Most lawn care professionals probably don't think much about the science and technology behind the products they choose to keep turf free of weeds, insect pests and diseases.

New active ingredient development for turfgrass use is not so dissimilar from that of a new pharmaceutical; costs are high, it takes many years to get to market and the chances of success are not guaranteed, even in the final stages of development. In fact, one might argue that pesticide development can be more complex than drug development as it includes not only efficacy and human safety testing but also detailed and costly monitoring of the environmental fate of the product.

Facts and figures

Today, the costs are considered to be closer to $240 million. As well as in-house R&D, Bayer Environmental Science alone invests approximately $3 million annually with about 42 major universities in North America. The work varies from basic research on the mode of action of new chemistry to efficacy profiling on pests, weeds and diseases. On average, it takes eight to 10 years to get a new active ingredient from the laboratory bench to the customer. If you invest $250 million in new technology, you clearly do your best to protect your investment with patents. The life of a patent in North America varies from 17 to 20 years, which means a company has only about 10 years after launch to recoup its investment before generic companies can encroach.

Discovering actives

How are new active ingredients discovered? Every year, our company runs as many as one million new molecules through a complex biological screening process. Much of the work is done with a process called combinatorial chemistry, in which new molecular structures are synthesized using complex robotics. Robots are also used to measure and weigh these chemicals, testing them for biological activity in biochemical screens.

These biochemical screens are often cell-based systems involving ion channels, receptor sites and signaling pathways. We are constantly researching new modes of action to improve performance, reduce costs, improve the toxicological and ecological profiles and combat resistance to established classes of chemistry. In spite of more than half a century of industry research, the number of different modes of action available is surprisingly small. Using insecticides as an example, the most commonly used active ingredients still offer only three distinct modes of action:

1. acetylcholinesterase inhibitors (organophosphates and carbamates)

2. sodium channel modulators (synthetic pyrethroids)

3. nicotinic acetylcholine receptor agonists and antagonists (imidacloprid).

Some of the chemistry under research involves well-understood modes of action, but much of the effort goes into the search for biologically active compounds among unknown chemistries. These biological screens run on nanograms or micrograms of active ingredient, and few (less than 1%) show biological activity on cellular systems or on whole organisms. Compounds that do elicit biological responses will progress to further levels of screening, eventually encountering many target and non-target organisms, such as weeds, fungi, nematodes, mites or insects. It is at this point that chemists will work closely on redesigning the structure of the new active molecule to optimize toxicology, biological performance, costs, physical properties and environmental fate.

Laboratory trials

Of the million compounds our company tests annually, fewer than 20,000 make it through the initial screens, and perhaps only 750 will show promising activity in further studies. All of these compounds will get full biological and chemical profiling in laboratory and glasshouse trials, but less than 10 per year will end up being field tested at one or more of the 25 research farms that the company manages around the world.

Because the target pests, methods of application and technology needs of the turf and pest control markets are different than agriculture, Bayer Environmental Science has its own Development and Training Center in Clayton, N.C. At the Clayton site, scientists test new products on more than 40 cultivars of turf and as many as 30 different insects and diseases important to residential and commercial turf and landscapes. From the synthesis of a new molecule it often takes three to four years before field testing is done. After several years of field screening as well as intense research on manufacturing process, formulation, mammalian toxicology, environmental fate and mode of action, the company will make a decision on whether to promote this new compound into full scale development.

Full scale development means a further investment of many millions of dollars, with no guarantee that the new chemistry can jump all the cost, regulatory and efficacy hurdles that it will face in the next 4-6 years of the development process. Making a decision to invest in a new active ingredient is not all based exclusively on biological performance. Every detail is scrutinized: how large the market might be, what the competitive products are, whether the product is a good strategic fit, whether Bayer will recoup its $240 million investment over the life of the product and what risks are associated with making a 'go' decision.