Backstory of  Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephens \cite{Gantz2015}.
Developing gene-drive technology:  In late 2014 Valentino Gantz, then a graduate student in my lab at the University of California, San Diego (UCSD), described to me an idea for a CRISPR-based strategy to uncover the effect of recessive mutations in a single generation by creating a self-propagating mutagenic genetic element.  In our discussion, it became clear that this element might also propagate itself through mating and be passed on to the next generation at frequencies much higher than predicted by  standard "Mendelian" inheritance, a phenomenon often referred to as gene-drive1.  Following a series of additional discussions within the lab and advisory faculty members at UCSD, including Marty Yanofsky (then chair of CDB), Bill McGinnis (Dean of Biological Sciences), Steve Wasserman, and Joseph Vinetz (member of UCSD Institutional Biosafety Committee), we planned, constructed, and safely tested (in Joe Vinetz's ACL2 insectary) this genetic system in the fruit fly Drosophila melanogaster.  We called this method the mutagenic chain reaction (MCR) in analogy to the polymerase chain reaction (PCR).  We now refer broadly to the use of self-propagating CRISPR-based genetic elements as "active genetics".
We submitted a manuscript for publication in Science on December 31, 2014, describing a simple proof-of-principle experiment in which an MCR element inserted into the Drosophila yellow gene, which is required for body pigmentation, was transmitted to nearly all offspring.  This paper, which was published online on March 19, 2015 \cite{Gantz_2015}, attracted considerable media attention and is credited with being the first to experimentally demonstrate a CRISPR-based gene-drive in a multicellular organism with a dedicated germline.  The study was cited as one of the primary reasons for CRISPR being chosen as the breakthrough of the year in 2015 by Science magazine.  This discovery also was ranked #11 overall and #2 in biology in the 100 top discoveries of 2015 by Discover Magazine.
Applying a gene-drive system to combat malaria:  One application of gene-drive technology under discussion since the mid-1960s \cite{CURTIS_1968} is to use one of many possible strategies  to generate an inheritance bias and spread a desired trait into a target population. For example, a gene-drive element could be used to either kill mosquitoes as a kind of genetic insecticide \cite{Burt_2003}, or to spread a trait throughout a mosquito population that rendered them incapable of transmitting malarial parasites \cite{2006}.  
Anthony (Tony) James at the University of California at Irvine (UCI) is one researcher who has dedicated his career to combatting malaria.  Tony was the first person ever to clone and describe a protein-encoding gene from any mosquito \cite{James_1989} and in his lab he first developed reliable methods for producing transgenic mosquitoes \cite{Jasinskiene_1998}.  His group then engineered sophisticated genetic cassettes that produce single chain antibodies that were capable of fully blocking transmission of malarial parasites \cite{Isaacs_2012,Isaacs_2011}. These antibodies bind to and neutralize malarial parasites following a female mosquito feeding on blood (only female mosquitoes bite).  James proposed to use a gene-drive approach to spread the immunizing antibody cassettes into mosquito populations, which should render those mosquitoes incapable of transmitting malaria to humans.  The final prescient sentence of his most recent paper on that topic published in 2012 stated: "If coupled with a mechanism for gene spread, antibody-expressing, malaria-resistance transgenes could become a self-sustaining disease control tool" \cite{Isaacs2012}
On January 9, 2015, shortly after submission of our paper to Science describing efficient transmission of the MCR element in Drosophila, Valentino and I contacted Tony to ask him if he might be interested in a collaboration in which we hooked up our gene-drive system to his "immunizing" gene cassette.  Tony enthusiastically agreed.  Based on subsequent discussions, Valentino designed and constructed an immunizing gene-drive element targeting insertion into a gene called kynurenine hydroxylase (kh), which is required for normal eye pigmentation.  Valentino sent the completed kh-MCR construct to the James group, who then injected this synthetic DNA into mosquitoes.  On July 29, 2015 the James team recovered 2 transgenic individuals carrying the kh-MCR construct (out of ~ 25,000 injected larvae screened).  The memorable email that Tony sent me reporting the first results indicating how the kh-MCR was transmitted to progeny was entitled: "Friar Mendel takes a break".  After analyzing the transmission of the kh-MCR element over four generations, we prepared a manuscript entitled "Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi\cite{Gantz08122015} , which is the subject of this Backstory.  This paper, published on November 23, 2015 in the Proceedings of the National Academies of Science (PNAS), described the highly efficient transmission of the kh-MCR element to >99% of offspring via male parents.  There was significant media coverage of this first demonstration of efficient CRISPR-based gene-drive in mosquitoes, which is still ongoing over two years later.
Addressing safety, ethical, and societal aspects gene-drives:  Given the potential of gene-drive systems to alter wild populations, Valentino, Tony, and I have devoted significant effort to engage scientists, social scientists, governmental regulators, and the public to initiate discussion regarding the ethical use of gene-drive systems to benefit society.  These efforts have encompassed areas including ethics, political science, sociology, health policy, as well as government regulatory agencies to provide transparent and informative explanations of active genetics technology and it applications.  For example, we jointly co-authored an opinion piece in Science with 23 other colleagues suggesting precautionary measures for safe use of gene-drive systems in the laboratory \cite{Akbari_2016} and organized a UCSD/JCVI workshop on regulation of gene-drives \cite{Adelman_2017}.  We also provided briefs to the NAS and federal risk assessment agencies (e.g., an Obama administration risk assessment panel comprising members of the FBI, CIA and Department of Homeland Security as well as presentations to the JASON study group) and a series of presentations to university Biosafety (e.g., IBC) and bioethics groups.  We continue to participate in forums for scientific and community engagement and contribute actively to ongoing discussions on these important topics.
A future vision for active genetics:  In January 2016, Valentino Gantz and I published our vision for the future of active genetics in a BioEssays review \cite{BIES:BIES201500102}.  In this review, we outlined applications of active genetics to gene-drive systems, auxiliary updating drive elements such as CHACRs, reversal drives such as ERACRs and eCHACRs, bi-partite trans-complementing drives, split-drive CopyCat site-directed transgenesis vectors, potential uses for human cell therapy applications, and a summary of the ethical and safety considerations associated with gene-drive technology.

Acknowledgements

The author thanks Anthony (Tony) James) and Valentino Gantz for helpful comments on this Backstory and for the joy of our shared adventure
 1Early geneticists referred to this phenomenon as ‘meiotic drive’