GMOs. Few acronyms induce as much debate at the dinner table, forming rifts between relatives about the very food on our plates. Tinkering with an organism’s genes is almost as divisive as politics. So why aren’t we talking about agriculture’s potential pollinator of the future: the genetically engineered honey bee?
Genetically engineered honey bees were first created by Christina Schulte and her colleagues at the Heinrich-Heine University of Düsseldorf, Germany.1 In 2014, it was breakthrough research. Motivated by a need for more advanced genetic tools to support honey bee scientific inquest, they painstakingly created, characterized, and catalogued the method for producing transgenic (genetically modified) honey bees, which was subsequently published in the high-profile journal PNAS. This opened endless possibilities for unraveling basic questions of honey bee biology. In the distant future, it could even enable industrial applications, like engineering honey bees to resist disease (although unlikely – more on this later). But four years after their seminal work, the literature has not blossomed with innovative revelations enabled by the technique; rather, the response has been more like the sound of crickets.
It’s not obvious why uptake of this method has been so slow, especially since honey bee researchers, who have been craving better tools for precise genetic manipulation, could benefit immensely. Schulte’s technique could, for example, allow us to introduce gene variants – different alleles – into the honey bee genome and watch how that changes their morphology, development, or behavior to decipher the gene’s specific function. Theoretically, it could help us pinpoint the causal mechanisms of anything from disease resistance to queen longevity, or assign functions to the thousands of honey bee genes whose jobs are currently unknown.2 Importantly, it could also allow us to manipulate economically useful traits independently of costly, laborious breeding programs. Whether it’s a good idea is up for debate, but either way, why hasn’t this technique been taken advantage of by scientists?
I was a new graduate student when I stumbled upon Schulte’s paper for the first time. Just a few months into my degree, I had already decided that my thesis topic was going to be working out the molecular mechanism of hygienic behavior. I even had a few genes in mind, whose functions suggested how they might be contributing to hygienicity, but which hadn’t yet been proven. Naturally, when I read about Schulte’s work on genetically modified honey bees, I thought, “That is SO cool!” I could use the technique to create honey bees that produce large amounts of the supposedly ‘hygienic’ genes, then observe what exactly these bees were able to do which regular bees couldn’t. By doing these tests, I should be able to decipher if and how those genes really cause hygienic behavior – that is, identify the underlying molecular mechanism of a complex trait: the pinnacle goal of my thesis. Several months later, I found myself in Germany learning how to do the technique from the pros. It was then that I realized this method would be a lot harder than it seemed.
The road to creating a genetically modified honey bee is not for the unenthused. I quickly learned that it involves collecting thousands of 0-1.5 hour old eggs straight from the colony, microinjecting them with a concoction containing a gene insert and an enzyme that splices it into the genome (all done manually, in a hot room, using a microscopically fine glass needle), incubating the injected eggs until they hatch, grafting the larvae into queenless colonies, retrieving capped queen cells to emerge in a cage, inducing them to lay drones by gassing them with carbon dioxide, then screening those drones to see how many actually contain the new gene in their germ line (reproductive cells), allowing it to be passed on from generation to generation (Figure 1). At every step, there’s a high likelihood of failure, and these layers of probable let-down compound with each other to make producing a real genetically modified queen a very unlikely event.
Eggs are collected from a hive and microinjected with a tiny amount of genetic material, including the gene to be inserted and an enzyme (transposase) that does the cutting and pasting. Many of these eggs die, but some survive and hatch, which are ….