Rust Never Sleeps

In his quest for world domination, James Bond’s nemesis Ernst Blofeld threatens to unleash a pathogen that would destroy global food supplies. Humankind now faces such a foe. But this villain doesn’t care about world domination, and it needs no evil genius to release it. The fungus known as wheat rust, one of history’s most feared and destructive plant pathogens, is already sweeping the planet. Wheat rust can turn a healthy crop into a black, tangled mess of broken stems and shriveled grains just weeks before harvest.

The battle between wheat and the fungus is an old one: Evidence suggests that wheat rust was a plague during biblical times. In ancient Rome it was considered a numen, a deity demanding appeasement via sacrifices and feasts.

Modern fungicides can fight rust, but the costs and quantities required often outweigh the benefits. So wheat breeders have kept the rust at bay by developing varieties with genes that resist it. For the most part, these breeders have helped wheat gain the advantage over its foe. But perhaps ritualized prayer shouldn’t be completely off the table. An especially virulent form of one type of rust, wheat stem rust, has recently emerged and proved immune to wheat’s genetic arsenal. Estimates suggest that 90 percent of the world’s wheat crop is now vulnerable.

Scientists everywhere have taken up arms against the rust. Tens of thousands of wheat varieties and wild relatives have been screened for anti-rust genes that can be incorporated into future arsenals. This spring, more than 500 researchers from 77 wheat-growing nations gathered for two major wheat conferences in St. Petersburg, Russia, to share strategies and discuss progress on various fronts. And in August, a team of British scientists released a very rough sketch of wheat’s genetic blueprint, which in a more complete form could simplify and speed up the breeding of rust-resistant varieties.

“There is a lot happening,” says wheat geneticist Jorge Dubcovsky of the University of California, Davis. “We are trying to develop better technologies, better breeding approaches.… I think at some point we will defeat the bastard.”

But scientists also lament a lack of funding, coordinated action and basic knowledge about wheat and its pathogens. A great deal more effort is needed to turn the first crack at wheat’s genome into information that’s meaningful for fighting the rust.

Worldwide, only a handful of labs do hard-core rust-related research, and many will accept samples of the fungus only during the winter months, when it’s too cold for potential escapees to survive. The rust is so feared that some trigger-happy researchers frantically deploy plants bred with single resistance genes — even though most scientists agree that a well-constructed genetic cocktail offers the best hope for staving rust off.

Rust’s reemergence

Wheat rust’s current rampage began more than a decade ago. In October of 1998, a plant breeder noticed a stem rust infection on wheat growing in his nursery at Kalengyere Research Station in Uganda. The discovery was perplexing because the wheat contained a gene called Sr31, which, along with a handful of others, had provided protection against the rust for more than a quarter century. A rust virulent enough to defeat Sr31 triggered alarm in the wheat community.

“Should the Sr31-virulent pathotype migrate out of Uganda, it poses a major threat to wheat production in countries where the leading cultivars have resistance based on this gene,” scientists from Africa and CIMMYT, the International Maize and Wheat Improvement Center in Mexico, wrote in Plant Disease in 2000.

Those fears have since been realized. This extremely aggressive strain of the fungus, called Ug99 (for the place of discovery and the year that the samples were analyzed), spread to most of the wheat-growing areas of Kenya and Ethiopia by 2003. The fungus’ spores, easily windborne, reached Sudan in 2006. Ug99 then crossed the Red Sea into Yemen, the doorway to major wheat-growing areas in the Middle East and southwest Asia. Ug99 has now been sighted in Iran. And not only is the rust still on the move, but it is also mutating: Within the Ug99 lineage, scientists have identified seven variants that can overcome additional important resistance genes in wheat. One Ug99 variant that overpowers Sr31 and the gene Sr24 caused epidemics in Kenya’s crops in 2007. Another Ug99 relative has turned up in Ethiopia and South Africa, and Kenya reported in June rust infestations in 80 percent of inspected fields.

Ug99 has yet to rear its ugly spores in the Americas. But that doesn’t mean U.S. wheat farmers are rust- or worry-free. In North America, Australia and Europe, as well as in Asia and Africa, a sibling of stem rust — the stripe or yellow rust — is taking a toll. In 2003, yellow rust wiped out a quarter of California’s wheat crop. Last year, it devastated crops in China. This year, farmers in the United States, the Middle East and northern Africa have already reported serious yellow rust infestations.

“The presence of two virulent and highly aggressive yellow rust strains … at high frequencies at epidemic sites on five continents (including Europe) may represent the most rapid and expansive spread ever of an important crop pathogen,” researchers from Aarhus University in Denmark wrote in an editorial in the July 23 Science.

When rust attacks

That crop pathogens spread so rapidly and widely highlights how humans have unwittingly taken the enemy’s side in the wheat-rust battle royal. By its very nature, agriculture lays out an all-you-can-eat buffet for the pathogen and rings the dinner bell.

“When we cultivate wheat, it is genetically uniform, spatially uniform and temporally uniform — those uniformities favor certain things to blow up rapidly,” says plant pathologist Yue Jin of the  U.S. Department of Agriculture’s cereal disease laboratory at the University of Minnesota in St. Paul.

In the wild, fields don’t ripple with amber waves of grain. Wild wheat usually grows in genetically distinct clumps, Jin says. Stands of such wheat don’t sprout, grow and yield grain in sync, and other nearby plants block traveling spores.

“You hardly ever see the disease really killing a native plant stand,” Jin says. “Ever.”

When wheat rust does attack, yellow-orange or reddish-brown blistering pustules can appear on infected plants within a week. That “rust” is just part of the fungi’s complex life cycles, which include a dizzying array of spores that aid in the pathogens’ dispersal and persistence.

Three of the 5,000-odd species of crop-attacking rusts are serious parasites of wheat: stem rust, stripe or yellow rust and leaf rust (all in genus Puccinia). When the pathogens’ spores land on wheat, they germinate and send out a threadlike structure that penetrates the plant. Once inside, the fungus starts sucking the plant’s nutrients and grows new structures that rupture the leaves and stem, crippling photosynthesis and disrupting the plant’s ability to control water loss. Those new pustules contain thousands of spores that, carried by the wind, can travel from field to field, or farther: One long-distance flier reportedly made it from southern Africa to Australia.

During the growing season, these spores move from wheat field to wheat field, destroying plants along the way. The fungi typically morph into black, thick-walled structures in the fall. And in  spring, these structures ultimately yield another kind of spore that must land on a different host plant to keep the life cycle going.

For stem rust, that host is the shrub barberry, and from 1918 through 1975 more than 100 million barberry bushes were eradicated in the United States alone in an effort to eliminate stem rust’s seasonal home. Since the rust’s sexual reproduction (which entails gene mixing) yields spores that can infect only barberry, the eradication program also stymied the pathogen by limiting its genetic diversity.

But the elaborate life cycles of the three rust varieties allow them to snub host removal efforts. Like a deadly broken record, the pathogens can persist by reproducing asexually, repeatedly making the types of spores that can infect wheat. In the United States these spores can survive winters in milder regions, such as near the Gulf of Mexico. Come spring, the spores move north with the wind, hopscotching from field to planted field.

Until the 1950s, in much of the world including the United States, wheat crops were on a boom-and-bust cycle: Years with robust yields were punctuated by devastating rust epidemics. Around that time, the U.S. Department of Agriculture and similar agencies in the rest of North and South America decided to formally collaborate in tackling wheat rusts. An international wheat nursery was established and — under the leadership of American agronomist Norman Borlaug, who would later win the Nobel Peace Prize for his efforts — breeders and scientists around the world began coordinating the exchange of wheat seeds and plants and cooperating to develop wheat varieties with rust resistance.

Wheat scientists refer to two general kinds of genetic resistance to rust. One is major gene resistance, sometimes also called race-specific resistance, in which the wheat proteins recognize specific rust proteins and quickly wipe out the invader. Then there’s nonrace-specific resistance, also called slow-rusting or partial resistance. In this case, the rust’s spores might germinate on the plant, but a full-blown infection never quite develops.

Major gene resistance is typically short-lived: Within two to five years, a fungus may acquire mutations that alter the shape of the protein that stimulates wheat’s immune response, and then it’s game over. But a combination of major and minor resistance genes offers longer-term protection.

Several such combinations arose in the 1970s, when Borlaug and researchers at CIMMYT developed wheat varieties that contained a good chunk of a chromosome from rye. Rye and wheat are close relatives, and both are susceptible to rusts. This bit of rye chromosome had the major resistance gene Sr31, which, along with others, was deployed into several wheat varieties around the world. These new varieties were what researchers call durably resistant, rarely succumbing to stem, stripe or leaf rust, or to powdery mildew, another pathogen.

The combination of genes kept rust under control for an exceptionally long time. Stem rust became virtually nonexistent in many parts of the world, an almost forgotten curse, geneticist Ravi Singh of CIMMYT and colleagues wrote in Advances in Agronomy in 2008. But as Borlaug noted, rust never sleeps.

“A lot of complacency developed and people assumed this was going to last,” says Cornell University’s Ronnie Coffman, director of the Durable Rust Resistance in Wheat project, an international collaboration funded by the Bill & Melinda Gates Foundation. “And a lot of other things happened to our institutions — budget issues, the Soviet Union collapsed, a lot of things went to pot in the public domain in that period. So when Ug99 came around, people weren’t really ready to deal with it.”

Fighting back

More than a decade later, researchers are still undertaking various efforts to try to rein the pathogen back in. Topping the list: Using genetics and molecular biology to better understand the mechanisms of wheat’s natural resistance to the fungus, which would enable scientists to streamline their breeding efforts and develop resistant varieties faster. Perhaps even before the rust epidemic gets much worse.

Modern molecular techniques have upped the pace of this research, but it can still be painstakingly slow. For one thing, rust resistance isn’t the only trait that wheat farmers care about. They also want plants that produce high yields, resist other wheat pathogens such as powdery mildew and thrive in the light, soil and water conditions of a particular region. If a wheat farmer has a stellar variety, yet it isn’t resistant to rust, it can take six generations of breeding to get the resistance genes in while keeping the other beneficial traits intact.

Breeding programs that bring wheat from one location to another to get two generations in a year can speed this process, but it still may take five to 12 years to go from finding a resistance gene in some wild, scrappy wheat plant to getting that gene into a variety that also has all the other desirable traits, says wheat geneticist Mike Pumphrey of Washington State University in Pullman.

And most scientists agree that deploying a variety with a single resistance gene has little value. The best strategy for combating rust is to harness a combination of genes, greatly diminishing the odds that a fungus will succeed.

“A good example is what we did with AIDS,” Dubcovsky says. “We were not successful at the beginning; we were putting out a medication and the virus was mutating and the medication was overcome. What is the current strategy? We have three different medications that work together that make it almost impossible for the pathogen to mutate in all of those three different pathways.”

In wheat, Pumphrey says, the approach could mean using one gene that attacks the rust as it threads into the wheat; another that hastens the death of cells around the rust, preventing its spread in the plant; and yet another to delay spore germination in the first place.

“That’s our greatest focus and promise,” Pumphrey says.

When wheat experts from around the world gathered in St. Petersburg for the Borlaug Global Rust Initiative 2010 Technical Workshop and the 8th International Wheat Conference, they presented status reports on efforts to combat the pathogen, discussed the role of climate change in its spread and reviewed the latest research on rice, the only agricultural cereal crop that is immune to rust.

The International Wheat Genome Sequencing Consortium, an international public-private endeavor to unravel all the genetic data in one wheat variety’s 21 chromosomes, gave a progress report: One and a half chromosomes have been well-mapped and funding has been garnered for several more.

Wheat has a gigantic genome — with 17 billion base pairs or “letters” of code, it’s about five times the size of the human genome, although less than 10 percent of wheat’s DNA makes up actual genes.

In August, British scientists released what they called a draft sequence of the wheat genome — with the emphasis on draft. The team did an initial shredding of the DNA of Chinese Spring wheat into digestible chunks of about 500 base pairs each, and then figured out the string of code in each of those chunks.

The data may be helpful, but until scientists figure out how all those tiny pieces fit together into a genome, linking resistance traits to specific genes will remain difficult. Such information will be crucial for launching a full-scale genetic attack against rust.

“We still have a long way to go,” says Singh of CIMMYT.

For now, it’s inch by inch, row by row. For example, last year Dubcovsky’s team and another group of researchers identified the role of two genes that confer resistance to rusts. It was such a feat that the results were published in side-by-side papers in Science.

If Ug99 has any plus side, it’s that it has raised the public’s consciousness of wheat pathogens, as well as that of private funders, such as the Gates Foundation. Wheat — be it in a boring old loaf of white, rigatoni, beer or chocolate cake — is taken for granted, and it’s difficult to imagine that something so commonplace, so integral to the world’s breaking of daily bread, could be threatened.

“People don’t think about food when there is abundant food,” Dubcovsky says. “But when there’s not abundant food, people start thinking about it again. And when there’s no food, that’s the only thing people think about.”