You may be among the millions of people who have seen a surprisingly specific warning like this one on the labels of the medications you take:
Avoid eating grapefruit or drinking grapefruit juice while using this medicine.
Such warnings are issued for dozens of substances, including docetaxel, an anticancer drug. erythromycin, an antibiotic. and some statins, the cholesterol-lowering drugs prescribed to more than a third of American adults over 40.
The problem is a set of molecules, the furanocoumarins. High levels of furanocoumarins interfere with human liver enzymes, among other processes. In their presence, drugs can build up to unhealthy levels in the body. And grapefruit and some related citrus fruits are full of them.
But there is no such warning for other types of citrus, such as tangerines and other oranges. Citrus researchers at the Volcani Center in Israel reported Wednesday in the journal The New Phytologist that, by crossing tangerines and grapefruits, they discovered genes that produce furanocoumarins in some citrus fruits. It’s a finding that opens up the possibility of creating grapefruit that doesn’t require a warning label.
Scientists had worked out the structures of the compounds and drawn up a basic flow chart of how they were made years ago, said Yoram Eyal, a professor at the Volcani Center. But the exact identities of the enzymes that catalyze the process—the proteins that cut a branch here or add a piece there—remained mysterious. He and his colleagues knew that one way to identify them was to breed citrus fruits high in furanocoumarins with those that did not. If the offspring of such a cross had different levels of the substances, it should be possible, by examining their genetics, to pinpoint the genes for the proteins.
“We were afraid to approach it, because it’s very time-consuming and takes many years,” he said, noting how important growing new trees from seed and evaluating their genetics can be. “But in the end, we decided we had to take the plunge.”
When they examined the offspring of a tangerine and a grapefruit, the researchers saw something remarkable. Fifty percent of the young plants had high levels of furanocurmaine and 50 percent had none. This particular signature meant something very specific in terms of how the ability to produce these substances was inherited.
“We saw that there was only one gene that could control it,” said Livnat Goldenberg, a Volcani Center researcher who is the lead author of the new study.
The researchers soon identified the gene that controls the production of furanocoumarins in the leaves and fruits, which produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD for short. Tangerines, it turns out, have a mutated form of this gene that prevents the enzyme from working properly. This version showed up in all the mandarin and orange varieties the researchers tested, explaining why they don’t cause the same problems as grapefruit in people taking prescription drugs. In these plants, furanocoumarin production is interrupted.
With gene editing technology, it should be possible to change the gene in grapefruit as well, Dr. Eyal suggests. The team at the Volcani Center is now investigating this project.
By looking at how widespread this mutant version is in tangerines and some other citrus fruits, scientists speculate that a gene located nearby in the genome must play an important role in a valuable trait. An ancient citrus breeder, selecting for some unknown quality, must have inadvertently spread this version of the furanocoumarin-destroying gene to an ancestor of modern mandarin and orange varieties.
All these years later, this person’s work is coming to light, under the gaze of geneticists, who may, at some point, put grapefruit back on the menu.
