From Chapter 7:  Triumphs of Tinkering

 

The idea came, as they say, out of left field. Actually, it hurtled into the field of biotechnology like an unwelcome projectile from the bleachers, from a bystander, an amateur plant engineer named John Sanford.

Sanford is a gentle man, soft-spoken, earnest, and deeply religious. He affects modesty, but underneath the surface, there lives a powerful, eccentric self-confidence. "Most people, I think - or a lot of people - have the dream of making a difference in the world. And a lot of people think thatís naive. But if you donít try, you never will," he says.

In 1980, Sanford earned his Ph.D. in plant breeding, and took a job at Cornell Universityís Agricultural Research Station in Geneva, New York. But Sanford became fascinated with a far more speculative endeavor, the project of inserting foreign genes into plants.

"It was my good fortune to be both naive and rather poorly informed," wrote Sanford, many years later. "If I had known how many brilliant, well-trained, and well-equipped scientists were way ahead of me, perhaps I would not have even bothered."

Sanford possessed only the most rudimentary laboratory equipment. He knew next to nothing about manipulating DNA or regenerating plants from tissue cultures, the two most crucial pillars of genetic engineering in plants. In short, he had no business playing in this game.

He tried anyway. While other researchers employed Agrobacterium to accomplish their goals, Sanford tried a cruder, more mechanical approach. He tried drilling tiny holes in the wall of a cell with a laser, hoping that bits of foreign DNA would seep through. It didnít work. But the attempt led to a conversation, in the fall of 1983, with Edward Wolf, then Director of Cornell Universityís National Submicron Facility.

The Submicron Facility (later called the Nanofabrication Facility) had little to do with biology. Engineers there deployed beams of ions or electrons to etch electrical circuits far smaller than the wavelength of light into wafers of silicon. Sanford wanted to know if such beams might be used to cut holes in the walls of plant cells. Wolf, after some thought, said no. He calculated that such beams would produce an electrical discharge powerful enough to destroy the cell.

Yet the problem awakened Wolfís imagination. Heíd grown up on a wheat farm in western Kansas, for one thing, and he had a weakness for odd, intriguing problems. He and Sanford took to calling each other on the phone, suggesting alternative ways to propel DNA into a cell. Wolfís thoughts turned to some tungsten powder that that he happened to have on hand; Sanford, meanwhile, had his mind on guns, as he was engaged in a personal battle with marauding squirrels at his home. And between them, the idea emerged: Perhaps they could soak microscopic particles of metal with DNA, and simply shoot them into plant cells!

So it was that three grown men - Sanford, Wolf, and a machinist on Wolfís staff - carried a toy pistol into Cornellís Submicron Facility during Christmas vacation of 1983. They donned white gowns, booties, and hair-hugging hats, as required by the facilityís rules. Then, standing amid various million-dollar ion beam accelerators, they proceeded to blast whole onions with charges of tungsten beads. (Sanford chose onions because they have such large cells, easily examined.)

"We would pump up the pistol, load a bit of tungsten powder into the end of the barrel, aim, close our eyes, and fire," recalls Sanford. "The air reeked of onion. Onion juice and bits of onion splattered over our sophisticated high-tech frocks." At the right distance, and with the right load of air pressure, the cells werenít destroyed. Through a microscope, Sanford could clearly see tungsten particles inside some intact cells. So far, so good. The next step would be to find out whether the beads could carry DNA, whether plant cells could survive such treatment, and if the plant would accept that DNA as its own.

Sanford wrote a description of his idea, and sent it to Cornellís Biotechnology Institute, asking for funding. "I learned later that the evaluating panelís first response was laughter and ridicule," he says. Fortunately for him, a single member of the committee spoke up in support of the idea, pointing out that this was exactly the sort of risky, innovative exploration that the institute had been set up to support. The institute approved enough money for Sanford to hire an assistant, a graduate student named Ted Klein, who ended up devoting the next six years of his life to perfecting the gene gun.

Laughter, in fact, was the standard response when scientists first heard about the gene gun. "It was just beyond the realm of the reasonable," recalls one researcher. "Like a hunterís idea of how you transform a plant." Respectable researchers were trying their own novel approaches, to be sure. Some inserted DNA directly into cells with microscopic needles. Others used electrical charges to open small pores in the cell wall, allowing bits of DNA to flow in. But shooting plants with a gun? It sounded like the punch line of a joke.