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Seeds of dissent

Is the party over for genetically modified crops? Some scientists are afraid it might be. But molecular biologist Richard Jefferson thinks the GM revolution is only just warming up. Jefferson heads CAMBIA, a non-profit plant biotechnology r

Is the party over for genetically modified crops? Some scientists are afraid it might be. But molecular biologist Richard Jefferson thinks the GM revolution is only just warming up. Jefferson heads CAMBIA, a non-profit plant biotechnology research centre in Canberra. Thirteen years after conducting the world鈥檚 first release of a transgenic food crop, Jefferson, 44, is turning conventional ideas about plant genetics on their head. For instance, he says you can get top-quality GM crops without introducing foreign genes into plants. Or, wait for it, that sequencing genes of plants like rice or maize is a waste of time. Ehsan Masood spoke to the man who鈥檚 challenging researchers to think smarter.

You launched CAMBIA a decade ago promising to do science differently. What鈥檚 the difference between CAMBIA鈥檚 approach to research and that at any other biotech lab?

There鈥檚 a tendency in science to ignore the development of methods and make it secondary to the elite act of gathering knowledge. Even a cursory inspection of the history of science will show that the vast majority of scientists exhibit a lemming-like tendency-which I鈥檓 told that lemmings do not have-to define problems in terms of what they can solve, not what needs to be solved. CAMBIA is there to provide an example of what鈥檚 possible. We鈥檙e there to invent, and to provide the disenfranchised with tools and technologies they themselves help to design. It鈥檚 basically what we call 鈥渄emocratising innovation鈥.

Fair enough, but how would you want to do things differently?

The classic example that I鈥檝e been harping on about for years is apomixis, or obtaining seeds without sex. Apomixis is the natural ability of many plants-dandelions, blackberries, you name it-to reproduce asexually, but through the seed. If a crop can reproduce from apomixis, it could mean that farmers don鈥檛 necessarily have to purchase new seeds every year for replanting. Also, and very importantly, it would greatly reduce the propagation of diseases from crops such as potato and cassava that carry viruses with each cutting planted. It is essentially the antithesis of the terminator, the technology that attracted so much attention because it was aimed at causing seed not to reproduce after one planting.

Terminator was developed so that seed companies could compel farmers to buy new seed every year. Apomixis means that farmers will never need to buy seed again. Surely, seed companies will never support it.

I thought that too. But I鈥檝e discovered that some of their top people dream of apomixis. It means they would no longer have to make such massive investments in seed improvement technology, and then worry about recovering it. Seed innovation and production is a costly and time-consuming business, whether it鈥檚 biotechnology-based or conventional. Apomixis would cut the time needed to evaluate new lines, and dramatically reduce the cost of hybrid seed production. You could be releasing hundreds of new varieties a year, each adapted to localised conditions. But it needs a big rethink in terms of intellectual property. If one of the seed companies had exclusive control of the technology it would be a nightmare for others. They鈥檇 be out of business in a flash. It鈥檚 a classic example of where sharing a technology is crucial.

You鈥檙e a critic of that other holy grail: sequencing the genes of important crops like rice. Why?

Imagine the keys of a piano. There are 88 keys on a piano. But they tell me absolutely nothing. I know what every key means but it doesn鈥檛 tell me how to do Beethoven. It doesn鈥檛 tell me how to do Brahms or Mozart. Yet all of that is locked up in those keys. The secret is not in the keys by themselves, but their combinations, the order, the duration and intensity. It鈥檚 the same way for genes. We鈥檙e not going to get to the secret that鈥檚 locked up in the genome from DNA sequencing. That鈥檚 just like looking at the keys of a piano. I sometimes liken DNA sequencing and the hugely fashionable work lumped into the term 鈥済enomics鈥 to a drunk guy underneath a street light late at night. He鈥檚 crawling on his hands and knees looking for his car keys, when someone walks by and says, 鈥淗ey buddy, what are you up to?鈥 The guy looks up at him and slurs. 鈥淲ell, I鈥檓 looking for my car keys.鈥 The passer-by bends down to help and they both spend 10 minutes looking, when he says to the drunk: 鈥淎re you sure you dropped them here?鈥 The drunk guy says, 鈥淛eez no, buddy, I dropped them farther down the street but it鈥檚 too dark to see there.鈥 We鈥檙e doing DNA sequencing because we can do it, not because it鈥檚 going to necessarily give us what we want.

But what about all the effort going into sequencing plant genomes, like rice and maize. Can鈥檛 it be put to good use?

Of course it will be put to use. But the question is: is it anywhere near as useful as having a different style of doing science? People will say: 鈥淟ook at all the things that have come out.鈥 But that鈥檚 because you have got lots and lots of people doing sequencing, and lots and lots of money being thrown at it.

I鈥檒l give you another example. There鈥檚 a great maize geneticist at the University of Wisconsin at Madison called John Doebley-I don鈥檛 even know him but his work鈥檚 great. He鈥檚 looking at the genetics of maize and teosinte, the ropy little weed-like thing that happens to be the very same species as the big, proud corn plant of the American Midwest. It turns out that almost all the differences between the two are caused by only a few genes, and a huge amount of the difference in shape between the two plants is associated with just one, single gene. After exhaustive back-crossing, Doebley sequenced that gene and what did he find? Much to everyone鈥檚 amazement, he found that the protein sequence of the teosinte gene is exactly the same as in the maize gene. There was a difference between the two, of course, and that was in the way each gene was expressed. In other words, how each gene regulates other genes. But you鈥檇 never find that information from a gene sequence.

Can you give an example of developing a useful GM crop without using gene sequence information and without inserting foreign genes?

There are plenty, using a method we鈥檝e developed called transgenomics. Imagine you want to cultivate a rice plant that has wide leaves instead of skinny leaves. Now you might ask why you鈥檇 want to do such a thing? Here鈥檚 why. In West Africa, where rice is becoming a very important crop, there鈥檚 a serious problem of weeds. Because of this, West Africans tend to grow Oryza glaberrima rice, because its wide, droopy leaves shade out the weeds. O. glaberrima is not, however, their preferred rice. Many people prefer classic Asian rice, a different species called Oryza sativa, but they don鈥檛 grow it because Asian rice has skinny leaves which allows weeds to proliferate. But what if we could get Asian rice to grow wide leaves?

This is where transgenomics comes in. It allows us to manipulate plant genomes in a whole new way. Because, unlike the current system, it doesn鈥檛 introduce a pre-defined DNA from a foreign species into the plant. Instead, we manipulate expression patterns in the plant鈥檚 own DNA to get a better result by simulating what a plant naturally does in evolution.

Any other examples?

Suppose you want to obtain wheat with very deep roots. If you use conventional plant breeding, you鈥檒l need to cross different types of wheat for many years before finally getting wheat with the desired traits. Even then, you might still end up with wheat that contains other traits of the plant that you didn鈥檛 want. So the challenge is this: can we speed up the process of targeted breeding? At the same time, can we rapidly and efficiently transfer only desirable traits? And here鈥檚 the really challenging bit: can we do this without using expensive DNA sequence information? After banging on doors for years, we鈥檙e finally at the point where it is about to happen. My colleague Andrzej Kilian has led the way. We鈥檙e tentatively calling his method 鈥渄iversity array technology鈥 or Dart. The method is phenomenal. Andrzej and his team can pretty much produce a genetic map overnight, a job that might take one or two people a year. And it doesn鈥檛 require any gene sequence information. I can鈥檛 go into too much detail now as Andrzej is about to submit a publication. But as far as we can tell, it鈥檚 gone through most of its teething pains, and we鈥檙e now ramping up its use for important tropical crops.

What do you make of the current GM controversy?

Let me tell you a story I think you鈥檒l find particularly amusing. I had a meeting recently with the top R&D manager for a big multinational biotech company. We were talking about the GM crisis and he laughed when I asked him about whether they were worried. You know what he said? 鈥淢y bean counters are delighted about the GM crisis.鈥 They鈥檙e making a lot more money by selling herbicides and pesticides now. The GM crop crisis has nothing to do with food safety or environmental safety. Let me tell you about a food that kills hundreds of people every year. It鈥檚 a known allergen-causing many thousands of reactions a year. It鈥檚 not banned. It鈥檚 not always labelled, even though its oils are used in countless foods.

What is it?

It鈥檚 called peanuts. But we know that it鈥檚 ludicrous to talk of banning peanuts. There鈥檚 a legitimate gripe behind the public disquiet over GM crops. But it鈥檚 about faceless capital, excessive control by multinationals, loss of communities, and that modern R&D is no longer being guided by principles of 鈥減ublic good鈥. Food and agriculture have been taken out of the hands of the small businesses and the family farmers and are now a small part of a faceless empire of capital. That frustrates a lot of people, including me. The core problem is not that these companies are evil, many of them have some very good ideas. But there needs to be a capability for smaller innovators to be real players-to contribute to local-scale agriculture, science and business. The current climate of consolidated patents for the key enabling technologies is making this seem hopeless, so naturally people are upset.

What other kinds of innovative applications can we expect to see in the field?

How about this idea? Most farmers would love to know whether or not they鈥檝e put enough nitrogen in their crop. What if we invented a sentinel plant, a biological instrument? And what if it could give you information about nitrogen by changing colour? If that colour was, say, a bright yellow or bright orange, it would mean 鈥測our field of crop needs more nitrogen鈥. You could use a similar system to indicate if a soil had other nutrient deficiencies or latent pathogens. And it will allow you to breed without expensive instrumentation. Or how about letting farmers decide when and where to turn on a gene in their fields? Perhaps even turning a gene on or off by pissing on a plant. Seriously. Urine contains compounds called glucuronides, which are the main way our bodies detoxify compounds. At CAMBIA, we have invented a technology that uses glucorinides to turn a gene on or off. The idea of engineering such a system means you don鈥檛 have to buy chemicals that would otherwise do this for you.

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