Inducing Heritable Structural Variation in Plants: A New Simple, Affordable, Safe, and Accessible Method Using the Cancer Drug Etoposide Can Replace Irradiation

     Radiation, or irradiation, has been used to induce mutation in plants, but it has safety issues, is impractical, and is random. It is used to induce genetic variety in plants. Selective farming of crops for centuries has led to more limited genetic variety and more difficulty in dealing with stresses such as dry conditions, high temperatures, and salty soil.

     A new method, known as etoposide mutagenesis, developed by researchers at the Whitehead Institute for Biomedical Research, uses etoposide, a cancer medication, to induce genetic variety in plants. It is also rather random, but researchers can select among the traits induced. As documented by Leslie Sattler for The Cool Down:

“When sprouting seeds encounter this drug, it disrupts an enzyme responsible for organizing DNA as cells multiply. Mistakes made during the cell's attempt to fix the resulting damage can scramble

“The technique requires only common lab supplies. Seeds initially grow in a solution containing the medication before being planted in soil to mature.”

"I was surprised at how efficient it was," said Mary Gehring, who teaches biology at MIT and led the research team, per Phys.org. "The diversity of new traits that you could see just by looking at the plants in the first generation was extensive."

     Testing indicates that about 66% of the treated samples led to new genetic traits. The method was first tested on the Arabidopsis thaliana plant. The researchers are now using the technique on pigeon peas, a legume food plant with great nutrition and protein profiles, but that has a limited gene pool. Better breeding for it can lead to it being a staple food for more people, especially across Africa and Asia. Pigeon peas are also in a lot of modern plant-based food products as the main protein source. Breeding more plants for the different heat, drought, and salinity conditions will lead to more successful crop yields and food with better nutrition.

“The process relies on standard laboratory tools: seeds are germinated on growth medium containing the drug, then transferred to soil to complete their life cycle.”

     Deletions, duplications, and rearrangements of DNA segments lead to the new genetic traits.

"All of the traits that we might want to see in pigeon pea are not present in the existing population," says Gehring. "The idea is to do a large-scale mutation experiment to increase genetic diversity."

     Another potential benefit of this new method is that it can be used on plants that are more challenging for gene-editing techniques like CRISPR to work.

“The new method complements existing genetic tools rather than replacing them. By providing a more accessible alternative to irradiation, chemical mutation could expand the availability of large-scale genetic changes and novel plant varieties.”

     Breeding by selection involves tapping the natural variation in the traits exhibited. However, that natural variation in traits may be limited now due to plant domestication and past selective breeding. The new method involves inducing new genetic traits. The new method is simple, affordable, and potentially applicable to a wide variety of plant species. Like irradiation, there is a random induction of traits.

     After treatment with etoposide, the mutants exhibited a variety of phenotypes and a spectrum of structural variation types. Etoposide treatment has been deemed an efficient method of inducing structural variation in plants.

 

Etoposide Mutagenesis Has Several Advantages and Can Replace Irradiation

     As detailed below, this new method can replace irradiation as a method of mutagenesis and be more accessible to more researchers.

 

   

References:

 

A simple method to efficiently generate structural variation in plants. Lindsey L. Bechen, Naiyara Ahsan, Alefiyah Bahrainwala, Mary Gehring, and Prasad R. V. Satyaki. PLoS Genetics 21(12): e1011977. A simple method to efficiently generate structural variation in plants | PLOS Genetics

Researchers make incredible breakthrough that could revolutionize how we grow food: 'I was surprised at how efficient it was'. Leslie Sattler. The Cool Down. February 8, 2026. Researchers make incredible breakthrough that could revolutionize how we grow food: 'I was surprised at how efficient it was'

New chemical method makes it easier to select desirable traits in crops. MacKenzie White, Whitehead Institute for Biomedical Research. edited by Sadie Harley, reviewed by Robert Egan.Phys.org. January 9, 2026. New chemical method makes it easier to select desirable traits in crops