Twelve Fifty-Two

I

On 14 September 1990, at twelve fifty-two midday, in a hospital in Maryland, a four-year-old girl received by vein a bag of her own cells, modified.

Her name was Ashanti DeSilva. She had been born with a disease in which an enzyme is missing, and without that enzyme a substance accumulates in the blood that poisons the defences. Children with that have no immune system and die of ordinary infections.

What they gave her were lymphocytes of her own, taken out weeks before, into which the laboratory had put a good copy of the gene she lacked, using a deactivated virus as the carrier.

The procedure lasted twenty-eight minutes [from twelve fifty-two to twenty past one]. Afterwards she went to eat with her parents.

There was no applause and no press conference that day; the press conference came later. What there was was a plastic bag with a thousand million cells and a wall clock.

II

It has to be said carefully what that demonstrated, because it was told wrong from the first moment.

Ashanti did not stop the treatment she was already on. She went on receiving the enzyme by injection [the modified bovine enzyme, once a week], an expensive drug that already worked, and she went on receiving it during and after the experiment. So that when she improved, there was no way of knowing how much was from the new cells and how much from the enzyme she had always had.

The authors themselves said so. The press did not.

What was demonstrated is the other thing, which is no small matter: that cells could be taken out of a person, their genetic material changed outside the body, given back, and that this did not kill her. The proof was one of safety and of procedure.

Thirty-five years later, the modified cells of that afternoon are still circulating in her blood.

That, which is quickly said, is the soundest fact in the file. It does not prove it cured her; it proves that what was put inside her stayed there, working, longer than most marriages last.

III

I sent my saliva by post in 2021, in a plastic tube with a blue cap, for ninety-nine euros.

You spit up to a marked line, it costs more than it looks, you close the cap that releases a preserving liquid and you put it in a prepaid envelope. I dropped it in the postbox on the corner on a Thursday [the envelope weighed less than a letter].

At six weeks an email arrived with a link and a forty-page report.

What it carried was a mixture. Where my ancestors came from with a debatable precision, a few variants associated with risks of common diseases with numbers that mean almost nothing for an individual, and a list of what the report calls “traits”, of the amusing sort [whether coriander tastes of soap to me, whether I have wet or dry earwax].

I read it for a whole afternoon and changed nothing in my life.

That is what can be bought today with the genome: reading it. Ninety-nine euros and six weeks to have the whole text of oneself in a PDF, and no capacity to touch a single letter.

The distance between reading and writing is the whole business.

Reading costs ninety-nine euros and is done by a company by post. Writing costs a hospital, a committee, a laboratory with permission to handle viruses and a lifetime of follow-up, and in 1990 it cost besides an argument of years over whether it could be done.

IV

Inside, the thing in 1990 was a courier operation.

The missing gene is a recipe; what had to be done was to put a good copy inside cells that already existed. For that a virus was used, which is the only thing in nature that knows how to do that well, because it is what it is dedicated to: getting into a cell and leaving its own material inside.

A type of virus was taken and the genes it uses to multiply and do harm were removed, and into the gap the needed recipe was put. The virus —emptied in that way— still knows how to get in and release the cargo, and no longer knows how to do anything else.

The cells were taken from the blood, put in a flask with the virus for a few hours, left to multiply and returned by vein.

The delicate part of this is not the entry. It is where it lands. The virus inserts the recipe into the cell's genetic material, and it does so where it falls. If it falls in the middle of a gene that controls when a cell should stop dividing, that cell can become the beginning of a leukaemia.

That was not a theoretical worry and it was confirmed a decade later, in a French trial with another similar disease. Several children were cured and afterwards developed leukaemia because of where the gene had landed.

The body, meanwhile, does what it knows: it recognises the virus as foreign and attacks what it can. That is why the cells are modified outside, in a flask, and not inside the person.

V

What was launched that midday was not a cure. It was a category.

Until then, a medicine was a substance that went in, did something and left, and had to be taken again. This is another thing. An instruction that stays inside and that the cell itself copies every time it divides.

In the papers of the time that was called “gene transfer”, and that name was more honest than the one we use now. From there comes the whole last part of this series. What is administered stops being a molecule and becomes information, and the body stops being the place where the drug acts and becomes the factory that runs it.

The price of that move appears at once and is the one we still argue about. A substance can be withdrawn; an inserted instruction cannot.

That forces a change in the question asked of a treatment. With an ordinary drug you ask what it does while it is inside and how long it takes to leave. With this you have to ask where it has got to, in how many cells, and what happens when those cells divide over the next forty years [nobody had forty years of data in 1990, and now we are beginning to have them].

VI

The objection is double and both parts are solid.

The first: that trial was approved under enormous pressure from its promoter, in a competitive atmosphere, and with a design that made it impossible to draw conclusions about efficacy. It was, strictly, a safety experiment sold as a therapeutic milestone.

The second is about me and I have had to say it other times. I have written that my ninety-nine-euro report did not change my life, and that is true and it is a privilege: it means nothing came out that forced me to decide. Whoever receives that same PDF with a serious variant on it has a different problem, and that problem does not come with instructions.

VII

Ashanti DeSilva is now the age I am. She has given the occasional interview, has said she considers herself a normal person with a not very normal story, and does nothing related to any of this.

The second patient of that trial, Cynthia Cutshall [she came in four months later], is also still alive.

The field, on the other hand, almost died. In 1999 an eighteen-year-old boy called Jesse Gelsinger died four days after receiving a gene therapy at another hospital, from a massive reaction to the carrier virus; it emerged afterwards that there were irregularities in the consent and in the prior data. Trials were stopped across half the world and the area took more than a decade to recover.

14 September 1990, twelve fifty-two midday.

Twenty-eight minutes of infusion.

A thousand million cells with a recipe added.

Thirty-five years and those cells are still there.

Reading a whole genome by post, today: ninety-nine euros and six weeks.