Marijuana, cocaine, and heroin are three of the leading illicit drugs in the world. In 2008, cannabis herb production was estimated at 13,300-66,100 metric tons, and cannabis resin production at 2,200-9,900 metric tons. In 2009, global production of cocaine was estimated to range from 842 to 1,111 metric tons. Potential opium production was estimated at 7,755 metric tons, about 37% of which was projected to be available on the drug market as opium and the remainder as morphine and heroin (UNODC 2010a).
Those drugs are derived from plants: marijuana from cannabis (Cannabis sativa), cocaine from coca (Erythroxylum coca and E. novogranatense), and opium, morphine, and heroin from opium poppy (Papaver somniferum). Illicit cannabis plants are grown in most countries of the world, and it is difficult to obtain reliable estimates of cultivation because they are increasingly grown indoors. The UN Office on Drugs and Crime (UNODC) estimated that 200,000-641,800 hectares of land worldwide were used for outdoor cannabis cultivation in 2008. Afghanistan is the major cannabis producer in the world (see Table 1-1). A survey conducted by UNODC and the Afghan Ministry of Counter Narcotics in 2009 estimated 10,000-24,000 hectares of cannabis cultivation and 1,500-3,500 metric tons of cannabis resin production in Afghanistan. The extent of indoor cannabis cultivation cannot be accurately calculated, but indirect measures indicate that it is increasing because it is less likely to be detected, the yields are higher, and several crops can be grown per year (DOJ 2010; UNODC 2010a).
Illicit coca is cultivated primarily in the Andean countries of Colombia, Peru, and Bolivia. UNODC (2010a) estimated that 232,772 hectares of coca bushes were cultivated in Colombia, 69,925 hectares in Peru, and 37,241 hectares in Bolivia in 2009. Of those estimates, about 68,000, 59,900, and 30,900 hectares of coca bushes, respectively, were harvestable after eradication efforts (see Table 1-2).
The major countries that cultivate illicit opium poppy are Afghanistan, Myanmar, and Mexico. In 2009, the estimated illicit cultivation of opium poppy
was 128,351 hectares in Afghanistan and 35,787 hectares in Myanmar. After eradication efforts, about 123,000 and 31,700 hectares of opium poppy were harvestable, respectively (see Table 1-3). Estimates for Mexico in 2009 were not available, but estimates from previous years suggest that it maintained its third-place status as in 2008. Other countries in which opium poppy is cultivated include Pakistan, the Lao People’s Democratic Republic, Thailand, Vietnam, and Colombia (UNODC 2010a).
The control of illicit-drug use and trafficking is difficult. It involves a variety of prevention, control, treatment, and law-enforcement strategies and the participation of local, national, and international government agencies. One approach in these endeavors, eradication of illicit crops, targets the beginning of the drug-supply chain by interfering with crop production in the fields. Croperadication measures include aerial application of herbicides, mechanical removal that uses tractors or other vehicles to harrow fields, and manual removal and destruction of plants.
TABLE 1-1 Major Cannabis-Cultivating and Cannabis-Producing Countries (2008, unless otherwise stated)
|Country||Cultivated Area. hectare||Eradication||Hanesiabie Area. hectare;||Pieduraoc ciealc ton:|
|Afghanistan||10.000-24.000 (2009)||10.000-24.000 (2009)||1.500-3.500 (2009)|
|Colombia||5.000 (2006)||—||—||—||4.000 (2006)|
|South Africa||1.300||1,275 hectares||25||—||—|
|United States||7.6 million outdoor plants. 451.000 indoor plants||3,149-7,349|
Source: UNODC 2010a. Reprinted with permission; copyright 2010. World Drug Report by United Nations Office on Drugs and Crime. Vienna. Austria.
TABLE 1-2 Global Illicit Cultivation of Coca and Production of Cocaine, 1995-2009
|Coca Bush Harvestable after Eradication, hectares|
|Potential Manufacture of Cocaine, metrictonsa|
aPotential manufacture refers to the amount of 100% pure cocaine that could be produced if all coca leaves harvested in an area under coca cultivation in 1 year were processed into cocaine, on the basis of information on cocaine alkaloid content of coca leaves and efficiency of clandestine laboratories. Estimates for Bolivia and Pern take into account that not all coca leaf production is destined for cocaine production.
bBecause of the ongoing review of conversion factors, no point estimate of cocaine production could be provided for 2009. Because of the uncertainty of total potential cocaine production, the 2009 fiaure was estimated as a ranee (842-1.111 metric tons).
Source: Adapted from UNODC 2010a. Reprinted with permission: copyright 2010. World Drug Report by United Nations Office on Drugs and Crime. Vienna. Austria.
TABLE 1-3 Global Illicit Cultivation of Opium Poppy and Production of Opiates, 1995-2009
|Opium Poppy Harvestable after Eradication, hectares|
|Potential Opium Production,b metric tons|
|Potential Manufacture of Heroin, metric tonsee|
aStarting in 2008. a new method was used to estimate opium poppy cultivation and opium and heroin production. The estimates are higher than the previous estimates but of a similar order of magnitude.
bPotential production is the amount of oven-dry opium of unknown morphine content that could be produced if all opium poppy cultivated in an area in 1 year were harvested in the traditional method of lancing the opium capsules and collecting the opium gum or latex.
cIn some countries, poppy straw is used to produce acetylated opium rather than opium gum. However, for reasons of comparability, it was assumed that all opium poppy cultivation is used for opium gum production.
dThese estimates represent the amount of opium that remains opium and is not processed into morphine or heroin. It refers only to Afghan opium because the amount of opium not processed into morphine or heroin in other countries could not be estimated. For years before 2004. no such estimate was available for Afghanistan.
ePotential manufacture is the amount of heroin of unknown purity that could be produced if the total potential opium production were converted into heroin, excludina the opium that is consumed as opium and not processed.
fThis series contains all heroin potentially manufactured worldwide, including heroin and morphine consumed and seized in Afghanistan. The amount of Afghan opium estimated to remain available as opium (potential opium, not processed) is not included in these figures.
Source: UNODC 2010a. Reprinted with permission: copyright 2010. World Drug Report by United Nations Olhce on Drugs and Crime. Vienna. Austria.
Some genotypes of parasitic fungi can infect a single plant species or a small group of closely related species, and the use of these fungal pathogens, or mycoherbicides, formulated and applied in the same ways as chemical herbicides, has been proposed as a means of controlling illicit crops. The fungi also have the potential to persist in the soil for many months or years and to affect later attempts to cultivate the crops (see Chapter 3).
The terminology of fungi used throughout this report can be confusing to those unfamiliar with the practice of taxonomy (classifying and naming organisms) and fungal characteristics. This section presents the names assigned to the fungi under consideration in this report and some of their distinguishing characteristics.
Organisms are classified with a hierarchical system of categories: kingdom, division (phylum), class, order, family, genus, and species. The Kingdom Fungi is subdivided into phyla. The proposed mycoherbicides considered in this report belong to the phylum Ascomycota. Ascomycota is the largest of the fungal phyla, containing more than 60% of described fungal species, including most species of plant-pathogenic fungi.
Fungi in Ascomycota may reproduce sexually to produce ascospores or asexually (clonally) by mitotic division to produce a different type of spore, a conidium. Most fungi in Ascomycota require a mating partner to form a zygote (cell formed by the union of male and female sex cells), which then undergoes meiosis (cell division for sexual reproduction) and produce ascospores (Figure 1-1). Some species can self-fertilize to produce a zygote which gives rise to ascospores (Figure 1-2). Ascomycota organisms that require a partner to complete the sexual cycle are termed heterothallic; those which can complete the sexual cycle without a partner are termed homothallic. The ability of fungi in Ascomycota to produce both ascospores and conidia has led to taxonomic complexity because each spore state may have its own name. Thus, a single fungus may be known by more than one name: one name when it produces sexual spores (sexual state; teleomorph), and another name when it produces mitotic spores or conidia (asexual state; anamorph). If there are two names, the teleomorph name would be synonymous with the name for the entire fungus (the holomorph). Many fungi in Ascomycota have not been observed to reproduce sexually, although they may produce abundant clonal spores (Figure 1-3).
In this report, we refer to the proposed mycoherbicides by the species names of the fungi intended for development. A species is commonly denoted by the name of a genus (a group of closely related species) and a species name that serves as an adjective or modifier of the genus name. The proposed mycoherbicides of cannabis and coca belong to the same species, Fusarium oxysporum. Some F. oxysporum names are followed by a special form name, or forma specialis (f. sp.) (the plural is formae speciales [f. spp.]), which indicates
that the fungus appears to infect a specific type of plant species or group of species. The proposed mycoherbicides against cannabis and coca are F. oxysporum f. sp. cannabis and F. oxysporum f. sp. erythroxyli. (Cannabis and Erythroxylum are the genera of cannabis and coca, respectively). F. oxysporum is known to produce conidia and is not known to produce ascospores, although fungi in many other species of Fusarium are known to reproduce sexually in both heterothallic and homothallic manners.
The proposed opium poppy mycoherbicides belong to two fungal species: Crivellia papaveracea and Brachycladium papaveris. These poppy pathogens were previously named Pleospora papaveracea and Dendryphion penicillatum, respectively. The changes in names of the poppy pathogens reflect a better understanding of their biology (Inderbitzin et al. 2006); they were found to be closer relatives of Alternaria spp. than of Pleospora spp. (see Figure 1-4). To connect the new names with those of fungi used in older literature, a table is provided in Chapter 5 to document the old and new names for the fungi. When it is unclear which of the two species was studied, we refer to both fungi in this manner: C. papaveracea/B. papaveris.
The Office of National Drug Control Policy Reauthorization Act of 2006 (Public Law 109-469, Section 1111) directed ONDCP to support a scientific study of the use of mycoherbicides in eradicating illicit crops. In response, ONDCP asked the National Research Council to form an expert committee to examine scientific issues associated with the feasibility of developing and implementing mycoherbicides to eradicate illicit crops of coca, cannabis, and opium poppy, including an evaluation of the potential human health, ecological, and environmental risks associated with their use and recommendations for the research and development needed for such use.
The committee was charged with addressing the following issues about the potential use of naturally occurring strains of mycoherbicides in eradicating illicit crops: (1) their effectiveness in eradicating target plants; (2) the feasibility of their large-scale industrial manufacture and delivery; (3) their potential spread and persistence in the environment; (4) their pathogenicity and toxicity to nontarget organisms, including other plants, fungi, animals, and humans; (5) their potential for mutation and resulting toxicity to nontarget organisms; and (6) future research and development needed for implementation, such as mode-of-action studies. The specific questions to be addressed are presented in Box 1-1.
The committee comprised experts in plant pathology; mycotoxins; fungal genetics, evolution, and ecology; mycoherbicide development, formulation, and application; plant-disease epidemiology; soil microbiology; medical mycology; human toxicology and risk assessment; and ecological risk assessment. This report presents the consensus findings of the committee.
The committee found that some elements of the statement of task were vague and open to interpretation. After discussions with the sponsor, the committee arrived at the following observations and clarifications on how to fulfill its task.
• The term eradication suggested to the committee that complete destruction of the target crop was the intended goal. Discussions with the sponsor made it clear that complete destruction was an unrealistic expectation and that the intended goal is substantial control of crop yields by causing disease or weakening a plant’s ability to produce the chemical compounds used to make illicit drugs. However, the sponsor did not specify the desired extent of control of the illicit crops. It was beyond the committee’s charge to determine what an appropriate extent of control would be.
• Are the drug crops (cannabis, coca, and opium poppy) known to be susceptible to the proposed mycoherbicides?
• Have the mechanisms of action of the proposed mycoherbicides’ toxicity to illicit-drug crops been established?
• Are the proposed mycoherbicides host-plant-specific?
• What quantities of mycoherbicides would be needed to eradicate illicit drug crops?
• How would the method of delivery affect the effectiveness of the mycoherbicides in eradicating the drug crops?
Feasibility of large-scale manufacture and delivery:
• What sort of facility would be required for the large-scale industrial manufacture of the proposed mycoherbicides?
• What sort of equipment and technology would be required for the delivery of the proposed mycoherbicides on a large scale?
• What is the overall technical feasibility of the large-scale industrial manufacture of the proposed mycoherbicides?
• What consideration would need to be made for large-scale delivery of the proposed mycoherbicides?
• What types of field trials of the proposed agents are needed? For example, is testing in tropical or arid environments required?
Persistence in the environment:
• How long are the mycoherbicides likely to persist in the environment after application?
• Do the mycoherbicides have geographic or climatic boundaries?
• What combination of environmental conditions (such as temperature, depth in soil, and pH) would favor persistence after application?
• What conditions would shorten the persistence of the proposed mycoherbicides in the environment?
• Could persistence of the mycoherbicides in the environment be controlled?
Toxicity to nontarget organisms:
• Would the proposed mycoherbicides harm licit crops or kill other soil fungi?
• Would the proposed mycoherbicides threaten biodiversity or pose other risks to the environment?
• What is the nature of the health risks to animals and humans posed by the use of the proposed mycoherbicides?
• What would be the range of transmission of the proposed mycoherbicides and what factors would influence their spread?
• Once released, would the pathogens be uncontrollable?
Potential for mutation and resulting toxicity to target and nontarget organisms:
• What would be the potential of the pathogens to mutate?
• Are there environmental or other conditions that would drive mutations in the mycoherbicides?
• Does the potential for mutation pose additional risks to nontarget organisms (including other plants, fungi, animals, and humans) or the environment?
• How might mutations affect the susceptibility of the target crops to the mycoherbicides?
• How might mutations affect the toxicity of mycoherbicides generally?
Research and development needs:
• Could the effectiveness of the mycoherbicides in eradicating illicit-drug crops be improved through research and development?
• What types of expertise would be most relevant for improving the effectiveness and safety of the proposed mycoherbicides?
• What types of research and technology would improve the production and delivery of the mycoherbicides?
• What type of testing would be needed before mycoherbicides could be safely and effectively used to eradicate illicit-drug crops (for example, mode-of-action studies)?
• What would be required under U.S. federal and state laws to test and approve a mycoherbicide of this type, and what guidelines of the International Organisation for Biological and Integrated Control of Noxious Animals and Plants would apply?
• Pathogenicity and toxicity are used interchangeably in the statement of task, but they have different meanings. Pathogenicity refers to the ability of a living agent (the pathogen) to infect and cause disease. The affected organism is termed the host. Toxicity is commonly used with two connotations: the capacity of any agent to cause harm to a living organism and the degree or extent of the harm caused by a chemical. In this report, pathogenicity is used to describe the former concept and toxicity to describe the latter concept. The distinction is important because the fungi of interest are competent plant pathogens and are capable of causing disease in the host plants that they colonize, but some also produce chemical metabolites that might adversely affect other plants, microorganisms, animals, and humans.
• Several of the task questions focus on the potential of the fungi to mutate. The term mutation often has a negative connotation, so it is important to define how it is used in the report. Mutation refers to change. In genetics, it means a sudden departure from the parental type in one or more heritable characteristics. A mutation results in a permanent, heritable alteration in the DNA sequence of a gene or the physical arrangement of a chromosome. Changes in a gene’s DNA sequence can alter the phenotype (an observable physical or biochemical
trait) by altering its expression. Changes in the physical arrangement of a chromosome also could result in new traits even if none of the genes on the chromosome has been otherwise altered. Induced mutations are heritable genetic changes that result from the exposure to chemical and physical agents that are capable of altering DNA or chromosomal structure. Spontaneous mutations occur without known exposure to a mutagenic agent. As used in the statement of task, mutation appears to refer to any stable change in the fungal phenotype that might occur.
• The question “What would be required under U.S. federal and state law to test and approve a mycoherbicide of this type, and what guidelines from the International Organization for Biological Control of Noxious Animal and Plants (IOBC) would apply?” is more a legal and regulatory question than a scientific one. The committee did not feel comfortable about developing a “checklist” of testing requirements that must be met, especially inasmuch as regulations vary widely by state and by country. It also was unclear to the committee why the work of IOBC was of specific interest to ONDCP. IOBC is an international professional society that promotes the development of biological control agents. Although the organization and some of its members were involved in the development of some international standards for testing pesticides and guidelines for transport and release of biological control agents, it does not have its own set of guidelines. To address the question quoted above, the committee took a broad approach of determining what general types of information would be necessary to test or use mycoherbicides under relevant national or international laws and agreements.
Issues Outside the Committee’s Task
Determining whether it is feasible to develop mycoherbicides requires defining the term feasible. Feasibility clearly encompasses the many scientific and technical questions in the task presented in Box 1-1. However, other issues are critical in determining the feasibility of developing and using mycoherbicides against illicit crops, such as the costs of conducting the research to support the registration of the mycoherbicides, the international procedures for getting mycoherbicides approved for testing and use in different countries, and other economic, social, and political factors. Evaluating those factors was not part of the committee’s charge.
The committee is aware that some researchers have proposed modifying the proposed mycoherbicides genetically to improve their virulence and efficacy in controlling illicit drug crops. However, the committee was asked to restrict its evaluation to naturally occurring strains of the fungi, so genetic modification is not considered in this report.
The committee held three public meetings to gather information to address its task. At the first meeting, on April 20, 2010, the committee met with officials of ONDCP to obtain background on the project and clarification on the scope of work. Representatives of the U.S. Environmental Protection Agency Office of Pesticide Programs gave a presentation on the agency’s experience with mycoherbicides and its requirements for registration. At the second meeting, on June 23, 2010, representatives of the Department of State shared their perspectives on the history that led to the request for the National Research Council study. The committee also heard presentations on research conducted by the U.S. Department of Agriculture’s Agricultural Research Service on mycoherbicides against coca and opium poppy; on the Forest Service’s struggle to deal with illicit drug crops in national parks and other public lands; on the biological control of witchweed (Striga hermonthica) in sub-Saharan Africa using a strain of Fusarium oxysporum; and on the commercial production of mycoherbicides. At the third public meeting, on September 15, 2010, the committee reviewed a potential technique for applying mycoherbicides. The committee heard from other interested parties during the open-microphone sessions at its public meetings and in written submissions.
As noted earlier, economic, social, and political considerations in determining the feasibility of developing and using the proposed mycoherbicides were outside the committee’s charge. Such considerations should be taken into account with the scientific factors by any agency or organization that might engage in the development of mycoherbicides against illicit crops.
To aid in the committee’s evaluation, literature searches were performed to identify relevant research, and ONDCP, the Department of State, and the United Nations were consulted for other relevant, publicly available information. The committee found that little information on the fungi of interest that could be used to provide well-informed answers to several questions in the statement of task was available. Thus, it answered many of the questions in a broad, qualitative context, drawing from general biological principles and from experience with approved mycoherbicides and related fungi.
The committee organized its evaluation by first providing some context for its review. Chapter 2 provides background on the biological control of undesirable plant species. All the mycoherbicides that are approved for use in the United States were developed to combat undesirable plant species. The committee considered general principles learned from developing those mycoherbicides and how they might be applied to developing mycoherbicides against illicit crops. The chapter also discusses issues that are applicable to all the proposed
mycoherbicides, including pesticide regulation in the United States, international considerations for testing mycoherbicides, and a conceptual approach to evaluating risks to nontarget plants and organisms. Chapter 3 provides a brief overview of the biology and cultivation of cannabis, coca, and the opium poppy. Chapter 4 considers the available data on the Fusarium mycoherbicides that target coca and cannabis and what is known about F. oxysporum in general. A similar review of C. papaveracea/B. papaveris is provided in Chapter 5. Chapter 6 provides answers to each of the questions in the statement of task.