Almost in bloom

T. SPIEGEL/CORBIS

In the heart of the United States, where the rolling Midwestern plains meet the Ozark Mountains, sits Saint Louis and its environs. The area is a fledgling agricultural biotechnology hub in the midst of the farm belt. But it hasn't quite reached critical mass: the key missing factor is start-ups, which provide risk-taking ideas and young, enthusiastic workers.

Agribiotech focuses on using new tools of genetic investigation and manipulation to try to develop products that outperform traditional crops. Vocal opposition to such products as untested and unnatural has undoubtedly restrained the sector. But increasing population and climate change could spur a large market for crops that offer more nutrition per hectare with fewer inputs such as fertilizer and pesticide. As agricultural biotechnology enters its 'second wave' — in which products are enhanced for the supermarket shopper rather than just the farmer (for example, soya beans that are omega-3 enriched rather than just drought-resistant) — the St Louis area is poised to become the paramount region for the industry in the Americas. Yet challenges remain.

"If you ask where is the most discovery science that leads to new inventions, I think St Louis is in the top five" Roger BeachyDANFORTH CENTER

There is agribiotech talent aplenty at Washington University, the various campuses of the University of Missouri, the non-profit Donald Danforth Plant Science Center and the area's industrial behemoth, Monsanto. But a combination of factors including a less-than-entrepreneurial culture and public resistance (or the perception of public resistance) to the technology's products has led to few new small companies being founded by scientists.

Much of the area's strength flows from Monsanto, where business is booming. The company is 'stacking' various yield-increasing traits together in single seed lines to rake in the cash, but its pipeline also contains second-wave crops with lipid or protein enhancements or complex traits such as drought tolerance.

In the 1990s and early 2000s, the company now known as Monsanto shed its chemical and drug parts to focus solely on agriculture. Net sales have grown each year since 2003. For fiscal year 2007, sales totalled more than US$8.5 billion, and research and development spending was $780 million, or more than $2 million a day. The company says it will invest 10% of its sales in research and development in 2008.

The advantages of working for Monsanto are many. The scientific talent and lab facilities are top-notch. The gene libraries are extensive and exclusive. At a lab in the suburb of Chesterfield, the company spends $4 million a year on electricity, mostly to run 122 growth chambers crammed with bar-coded plants and plant tissue — each one a potential blockbuster.

But Monsanto is also extremely secretive, even keeping exact employee numbers hush-hush for "competitive reasons". All employees sign a confidentiality agreement. Publication can follow only after patent protection. The tour guide at the Chesterfield lab even hints at "all kinds of fun toys I can't show you". Because of the culture of secrecy, and because of their number, scientists at Monsanto have their own internal community with poster sessions, a competitive fellows programme, and even awards, complete with ceremonies at the Ritz-Carlton Hotel.

According to Karen Wishart, vice-president for human resources at Monsanto, the culture is very "team oriented", with rewards and incentives being doled out to the interdisciplinary teams that the company shuffles to keep things fresh and its employees engaged. The company is also very "results oriented", meaning it doesn't forget that the goal is to make products that farmers want to buy — and it makes sure its employees don't forget either. Monsanto employs about 3,300 scientists worldwide, double the number of four years ago. About 2,500 are in the United States, and most of those are in Missouri.

Monsanto is still hiring. "We're growing quickly," says Wishart. "And the baby boomers are retiring on top of our growth phase." According to Alexandra Doronkin, who heads recruitment for scientific and regulatory positions in Monsanto, the company's research and development corps is hiring several hundred scientists a year.

And Doronkin has a wish-list: researchers with the core skills that Monsanto will need for the foreseeable future — molecular biology, biochemistry, systems biology, agronomy, pathology and genetics — plus traditional plant breeders, scientists with business training and bioinformaticians. Its mammoth greenhouses are growing hectares of data that need to be mined and analysed. And sifting through millions of genes for the ones that will boost yield, resist pests, increase nutritional value and, above all, sell, requires more than just molecular-biology skills; business savvy counts. But she realizes what attracts scientists. "The main drive for the scientists is the cool science, the cool technologies and the incredible impact," she says.

Across the street from the concrete solidity of the Monsanto campus lies the non-profit Donald Danforth Center, which looks a little like a kitchen island. Here, Roger Beachy, whose disease-resistant tomato was the plump red opening note to the agricultural biotechnology era, runs a team of scientists intent on using agribiotech advances to aid humanitarian efforts. The Danforth Center is in some ways the hip young kid on the block. Established in 1998, it is just now hiring the last of its core investigators.

The Danforth, with its 19 principal investigators, is much smaller than Monsanto, and consequently hires less, but it too is interested in bioinformatics. The most qualified people have good molecular-biology and plant skills, according to Billie Broeker, director of human resources for the organization. "We need people who can do greenhouse work and tissue-culture work in sterile conditions," she says. Researchers work with everything from mass spectrometry to exotic tissue culture. "You don't have to just work in Arabidopsis; you can work in corn, soya, cassava," says Jan Jaworski, vice-president for research.

Recently, Enterprise Rent-A-Car donated $25 million to the Danforth to create an institute of renewable fuels. Despite the potential downsides of corn-based ethanol and other biofuels, they are likely to be a part of the energy future in the United States. The recently passed energy bill has substantial research funds: $75 million for research on "biofuel production technologies in states with low rates of ethanol production", and $50 million for university-based research on cellulosic ethanol. This year's farm bill is expected to have hundreds of millions for biofuel research.

"The future is interaction with engineering and physical sciences." Ralph QuatranoJ. ANGELES/WASHINGTON UNIV.

Beachy's office is studded with African masks and other reminders of the part of the world in which he hopes agricultural biotechnology will be most revolutionary. He seems a bit weary when it comes to questions about why European activists hate genetically modified crops. But when asked about St Louis as a possible agribiotech hub, his blue eyes engage. "If you look at it and say where is the most discovery science that leads to new inventions — I think we are in the top five," he says. He estimates there are about 500 plant-science PhDs in the St Louis area.

But Beachy admits that St Louis has yet to dominate the sector. "I lived in San Diego and felt the energy, excitement and upbeat attitude. People were starting things in garages," he recalls. "We are not there; we have to mature. And if you look at the venture-capital market, it is more conservative than it was five years ago." He laments the negative impact of the Ventria Bioscience case, in which politicians and companies such as the brewery giant Anheuser-Busch unexpectedly blocked Ventria's plans to cultivate anti-diarrhoeal genetically modified rice in Missouri. They worried the rice would contaminate other fields. "It stunned the state," says Beachy, suggesting that lawmakers bowed to the pressure too readily.

Still, rosier days could be ahead for biotech. Missouri is using some settlement money from a tobacco-company lawsuit to stock a life-sciences research trust fund. A total of $13.1 million was split among 14 projects in Missouri, including a bioplastics collaboration between the Danforth and Boston-based Metabolix, which will open an office at the Nidus Center, an incubator in St Louis.

Transparency and secrecy: greenhouses (inset) at the Danforth Center (far left) and Monsanto's crops (above centre and right).DANFORTH CENTER, E. MARRIS, MONSANTO

Another project funded with tobacco money is the new International Center for Advanced Renewable Energy and Sustainability at Washington University. Run by Himadri Pakrasi, this $55-million endeavour, with a building currently under construction, will research biofuels in collaboration with scientists worldwide. "We are going after carbon sequestration, biofuels, cellulase enzymes and micro algae," he says. There will be five new endowed positions.

Washington University has had a long tradition of plant sciences, carried on by Ralph Quatrano, chairman of the biology department and co-leader of a team that has just sequenced the genome of the moss Physcomitrella patens. The department has strong links with the Danforth Center and the Missouri Botanical Garden, which specializes in plant ecology and taxonomy. "The future," says Quatrano, "is interaction with engineering and physical sciences. We have these huge data sets in the genomic age. Quantitative computational expertise is absolutely necessary."

St Louis is pinning its hopes on growth within the agribiotech sector with crops such as maize (left) and soya.E. MARRIS; MONSANTO

Meanwhile, two hours' drive east of St Louis is the University of Missouri, in the college town of Columbia. Faculty members here are more explicitly focused on agricultural research, especially on creating crops that do more than pack calories into hectares. There is a spotlight on human health, such as adding nutrients and medicines to crops. "I think this is what the future of agriculture is going to be in the United States," says Thomas Payne, dean of the College of Agriculture, Food and Natural Resources. "We have a lot of competition in commodity agriculture around the world." So the United States, he says, can make the complex boutique crops.

Optimistic: Himadri Pakrasi (top) and Nick Kalaitzandonakes.J. ANGELES/WASHINGTON UNIV.G. CHRONIS

The biggest challenge at the University of Missouri is money. The state is less generous than it once was, and federal budgets are tight at the National Institutes of Health, the National Science Foundation and the Department of Agriculture. Payne is seeing his faculty members recruited away from him. "We are the bottom of the barrel in terms of compensation," he admits. The college is letting its faculty numbers drop a bit, so it can give more to the remaining faculty members. Any new hires are likely to be what Payne calls "professional track" — faculty members eventually destined for the public sector, who pay their own way with grants.

On the same campus is the headquarters of the Illinois–Missouri Biotech Alliance — the office of Ken Schneeberger, an assistant dean under Payne. The alliance used to fund biotech science in soya and maize (corn) to the tune of $1 million a year, until Washington cut off its funds. Schneeberger hopes that it will be back in the 2009 budget. Its biggest achievement so far has been developing some lines of soya bean that are resistant to cyst nematode.

The lack of start-up companies in Missouri continues to be an issue, says Nick Kalaitzandonakes, head of the Economics and Management of Agrobiotechnology Center at the University of Missouri. Yet he is optimistic about the region. "If you read the newspaper, you would think that agricultural biotechnology is going nowhere," he says. "But if you look at the acreage being planted with it, the future looks pretty good." He blames onerous federal safety regulations and a culture that does not reward entrepreneurialism for the shortage of start-ups. "The industry has a small number of large players," he says.

Still, he says, the University of Missouri system and Washington University together will probably spend between $400 million and $600 million on research in the field. All that is needed are some business-savvy scientists to really get things humming. Kalaitzandonakes' advice to young scientists shaping their career in agribiotech is simple. "Take a few business classes. Go visit your local angel investor and put yourself out there."

Start-up activity is picking up, says Robert Calcaterra, head of the Nidus Center, which opened in 1999. He has worked with 20 baby businesses, some of them agricultural biotechs. "In 1999, I could count on two hands the number of companies in the plant biosciences," he says. Now, with Nidus, an incubator called the Center for Emerging Technologies and other fledgling companies working alone, he estimates the total could be as high as 35. Calcaterra hopes to see significant growth in another five years.

St Louis itself, the centre for all this would-be entrepreneurial action, is a slightly shabby depopulated former industrial town with the classic crime-ridden core ringed by car-friendly suburbs. It is number two on the latest list of most dangerous US cities, compiled annually by Congressional Quarterly, although there are some revitalization schemes. According to Bob Kranz, a researcher at Washington University, it can be hard to tempt graduate students in from the coasts, despite the low cost of living.

It's one of several challenges. If St Louis is to become a hip, feisty biotech hub, it will have to overcome public perceptions about genetically modified organisms, about St Louis, and about the wisdom of betting on a fledgling biotech cluster that has yet to prove its mettle despite ample promise. Only then might it become the centre of another agricultural revolution.