Considering their role in pollination, honeybees are among the most beneficial insects on earth. This is because they are social insects that share tasks and live in hives consisting of thousands of workers and one queen. Although the workers and queen are genetically identical, the queen has a larger body, develops in a shorter time and lives much longer than a worker bee. Moreover, the queen is the only bee in the hive that lays eggs. It has been known for more than 100 years that larvae continually fed on royal jelly – a special diet secreted by workers – transform into queens. However, the identity of the jelly's active component was unknown. In a recent study published in Nature, Masaki Kamakura from the Toyama Prefectural University, Japan, performed exciting experiments identifying one component of royal jelly that transforms workers into queens.

Royal jelly is a quite peculiar juice. It is a complex mixture of different nutritional ingredients and hence not easy to analyse, in particular because some of the components are unstable. But it was this characteristic that helped the Japanese scientist to find the queenmaker. He harvested royal jelly from queen-less workers, stored it for different lengths of time, and tested whether it was still able to induce queen differentiation in larvae. Long-term storage decreased the jelly's biological activity significantly. Then he went on to analyse the jelly's protein composition. He recognised that only a few proteins were degraded over time, and he concluded that one of them must carry queenmaker activity. Among the candidates was a 57 kDa protein, which he named royalactin. Indeed, when he purified this protein from royal jelly and added it to a diet that was not able to induce queen differentiation, the larvae developed into queens. Kamakura obtained a similar result when he used artificial royalactin that had been synthesised by bacteria.

Because of the lack of genetic tools in bees, the underlying signalling pathway is difficult to examine. Therefore, Kamakura switched to Drosophila and performed an ambitious experiment where he fed fly larvae with a medium containing either active royal jelly or inactive royal jelly supplemented with royalactin. The result from this simple but brilliant experiment was stunning, as the flies acquired many of the attributes of queen bees. Both diets led to a shortened developmental time, an extended life span and an increase in the flies' body size. Moreover, he observed similar effects when he overexpressed royalactin in the flies' fat body. Next, Kamakura worked out the signalling pathway for royalactin-mediated changes by testing its action in mutant flies defective in central components of several signalling pathways. In doing so, he showed that royalactin acts through a mitogen activated protein kinase pathway initiated by the epidermal growth factor receptor (Egfr) in the flies' fat body. This signalling cascade appears to also function in bees, as knockdown of Egfr expression by RNA interference suppressed queen differentiation in bee larvae reared on royal jelly.

Kamakura has done an incredible job and he must have worked day and night to find the active ingredient in royal jelly and decipher its mode of action. However, many questions remain unanswered and insect scientists around the world will now go on to further examine how royalactin works precisely and address the question of whether similar proteins have comparable functions in other social insects such as ants.

Royalactin induces queen differentiation in honeybees