to be interrupted]. Nothing else is recorded, and it is not recorded because the protocol forbids it being recorded.

The register is complete. It has everything a phase one trial should have [n, design, steps, withdrawal criteria] and it has nobody inside it.

II

The whole catalogue of the targeted has promised the same thing since the nineties.

The promise is that the molecule stops ignoring you and starts selecting you. The right body is needed, the one that carries the mark; whoever does not qualify is left outside, and that was decided by a test before anybody signed anything. That is the border crossed in 1992 with the sixteen women of trastuzumab.

This drug is in that catalogue and does the opposite.

It grabs six families of receptors at once. The three that receive the order to make new vessels, the four of another family that builds tissue, the one for the platelet factor and two more that are involved in different cancers [one of them is the one that goes wrong in the thyroid]. There is no prior test deciding who goes in; the indication is anatomical and not molecular, and it is written like this: thyroid that has stopped taking up iodine.

It does not kill the tumour. It cuts off its supply.

A shotgun in a catalogue of rifles, sold at the same counter and with the same argument.

III

The cheapest thing in this series has cost me nineteen ninety.

It is an arm blood-pressure monitor, from the chemist's, with a velcro cuff and two batteries. You press a button, the cuff inflates, squeezes, lets go and gives three numbers on a large screen designed for the elderly.

I put it on as the instructions say, “seated, with your back supported and without speaking”. A hundred and twenty over eighty, sixty-two beats.

That device is the instrument with which the drug this piece is about is monitored. In four out of ten patients the blood pressure rises in the first weeks, and it is a rise that appears before any imaging test. When you order the vessels of the whole body to stop widening and repairing themselves, the blood leaving the heart meets harder, less plastic tubes, and the number on the cuff goes up.

So the first signal that the thing is working inside does not come from a thousand-euro scan. It comes from this.

I have it on the table while I write. Nobody is cutting off my supply; all my device measures is the normal blood pressure of a man who sleeps badly.

IV

A small tumour needs none of this. At a couple of millimetres what reaches it by diffusion from the vessels of the neighbourhood is enough, as a damp patch makes do with the wall.

To get past that it has to ask for plumbing, and it asks by shouting.

The cells that line the vessels inside carry an aerial that juts outwards and that is put there to receive that shout. When they receive it, they set to building. They stretch, they separate, they make a new conduit and connect it up. The tumour shouts far louder than a healthy tissue, and the plumbing that comes out of that shout is badly made —crooked vessels, with holes, that leak fluid and strangle themselves— because nobody supervises a job done by shouting.

The capsule is swallowed in the morning, comes apart, crosses the wall of the gut and goes into the blood. The molecule is small; it weighs some three hundred and fifty times less than an antibody [four hundred and twenty-seven daltons against a hundred and fifty thousand] and goes in where it likes. What it is looking for is the aerial's switch, which is on the inner face of the cell.

There it gets into the gap where the piece that turns the switch on fits, and it gets in in a particular way: as well as the gap, it grabs a groove alongside, and that is why it comes off more slowly than others of its family.

The shout goes on. Nobody attends to it.

What happens afterwards is slow and has the shape of an abandonment. The work stops, the badly made vessels already in place collapse first, and the tumour is left with the supply it had and without the one it was going to have.

The body responds to this wherever it also makes vessels, which is everywhere. The tufts of the kidney let protein through. Wounds do not close, because closing a wound consists of laying new plumbing. The hands crack and the blood pressure rises, and that pressure has to be treated with another tablet for as long as the treatment lasts.

V

Where there is no single mechanism to explain, there is no single body to show either.

The earlier pieces had both things at once —a target and a body— and they had them for the same reason. A drug that grabs one particular target lets itself be told through one particular person, because the person is the proof that the target existed.

Here there is no target, there are six. There is no clinical history, there are eighty-two dose steps and a median. The trial with its cohorts is not a substitute for the missing patient, it is the only way this drug has of existing in a file.

What is sold as “targeted” is not the molecule. It is the bookkeeping.

Eighteen months and three tenths without the disease advancing, against three months and six tenths with placebo. That pair of figures from the large trial is everything this drug is capable of saying about itself, and it is more than half the drugs in this series ever said.

VI

Against me, and it is serious: the shotgun may be the reason it works.

When only the route that asks for vessels is blocked, the tumour takes little time to use another to ask for the same thing, and the plumbing grows again by the road alongside. Blocking both at once shuts its emergency exit. Seen that way, grabbing six families stops being a lack of aim and becomes the design.

The anonymity is not a wound either. In a thyroid cancer that has stopped responding to iodine there was nothing, and what there is now is known because three hundred and ninety-two patients were shared out at random between the drug and an empty tablet [two hundred and sixty-one against a hundred and thirty-one]. That randomness is what erases the names and what produces the fact.

My complaint is aesthetic. The eighty-two did not complain about that.

VII

I come back to the thirty-two milligram step.

There is a person, alive or dead, into whose urine in 2006 went the protein that should have stayed in the blood, and that set the ceiling for everything that came after. The dose approved nine years later is twenty-four milligrams a day, one step below where their kidney said enough.

Every capsule a thyroid patient swallows today is calibrated with the damage of a body nobody can name. The file recorded everything about that body except who they were, and it did right: that was the promise made to them on entering.

Twenty-seven patients in the Japanese trial, eighty-two in the European one.

Steps from two tenths of a milligram to thirty-two; ceiling at twenty-five; approved dose, twenty-four a day.

Approved on 13 February 2015, nine years after that escalation.

Eighteen months and three tenths against three and six.

High blood pressure in four out of ten of those who take it.

Average cost per prescription in the public data of the United States system for the elderly: eleven thousand five hundred and twenty-six dollars. Per year, per patient, some hundred and four thousand.

My blood-pressure monitor: nineteen ninety, batteries included.