Patient One

I

In April 2012, in Philadelphia, a six-year-old girl received by vein her own white cells after a laboratory had added to them a piece that does not exist in nature.

Her name was Emily Whitehead. She had a leukaemia that had come back twice, she had exhausted the chemotherapy and there was no compatible marrow donor. The doctors had told her parents to take her home.

She was the first girl in the world to receive this treatment [in adults a round had already been done]. In the trial papers she appears as “patient one”.

Within a few days she began to get worse. Very high fever, blood pressure on the floor, her lungs filling with fluid, and within hours she was in intensive care on a ventilator, swollen and in an induced coma. The doctors thought she was dying and called the family in.

What saved her was a reasoned coincidence.

II

That coincidence has to be told slowly, because it is the best thing this file has.

While the girl was going out, the team analysed her blood looking for what was producing that storm. They found one inflammatory signal in particular fired a thousand times above normal.

The doctor running the trial —Stephan Grupp— knew there was a drug against that exact signal, and it was not an oncological one. It was a treatment for rheumatoid arthritis that his own daughter took.

He asked for it, got it that same afternoon and it was given to her.

Within hours the fever came down and the blood pressure recovered. She woke a few days later, on the day she turned seven.

Three weeks after the infusion, not one leukaemia cell was to be found in her marrow.

III

I donated plasma for the first time at thirty-eight and I did it out of curiosity.

It is a machine that takes blood out through one arm, spins it in a centrifuge that separates the components by weight, keeps the liquid part and gives you back the rest, warmed, through the same arm. It lasts between forty-five minutes and an hour [the needle is thicker than the one for a blood test].

The odd part is the sensation of the returned blood, which comes in cold even though they warm it, and the metallic taste that sometimes appears from the anticoagulant they use.

In Spain it is not paid: they give you a juice, a packet of biscuits and a piece of paper.

What they do with my cells has nothing to do with the matter of this piece, which modifies them, whereas from me they take a liquid and separate it. But the machine is the same family of machine and the gesture is identical: the blood goes out, goes to a place where something is done to it, and comes back.

The first time I watched the tube the whole while. The second I was already reading my phone.

IV

Inside, this is the strangest thing in the whole series, because the medicine is alive.

The patient's own lymphocytes are taken out, the cells whose business is recognising and killing what should not be there. The problem with a cancer is that it does not convince them. Tumour cells come from the body itself and carry nothing on them that clearly says foreigner.

In the laboratory a gene is added to those lymphocytes that makes a new piece, designed by hand, which sits across the membrane. Outside it is a hook that recognises a particular mark on the surface of the diseased cells; inside it is the ignition button of the cell itself.

When the hook catches, the button lights. The lymphocyte kills what it has grabbed and, besides, multiplies.

There is the difference from everything before. This does not work like a dose; it is a population that grows inside. A bag with a few million cells can become thousands of millions in two weeks, and the drug manufactures more drug for as long as there is an enemy.

That also explains the storm. When millions of cells are activated at once, they release at once the chemical signals with which they alert one another, and those signals in quantity produce fever, a drop in blood pressure and organ failure. It is not an allergic reaction [there is no allergy to one's own cells]; it is the treatment working too well and too fast.

When the enemy runs out, the population withdraws. A part stays for years, keeping watch, because that is what lymphocytes do.

V

What this case changed is not the prognosis of a childhood leukaemia.

It is the category of what can be sold in a vial. A living medicine, made with the cells of one particular person, that cannot be mass-produced or kept in a warehouse, that is made to order for a single body and that carries her name stuck to the bag from the moment it leaves the hospital until it comes back.

That breaks the whole industrial chain. There are no batches, there are patients. There is no stock; there is a diary. The product expires, travels frozen and depends on the person still being alive when it is ready [weeks pass between the extraction and the infusion], which is a condition no other drug has.

VI

The objection is not the technique and it is predictable: the price.

This treatment was approved in 2017 [the first of its class in the world] and its list price was around four hundred and seventy-five thousand dollars, for the infusion, once only. With the admission, the intensive care if it is needed and the follow-up, the complete bill goes considerably higher.

Of that first round of adult patients several died; Emily was the first girl and the one who came through. In the trials that came afterwards, the storm that almost killed her stopped being a surprise and became a section of the protocol, with its severity scale and its rescue drug waiting in the ward fridge.

It is paid for once and it can cure. That means health systems do not know how to account for it, because they are built to pay for monthly treatments, and there are countries that have negotiated to pay only if the patient responds.

That formula has a name and it is recent, “payment by result”. It means the hospital gives the money back if the patient does not improve within a period, and it means too that somebody has to define by contract what counts as improving and who measures it. It is the first time a medicine has been sold with a guarantee, like a household appliance.

Against me, the same thing again: I donate plasma free in a room with biscuits, and what is done with other people's cells costs half a million.

VII

Emily Whitehead turned seven in intensive care and has not had leukaemia again. She finished secondary school, went to university and gives talks when she is asked.

The drug that saved her from the storm is still the same one used today for that, and it is still, in its origin, a treatment for arthritis.

April 2012, patient one.

Days in intensive care on a ventilator and in an induced coma.

An arthritis drug ordered that same afternoon.

She woke on the day she turned seven.

Three weeks later, not one leukaemia cell in the marrow.

2017, approval: four hundred and seventy-five thousand dollars per infusion.

Plasma donation, today, in Spain: a juice and some biscuits.