I learned, 5/6/16

How the highest profile biotechnology failure of the 1980s led to a longer ski season.

The company, Advanced Genetic Sciences (founded 1979) was the world’s first agricultural biotech company, and their proposed product was, scientifically, one of the coolest things I have ever heard of.

To understand their technology, you first have to know about how hard it is to make ice.

Water, it turns out, doesn’t actually freeze at 0°C – at least not at any reasonable speed. When cooled below freezing, water molecules continue bouncing around at random, and the first crystal of ice forms only when a cluster of molecules randomly find themselves in just the right ice-like orientation. From there, a template is available, and the rest of the molecules glom on fast. But at 0°C, or even -10°C, that first crystal is really, really slow to form.

Enter the bacteria Pseudomonas syringae. This little yellow bacteria is everywhere – it covers much of the plant matter on the planet – and its success is attributable to a protein it synthesizes that speeds up the crystallization of ice.

P syringae makes a protein that is spectacularly good at nucleating that first crystal of ice. And it makes it because it is a vicious killer – the ice crystals form little needles that grow outwards from the bacteria to puncture the cells of the plants, giving P syringae food to eat. And it is so good, it can crystallize water quickly at only -2°C. (To see it in action, click on the linked video.)

But what is good for this bacteria is bad for world agricultural production, which loses billions of dollars of produce every year when an early frost – a frost that forms on leaves only because of P syringae – takes out a crop.

So Advanced Genetic Sciences set out to make a mutant of P syringae with a damaged ice-forming protein. The idea was to spray the genetically engineered bacteria onto the leaves of critical crops. There, the engineered bacteria would outcompete natural bacteria and prevent ice from forming on the sprayed leaves. No ice, no damage.

It seemed like an ideal first trial for a genetically engineered organism. First, there were other “ice negative” strains of P syringae in the wild – it was completely natural for this protein to become defective through mutations. Second, since the ice-forming protein is critical for the bacteria to get food, it seems nearly impossible for the modified organism to outcompete natural bacteria outside the lab. The risks were essentially zero.

However, the world outside of science didn’t see it that way.

First, the folks at Earth First and other eco-activist groups didn’t take kindly to the story of man messing with genetic code, and the details of the science were not that important to them.

Secondly, in 1982b, just before the first request was made to the FDA for field testing, a plant physiologist at Montana State University discovered that P syringae were in fact responsible for the nucleation of ice in clouds. These bacteria quite literally made it rain. And so while the corporate scientists were almost certainly right in their analysis that there was no risk in modified P syringae escaping from fields and going native, if by chance they were wrong the down side would have been a dramatic change in the pattern of global precipitation. This caused pause.

But only a pause. Despite warnings of global catastrophe, Advanced Genetic Sciences was allowed by the FDA to test the bacteria in the open in 1987. And the sky did not fall. No bacteria were found outside the test area. Better, the test worked – the sprayed potatoes and strawberries fared better in a frost than untreated controls.

However, that wasn’t enough to save Advanced Genetic Sciences. Because in all of that effort – all of the science, the planning, the regulatory submissions, the publicity – no one had bothered to calculate whether these genetically modified organisms would work better than chemical treatments that were already in use. And they didn’t. The bacteria were far, far more pricey than existing alternatives, yet not really any better. The entire effort was, from an economic perspective, a complete waste. Advanced Genetic Sciences sold to a competitor the next year.

OK, deep breath. So what does this have to do with skiing?

In order to perform these first tests with genetically modified organisms, the company had to learn how to grow the naturally occurring bacteria. And they got very good at this – good enough that someone had the keen idea to sell P syringae to ski resorts to improve their ability to make artificial snow in relatively warm weather.

Not only did P syringae work for snowmaking, they were economical too. Dead P syringae were loaded into a snow machine and blasted into the air with water, and nearly all the water fell to the earth as fluffy white powder. Even at just a few degrees below freezing.

So thirty years later, anyone who skis on artificial snow is probably skiing on the legacy of this first, failed biotech company. The product, Snomax, today is purified bacterial protein (rather than whole killed bacteria), but it’s a direct descendent of that original invention. And it is used worldwide, in every country that has skiing.

I guess that the moral of the story, if there is one, is that if you are working on something cool enough, good things will happen down the road. Just maybe not what you were expecting.

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