Gene Drive and Genetic Biocontrol Timeline
The first observations of the skewed inheritance patterns that are characteristic of what we now refer to as ‘gene drive’ were made by a Russian researcher. The year was 1928 and he was studying a species of Drosophila – a fruitfly. The first half of the 20th century saw the discovery of ‘jumping genes’. These are now referred to as transposable elements. They are a common, abundant and very diverse group of ‘gene drives’. They achieve ‘drive’ by creating copies of themselves and inserting them randomly into chromosomes. In the late 1950’s a type of ‘gene drive’ known as ‘meiotic drive’ was discovered. Scientists quickly realized that ‘meiotic drive’ might be used to control insect pests. While notable and important research in the early 21st century is frequently cited as foundational to the history of ‘gene drive’, the timeline presented here illustrates that important ideas originated long before. Only in the 21st century have the technical capabilities been available to readily create ‘gene drives’ in the laboratory.
Contemporary genetic biocontrol research and development, including gene drive, is a culmination of work beginning in the early 20th century. This collection of knowledge from the Virtual Institute’s knowledgebase highlights notable research in the history of genetic biocontrol technology, showing the depth and breadth this ‘field’ of genetics.
Note that ideas emerge in science before they appear in publications. This timeline is intended only to reflect ‘first to publish.’
1900-1950
Early Observations
Barbara McClintock
(1902 – 1992)
Discovered transposable elements, a class of selfish genetic element1950-1975
Basic Genetics & Applications
Edward F. Knipling
(1909 – 2000)
Explored genetic control of insect vectors of human pathogens and parasites1975-2000
Molecular Genetic & Transgenic Technologies
Christopher Curtis
(1939 – 2008)
Explored genetic control of insect vectors of human pathogens and parasites2000-today
Gene Editing Technologies
Austin Burt
First proposed the use of homing endonucleases as gene drive platforms.
1900 - 1950
Early ObservationsBarbara McClintock (1902 – 1992)
Discovered transposable elements, a class of selfish genetic elementThe earliest reports of skewed patterns of inheritance which today we would refer to as ‘drive’ were made in the first half of the 20th century, although the term ‘drive’ was not used until 1957. This period also saw the earliest ideas and experiments involving genetic biocontrol.
Gershenson (1928) made a very early observation of ‘drive’ while studying Drosophila fruitflies.
Serebrovskii (1940) describes how chromosome translocations and the resulting sterility translocation heterozygotes could be the basis for controlling insect populations, the earliest articulation of the idea of genetic biocontrol.
Rhoades (1942) made the first recorded observation of ‘meiotic drive’ in plants while studying maize.
Östergren (1945) was the first to refer to the behavior of ‘B chromosomes’ as parasitic, a concept that preceded ‘selfish genetic elements’.
Potts (1944) and Vanderplank (1944) describe the idea of using hybrid incompatability as a insect control tool independently of Serebrovskii (1940).
Vanderplank (1947) reports extensive hybridization experiments among tsetse species and an attempt to remove a species through the use of hybrid incompatability in the field, one of the earliest attempts of genetic biocontrol.
McClintock (1948) reports the ‘transposition’ of Ac/Ds in maize, a transposable element system. This is a seminal paper not only in the history of the study of selfish genetic elements but in the history of genetics.
Citations
1950 - 1975
Basic Genetics & ApplicationsEdward F. Knipling ( 1909 – 2000)
Explored genetic control of insect vectors of human pathogens and parasitesThis period of 25 years saw the development of solid foundations in the study of selfish genetic elements (gene drive), the first successful application of genetic biocontrol to control an insect and the birth of the idea of ‘population replacement’ as a malaria control measure.
Knipling (1955) was the first peer-reviewed publication in which the inventor of the first genetic biocontrol technology, the sterile insect technique, describes the concepts and genetics.
Baumhover et al. (1955) report the successful application of the sterile insect technique to a significant livestock pest on the island of Curaçao.
Sandler and Novitski (1957) review genetic phenomenon of skewed inheritance and coin the terms ‘meiotic drive’, ‘chromosomal meiotic drive’ and ‘genic meiotic drive’; the first use of the term ‘drive’ in relation to transmission ratio distorting genetic systems.
Dunn (1957) describes the distorted transmission of the tailless locus in mice, one of the earliest descriptions of ‘drive’ in mammals.
Cameron and Moav (1957) describe a ‘meiotic drive’ system in tobacco that they refer to as pollen killer, a heretofore unique mechanism of achieving ‘drive’.
Jones (1957) proposes the replacement of malaria susceptible mosquitoes with refractory strains as a way to control malaria. This is an early expression of the idea of population replacement that continues to motivate vector control research and development.
Sandler et al. (1959) describe a newly discovered locus in the fruitfly, Drosophila melanogaster, displaying ‘meiotic drive’ called Segregation Distorter (SD). SD went on to be a continuous source of great insights into selfish genetic elements and ‘gene drive’.
Craig et al. (1960) describe a sex-ratio distorting genetic ‘factor’ in the yellow fever mosquito, Aedes aegypti, that results in a preponderance of males and how it could be the basis for genetics-based mosquito control strategies.
Von Borstel and Buzzati-Traverso (1962) are the first to recognize and propose that ‘meiotic drive’ might form the basis for controlling economically important and undesirable populations of insects. This is the published report of a paper presented at a meeting in 1960.
Hamilton (1967) publishes his comprehensive consideration of the biology and evolutionary implications of sex-chromosome drives and includes a discussion of the potential use of these selfish genetic elements as the basis for controlling harmful pest populations.
Lavan (1967) reports on the local eradication of Culex pipiens fatigans in Burma using cytoplasmic incompatibility.
Curtis (1968) describes how translocations could be used to drive and fix desirable genes into pest insect populations.
Childress (1972) reports laboratory population cage data using Drosophila melanogaster that illustrate the use of compound chromosomes to change the genetic structure of insect populations.
Citations
1975 - 2000
Molecular Genetic & Transgenic TechnologiesChristopher Curtis (1939 – 2008)
Explored genetic control of insect vectors of human pathogens and parasitesThe emergence of molecular genetic technologies including transgenic technologies for insects, animals and plants motivated interests in genetic biocontrol technologies. Transposable elements were major platforms for genetic engineering technologies and were considered possible systems for introducing and spreading (‘driving’) transgenes into selected populations of harmful insects.
Curtis (1976) reports the first field cage experiment testing a gene drive system based on cytoplasmic incompatibility in the mosquito Culex fatigans.
Wood et al (1977) successfully use a natural meiotic drive system in the mosquito Aedes aegypti to drive an allele of the redeye gene into laboratory cage populations.
Lyttle (1977) experimentally demonstrates the use of a ‘pseudo-Y’ drive to eliminate cage populations of Drosophila melanogaster.
Graves and Curtis (1982) report an early experimental attempt in laboratory populations of Anopheles mosquitoes to replace malaria susceptibility with refractoriness (malaria resistance). These experiments were conducted without the use of a ‘drive’ system.
Rubin and Spradling (1982) report their invention of the first transgenic insect technology. It uses a trasposable element platform and they used it to create transgenic fruitflies, Drosophila melanogaster.
Good et al (1989) demonstrate experimentally how the transposable element P from Drosophila melanogaster could rapidly spread in laboratory populations of Drosophila melanogaster.
Kidwell and Ribeiro (1992) review and explain how transposable elements could be used to drive genes of interest into populations of insects.
Curtis and Sinkins (1998) propose the use of Wolbachia as a gene drive.
Loukeris et al (1995) report the creation of the first transgenic insect that was not a species of Drosophila. The technology for creating transgenic Drosophila was limited to insects of that genus. Loukeris (1995) report the creation of transgenic Mediterranean fruitfly, Ceratitis capitata, using a new, more robust and species-independent transposable element-based technology.
Coates et al. (1998) and Jasinskiene (1998) report on the creation of the first transgenic mosquitoes (Aedes aegypti) using two newly developed transposable element-based technologies with few species limitations.
Citations
2000 - today
Gene Editing TechnologiesAustin Burt
First proposed the use of homing endonucleases as gene drive platformsThere was a decided shift away from gene drive systems based on transposable elements in favor of more active and efficient homing endonucleases (meganucleases) and, more recently, RNA programmable DNA endonucleases such as those associated with CRISPR systems found in bacteria.
Burt (2003) proposes that homing endonucleases could be useful platforms for creating active gene drive systems.
Chen et al (2007) create a synthetic cytoplasmic incompatability gene drive system in Drosophila melanogaster based on maternal-effect selfish genetic elements known as Medea found in flour beetles and show its ability to efficiently drive to high frequencies in laboratory populations.
Windbichler et al (2007) describe successful gene targeting in cells and embryos of the human malaria vector, Anopheles gambiae, using a homing endonuclease.
Windbichler et al (2011) report the successful creation of the first engineered gene drive system in the human malaria vector Anopheles gambiae. This meiotic drive system resulted in a distortion of the sex ratio strongly in favor of males.
Harris et al (2011) report the first open field trial of a genetically modified mosquito – Aedes aegypti.
Esvelt et al (2014) first published report of using programmable RNA dependent DNA endonucleases such as Cas9, from the CRISPR system of Streptococcus pyogenes, to serve as versatile platforms for the creation of homing endonuclease-like gene drive systems.
DiCarlo et al (2015) report the creation of the first engineered homing-endonuclease-like gene drive system using the programmable RNA dependent DNA endonuclease, Cas9. They create and test their system in the laboratory using the yeast, Saccharomyces cerevisiae.
Gantz and Bier (2015) create a gene drive system based on the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes and demonstrate its effectiveness in the fruit fly, Drosophila melanogaster, in the laboratory.
Gantz et al (2015) create a gene drive system in the human malaria vector Anopheles stephensi using the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes.
U.S. National Academies of Sciences, Engineering, and Medicine (2016) publish their recommendations for the responsible conduct of gene drive research in non-human organisms.
Hammond et al (2016) create a sex ratio distorting meiotic drive (gene drive) system in the human malaria vector, Anopheles gambiae, using the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes.
Kyrou et al (2018) demonstrate engineered gene drive mediated population suppression in laboratory cages containing the human malaria vector, Anopheles gambiae.
Grunwald et. al (2019) introduce an engineered gene drive into the house mouse, Mus musculus, in the laboratory.
