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Corn breeding provides the best illustration. Ever since innovative farmers such as Henry Wallace, FDR's second vice president, began hand-emasculating one line of plants in the early 1900s and then crossing these "female-only" plants with another line of corn, yields surged by 300 percent. This kind of "castration" is not only hard work, but also expensive. Furthermore, such castration is possible only because the cornstalk's male organs develop into large tassels that can be quickly hacked off. Most other crops are not so constructed. "In rice and canola, for example,"says Goldberg, "the male reproductive organ is so small and so far inside the flower that it wouldn't be feasible to tear it off by hand on a large scale." Goldberg and PGSagreed to join forces to find that "clever way" of using his male-specific genes to destroy the pollen-producing cells of the anther selectively, using a "genetic lasar." Collaborating came easily to Goldberg, this year's winner of the prestigious Gold Shield Prize for Faculty Excellence, whose undergraduate courses in molecular biology and genetic engineering are legendary among UCLAstudents. He knew the advantages of help and support, understood the rewards of collective research traditionally independent-minded scientists have tended to resist. "These days science is too big to do individually," observes Goldberg. "You need a large team, you need people working together, you need to share everything—both the work and the rewards." In earlier work, Goldberg's lab had isolated anther genes that likely played a role in pollen production and pioneered techniques for
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visualizing the mRNA products of these genes inside cells. In addition, he identified a DNAswitch, or promoter, that activates these genes in specific anther cells critical for pollen production. The Belgian scientists, headed by Goldberg's friend, Titti Marianni, worked to fuse Goldberg's anther-specific promoter with a toxin gene encoding RNase. Their idea was to introduce the genetically engineered toxin gene into the plants when the anthers develop in the flower. The promoter switch Goldberg discovered would activate the toxin gene, destroying the pollen-producing cells and making the plant male-sterile. PGShad found a way to genetically engineer for male-sterility. "We were delighted," says Goldberg. "It was the first time anyone had sterilized plants like that, and we were very excited to have our results published as a cover article in Nature. Furthermore, we determined that our 'genetic lasar' worked in a variety of crop plants." This was a major breakthrough in crop breeding. But the scientists didn't know how to reverse the process. "If the male lines are sterile," says Goldberg, "then how do you reproduce them? That was a huge problem." The Goldberg-PGSteam needed some kind of genetic agent to slip into the male-sterile plants that would disarm the already encoded RNasetoxin. As often happens in science, serendipity intervened. "About that time, the lead PGSscientist, Marianni, was walking down the hall at PGS, past a lab where scientists were working on proteins," explains Goldberg. "Well, one of these researchers saw her and said, 'Look at this,' handing her a paper. It was an obscure paper by someone at NIH, all about RNase barnase and something called 'barstar,' which few people had ever heard of." As it happens, barstar is yin to barnase's yang; the very same bacillus that synthesizes barnase to fight off outside pathogens also produces barstar to neutralize its own toxin, in case of mistakes. "It's kind of a fail-safe system," says Goldberg. "It's what the bacillus uses to cancel the effect of barnase in case it makes a mistake and the barnase toxin attacks the bacterium cell itself." Marianni fused Goldberg's gene switch to barstar and introduced the anti-lasar gene into male-sterile plants expressing the barnase toxin. Barstar worked in the plant anthers exactly the same way it worked in the bacillus. Goldberg and his colleagues in Belgium had managed to produce plants whose male organs are sterile for crossbreeding, and then could be made fertile again, in order to reproduce the original inbred line. "It was a huge piece of luck," acknowledges Goldberg. |
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