In Her Own Words: Mary-Dell Chilton's Path to Greatness, and Her Call to Action


 
Mary-Dell Chilton, Ph.D. -- Courtesy of Syngenta

If anybody wants to question the importance of North Carolina’s foothold on agricultural biotechnology, have them talk to a local resident who knows firsthand: Mary-Dell Chilton, Ph.D.

She is, after all, the mother of plant genetic modification.

Chilton was surrounded by a few hundred of her admirers Wednesday afternoon at the North Carolina Biotechnology Center for a summer social event, part of the Center’s ongoing series of Ag Biotech Professional Forums.

This wiry, cane-wielding woman with thick graying hair and a quick smile might remind you of a favorite aunt when you encounter her in public places around the Research Triangle area. These encounters aren't uncommon.

Still, even if she is your favorite aunt, she’s also a giant of science -- the founder and distinguished scientist at Syngenta Biotechnology in the Research Triangle Park.

During her talk to the enthralled, standing-room-only crowd at the Biotech Center, she recalled how her scientific tenacity resulted in her academic failures-cum-successes, and her eventual corporate involvement that started with disappointment and struggle but led to global recognition and the ultimate foundation for North Carolina’s worldwide leadership in the field of agricultural biotechnology.

Chilton hasn’t yet won a Nobel Prize. Yet. But her trophy case is already full of bioscience biggies. This year, for example, she was finally inducted into the National Inventors Hall of Fame. And she was made a World Food Prize laureate in 2013. In 2002 she received the Benjamin Franklin Medal from the Franklin Institute in Philadelphia, joining a roster of winners including Alexander Graham Bell, Thomas Edison, Pierre and Marie Curie, Albert Einstein and Stephen Hawking. 

Her scientific chops hearken most notably to her work in the late 1970s and early 1980s, culminating in academic achievement when she led a collaborative research study at Washington University in St. Louis that produced the first transgenic (genetically engineered) plants.

Her work pioneered the field of agricultural biotechnology and forever changed the way plant genetic research is conducted – and where it became geographically concentrated: North Carolina.

For those who were unable to get into the sold-out auditorium at NCBiotech’s Hamner Conference Center, Chilton was kind enough to share the text of her amazing talk.

Here's the text of Mary-Dell Chilton's talk at NCBiotech 7/15/15:

For those of us who are involved in plant science and agriculture, we are in the best of times and the worst of times. 

These are the worst of times because hunger is already a problem and experts foresee a 30% increase in world population by mid-century. Even worse, the CO2 produced directly and indirectly by that population is causing changes in climate that will impact food production. 

And yet…if you enjoy research…if you thrive on challenge…if competitiveness is your middle name…then without question, you have been born into the best of times. We have the resources, we have the will and we have the tools to meet these challenges. And not only are we in the right time, we are in the best place: we are in North Carolina, at Duke, at NC State, at Carolina…we are in the Research Triangle Park. If agriculture and plant science can be said to have a pulse, we feel it. All of us. Each of us.

How did all of this come to pass? I don’t know about you, but I at least was not born with a vision of future scientific inquiry. As a kid, all I wanted to do was ride horses, draw and paint horses and read books about horses. The closest I came to science was a dusty old library book entitled Astronomy with an Opera Glass. (An opera glass, for those of you too young to know, was an ornate low-magnification pair of binoculars used for seeing operatic stars from back-row seats). 

I had far to go.

Undergrad chemistry major first hears term 'molecular biology'

I was a chemistry major at the University of Illinois, and was a student at the time the term molecular biology was coined. What captured my imagination was the seeming intelligence of DNA, the purified chemical that carried genetic traits. In a process called bacterial transformation, you could add pure DNA from a healthy bacterium to a mutant one and the DNA would find its way to the altered place and repair the mutation. And it did this with astonishing efficiency! The only requirement was that the DNA had to come from the same kind of bacterium. If the DNA didn’t match, the repair—called recombination didn’t work. 

Several years later I heard about Agrobacterium, a microbe that caused galls on plants. Some scientists claimed that it contributed DNA to the plant cells, and that caused the gall to grow. I knew immediately that it must be a mistake: the DNA could not match plant DNA. No homology, thus no recombination. 

Working with a group of students, postdocs and professors at the University of Washington in Seattle, I designed an experiment that would give an answer either way, a clear yes or a clear no. Skipping over some twists and turns in the plot, it turned out that Agrobacterium was indeed guilty as charged! This indisputable proof was nevertheless difficult to publish. The referees of our manuscript didn’t want to believe it either.

Publication finally came in 1977

But they finally accepted it in 1977. We now know about a different type of DNA repair called non-homologous end joining, used by the plant cell to repair accidental chromosomal breaks. This process seems to be the mechanism that Agrobacterium has adapted to smuggle its genetic package into the plant cell chromosomes. With hindsight, we now see Agrobacterium as a natural genetic engineer. The genetic package it delivers, called T-DNA, specifically causes the gall cells to divide rapidly. T-DNA also makes them produce a metabolite (opine) that Agrobacterium can metabolize readily while competitor bacteria cannot. 

Knowing how to put new genes into galls is fine as a hobby, but it is far from being a profitable business. But by 1983 I had moved to Washington University in St. Louis and in collaboration with Andrew Binns at the University of Pennsylvania, we managed to disarm T-DNA. We knocked out one single gene in T-DNA and added a yeast gene in its place, the gene for alcohol dehydrogenase. This is the gene we use to detoxify alcohol when we have had too many martinis. 

From galls to martinis to tobacco to ... useless, but great, transgenic plants!

The resulting Agrobacterium strain would not make galls for us. Binns, an expert on tobacco cells, worked with this T-DNA and found that it made transgenic tobacco cells that would grow only if you gave them cytokinin. Unlike the gall cells we expected, these transgenic cells could regenerate into plants! They still carried the T-DNA and the yeast trans-gene we had added. The transgenic plants produced seeds that carried our transgenes to the next generation. This was the first genetically engineered plant. It was totally useless. But it showed that we could do it.

In 1983, perhaps as a result of this achievement, I was offered a job by CIBA-Geigy (now, two consolidations later, called Syngenta) to establish a new agricultural biotechnology laboratory in the Research Triangle Park—hire the people, erect a new  laboratory facility in Research Triangle Park, North Carolina and develop a project portfolio.

Early move to corporate life was 'an unhappy marriage'

I took the job—but CIBA-Geigy and I soon discovered that we were to have an unhappy marriage. They had a monocot seed business—hybrid corn seed—and I was a dicot genetic engineer who knew nothing but tobacco! 

Fortunately this was to be corrected in due course by further research, both here and elsewhere.  Monocots were found to be transformable by Agrobacterium, and other “physical” methods of introducing DNA into monocots were also found. The gene gun could deliver DNA-coated gold particles to either cells or protoplasts. 

In addition, protoplasts could be transformed by naked DNA or by liposome-encapsulated DNA. Alternatively, DNA uptake could be induced by electroporation or polyethylene glycol. It turned out that monocot protoplasts had an unfortunate tendency to lose fertility upon regeneration, and physical methods of delivery were generally untidy compared with Agrobacterium T-DNA, introducing multiple scrambled broken DNA fragments. In the end, my old friend Agrobacterium T-DNA has been found the technology of choice for most practical applications.

Current technology 'pretty good,' but challenges are daunting

So here we are with pretty good technology for crop improvement. It needs to be better if we are to meet the challenges ahead, and indeed it is improving at an astonishing rate. What an amazing time to be involved in agricultural research!

But do not forget the numbers. By 2050, there will be 9 billion people on the planet. That’s 2 billion more than we have today. Just in the next 10 years alone, it’s estimated that we’ll add 750 million more people, which is basically the population of Europe, in just the next decade. 

Syngenta is committed to feeding a growing population by improvements in efficiency. We call it the Good Growth Plan. We want to rescue more farmland. We want to help biodiversity flourish and to empower smallholders. 

A call to action

We cannot do it alone. This room is filled with many of the best minds in agriculture, and our combined efforts are going to be required to ensure that agricultural biotechnology keeps pace with the needs of a growing population.

Growers are rapidly adopting combined-trait crops for insect control, water optimization, yield improvement, oil and protein quality and improved bioprocessing. Ultimately these technologies help reduce chemical applications and provide simpler, more environmentally friendly farming practices, such as no-till.

So that is our challenge, our plan, our rationale for what we do. It will not be easy. And curiously, the most urgent challenge of all is to contribute to public acceptance of our technology. 

Research Triangle Park, North Carolina is an important place to spread enlightenment about the value and need for our work. I am committed to that goal. I hope that you will join me in that effort.

For questions or more information, contact:
Jim Shamp
Director of Public Relations

Corporate Communications

919-549-8889 | jim_shamp@ncbiotech.org

Thu, 07/16/2015 - 00:00