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Summary
The control of illicit-drug trafficking and drug use is a difficult and com-
plex process that involves a variety of prevention, control, treatment, and law-
enforcement strategies. Eradication strategies for controlling illicit-drug crops
are used to target the beginning of the drug-supply chain by preventing or reduc-
ing crop yields. Mycoherbicides have been proposed as an eradication tool to
supplement the current methods of herbicide spraying, mechanical removal, and
manual destruction of illicit-drug crops. Mycoherbicides are developed from
plant pathogenic fungi that occur naturally in the environment. Some people
regard them as preferable to chemical herbicides for controlling illicit-drug
crops because of their purported specificity to only one plant species or a few
closely related species. As living microorganisms, they have the potential to
provide long-term control if they can persist in the environment and affect later
plantings. Research on mycoherbicides against illicit-drug crops has focused on
three pathogens: Fusarium oxysporum f.sp. cannabis for cannabis (Cannabis
sativa), F. oxysporum f.sp. erythroxyli for coca (Erythroxylum coca and E. no-
vogranatense), and Crivellia papaveracea or Brachycladium papaveris (for-
merly known as Pleospora papaveracea and Dendryphion penicillatum, respec-
tively) for opium poppy (Papaver somniferum).
In response to a congressional mandate (Public Law 109-469), the White
House Office of National Drug Control Policy (ONDCP) requested that the Na-
tional Research Council form an expert committee to examine the scientific is-
sues associated with the feasibility of developing and implementing naturally
occurring strains of the mycoherbicide fungi as a means of eradicating illicit
cannabis, coca, and opium poppy crops. The study was also to evaluate the po-
tential human health, ecological, and environmental risks associated with the use
of these mycoherbicides and to identify future research and development needed
to support their use. The committee was charged with addressing the following
issues about the potential use of the proposed mycoherbicides: their effective-
ness in eradicating their target plants; the feasibility of their large-scale indus-
trial manufacture and delivery; their potential spread and persistence in the envi-
ronment; their pathogenicity and toxicity to nontarget organisms, including other
plants, fungi, animals, and humans; their potential for mutation and resulting
3
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4 Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops
effects on target plants and nontarget organisms; and research and development
needs.
To address its task, the committee reviewed publications and other pub-
licly available information on the three proposed mycoherbicides and relevant
publications on related fungi and other mycoherbicides that have been devel-
oped against undesirable plant species (weeds). The publications were identified
through literature searches and by consulting the ONDCP, the U.S. Department
of State, the U.S. Department of Agriculture, and the UN Office on Drugs and
Crime. The available studies on the proposed mycoherbicides were few, were
not all peer-reviewed, and were primarily greenhouse, growth-chamber, and
small field studies conducted under controlled conditions. Those limitations
made it difficult for the committee to draw conclusions or to make predictions
about the performance of the proposed mycoherbicides in larger field settings
and under natural conditions.
On the basis of its review, the committee concluded that the available data
are insufficient to determine the effectiveness of the specific fungi proposed as
mycoherbicides to combat illicit-drug crops or to determine their potential ef-
fects on nontarget plants, microorganisms, animals, humans, or the environment.
The questions normally asked before a fungal pathogen is registered as a myco-
herbicide in the United States have not been adequately addressed. The commit-
tee offers the following assessment of what can and cannot be determined at the
present time regarding each of the issues raised in the statement of task.
EFFICACY
The degree of control that might be provided by the proposed mycoherbi-
cides, the mechanisms by which they cause disease, and how control of the tar-
get plants could be maximized have not been established. Although each of the
proposed mycoherbicides has been shown to cause disease in its target plant,
disease severity was inconsistent and depended on biotic factors (such as age of
plants and strain of fungus) and abiotic factors (such as moisture level, tempera-
ture, and ultraviolet radiation). For example, the cannabis mycoherbicide caused
plant death in one study but low to moderate disease severity in a second study.
For the coca mycoherbicide, published mortality ranged from 35% to 94%, but
the background incidence of disease and background mortality in noninoculated
plants also were high, sometimes approximating those observed in inoculated
plants. Some varieties of cannabis were found to be resistant to the mycoherbi-
cide and exhibited no effects or less severe disease.
In studies of the opium poppy mycoherbicide, a range (6-100%) of leaf
necrosis in greenhouse and growth-chamber experiments was reported. Disease
severity depended on the type of inoculum used (sexual or asexual spores), the
age or growth stage of the plants, and environmental conditions, particularly the
dew period and temperature after inoculum application. Plants in early devel-
opment stages were killed or suffered foliar damage; at more mature stages,
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5
Summary
poppy capsule number and size were reduced, and the poppy seeds had lower
viability.
The types of diseases observed to be produced by the proposed mycoher-
bicides in their target plants are wilts in cannabis and coca and blight of the ae-
rial parts of opium poppy. However, the mechanisms underlying the host-
pathogen interactions and secondary spread of disease, which are critical deter-
minants of mycoherbicide efficacy, have yet to be documented.
INOCULUM PRODUCTION AND DELIVERY
Large-scale production of the proposed mycoherbicides appears to be fea-
sible, although available fermentation capacity might not suffice to combat il-
licit-drug crops on a global scale. The production process could be adapted from
technology developed to produce microbial biomass for pharmaceutical, food,
biotechnology, and other commercial uses. Large-scale production of mycoher-
bicides for commercial use is typically undertaken by industries that have mi-
crobial fermentation capabilities. The process involves the production of large
amounts of fungal biomass by liquid fermentation, solid-substrate fermentation,
or a combination of the two and has been used to produce commercial quantities
of mycoherbicides.
It is difficult to estimate the quantity of mycoherbicide needed to control
cannabis, coca, or opium poppy crops. Rough estimates based on the few avail-
able studies suggest that tens to hundreds of kilograms of dry formulation per
hectare would be required for a single application of the cannabis and coca my-
coherbicides. More accurate estimates require tests of the finished mycoherbi-
cides under conditions that simulate field operations. Producing the amount of
mycoherbicides required for global control efforts may or may not be feasible in
light of cost or technical limitations; no mycoherbicide has ever been produced
on such a massive scale. Studies of disease of opium poppy have used liquid
spray formulations consisting of spores of the mycoherbicide fungus suspended
in water or water amended with a surfactant or a vegetable oil. At the rates re-
ported in publications, hundreds to thousands of liters of liquid-spray formula-
tion (containing billions to trillions of spores) per hectare would be required for
a single application of the opium poppy mycoherbicide.
The methods for delivering the proposed mycoherbicides to target sites
would affect their performance in the field. The cannabis and coca mycoherbi-
cides are soilborne and root-infecting and would have to be applied to the soil on
or near plant roots for greatest efficacy. Several dry formulations (such as pel-
lets) have been developed for this type of application. The opium poppy myco-
herbicide, in contrast, would attack primarily aerial parts of the plant, so applica-
tion of a liquid formulation to foliage would provide the greatest efficacy. For
all three mycoherbicides, on-ground application would allow the most precise
and uniform application. However, ground applications are unfeasible because
of uncooperative and possibly hostile growers, who are likely to try to prevent
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6 Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops
application of the mycoherbicides. Aerial application of mycoherbicides from
airplanes as dry formulations on cannabis and coca fields could reduce their
efficacy because the formulations would be subject to scattering by wind, which
would lead to nonuniform, discontinuous placement of the inoculum over the
target area and reduce the size of the plant-pathogen interface. A similar limita-
tion applies to aerial application of liquid mycoherbicide formulations on opium
poppy. But an even more important limiting factor is the availability of water
needed for the liquid formulation and the ability to transport and apply the re-
quired quantities to the target area.
PERSISTENCE
Another issue is how long can the mycoherbicide fungi persist in the soil
after application. It is important to determine whether the population density of
the mycoherbicide fungi would remain high enough and for a long enough pe-
riod to infect the target crops and whether they could survive in the soil and or-
ganic matter at levels necessary to affect later plantings of the crop. Another
consideration is whether the mycoherbicide strains would pose any additional
risks to nontarget organisms after release, in which case the prolonged persis-
tence of these strains would be a disadvantage rather than an advantage.
Only a few studies on the long-term survival of the proposed mycoherbi-
cides against coca and opium poppy are available, and essentially no data on the
proposed cannabis mycoherbicide are available. In the available studies, the
coca mycoherbicide strain survived for up to 7 months after application, and the
opium poppy mycoherbicide strain survived in treated fields for two growing
seasons. Those fungi are indigenous where their host plants are grown and have
been linked to periodic, natural epidemics, so at least the fungal strains related to
the mycoherbicide strains survive for a long time in the presence of their hosts.
Survival of the mycoherbicide fungi would also depend on the environ-
mental conditions. Moisture (from dew, high relative humidity, or rainfall) for
several hours and over several days is usually required with favorable tempera-
tures for the fungi to become established on the target plants. In the case of the
specific fungal strains studied (such as F. oxysporum f.sp. erythroxyli), data on
moisture, temperature, and other requirements for disease development and sur-
vival in soil are based on results with one or a few strains collected from rela-
tively small areas. There is no reason to expect these strains to be adapted to any
environment other than the one from which they were recovered; therefore, the
strains may not be capable of attacking coca throughout its entire range. But the
data are also not sufficient to conclude that strains of the mycoherbicide fungi or
the diseases that they cause cannot occur throughout the entire geographic and
climatic range where the target drug crops are grown.
The mycoherbicide strains might be able to survive on plants other than
their target plants or as saprophytes on decaying organic material. Thus, it is
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7
Summary
likely that the mycoherbicide strains would persist at some level as part of the
indigenous pathogen population once they are introduced in large numbers into
the environment. The pathogens also might be spread from the site of applica-
tion by wind, water, insect or animal carriers, or infected seeds, soil, or plant
material. Conditions that might reduce survival of the mycoherbicides include
lack of adequate moisture, extreme temperatures (too high or too low), competi-
tion or suppression by soil microorganisms, and other biotic factors.
Once the mycoherbicides are applied, their persistence might be shortened
through the intentional application of chemicals, such as fungicides or soil fumi-
gants, by growers. Such a control strategy would be most effective for contain-
ing mycoherbicides in small areas but would be impractical or impossible for
large areas. The chemicals also could affect indigenous microbial communities.
There is some evidence that high population densities of the mycoherbicides
could be maintained for several months, but the data do not support the hypothe-
sis that the mycoherbicide strains can persist indefinitely at higher population
densities than those of indigenous strains of the same fungi.
EFFECTS ON NONTARGET PLANTS AND ORGANISMS
Because of the complexity of native and agricultural ecosystems, it is dif-
ficult to predict or quantify the risks to nontarget plants and organisms accu-
rately. Other fungi, soil organisms, plants, animals, or humans could be exposed
to a mycoherbicide strain by several environmental pathways. For example, in-
sects, reptiles, and birds might be attracted to a mycoherbicide formulation as a
food source, and wind and rain can carry fungal propagules over long distances.
Infested soil, plant material, and seeds can be moved to other crop sites by hu-
mans or other vectors. Such dispersal would inadvertently expose native plant
species to the mycoherbicides and could pose risks to local ecosystems. The
coca mycoherbicide, for example, could cause increased disease epidemics of
native relatives of coca plants that could lead to adverse effects on local biodi-
versity or increase erosion if native coca communities on steep hillsides are re-
duced in size or density. Inadvertent infection of licit crops of cannabis, coca,
and opium poppy could have important cultural and economic consequences.
The proposed mycoherbicide strains can cause disease on their target
plants, including those grown legally and those indigenous to the area. However,
the few host-range studies conducted with nonrelated species are of little value
because they report only that the mycoherbicide strains did not cause disease on
particular native plants and crops without providing experimental details (and in
some cases even the names of the plants). Furthermore, none of the available
studies used a standard, systematic process to select the most relevant plants to
test in host-range studies. For example, of about 200 species of Erythroxylum
native to South America, only two have been tested for sensitivity to the coca
mycoherbicide. Thus, the data are insufficient to conclude that the proposed
mycoherbicides would not pose a risk to other plants or crops.
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8 Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops
Likewise, no data are available on the effects of the proposed mycoherbi-
cides strains on soil microorganisms, animals, or humans. Such effects could
include competition with indigenous microbial populations, diseases resulting
from direct infection of animals or humans, and disorders resulting from contact
with or consumption of toxins produced by the mycoherbicide strains. Although
fungal species and strains related to the proposed mycoherbicides might cause
such problems, there are no data to suggest that the proposed mycoherbicide
strains would produce similar infections or toxins.
It will be all but impossible to control or contain the mycoherbicide strains
after they are released. The strains are living organisms that interact with and
adapt to their environment. Their ability to survive, propagate, and disperse be-
yond the target area depends on environmental factors that can be neither pre-
dicted nor controlled. The persistence of indigenous strains of these fungi
throughout the native ranges of their hosts is consistent with the conclusion that
the mycoherbicide strains are unlikely to be contained or eradicated once they
are released.
MUTATION
The committee was asked to consider the potential of the fungi to mutate
and the possible consequences, but no data on the mutability of the proposed
mycoherbicide strains in particular are available. The potential for these myco-
herbicide strains to mutate is expected to be similar to that of fungi in general.
The genetic makeup of fungi can change by nucleotide substitution, the gain of
genetic material from other fungi, the duplication of genetic material, and the
loss of genetic material. Some species of Fusarium are well known for their
spontaneous mutations to new morphologies. Gene transfer between distantly
related strains of Fusarium occurs under laboratory conditions, and there is cir-
cumstantial evidence of such transfers under field conditions between strains
that belong to different species. There are no data documenting the occurrence
of such events in the Fusarium strains proposed for use as mycoherbicides or
any strains of C. papaveracea or B. papaveris. Because indigenous strains of
these fungal pathogens are present where the drug crops are grown, it is unlikely
that mutations would occur in the introduced strains that have not already oc-
curred in the indigenous population or that the mutations would pose novel risks
to nontarget plants or other organisms, including humans or other animals. It is
not possible to predict what types of mutations might occur, how a pathogen or
target plant might be affected, or whether the mutations would be favored by
natural selection.
New genetic variation results from mutation, and mutations can become
established in fungal populations by natural selection or by chance. Natural se-
lection results in adaptation to changing environments, including adaptation to
new cultivars of a target species or to new host species. Adaptation might occur
in fungi that reproduce sexually or asexually. Sexual reproduction allows new
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9
Summary
genotypes to be produced more quickly through recombination than through
mutation alone, as would occur in asexually reproducing organisms.
The evolutionary processes of mutation and adaptation also apply to the
target plants. Plant cultivars resistant to a mycoherbicide could exist or emerge
through natural selection and replace their sensitive predecessors. Thus, the de-
velopment of effective mycoherbicides is a continuous rather than a one-time
process.
RESEARCH AND DEVELOPMENT
The data available on the proposed mycoherbicide fungi reviewed by the
committee are insufficient to determine the feasibility of their development as
mycoherbicides or the risks that they might pose to nontarget plants, animals,
humans, microorganisms, or the environment. Additional research is needed to
address those concerns. At a minimum, a scientific team with expertise in plant
disease epidemiology; plant pathology; fungal genetics; fermentation, formula-
tion, and application technology; and nontarget risk assessment is needed to
develop the proposed strains as mycoherbicides and to assess their safety and
effectiveness. Initially, research is needed to study several candidate strains of
each fungus and to identify strains that are the most efficacious under a broad
array of environmental conditions. The resulting information would guide for-
mulation development, the selection of a delivery method, and the scaleup re-
quired to generate enough mycoherbicide product to achieve a significant level
of control.
Multiple regulatory requirements must be met before a mycoherbicide
could be deployed. Many of the regulations focus on evaluating the risk to the
environment posed by the introduction of the mycoherbicide. Little research of
this sort has been conducted with any of the proposed mycoherbicide strains.
Before the mycoherbicides could be used outside the United States, additional
regulations in one or more international agreements might also need to be met,
including the International Plant Protection Convention, International Standards
for Phytosanitary Measures, the Biological Weapons Convention of 1972, and
legal requirements in the country where the mycoherbicides are to be used.
OVERARCHING FINDINGS
Studies of the cannabis, coca, and opium poppy mycoherbicides that have
been published or were made available to the panel are preliminary, exploratory,
and insufficient to determine their suitability for controlling illicit-drug crops.
The available data do not answer all the questions normally asked before a fun-
gal pathogen is registered as a mycoherbicide in the United States. The rigorous,
lengthy testing required by the U.S. Environmental Protection Agency has not
yet begun, and conducting the research is not a guarantee that a registered my-
coherbicide product will result. Mycoherbicides for the control of illicit-drug
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10 Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops
crops will face additional difficulties in that the people cultivating the crops will
be working to prevent the mycoherbicides from having their intended effects.
Potential Impediments
International Approval and Cooperation: Mycoherbicides proved to be
safe and effective might not be approved for use in other countries. At least
some tests of the mycoherbicide strains must be performed in the countries
where the mycoherbicides might be used or in other countries that have similar
climatic and environmental conditions. The testing requires the approval and
cooperation of those countries and has been difficult, or impossible, to obtain.
Country-specific requirements for such applications must also be satisfied.
Difficulties in Implementation: Commercial success of mycoherbicides
developed to control weeds requires collaboration with the growers. Farmers
who welcome attempts to control unwanted plants will tolerate aerial application
from aircraft flying at low altitudes and at low speeds or from ground-based
equipment, as needed, for the effective application of mycoherbicides, and they
will permit or assist in the on-the-ground monitoring needed to assess the effi-
cacy of the mycoherbicide. The proposed mycoherbicides for illicit-drug crops
would not have similar cooperation from their growers, and this would constrain
aerial application methods and limit on-the-ground monitoring. Technology for
the effective application of mycoherbicides from high altitudes has not been
developed.
Difficulty in Assessment of Effectiveness: The available data indicate
that that proposed mycoherbicide strains are unlikely to kill large numbers of the
target plants quickly. The combination of lack of rapid, aggressive action with
little or nonexistent on-the-ground assessment would make it difficult, or even
impossible, to determine the effectiveness of the mycoherbicide applications.
Development of Countermeasures: Producers of illicit-drug crops have
an incentive to prevent damage to their crop yields and should be expected to
develop countermeasures that reduce the efficacy of the mycoherbicides. Such
countermeasures could include the use of fungicides or soil fumigants to kill the
mycoherbicide strains directly or the cultivation of plant varieties that are resis-
tant to the mycoherbicides.
Unavoidable Risks
Risks to Legal Crops and Native Plants: Cannabis, coca, and opium
poppy are grown in several countries for licit uses and are part of the native flora
in some regions. Plants in those settings could be vulnerable to the mycoherbi-
cides. In addition, the mycoherbicides could spread beyond the geographic range
of the illicit crops.
Risks to Nontarget Organisms: The mycoherbicide strains could have
direct and indirect effects on other plants, microorganisms, animals, or the envi-
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Summary
ronment. Those effects cannot be completely characterized even if research is
performed to learn more about the infectivity and toxicity of the strains, if any,
to nontarget plants and organisms. Mycoherbicides consist of living organisms
that interact with and adapt to their environment, and it is difficult to predict
how they might behave when released in substantial numbers into an ecosystem.
