Clone rangers: Meet the two Indians behind the world’s first self-cloning rice

Venkatesan Sundaresan and Imtiyaz Khanday have already moved on to maize, millets. ‘What works with rice potentially applies to all flowering plants,’ they say.

It is one of mankind’s oldest questions: How can we grow enough food?

Venkatesan Sundaresan and Imtiyaz Khanday. (Jael Mackendore/ UC Davis)

Indian-American plant biologists Venkatesan Sundaresan, 73, and Imtiyaz Khanday, 40, weren’t even looking to answer it, really.

In 2015, they were studying exactly how plant embryos work at the cellular level, when they identified a set of genes in rice flowers that appeared to kickstart it all. Used right, they realised, these genes could help rice become the world’s first engineered self-cloning plant.

While certain fruits, berries and weeds (such as the blackberry and dandelion) do reproduce asexually (or clone themselves) in the wild, the world’s major food crops are inherently sexual. For more than 30 years, efforts to get them to clone themselves had failed.

By the time Sundaresan and Khanday isolated their group of rice genes and published their first paper on their research in 2015, though, something massive had shifted.

In 2012, the biochemist Jennifer Doudna and her fellow researcher Emmanuelle Charpentier created the CRISPR-Cas9 “molecular scissors” (for which they would win a Nobel Prize in 2020).

Genes could now be snipped, cut and pasted quickly, precisely and easily. The tool revolutionised medical research, conservation efforts, food hybridisation, resilience-building in crops.

At University of California, Davis, it gave two professors working on rice flowers a means towards a long-awaited end.

Working with teams of researchers in France and Germany, in 2017, they successfully engineered a rice plant whose seeds grew into a clone of the parent. In 2018, they published a paper on their work in the journal Nature.

Since then, they have worked to raise success rates from about 30% to 95%. The next step will involve limited field trials.

Sundaresan and Khanday have now won the prestigious $500,000 VinFuture Prize, awarded by the Vietnamese construction billionaire Pham Nhat Vuong’s VinFuture Foundation, for research that seeks to address some of the world’s most pressing problems.

Because this isn’t just about rice. “We are already working on maize, millets and mustard,” says Sundaresan. “What’s important here is that whatever you find in rice is a model. If it works with rice, it is potentially applicable to all flowering plants.”

Is that as dramatic as it sounds? Excerpts from an interview.

.

* What were you trying to study, when you realised you could give the world its first engineered self-cloning plant?

Sundaresan: What we were trying to understand in my lab was exactly how the embryo begins in a plant. The beginning of plant life is the fusion of two cells — one from pollen (the male unit of the flower) and the other from the ovule (the female unit). As with animals, this fusion miraculously creates an embryo, in this case within a seed, which can then grow into a baby plant.

We extracted genetic data in the form of RNA, analysed it and found that some genes were being switched on early, as soon as the two cells fused. They were master genes, switched on in the sperm cells.

Khanday: So we switched on those genes in the egg cells and ended up with an embryo formed without the participation of a sperm. An egg cell with this one activated gene can generate an embryo.

.

* But even this wouldn’t be a clone…

Khanday: Exactly. This is where our collaborators (Raphael Mercier from the Max Planck Institute for Plant Breeding Research in Cologne, Germany and Emmanuel Guiderdoni and Delphine Mieulet from the French agricultural research centre CIRAD) came in. What they figured out is that we can actually bypass the mixing of genes by deleting any new ones — creating a process not so much like reproduction as it is like normal cell division.

Put simply, once the process is done, the genetic makeup of the offspring is now exactly like any other body cell of the mother plant. This process is what we call synthetic apomixis.

Sundaresan: That’s from the Greek “apo” or “without” and “mixis” for “mixing”. Apomixis is how blackberries and other such plants clone themselves to reproduce asexually in nature.

.

* And this isn’t just about rice?

Sundaresan: What’s important here is that whatever you find in rice is a model. If it works with rice, it is potentially applicable to all flowering plants.

Khanday: I think we were very fortunate that most of the things that we tried actually worked. And we had the technology. First, next-generation DNA sequencing. Then, CRISPR-Cas9. With that gene-editing tool, it is possible to achieve in a few months with extraordinary precision what would previously have taken decades, and ended without anything like the same degree of certainty.

Sundaresan: To actually see it work in a lab was remarkable. Apomixis is something scientists have been attempting for over 30 years. I like the fact that it was finally cracked by a team of two people from opposite ends of the subcontinent.

.

* What comes next?

Sundaresan: The idea is to eventually grow more by using less resources, especially water and land.

This is just the beginning when it comes to gene-editing at the embryonic level for plants. We could potentially make plants more drought-tolerant or disease-resistant. We could work to raise yields further than humans have already done, to protect forest land from becoming farmland.

Khanday: I have been working with potatoes as well. It’s slightly different from cereals, but given how quickly we have made progress with rice, in four years instead of the 10 to 15 we projected, I think it might progress quite fast.

.

* How would something like a self-cloning hybrid be rolled out?

Sundaresan: In terms of challenges, the main thing remaining are the field trials. The proof of concept is ready. Imtiyaz and I both have plans to work on other crops now. In each crop, we have to identify the same types of genes. We have already looked at maize and made good progress there. We have started a project with pearl millets and Indian mustard.

.

* So, the hybrids could eventually be subsidised and distributed in India?

Khanday: China actually uses about half the land that India does to produce almost twice as much rice. This is because of hybrid cultivation. Almost 50% of the rice grown in China consists of hybrid varieties, while this figure stands at about 8% in India.

The reason India and many developing countries aren’t doing the same is because of the economics of hybrid seed production. They’re really expensive and that’s not feasible for farmers. Apomixis could change this because it is self-cloning. That could have a really huge impact, particularly on small-holdings farmers. We are hoping that is where our research has the most impact.

.

* What about the vulnerability this might introduce, in terms of entire swathes of a crop being equally vulnerable to a disease or infestation?

Khanday: The short answer is that synthetic apomixis does not push agriculture toward a single genetic solution; it enables more genetic diversity. It enables us to fix any genotype, and choose traits before deployment. This means we could potentially tailor plants to specific environments and production systems, preserve some of the diversity that is being lost, and, in case a pest or pathogen overcomes a particular genotype, rapidly fix and deploy alternative hybrids with different resistance profiles.

Safeguards such as availability of diverse varieties, resistance gene stacking, and region-specific deployment would remain essential.

.

* When you aren’t working with plants, where would we find you?

Sundaresan: I like to listen to Indian classical music. I also play the tabla, which I believe is not uncommon among scientists. (Laughs)

Khanday: I love to hike. Here in the California Valley, we live in this amazing location. Drive 90 minutes and you’re in the mountains; drive in the opposite direction and you’re at the beach. Two or three hours away is the desert. I do love to garden too. (Laughs) That takes my mind off of everything… working with soil.

.

REAR VIEW: The backstory

* Venkatesan Sundaresan, 73, is from Tamil Nadu, grew up in Delhi, and fell in love with science early. “In college, I picked physics because I was trying to understand how the world works,” he says. He switched to biology at the PhD level. Growing up amid talk of famines and in an era of ration shops, “I wanted to contribute to the study of agriculture and help our country feed its people,” he says.

* Khanday grew up in the Kashmir Valley, and has a Master’s in immunology, and switched to developmental biology. He has a PhD in plant molecular biology from the Indian Institute of Science (IISC), Bengaluru. “I come from a rice-farming family and our techniques have not changed in over 40 years. This fact is hugely motivating. I want to make hybrids more viable,” he says.

* Now that they are heading towards field trials for the world’s first engineered self-cloning plant, the researchers plan to diversify. They have begun work on other plants, including maize, pearl millet and mustard. Experiments have also begun on the potato. “Given how quickly we have made progress with rice, in four years instead of the 10 to 15 we projected, I think we might progress quite fast,” Khanday says.