Fighting Penicillin’s Monster: Elizabeth Hazen and Rachel Brown. (Women in Science 68)

Who (besides, obviously, bacteria) doesn’t love penicillin?  It’s on everybody’s shortlist of the most important things we’ve discovered to improve our lot on this world.  Just a hundred years ago, an infected wound often meant an amputated limb, there being no weapon to stop the spread of infection this side of Chopping the Damaged Area, And Everything Near It, Off.  Good on you, penicillin, for making that happen very much less frequently.

I come here not to bury penicillin, but to remind us all of the monster its very effectiveness left in its wake, and of the two people who solved that potentially disastrous problem for us.  Right now, you have, tumbling about inside of you, all manner of fungi that, left to their own devices, would do their best to proliferate throughout your body and kill you.  What keeps them solidly in check, however, is the overwhelming numerical superiority of the bacteria growing inside of you.  They keep the fungus at bay, and you go about your day.

But, what happens when you have a surgery, or an infection, and take an antibiotic to wipe out the bad bacteria?  Unfortunately, the good bacteria are wiped out too, and that leaves the field wide open for the fungi to do pretty much whatever they want, which was why, in the years after penicillin’s mass production, the number of fungal disease related deaths started ticking ominously upwards.

Complicating the matter was the fact that a lot of fungal diseases look a lot like other, more popular diseases.  Pneumonia, tuberculosis, rheumatoid arthritis, all have symptoms that match up with those of some of our nastier fungi and, since mycology has historically been one of the most neglected areas in terms of what physicians are expected to know, such illnesses were nearly always treated by familiar means (antibiotics or hormones) that, if anything, made it even easier for the fungi to have their way.

There were anti-fungal products available, but none that weren’t massively toxic to humans.  If we were going to, as a civilization, continue using penicillin and its derivatives, we needed an effective, non-toxic treatment, a job that fell to a pair of women who, beginning from nothing, cracked the case within four years, Elizabeth Lee Hazen (1885-1975) and Rachel Fuller Brown (1898-1980).

When they set out on their quest to stop a fungal epidemic before it had a chance to begin, Hazen was already in her late fifties and Brown in her mid forties, both with a history of solid if largely unknown work behind them.  Hazen was a tiny, acerbic microbiologist from Mississippi obsessed with fashion, and Brown was a tough and athletic chemist with a reputation for exactitude.

Before teaming up, they had both been toiling away to alleviate the diseases of man.  Hazen had a long road of it.  Her education at the University of Mississippi was not accepted as sufficient by the big universities of the Northeast, forcing her to start over again, an education that was interrupted by her volunteer work during World War I.  She didn’t receive her PhD until the age of forty-two.  Her real work began in 1944 as a microbiologist for New York’s Department of Health, where she developed her expertise in recognizing and handling the diseases found in samples sent from all over the state, and in the processes involved in creating medically pure serums to combat them.

Brown, meanwhile, had had a more direct path of it, though for the first eighteen years of her life she had thought she’d be a historian, not a chemist.  It wasn’t until a fateful chemistry class that she was forced to take in college that she realized her love of analyzing samples, of pulling apart the tangled chemical web of a given vial to get at its hidden components.  Her specialty was in teasing out what parts of a concoction deemed medically effective actually did the heavy lifting.

Given a sample taken from a bit of earth that showed anti-bacterial properties, what part of the sample was doing it?  Her mastery of chemical techniques and endless patience made her the person to call when you had a miracle on your hands, and wanted to know what actually made it do what it did.

When the rise of fungal disease was making itself known, Hazen was tasked with creating a reference library of samples to improve identification of fungal infections, and with starting a search for an effective, non-toxic fungal remedy.  Her instinct was to let nature guide her hand, to gather as many different soil samples as possible and see if they contained something that worked to destroy fungus.  Why try and invent a killer compound from scratch if evolution has already created a tailor-made assassin for you?

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Her approach yielded results unreasonably quickly.  She found something in one of the soil samples she had dug with her own hands in a friend’s yard that seemed to work against two of the most common and deadly strands of fungus.  Something, however, usually doesn’t cut it.  Enter Rachel Brown, who was referred to Lee as the best person to isolate the effective component of her sample.  Working together, shipping new preparations back and forth between their labs, the team found nystatin in 1950, a compound they named after New York State, and which caused fungal cell walls, but not those of animals or plants, to leak potassium.

They patented their work to ensure the quality of its production, but signed away all profits they would have made to a foundation they created to support scientific research, the training of a new generation of mycologists, and the encouragement of women desiring to study science.  Over the seventeen years of the patent, they were able to distribute millions of dollars of funding to both fundamental and applied research.

Meanwhile, nystatin took on something of a life of its own.  Not only was it effective in combating fungal infections for humans, but it was also soon pumped into the xylem of trees suffering from Dutch Elm disease to great effect and even, during the great flooding of Florence, applied to the masterpieces housed there in danger of being entirely destroyed by moisture-loving fungus.  Nystatin, it turned out, nixed the fungus without changing the pigments, and without it we might have entirely lost a significant portion of Western Art’s most cherished pieces.

Hazen and Brown. (Photo NY Dept of Health)
Hazen and Brown. (Photo NY Dept of Health)

Whereas penicillin took over three quarters of a century to move from discovery to mass production, Lee began looking for an anti-fungal in 1948, found it with Brown in 1950, and saw its large-scale distribution by 1954.  For the rest of their careers, the team divided their time between overseeing the distribution of funds from the nystatin profits and pushing on with the search for new antibiotics (discovering phalmycin and capacidin) and new applications of the ones they had already discovered.  They were both disturbed by the downplaying of mycology in physicians’ training, and did what they could, with their fame and their funding, to ensure that the succession of medical mycological research was ensured.

Unfortunately, there was not a great deal of time left.  Lee was 69 when nystatin went into production, and Brown 56.  As nystatin’s promise grew, so did their fame, but Brown was increasingly the only person healthy enough to receive the awards and honors made out in both of their names.  Lee ended her life in a nursing home, eager and expecting to return to work to the very end.  Brown died five years later, suddenly and without fuss, a definitive period cast at the end of a precision career.


FURTHER READING: The Fungus Fighters by Richard S. Baldwin (1981) is a curious book that spends a third of its time on the state of mycology generally in the twentieth century, another third on Lee and Brown’s discoveries and their applications, and another third in very detailed accounts of the minutiae of their foundation.  Baldwin really gives you a blow by blow description of the administration of a private grant-giving scientific foundation, which is an interesting world most authors don’t generally let you see in anything more drawn out than a few cavalier sentences.  You’ll either find those parts unbearably dull or incredibly welcome for what they bring to the picture of the modern scientist at work.




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