An Interview with Pamela Ronald

Annual Reviews Conversations Presents An Interview with Pamela Ronald

Annual Reviews Audio. 2012 Anna Rascouët-Paz: Hello, and welcome to Annual Reviews First published online on May 3, 2012 Audio, part of the Conversation Series from Annual Reviews, where Annual Reviews Audio interviews are online at insightful research begins. I am your host, Anna Rascouët-Paz. www.annualreviews.org/page/audio In our show, we speak to top scientists in fields ranging from

Copyright © 2012 by Annual Reviews. astrophysics to sociology. Today, we are talking to Pamela Ronald, All rights reserved Professor of Plant Pathology at the University of California, Davis. Professor Ronald is also Director of Grass Genetics at the Joint Host: Anna Rascouët-Paz Bioenergy Institute. Her laboratory has engineered rice for resistance to disease and tolerance to flooding, which seriously threaten rice crops in Asia and Africa. She led the isolation of the rice XA21 immune receptor, the bacterial AX21 quorum-sensing factor, and the rice sub1A submergence-tolerance transcription factor. In 1996, she established the Genetic Resources Recognition Fund, a mechanism to recognize intellectual property contributions from less-developed countries. She and her colleagues were the recipients of the US Department of Agriculture 2008 National Research Initiative Discovery Award to their work on rice submergence tolerance. Professor Ronald is an elected fellow of the American Association for the Advancement of Science. She is a coauthor—with her

1 husband, Raoul Adamchak, an organic farmer—of Tomorrow’s Table: Organic Farming, Genetics, and the Future of Food. Bill Gates calls this book “a fantastic piece of work.” In 2011, Fast Company magazine named Professor Ronald “one of the world’s 100 most creative people.” Professor Ronald, welcome to our show.

Prof. Ronald: Thank you very much.

Anna Rascouët-Paz: You are the author of a review that is appearing in the 2012 volume of the Annual Review of Plant Biology, titled “Plant innate immunity: perception of conserved microbial signatures.” Let’s talk about innate immunity. What is innate immunity, which organisms have it, and how does it differ from adaptive immunity?

Prof. Ronald: Both plants and animals have these innate immune systems, and the past 15 years have been a very exciting time in this area for several reasons. Even 20 years ago, we didn’t know how plants resisted disease, and yet disease-resistance genes are very important to agriculture because breeders use them so that plants have resistance. They don’t have to spray insecticides or other types of pesticides on the plants. Even though we have been using these genes for years, no one really knew what they were. Unbeknownst to plant biologists, at least most plant biologists, animal biologists were also trying to look for an unusual immune system, and it has been known for many years that animals have an adaptive immune system, which consists of highly specialized cells that can prevent pathogenic growth. This type of immunity is considered adaptive because you can use genetic recombination of different receptors to generate a lot of different recognition specificities. Most people are familiar with antibodies, and that is a key point of the adaptive immune system. It turns out that animals have a second immune system called the innate immune system. That system is very, very similar to plant immunity.

Anna Rascouët-Paz: In 1995, you and your team identified XA21, which is the receptor of microbial signatures in rice. What are these receptors, and what is their role in plant immunity?

Prof. Ronald: These receptors can be cell-surface receptors or sometimes intercellular receptors. The class that I work on is quite interesting because it recognizes a small molecule that is highly conserved in the microbe. The reason this is important is that the plant then can recognize not only a specific race of the microbe but all members of that class. There is a similar situation in animals: These immune receptors also recognize highly conserved microbial determinants.

Anna Rascouët-Paz: Late last year, you made another discovery about AX21, which is the quorum-sensing factor. What is the mechanism there? How does it work?

Prof. Ronald: This has been a very interesting story because we knew from the work of breeders over 30 years that XA21 confers a very broad-spectrum resistance. We hypothesized, nearly 20 years ago now, that the rice pathogen Xanthomonas must carry a conserved microbial molecule. We spent a lot of time trying to isolate that, and we were able to do a little bit of sleuthing by looking at a lot of different types of bacterial systems. We carried out some biochemical and genetic approaches and identified a protein that didn’t fall into any previously characterized class. It was unknown how it functioned, but we were able to figure out that it functions in bacterial communication, and that is called quorum sensing. The bacteria are sending this protein back

2 Ronald and forth, and they can perceive that small protein at a certain density. The bacteria trigger a completely new transcriptional program. We believe that the plant has evolved to recognize this bacterial sealing factor.

Anna Rascouët-Paz: Quorum sensing is a mechanism of, as you say, communication between bacteria. It was better understood and studied very deeply by Bonnie Bassler, who happens to be the Editor of the Annual Review of Genetics. She didn’t exactly discover this, but what you have shown is that this happens in plants. Other researchers have shown that this also happens in animals and humans. What does this mean on a larger scale in terms of our ability to fight diseases and in terms of antibiotics for humans or animals or plants? What are the techniques that could help?

Prof. Ronald: For many years, Bonnie has been characterizing an interesting small molecule called AHL quorum-sensing factor, and it was thought for many years that gram-negative bacteria carry only this type or related types of quorum-sensing factor. What we discovered is quorum sensing in gram-negative bacteria, so it is not quorum sensing in plants but quorum sensing of the bacterial pathogen that infects the plant. The bacteria are sending a molecule back and forth, and when the plant perceives that bacterial factor, the plant then launches a robust immune response. The bacterial molecule that we identified is in a completely different class than the one that Bonnie Bassler discovered. In fact, it is a small protein with a process leader, and it turns out it is also present in pathogens of grape and also pathogens of human. It is a brand-new type of quorum-sensing factor that had not previously been identified in gram-negative bacteria. The terminology is probably a little confusing because the plant receptor in rice is called XA21 and the bacterial quorum-sensing factor is called AX21, and it is the bacterial factor that is conserved in both plant pathogens and human pathogens that is a small protein. On the receptor side, the protein is called XA21.

Anna Rascouët-Paz: It’s hugely significant both for plants and for animals. It seems that cures could be found more easily; ways to control immune systems, or reactions at least, in plants and animals could be found. I want to go back to your book, Tomorrow’s Table, which you wrote with your husband. What exactly do you say in this book? He is an organic farmer and you engineer genes, so what do you have in common?

Prof. Ronald: We have a lot in common. I think we got into the areas of our life’s work because we are both interested in sustainable agriculture. The goal of what both of us do is an ecologically based agricultural system. In sustainable agriculture, it is critical that we reduce the amount of harmful inputs into the environment and that we produce enough food to reach the poor and malnourished. We have critical issues: land, water, and the reduced availability of both of these important resources for growing food. These are the kinds of issues both of us have been interested in for a very long time.

Anna Rascouët-Paz: You seem to have approaches that are not compatible at all, in the eyes of somebody who is less informed about this kind of stuff. How exactly do you combine the techniques of organic agriculture or sustainable agriculture with genetic engineering?

Prof. Ronald: Organic agriculture is an important part of agriculture. It is a collection of farming practices, and those farmers seek to reduce the amount of input used in the environment.

www.annualreviews.org • An Interview with Pamela Ronald 3 But it is not necessarily considered sustainable agriculture because sustainable agriculture looks much more broadly at the impact of land and water, insecticide, productivity, and the farmers making food available to broad groups of people. Organic farmers have always relied on improved seed; they use genetically improved seed and hybrid seeds. Farmers are all very familiar with the importance of improved seed; I work on the seed side of things. I think the polarization has occurred because organic farmers are not allowed to use genetically engineered seeds, so they don’t have access to genetically engineered seeds. The goal of sustainable agriculture is critical to organic farmers; they just have one less tool available to them.

Anna Rascouët-Paz: Humans have been moving genes around for a long time through conventional breeding. What are some of the techniques that you have in mind when you say that? What have humans been doing that could qualify as moving plant genes around?

Prof. Ronald: Genetic engineering is very different from conventional breeding because genetic engineering moves one or two very well characterized genes into a particular variety favored by farmers, whereas conventional breeding includes a diverse group of techniques that usually changes many genes at once. Of course the other major change between conventional approaches and genetic engineering is that with genetic engineering, a gene from any species can be moved into a variety, whereas with conventional breeding, that transfer is generally between closely related species. Those are the major differences. Of course, everything that we eat has been genetically improved in some way, whether through conventional breeding or genetic engineering. Everything you eat—breakfast, lunch, and dinner— has been developed through modern genetic approaches. This started approximately 10,000 years ago through, at that time, permanent seed selection. Collecting seeds has advanced over the years into a number of different techniques; one of the techniques that is being increasingly used today is genetic engineering.

Anna Rascouët-Paz: Genetic engineering tends to scare a lot of people. A big worry is safety. Another one is the coevolution of species of organisms of plants and insects. How do you respond to that? How do you convince people who present those arguments to you?

Prof. Ronald: I think it’s important to look at the science. We do know from many, many studies all over the world that genetically engineered crops that are in the environment now are safe to eat and safe for the environment. It doesn’t mean that every new plant variety, whether it is conventionally grown or genetically engineered, will be as safe or beneficial as the crops currently in the environment, but at least people don’t need to worry that there is something toxic out there right now. I always urge people to look at the National Academy of Sciences—actually, any academy of science in any country. Mexico, France, the United Kingdom, the United States—all these countries’ leading scientific agencies have concluded that genetically engineered crops on the market are safe to eat and safe for the environment. I think scientists understand the concept of scientific consensus, but it is a little bit more difficult for the general public, who are not familiar with the scientific method and testing. Most people don’t even know what the National Academy of Sciences is. It’s harder for them to be reassured by the science. The National Academy of Sciences puts it in a very nice way. Of course anything we eat poses some risk, but the way they phrase it is that the risks are similar whether the genes are introduced through conventional breeding or through genetic engineering. The processes prove that similar

4 Ronald risk—and it is the end product that matters. Through conventional breeding, you can develop, and we have developed, highly toxic plants. For example, there is a celery that was developed through conventional breeding that, when farm workers harvested it, caused them to get a rash. We have seen these unintended consequences through conventional breeding, and at least to date, there have not been these types of negative consequences with genetic engineering. Certainly, there is no such thing as no risk. There is always some risk, and the risks and benefits need to be looked at very carefully.

Anna Rascouët-Paz: Can you think of an example of integrated farming that works really well and that takes into account the insects that benefit the plants? Do you have anything in mind that you can use as a shining example of how this can work?

Prof. Ronald: There are many examples. One of my favorite examples is genetically engineered papaya, which was developed through public funding. It confers resistance to a really devastating viral disease. A Hawaiian developed this genetically engineered papaya that is immune to the virus, and it’s still the only way to combat this disease. I like to think of it as an appropriate technology; genetic engineering is not always going to be the most appropriate technology. There may be farming methods or other types of methods to combat a particular problem. But, in this particular case, it is a fantastically appropriate technology, and these papayas yield 20-fold more [fruit] than conventional or organic papayas in the area. All the papayas that we get in California—something like 90% of them—are genetically engineered. That’s a nice story, I think, of the way genetic engineering is mechanistically different but conceptually similar to a polio vaccine or a smallpox vaccine; those types of vaccines have led to the virtual eradication of diseases.

Anna Rascouët-Paz: The thoughtful approach to farming, to breeding—this is what you are advocating.

Prof. Ronald: That is certainly what we need to look at. Genetically engineered crops need to be embedded into an integrated farming approach. If you rely on the seed alone to solve all your problems, you are not going to get very far because we have known through 100 years of agriculture that if you use one tool you are likely going to develop pathogens that can overcome that tool. That is why the genetically engineered cotton in Arizona has been such a success: Farmers and breeders and entomologists have all worked together to develop an integrated program down there. They have seen reductions in approximately 50% of the insecticides used on cotton in Arizona because of these integrated approaches that combine genetically engineered crops with other types of farming methods.

Anna Rascouët-Paz: Pamela Ronald, thank you so much for participating in this interview with us. It’s been a real pleasure talking to you.

Prof. Ronald: Thank you very much.

Anna Rascouët-Paz: You’ve been listening to Annual Reviews Audio. For 80 years, Annual Reviews has guided scientists to the essential research literature in the biomedical life, physical, and social sciences. Learn more at www.annualreviews.org. I’m Anna Rascouët-Paz. Thanks for listening.