Pest Control with Enhanced Environmental Safety - ACS Publications

Chapter 6

Perspectives on Providing a Realistic Technical Foundation for the Commercialization of Bioherbicides P. S. Zorner, S. L. Evans, and S. D. Savage

Downloaded by RUTGERS UNIV on May 29, 2018 | https://pubs.acs.org Publication Date: March 12, 1993 | doi: 10.1021/bk-1993-0524.ch006

Mycogen Corporation, 5451 Oberlin Drive, San Diego, CA 92121

Biological weed control has been an active research area for several decades, but certain key technical barriers have prevented broad commercial adoption of this technology. The last 10 years have been a productive decade for the discovery of new microbial herbicides in that over 100 pathogens have been described in the literature as having potential as biocontrol agents, and a recent survey has identified 200 scientists working in this area. Unfortunately, only two pathogens have been developed to the point of commercialization. A commercial product is defined as one that works consistently in a field environment, and that also can be economically produced and formulated in a form that will maintain the viability of the organism through a commercial distribution process. It appears that limitations to development of additional commercial products are not due to the failure to discover pathogens or due to insufficient personnel involved in research. We conclude that commercialization of additional bioherbicides depends upon devoting major efforts toward developing appropriate fermentation, stabilization and delivery technology.

The use of classical synthetic herbicides is becoming more complicated for industry and their customers as legislative and efficacy issues arise. Weed resistance is limiting efficacy (1). Chemical residues are being found in ground water (2). Persistence of some herbicides beyond a single growing season affects rotational crops (3). Environmental and social concerns are causing some chemicals to be taken out of smaller cropping segments as industry finds these markets cannot financially support the costs of reregistration. These issues and others are making modern weed management a complex process that goes far beyond simple efficacy issues. Biological herbicides may offer some relief to these problems. Generally, they have low registration costs. Mycogen estimates these costs to be no more than

0097-6156/93/0524-0079$06.00/0 © 1993 American Chemical Society Duke et al.; Pest Control with Enhanced Environmental Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1993.

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one million dollars for naturally occurring biological herbicides. The fixed costs for production are low because it is not normally necessary to build a specialized manufacturing facility for these materials. Plenty of excess fermentation capacity exists in the world to handle fermentation of bioherbicides. Bioherbicides have a positive public image that is associated with the overall perception of biological pest control. Bioherbicides also offer a killing action that is different from synthetic herbicides, so they should be efficient tools in combating weeds resistant to specific chemicals. However, despite these obvious beneficial traits, the technology has not realized broad commercial utility even though the technology has been under development for over 25 years (4).

Current Scientific Effort on Bioherbicides The lack of success in developing this technology does not appear to be due to a lack of scientific effort or effective microorganisms. Charudattan reports that in 1989 mycoherbicide research was being conducted in 44 different locations across 16 different countries (4). A recent survey for the Weed Science Society of America identified over 200 scientists in North America working to some extent on biological weed control (Zorner, P.S., Mycogen Corporation, unpublished data). These people have been relatively successful in finding effective microorganisms. In a recent survey, Charudattan listed over 109 pathogens that have been in various stages of development over the last couple of decades (4). In the last 10 years 73 organisms were placed into commercial development programs (4). However, only two of these organisms have been commercialized, and there have been no commercial introductions in the last ten years. Despite this lack of commercial success, Charudattan reported that about 10 percent of the persons surveyed reported that commercial use of the organisms they were working on was considered to be "imminent" (about 9 organisms). The optimistic projections create the impression that weed biocontrol technology has recently overcome major commercial limitations and that people are very confident in their current projects. However, this does not seem to be the case. However, Charudattan also found that over 60% of the more than 100 scientists that he polled felt the chances for commercial success of the pathogen they were working with were less than fair or had unknown chances of success. It appears that one basic problem facing this technology is that basic researchers do not understand what is needed to successfully commercialize a biological product and therefore, do not focus their energy and resources on resolving the key technical issues. In any event, it appears that a strong technical foundation for commercial success of biological weed control has not yet been achieved, despite the efforts of many people and their evident success in finding microorganisms capable of killing plants.

Duke et al.; Pest Control with Enhanced Environmental Safety ACS Symposium Series; American Chemical Society: Washington, DC, 1993.

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Factors Important to Establishing a Commercial Product Unfortunately, providing a solid technical foundation for effective commercial utility involves much more than just finding microorganisms capable of killing weeds. It also requires developing formulations that allow them to work consistently under diverse field conditions. It requires an ability to stabilize these living organisms to the point that they can survive a distribution process in which the formulated product may remain in a warehouse for as long as 18 months between packaging and use. It requires showing that the plant pathogens that form the base of the commercial weed control product do not pose an environmental threat to other plants or segments of the ecosystem in which they will be used. Addressing all aspects of this commercial foundation is a great deal of work and many people feel that biological weed control is severely resource limited, and thereby cannot address all the critical issues. It is also our opinion that the science of biological weed control is not resource limited, but is concept and/or idea limited i.e., that as a group we don't fully understand what technical barriers are limiting our progress. It does not seem reasonable to blame a lack of commercial success on a lack of resources when the last 10 years has seen the discovery of 73 developmental leads (4), and when 200 people in North America alone indicate they are working in this area (Zorner, P.S., Mycogen Corporation, unpublished data). The fact that 73 developmental leads have been found and never commercialized indicates that too much effort has been put on finding new organisms, and not enough effort has been placed on developing the technology to address the other important parts of the commercial foundation mentioned above, such as obtaining consistent efficacy under field conditions and providing prolonged stability of a live organism in a commercial formulation. Recognizing Basic Biological Principals Reviewing the classical disease triangle allows some insight into the nature of the problem of obtaining consistent field efficacy with a living plant pathogen (5). The onset of disease in a function of having a viable pathogen in contact with the correct plant host under environmental conditions that are required for the pathogen in question. The whole foundation of biological weed control is to push the disease process by tipping the ecological balance in favor of the pathogen. People have generally done this by looking for the "right" pathogen or one that will work in a diversity of environments. Thus, we get 73 new organisms as people look for that one organism that will work consistently in the market they want to address. However, the key to the process is not to concentrate on the pathogen itself, but to tip the ecological balance in favor of the pathogen being used by applying it in a viable form, at inoculum levels high enough to initiate an infection and trying to manipulate the micro-environment for a long enough period of time to make sure that an infection gets to the point that it can perpetuate itself.



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Progress won't be made by serving a research philosophy that is based in the concept that if we screen enough organisms, we will eventually find a few unique pathogens that have all the inherent properties necessary to support a commercial product. A greater level of effort is needed in developing technology that can modify the microenvironment and/or enhance the survival of organisms selected to function in a weed control market that is well-suited for a biological organism. The problem in obtaining even an initial infection with the current leads summarized by Charudattan is that they are all fungal pathogens (4). The underlying technical problem with these fungi is that infection requires some period of dew on the surface of the plant so that the fungal spore can germinate and infect the plant. The dew periods of known bioherbicides can approach 72 firs and are at least 8 hrs (6,7). Unfortunately, few natural environments provide more than a few hours of dew, and as summarized by Charudattan, field tests of these fungi demonstrate a great deal of inconsistency (8). The situation is not unlike planting crop seed. Seed is seldom scattered on fallow land and left to germinate and initiate a crop without any further efforts to manipulate the process. Weeds are generally removed, the soil prepared, the seed placed at a soil depth that provides some consistency in moisture, some fertilizer placed with the seed and even a few pesticides applied to give the seed an advantage over indigenous pathogens, insects and weeds. A fungal bioherbicide spore also requires manipulation. It will infect and kill the plant if it is viable and is given the appropriate environmental stimulus to carry out its life cycle. It will die if these environmental requirements are not met. A few people are working on these problems (9). Unfortunately, this technology has not been developed to the point that it economically allows appropriate manipulation of the micro-environment, and thus most applications of bioherbicides in the field provide little or no help to the organism in serving the agricultural function it is being asked to provide. However, people continue to search for new fungal pathogens and test their efficacy under field conditions. In some instances people have chosen organisms for which it is hard to imagine any technology providing the necessary environmental assistance, such as a fungal pathogen that requires a 48 hr dew period (7). Working with an organism of this type beyond the stage of initial discovery makes little sense when no known commercial technology exists that will economically and consistently improve the field performance of an organism, such as Alternaria cassaie, that has only an 8 hr dew period. Bacteria as Bioherbicides It has recently been shown that it is also possible to consider the use of bacteria as biological control agents. Thus, it may be possible to escape the limitations of a dew requirement. Xanthomonas campestris pv. poannua is being developed as a biocontrol for Poa annua in turf (10). It has been shown not to require a dew period because the infection process occurs through movement of the bacteria into the host via a direct wound introduced by a mowing operation. Field efficacy was shown to



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be quite consistent in the southeastern United States. However, disease development and plant death required as long as 50 to 60 days. The researchers involved reported no dew period requirements for disease progression, but did report a strong degreeday requirement (11). This organism requires about 800 degree days above a baseline of 3°C in order to provide 80% weed control. This is a prolonged period of warm temperatures and may prove to be as important a limitation in cooler climates as a dew period limitation is for various fungi. A point of interest here is that bacteria can be used as effective biocontrol agents, and that they may allow people to develop effective bioherbicides in the absence of technology to resolve dew period requirements. However, environmental limitations on efficacy are not avoided with bacteria. They simply have been transformed from a dew period requirement into a temperature requirement, and a requirement for some form of mechanical wounding to allow penetration. Since all bioherbicides are living organisms, it is likely that all potential pathogens will carry some sort of environmental limitation on efficacy and this is a fact that must be dealt with in any discovery program. Choosing the Correct Target Recognizing that environmental limitations cannot be avoided is an important part of any discovery program, because it puts a greater emphasis on appropriate target selection. "Target" is being used here to represent not only the weed species being selected for control, but the cropping system in which that weed is a problem. Logical bioherbicide targets are normally considered to be weeds which escape chemical controls, weeds which escape cultural controls, weeds in environmentally sensitive settings, and weeds in organic cropping systems. In practice, the ideal target is a weed in an agricultural system that may allow for some environmental modification and where people have an economic incentive to make those modifications. Thus, commercial development of bioherbicide candidates into markets such as corn or dry land wheat make much less sense than targets such as turf or high value fruits and vegetables, especially in the absence of technology to manipulate the micro-environment through the formulation process. The logic behind this statement is based on the opinion that corn or wheat are large enough markets to support registration of new, effective and reasonably priced chemicals. Bioherbicide technology would have a difficult time competing on an economic basis and there is little incentive to a grower to use these products at this time. But probably more important is the fact that these and other row crops are grown in a diversity of environments and prolonged dew periods or the ability to manufacture them would be rare. Consistent efficacy would be a problem. Turf, on the other hand, is generally located in environmentally sensitive locations where people have major concerns about pesticide use, irrigation or mowing is a part of the management system, and thus would not be a limitation if needed to move a pathogen into the weed. This is not to say bioherbicides won't eventually be used in row crops. The point is that other markets make more sense for initial introduction of a technology


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that is still in its infancy. In summary, a productive discovery effort not only turns out active pathogens, but turns out pathogens that are well suited for the market in which they will ultimately be used and which are well suited for the delivery technology which exists at the time.


Other Key Technical Barriers As discussed previously, regulatory, fermentation and delivery issues are also major barriers to developing effective commercial bioherbicides. Regulatory, however, is not so much of a technical barrier as it is recognizing that these plant pathogens must be shown to pose no significant risk to the environment in which they will be released. The process of doing this is somewhat confusing because no set regulatory guidelines for doing this have been published by the federal government. The process is basically dependent on a strong and continual interaction with the federal Animal and Plant Health Inspection Service (APHIS). Our experience with APHIS suggests that this process is time consuming, but is not a major technical challenge. Early interaction with APHIS is critical to setting the questions to be answered for any particular organism. These questions generally revolve around host range, environmental distribution, clear identification of the organism and the dynamics of population survival following an inundative release. Technical protocols for providing these data usually exist or are not hard to devise, and thus it is simply a matter of doing the work and communicating on a frequent basis with regulatory authorities. On the other hand, technology for submerged fermentation, stabilization and delivery of a broad range of living biological herbicides does not exist. Bioherbicides will never be widely used as commercial weed control agents until this technology is developed because it impacts their cost, their ability to maintain viability during the distribution process and their ability to work consistently in a field environment. A review of the current technology has been written by Stowell (12). In our opinion this area represents the major technical limitation to establishing bioherbicides as a commercial reality. Yet, in the survey conducted for the WSSA, only 15 of 200 people who responded to the survey indicated that they were working in this area (Zorner, P.S., Mycogen Corporation, unpublished data). This must change if progress is to be made is resolving the key technical issues. Fermentation and Stabilization as Essential Issues The importance of delivery technology was stated previously. Some explanation of why fermentation and stabilization issues are so important also seems appropriate. To do this, consider an imaginary organism produced at a yield of l O ^ colony forming units (cfu's)/ml or spores/ml in the case of fungi. Furthermore, assume that we obtain 50% recovery of viable propagules through the process that leads from the fermentation broth to a formulated product. Finally, assume that it requires 10^ cfu's/ml (or spores/ml) delivered in 400 liters/hectare of volume in the field to obtain 1



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efficacy, and that the associated costs of production for this product, at this use rate are $10/hectare. The importance of making improvements or losing ground relative to the number of viable propagules can be recognized by looking at how dramatically this $10/hectare figure can change with various losses or gains in the system. For example; if yields fall an order of magnitude during scale-up from small fermentors to tanks, production costs rise to $100/hectare. On the other hand, if yields can be increased by an order of magnitude through a clear understanding of those events that support high density fermentation, the costs of production would fall to $1.00/hectare. These two extremes in cost would have a tremendous effect on a business decision to commercialize a living biological. A similar scenario can be set up for stability of the organism once it is formulated. A stable organism may not lose any viability over a one year storage period. An unstable organism could lose one or even two logs of activity. The costs of overformulating to compensate for this loss could drive the cost per acre from $10 to perhaps $1000/hectare. Obviously, these are all imaginary examples, but the point is that micro organisms operate in log scales and logarithmic changes in viable cell or spore count, or even a portion thereof will have a huge impact on the commercial feasibility of bioherbicides. However, despite the critical nature of these processes and a lack of public information on how to control these processes, fewer than 10% of the people involved in bioherbicide research in North America are focusing on this area. It seems logical to assume that this is why only two commercial organisms exists from a pool of 73 leads placed into development over the last 10 years. Summary In summary, it is our opinion that the current lack of commercial bioherbicide products arises from an unnecessary emphasis of current research efforts on finding new organisms. Discovery of active bioherbicides is not the major limitation to developing this technology. Much more effort needs to be placed on developing technology to economically ferment, stabilize and deliver these organisms in a form that will provide for consistent field efficacy. Individual scientists need to form liaisons with people who have these skills and begin to work in multidisciniplinary teams. If these issues are not resolved, they will effectively prevent broad commercial adoption of bioherbicides as effective weed control tools.

Literature Cited 1. Holt, J.S.; LeBaron, H.M. WeedTechnol.1990, 4, 141-149. 2. Carter, A.D.; Hollis, J.M.; Thompson, T.R.; Oakes, D.B.; Binney, R. Brighton Crop Protection Conf., Weeds 1991, Vol. II, 491-498. 3. Stougard, R.N.; Shea, P.J.; Martin, A.R. Weed Sci. 1990, 38, 67-73. 4. Charudattan, R. In Microbial Control of Weeds; Editor, D.O. TeBeest; Chapman and Hall: New York, NY, 1991, 24-57.



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5. Sharvelle, E. Plant Disease Control; AVI Publishing Company: Westport, CN, 1979, 16-34. 6. TeBeest, D.O. In Microbial Control of Weeds; Editor, D.O. TeBeest; Chapman and Hall: New York, NY, 1991, 97-114. 7. Connick, A.C.; Dagle, J.S.InMicrobes and Microbial Products as Herbicides; Editor, R.E. Hoagland; ACS Symposium Series No. 439; American Chemical Society: Washington, DC 1990, 286-304. 8. Charudattan, R. In Microbes and Microbial Products as Herbicides; Editor, R.E. Hoagland; ACS Symposium Series No. 439; American Chemical Society: Washington, DC 1990, 132. 9. Boyette,C.D.;Quimby, P.C.; Connick, W.J.; Daigle, D.J.; Fulgham, F.E.In Microbial Control of Weeds; Editor, D.O. TeBeest; Chapman and Hall: New York, NY, 1991, 209-222. 10. Haygood, R.A. WSSA Abstracts, 1992, 32, 28. 11. Kalmowitz, K; Monaco, T.; Zorner, P.; Evans, S. WSSA Abstracts, 1992, 32, 50. 12. Stowell, L.J. In Microbial Control of Weeds; Editor, D.O. TeBeest; Chapman and Hall: New York, NY, 1991, 225-261. RECEIVED September 14, 1992


Pest Control with Enhanced Environmental Safety - ACS Publications

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