Scientists may be able to adapt grapefruits to the drugs they currently affect

You may be one of the millions of people who have seen a surprisingly specific warning on the labels of the medications they take:

Avoid eating grapefruits and drinking grapefruit juice while taking this medicine.

Such warnings are issued for several dozen substances, including: docetaxel, an anticancer drug; erythromycin, antibiotic; AND some statinsprescribed cholesterol-lowering medications more than one-third of American adults over 40.

The problem is a set of molecules, furanocoumarins. High levels of furanocoumarins disrupt, among other things, the functioning of human liver enzymes. In their presence, drugs can build up in the body to unhealthy levels. And grapefruits and some related citrus fruits are full of them.

However, there is no such warning for other types of citrus fruits, such as mandarins and other oranges. Citrus researchers at the Volcani Center in Israel reported on Wednesday in the journal The New Phytologist that by crossing tangerines and grapefruits, they discovered genes that produce furanocoumarins in some citrus fruits. This discovery opens the possibility of creating a grapefruit that does not require a warning label.

Scientists developed the structures of the compounds and established the basic blueprint for their preparation many years ago, said Yoram Eyal, a professor at the Volcani Center. But the exact identity of the enzymes that catalyze this process – the proteins that cut off a branch here and add a piece there – has remained mysterious. He and his colleagues knew that one way to identify them was to cross citrus fruits rich in furanocoumarins with those that did not. If the offspring of such a cross had different levels of these substances, it should be possible to locate their protein genes by delving into their genetics.

“We were afraid to approach this because it is very time-consuming and takes many years,” he said, noting how involved growing new trees from seeds and assessing their genetics can be. “But we finally decided we had to take the plunge.”

When they studied the offspring of a tangerine and a grapefruit, scientists observed something unusual. Fifty percent of the young plants had high levels of furanocurmene 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 noticed that only one gene could control it,” said Livnat Goldenberg, a researcher at the Volcani Center and lead author of the new study.

Scientists soon identified a gene that controls the production of furanocoumarins in leaves and fruits, which produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD. It turns out that tangerines have a mutated form of this gene that prevents the enzyme from working properly. This version appeared in all tangerine and orange varieties reviewed by researchers, explaining why they do not cause the same problems as grapefruits in people taking prescription drugs. In these plants, the production of furanocoumarin is stopped.

Dr. Eyal suggests that gene editing technology should also make it possible to change the gene in grapefruit. The Volcani Center team is currently investigating this project.

Given the prevalence of this mutant version in mandarins and some other citrus fruits, scientists speculate that some gene near the genome must play an important role in the highly valued trait. Long ago, a citrus grower, choosing some unknown quality, must have unknowingly passed on this furanocoumarin-destroying version of the gene to the ancestor of modern varieties of mandarins and oranges.

After so many years, this person’s work is coming to light under the supervision of geneticists who may one day include grapefruits on the menu again.