The Daughter of the Man Who Found It

I

In December 1935, in a house in Wuppertal, a girl was coming down some stairs with Christmas decorations in her hands, tripped, and the sewing needle she was carrying went in and broke off inside her, down to the bone of the wrist.

Her name was Hildegard Domagk. In the accounts of the period she is given as six and in other sources she comes out as eight, according to where her birth is fixed; I do not give the figure because I cannot fix it. The wound became infected, the infection climbed her arm, she was operated on several times [successive drainages, without result] and there came a point at which the doctors proposed amputating. It was a streptococcal infection; at that moment that killed young, healthy people with an efficiency it is hard to imagine today.

Her father worked in a pharmaceutical laboratory and had spent years testing dyes in mice —hundreds of mice, one after another, without result—.

Gerhard Domagk had found in December 1932 that one of those red dyes, used for colouring fabrics, saved mice infected with streptococcus. It worked in the animal and did not work on the culture plate; a contradiction with no apparent sense, which held the matter up for years.

With his daughter in bed and the amputation on the table, he took the compound from the laboratory and gave it to her [without anybody's permission, with no established dose, with no human precedent].

The girl recovered. She kept her arm and her skin was left a reddish shade for quite some time; that thing was, literally, a dye.

II

It has to be said what the previous sentence means, because it is not an ornament: the first effective antibacterial in history was a dye for cloth.

The idea came from a very old intuition of German chemistry. If a dye attaches selectively to one fibre and not to another, perhaps there exists a substance that attaches selectively to a microbe and not to the patient's cells. That was called “the magic bullet” and it was sought for thirty years in the dye industry, which in Germany was the most powerful in the world.

Domagk's red compound was that. They called it Prontosil, and it was sold in red bottles and dyed everything it touched.

Then came the humiliating part for the company. A group at the Pasteur Institute discovered that the dye itself did nothing: the body split it in two and the active piece was the other half, a small, colourless, unpatented molecule known since 1908.

Sulfanilamide belonged to nobody [the patent had expired twenty years before anybody knew what it was good for]. Anybody could make it, and within two years there were hundreds of preparations on the market.

III

I carry an allergy noted on the pharmacy's file and I do not know where it comes from.

It says sulfonamides, in capitals, and it has been there since I was a kid; there is a family story about a rash at seven that nobody remembers properly [not even my mother, who remembers everything]. Every time I am prescribed something, somebody looks at the screen, sees that word and changes the drug.

That means the molecule of this piece is the only one in the whole series I cannot take.

What I have had is what it prevented. A throat infection of the real kind, at thirty-four: thirty-nine degrees of fever for four days, glands in the neck like marbles and a pain on swallowing that made you plan every swallow.

They gave me something else, from another family: eight days, fourteen euros with the prescription.

By the third day I was in the kitchen eating soup standing up at eleven at night, with that odd hunger that comes after a fever [the kind that appears all at once and disorders the house]. All that was left was a week of tiredness.

With what I had, in 1934, there was a real probability of that thing going on down towards the chest or up towards other places. Not a remote possibility. A probability with numbers. The difference between the two scenes is eight tablets and one afternoon.

That is what I want to stay, because it is what is least noticed. The sense that a throat infection is a nuisance and not a risk is a recent invention, from nineteen-thirty-something, and it rests on an industrial chain that works every day without anybody looking at it.

IV

Inside, this molecule makes the most elegant move in pharmacology, and it makes it by resemblance.

Bacteria have to make their own folic acid, which is a vitamin indispensable for building new genetic material, and they make it out of a small piece called, for short, PABA. We do not make it: we eat our folate, it comes in vegetables, and that is why we do not have that assembly line.

There is the difference that explains everything.

Sulfanilamide resembles that small piece enormously. So much so that the enzyme that assembles it mistakes it, grabs it and sets to work with it; and since it is not the right piece, the line jams.

The bacterium stops making folate. Without folate it cannot copy its genetic material, and without copying it it cannot divide.

Notice what it does not do: it does not kill it. It leaves it halted, unable to multiply, and the work of killing it is finished by the patient's immune system, which was the one losing the race on numbers.

That is why sulfanilamide was of no use at all on the laboratory plate if the plate carried the wrong material [with broth rich in PABA, nothing happens], and that is why Domagk took years to understand his own results.

And that is also why resistance appeared fast. It is enough for the bacterium to change the shape of that enzyme a little so that it stops being fooled, or to get folate from its surroundings, and the trap is over.

V

What happened over the following two years has nothing to do with chemistry.

With the active molecule unpatented, dozens of companies set to selling it without control, and in 1937 a United States company dissolved it in a sweet liquid to make it easier for children to take. The solvent was diethylene glycol; that is to say, antifreeze.

No toxicity test was done because there was no law requiring one.

A hundred and seven people died, most of them children; the chemist who prepared the syrup killed himself before the trial.

From there, and only from there, came the United States law of 1938 that requires proof that a medicine is safe before selling it. The whole modern regulatory edifice begins in that syrup [and not in any prior ethical reflection].

The chronology is worth reading twice. First it was sold, then the children died, then the law was written. Nobody got there first. The law that came out of there is the one that today requires proof that something does no harm before putting it on sale, which is the rule we take as self-evident every time we open a box.

The same molecule that saved its discoverer's daughter killed a hundred and seven people two years later, and for reasons that were not pharmacological but administrative.

VI

Against me, and it goes to an uncomfortable place.

I have written that Domagk treated his daughter with an experimental compound and I have told it the way it is always told, with tenderness. Seen another way, it is a father administering to a girl a substance that had never been tested in humans, with no authorisation but his own.

It worked, and that is why it is a pretty anecdote instead of a case file.

It is the third time in this work that the same structure appears: somebody with privileged access to a substance uses it on a body close to them because there is no time or there is no permission, and history judges them by the result. Had the result been otherwise, the sentence we would be writing would be different and the substance would be the same.

VII

Domagk was given the Nobel in 1939 and the Gestapo arrested him so that he would refuse it, because the regime had forbidden accepting it. He signed the renunciation —they held him for a week— and collected the medal in 1947, without the money, which had already lapsed.

His daughter lived. Her skin went back to its colour, and she reached old age without anybody speaking of the matter in public again.

Of everything that happened in that house there remains a family photograph and a paragraph in a biography. There is no clinical history, no dose noted and no follow-up. The first person treated with the first antibacterial in history was a girl nobody considered a case, because she was not one: she was the daughter of the man who found it, and what was done with her was desperation with access to the cupboard [the distinction matters, and appears in no textbook].

1932, the dye that saved mice and did nothing on the plate.

December 1935, a needle broken inside his daughter's hand, down to the bone of the wrist.

1937, a hundred and seven dead from a syrup's solvent.

1938, the law requiring safety to be proved before selling.

Throat infection today, eight days of treatment: fourteen euros.