A better understanding of the Earth's biodiversity for a better life

Biologist Virginie Courtier-Orgogozo studies the genetic mechanisms involved in evolution, in order to better understand the origins and future of species, with an approach that is as scientific as it is philosophical. She is also working on an experimental biotechnology, genetic forcing, and assessing its short- and long-term risks.

She is a guest at the Biodiversity and Ecosystems Annual Chair, which is supported by the Jean-François and Marie-Laure de Clermont-Tonnerre Foundation.

How did your interest in the evolution of species and its underlying mechanisms originate ?

Virginie Courtier-Orgogozo : I've always had a desire to understand the living world. At the age of fifteen , I borrowed a microscope from my SVT teacher for the summer vacations and marveled at the microorganisms. Naturally, this led me down the path of research. During my thesis, I studied the molecular and cellular mechanisms by which complex organisms develop from a single cell. Then I became interested in evolution and, after my thesis, I chose to use the genetic approach to try and better understand the mutations that appear and are responsible for changes in character traits. I wanted to see if we could refine evolutionary theory to include these genes and mutations. In the years 2000, some genomes were already known. Then genomics techniques developed, for example with high-throughput sequencing, leading to an explosion of discoveries about genes and mutations. We already knew that evolution often repeats itself in different parts of the world. In snowy environments, for example, different species have white coats. By studying genomes, it became clear that this convergence of traits was often the result of mutations in the same genes, which appeared independently in different species or populations. Evolution not only repeats itself at the trait level, but also follows a limited number of genetic pathways. This means that, within a genome, there are not as many possibilities as one might imagine for evolving towards a given form. A whole area of evolution, once thought to be highly random, is in fact quite repetitive.

If evolution follows a limited number of " genetic paths ", does this imply, as the English evolutionist Simon Conway Morris suggested, that even with different initial conditions, evolution would follow a similar path ?

When I began my research, I was rather close to the ideas of the American paleontologist Stephen Jay Gould, who believed, on the contrary, that evolution involves many unpredictable random phenomena and that the human species is a pure product of chance. For him, nothing predisposed human ancestors to success. Other groups of species could very well have acquired a dominant position on Earth, in our place. He was interested in the Burgess fauna, and in particular in the small fossils of Pikaia gracilens, precursors of eel-like vertebrates, which had nothing in particular to differentiate them from other animals of their time. Interestingly, Simon Conway Morris, a renowned English paleontologist, studied the same fossils as Gould and came to a diametrically opposed conclusion. The evolution of life is a process that has occurred only once on Earth. One wonders whether, under other conditions, it would have produced the same thing. It's an interesting thought experiment, but fundamentally, we don't know. For Morris, on other planets, if the conditions are right for life to evolve, we'll find trees that form green forests just as we do here. In fact, to capture light energy, there will be competition between living beings. So, the tallest will dominate and form trunks. Leaves will also be present, as they maximize the surface area available for absorbing light. And they'll be green, because that's the color of the molecule best able to capture this light energy : chlorophyll... Asking whether evolution would follow a similar path, if we were to restart it with slightly different initial conditions, is above all a philosophical question, but it's also a question with practical aspects : to search for and detect other forms of life in our universe, we need to imagine what life might look like elsewhere.

You created the ^Gephebase1 database, which lists the genes and mutations responsible for morphological, physiological and behavioral differences in plants and animals. How did you set up this compilation ?

When I was a postdoc at Princeton University in the United States, every laboratory in the world was interested in a small group of closely related species, studying differences in one or two traits. There was no general synthesis of all this data collected by different teams. So, with my director David Stern, we thought it would be interesting to bring them all together. This began with an Excel file containing 331 cases, published in a scientific article. I felt it was important to pursue this project, but it was a huge job, as hundreds of articles had to be reviewed every year. So when Arnaud Martin, whom I didn't know at the time and who has since become one of my great collaborators, contacted me by e-mail to continue this work, I told him it wasn't possible : it would take too much time. I'm delighted that he didn't take my advice and decided to complete the Excel file on his own. He got back to me once he'd reached a thousand cases and, impressed by what he'd undertaken, I started working with him. We received funding to create a database-driven website, accessible to all, that facilitates article curation and data entry. Today, Gephebase is used by researchers all over the world as a bibliographic reference base for finding articles on a particular subject, or for meta-analysis of the data it contains.

You are also working on the notion of genetic forcing. What is this ?

It's a new biotechnology currently being developed in laboratories. Its aim is to rapidly propagate a desired genetic modification in a natural population. A few " super GMO " individuals are released into the wild, and it is expected that within ten or so generations the entire population will possess the chosen modification. Normally, a parent has a 50/50 chance of passing on a given gene to his or her offspring. With genetic forcing, they pass on the genetic modification to 99 % of their offspring. Two approaches are envisaged : modifying a population by incorporating a given gene ; or eliminating a population by propagating, for example, a gene that will render all females sterile. Genetic forcing has potential applications in agriculture and public health, notably in the fight against malaria. To date, no method has been able to eradicate this disease, caused by a parasite transmitted by the Anophelesmosquito . Every year, malaria kills around four cent thousand people, mainly children in Africa. Genetic forcing appears to be a promising new technique for combating this parasitic disease, which is the most widespread in the world. The aim here would be either to make mosquitoes resistant to the parasite that transmits malaria, or to eliminate mosquitoes altogether. Laboratory experiments have shown that by adding 25 % of individuals carrying a genetic forcing gene to a large cage containing six hundred mosquitoes, the population was totally eliminated after a dozen generations. In agriculture, genetic forcing has applications in pest control. A great deal of work is underway in laboratories in the United States and Europe, to try and perfect the technique and make it effective. For my part, I'm trying to assess its risks through theoretical studies.

What are these risks ?

One of the non-negligible risks is that the DNA containing the forcing gene may be transmitted to populations other than the one targeted : either in the same species, or in distant species with which there may be exchanges of genetic material. To limit this risk, my colleagues and I have shown that it is important for the DNA fragment to be inserted in a region of the genome with few repeated elements and few genetic sequences that are identical in other organisms. The more similarities there are between the DNA sequences of different organisms, the greater the chance that the modified gene will pass from one species to another. Another risk is that gene-forcing DNA may change over time, accumulating mutations or integrating elsewhere in the genome. It then becomes very difficult to predict the impact of this gene on natural populations over the long term. Finally, there may be unforeseen repercussions on species interacting with the population modified by genetic forcing : their prey, predators, etc. Genetic forcing is mainly developed by geneticists - experts in molecular biology, but generally lacking in-depth knowledge of ecosystems . However, it is very difficult to imagine the long-term consequences of this technique on ecosystems. Mosquitoes carrying genetic forcing genes will not stop at borders. International agreements are needed. For the moment, discussions are underway, but there are no international regulations yet.

As a researcher in the field of genetic forcing, how do you approach the ethical questions and concerns raised by this technique among the general public?

In my opinion, this technique of genetic forcing is not sufficiently well known to the general public. I'm working hard to bring it out of the shadows and encourage a debate that would involve the whole of society, notably by giving lectures, responding to journalists and students, or through the lectures I'll be giving at the Collège de France. In the case of the mosquito, one of the options being considered is to release mosquitoes carrying the forcing gene on a regular basis. It is therefore essential that the local population be informed. Indeed, it's counter-intuitive to imagine that, to combat malaria, we're going to release even more mosquitoes, when the aim is to eliminate them. Personally, I don't think we should reject this technique out of hand. It's easy for us, who live in France and whose children are not at risk of dying from this disease, to dismiss this technology. If we lived in Africa, we might be enthusiastic about the possibility of a new approach to the fight against this disease. The question of using genetic forcing in nature needs to be examined in depth, independently for each potential application. Just because genetic forcing has been used successfully against malaria, it doesn't mean that we should accept its use against a crop pest. I believe that at this stage, we absolutely must facilitate debates throughout society and take into account the diversity of opinions.

This year, you are the holder of the Biodiversity and Ecosystems Chair. How does this appointment inspire you ?

This appointment is an opportunity to bring my thoughts on the field of biology to the attention of the general public. Until now, my research has focused on understanding the living world. Faced with this major biodiversity crisis we're experiencing, I'm wondering about the contributions of biology and what has led us humans to the current situation, despite all the knowledge we've acquired. I'd like to take advantage of these lectures at the Collège de France to take a more critical look at my discipline and talk about our human biases. I'll be looking at new findings in biology and reflecting on the new visions of life that are emerging from this research, in the hope that they can help new generations to ensure that our planet remains habitable for as long as possible. There's this fanciful idea that this crisis isn't so bad, because we'll be able to go and colonize other planets. But that's not an option. We only have one planet, our own. Our species is not adapted to travel and settle elsewhere in the universe. We need a better understanding of biodiversity on Earth to live better. As humans, we are often fascinated by the machines we create, such as the latest smartphone. On the other hand, buying a tomato at the market doesn't fill us with wonder. We take it for granted. Yet plants are amazing : they can use light energy and produce tasty fruits like tomatoes. This example speaks for itself. It illustrates the fact that nature today is almost always connected to humans. Tomato plants need stakes erected by gardeners. I'd like to deconstruct this idea that humans are separated from the rest of nature, and rekindle in everyone that spark of wonderment in the face of nature ; not only to live better within it, but also because its effects are beneficial. We know that people recovering from illness recover more quickly when their bedroom window looks out on trees rather than a wall. Or that having a dog reduces the risk of cardiovascular disease by 20 % to 30 %. What I hope to achieve with my lectures is to show that the living world questions us about ourselves, about what we took for granted...

Interview by William Rowe-Pirra, journalist

[1] gephebase : https://www.gephebase.org/.