Sunday, May 31, 2015

2015 EPO Awards: GMP - Genetically Modified Pests

Copyright © Françoise Herrmann

According to the Elsevier journal Biological Control, biological control refers to “environmentally sound and effective means of reducing or mitigating pests and their effects through the use of natural enemies” [Elsevier]. The term “pests” in this domain usually includes arthropods such as insects, mites and fleas, invasive plant species such as weeds, and other animals that attack crops, food and livestock, and by extension humans. Thus, biological control arises at the intersection of various fields, including but not limited to agriculture and health, entomology (the study of insects) and epidemiology. 

Ceratitis Capitata  - The medfy
In the domain of agriculture, methods of biological control include quarantine and removal of infested plants, regulations preventing possibilities of importing or introducing pests; ground and aerial spraying of insecticides, herbicides and pesticides; and genetic engineering of seeds, various species of pests, and of the biological control agents [USDA1].

In the domain of health, the need for biological control arises for example with vector-borne diseases, that is, neglected tropical diseases (NTDs) such as malaria, dengue, yellow fever, Chagas and leishmaniasis, or even more local diseases such as Lyme disease, transmitted through organisms such as insects, mosquitoes, ticks and flies [WHO 1]. 

 Aedes aegypti - dengue virus vector
 UN World Health Day 2014 was dedicated to raising awareness of vector-borne diseases. The theme was “Small bite: Big threat”.  Indeed, dengue fever for example, is one of the fastest growing diseases of the world: the incidence of infections worldwide is 30-fold what it was 50 years ago [WHO 2]; and it is estimated that 40% of the world population is at risk [WHO 3].

Methods of protection against bites and the control of dengue virus infections in particular include: implementation of methods for early detection of cases and case management of severe infections,  coordinated epidemiological and entomological surveillance, locally-adapted methods of vector management, including household water-management in urban areas, and enhanced communication (education) to enlist behavioural action; and finally a renewed call for research on neglected tropical diseases, for treatment methods, prevention or management. [WHO2].
The European patent EP1246927 titled BIOLOGICAL CONTROL BY CONDITIONAL DOMINANT LETHAL GENETIC SYSTEM, finalist and contender for a 2015 European Patent Award in the research category, precisely arises within this research context as an effective method of controlling pest populations such as the Mediterranean fruit fly (Ceratitis Capitata) in particular, or the Aedes aegypti species of mosquitoes, the females on which are vectors of the dengue virus.

The patented method of control consist in a novel approach to the prior art of releasing sterile male insects (SIRM – Sterile Insect Release Method) that mate, and produce no offspring, and thus reduce the overall population of insects. The SIRM subsumes production of both a sterile insect and a single-sex population (separation of the insects by sex), so that sterile males-only are released, essentially because females also bite when sterile (whether it is the dengue virus-carrying female species of insects or the medfly…). Of course, the trick is to produce a genetically modified insect of a particular sex that remains as fit as the wild-type, despite all the chemical and radiation manipulations since both will compete for mating purposes!

This invention thus specifically addresses the issue of fitness resulting from genetic manipulation in view of producing effective and viable insects of a single sex capable of transmitting modified population control traits, by inserting a single conditional dominant sex-specific lethal genetic system into the organism. This lethal genetic trait is controlled in the permissive laboratory environment, and expressed under the restrictive conditions of a natural environment, where a condition from the lab is absent which triggers the expression of the lethal system, such as for example killing all female insects. (The invention is actually sex-specific lethal to males or females, and incidentally females for the case of the dengue vector and medfly only because it is females that bite.) 

This novel genetic engineering method enables all the insects to be released in nature where the lethal genetic trait will be expressed (in the absence of a specific lab condition), and thus for the males only to survive, and mate with wild types (without having to resort to an extra step for killing all the females in the lab, prior to release, risking damage to the male insects). Alternatively, the lab condition preventing the expression of the lethal system (or permissive of survival) can be turned off in the lab, so that only males are released in nature (again without resorting to an added sex selection method whether chemical or radiation-based). The females then born of this mating will die, and the males will have inherited the trait… all of which results in the desired insect population control!

The sorts of natural trigger conditions include a certain temperature of the environment (e.g a temperature in the natural environment that is below lab breeding temperature), diurnal cycles (e.g. light and dark conditions of breeding that differ from the wild) or, in the specific case of this patent-related research with Drosophilia (the medlfy), a food or water additive was used for breeding in the lab, the absence of which triggers the sex-specific lethal system, after release in a natural environment.  

Of course no one can argue against controlling insect populations responsible for vector-borne diseases, especially those vectoring the dengue virus, one of the fastest growing diseases on earth which, in contrast to the 3500 species of mosquitoes vectoring malaria, is only vectored by a single species of mosquitoes [WHO 4]. Similarly, no one can argue against biological control of the dreaded medly infestations responsible for extensive fruit crop damages. Indeed, compared to aerial spraying of malathion insecticides, for example, which pose even greater threats to humans, biological control certainly offers a softer form of control, and this invention is one inventive step beyond the release of sterile male insects, used in the prior art.  
There are, however, theoretical arguments and well documented research projects, questioning the benefits, wisdom, long-term effectiveness and practicality of this sort of genetic engineering approach to biological control, precisely because it tends to reduce nature to the very deterministic level of machines. For example, the prolific and well known physicist, feminist and activist, Vandana Shiva (e.g.;1997, 2000, 2012),  points out that , engineering applied to nature does not work in same way as it does for objects and complex machines. When machines break down, their parts are replaced and they are fixed. When nature breaks down, it adapts, compensates, re-organizes and behaves in ways that are not fully predictable. This is particularly well documented in the domain of agriculture where seeds  in association with special triggers and fertilizers are engineered to become weed-, pest-, insect- or weather-resistant, for example, and where, as a result of the genetic manipulations, nature then produces super weeds, super bugs and super pests, able to counter the genetically modified crops and their fertilizers, and thus compounding the initial problems (e.g.; Newman & Pollack, 2010, The Editors - Pollan, et al., 2010). 

The point of Shiva's argument, stripped from its details, is that growing and breeding are different from engineering. A genetic modification inscribes itself relationally in a web of macro and micro-activity systems, incompletely known, where the effects of one modification are not fully predictable. Thus, the voices of dissent call for much more caution in the excitement generated by the possibilities of genetic engineering and the testing of genome hypotheses, all of which appear unquestionably justified by the necessity of providing immediate solutions. Indeed, on a macro level, there are already quite a few unexpected socio-cultural consequences of genetic engineering (i.e.; in the lives of farmers) well worth consideration and understanding in the laboratory [e.g.; Shand, 2004]. 
Below you will find the abstract for this invention, and above images of insect vectors of disease and agricultural havoc.
BIOLOGICAL CONTROL BY CONDITIONAL DOMINANT LETHAL GENETIC SYSTEM A method is disclosed for the control of insects using a dominant sex-specific lethal genetic system which is conditional i.e. expressed when the insect is in its natural environment. The system may be conditional on temperature or a dietary additive which suppresses expression when supplied to insects in the laboratory. This suppression is removed once the insect is in its natural environment where the additive is not found in its food. The lethal effect may be expressed in the laboratory or natural environment so that only one sex e.g. males is released or survives to interbreed with the wild population thus passing on the genetic system. Alternatively, the lethal system may be sex-specific in an adult organism but be lethal to both males and females in the larval stage. The method can be applied for the control of plants wherein one sexual entity of a plant is killed. Abstract EP1246927

The Editors  (May 7, 2010) Invasion of the Superweeds. NewYork Times. Room for Debate, A NYTimes Blog. 
Elsevier Journal Biological Control
Neuman W. &  A. Pollack (May 3, 2010) Farmers Cope With Roundup-Resistant Weeds. NewYork Times, Business Section: Energy & Environment, May 3, 2010
Shand, H. (2004)  Interview –
Shiva, V. (1997) Biopiracy: The plunder of nature and knowledge. Boston , MA: South End Press.
Shiva, V. (2000) Stolen Harvest: The hijacking of the global food supply. Cambridge, MA: southe End Press. 
Shiva, V. (2012) Making peace with the earth: Beyond resource, land and food wars. New Delhi, India: Raj Press. 
USAD 1 - Mediterranean Fruit Fly 
WHO 1 - Vector-borne diseases
WHO (2) WHO global strategy for dengue prevention and control 2012-2020
WHO 3 – Vector Borne diseases
 World Health Day 2014, post at Patents on the soles of you shoes on April 7, 2014

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