The answer to this question is complex: there are two perspectives, one general and one more personal, based on my experience with Innate Pharma.

From a personal perspective, with a positive outlook, I would say there are real therapeutic and technological applications. One example: building on our fundamental research, we contributed to creating a biotechnology company, Innate Pharma, which, within five years, employs over 50 people and has secured major contracts with large international pharmaceutical companies. It’s a true success, and I cannot believe that Innate Pharma is the only "success story" in France. Innate Pharma was created from a basic observation. We work on NK cells (Natural Killer cells), which are part of the innate immune system. We see that T and B cells, as important as they are in adaptive immunity, cannot directly recognize antigens. The attacker must first be recognized by a frontline defense from the innate immune system, which, if activated, then alerts the adaptive immune system—the second line of defense involving T and B cells. We started with a simple idea: could we pharmacologically modulate, in other words, intentionally manipulate, the innate immune system to fight off attackers? By acting on the two functions of innate immunity (1) fighting directly against the invader, and 2) alerting adaptive immunity), one could ask if this might provide a powerful tool. This potential is especially noteworthy since there is an untapped market, as interest has focused heavily on antibodies and T lymphocytes while other cells receive less attention. We have been working on cancer and NK cells for over ten years. The initial idea was simple and clear: to harness NK cells to fight cancer. The results are compelling: in vitro, modulated NK cells kill cancer cells. Similar results have been achieved with other innate immune cells, gamma delta cells, in collaboration with Marc Bonneville and Jean-Jacques Fournier. Simultaneously, we are developing in vitro tests using other drugs already in stock. Thus, we are on a promising research path to combat cancer-related diseases. Note, I'm not claiming that NK cells are a magic bullet, but rather that they have specific qualities that can be harnessed for the patient's benefit. I should also add that this discovery is thanks to a community of researchers who have contributed to understanding NK and gamma delta cells.

From a general perspective, there is, indeed, a bit of a lag in France compared to England, Germany, or the United States in capitalizing on the direct outcomes of fundamental research through biotechnology enterprises. However, several companies have recently been created, or, after being founded, have survived. There are two distinct issues: creating a biotech company and ensuring that it survives. One cannot simply take a snapshot of biotech companies across European countries and grasp the impact of biotech research within a nation; this requires a long-term view. Some French companies are indeed thriving. The situation in France is not dire; on the contrary, given that basic immunology research is robust and that France’s position is well-regarded internationally, there is a notable interest in industrial applications, with more people investing in these. People may complain that things aren’t “at their best”—and, indeed, there is always room for improvement, particularly in the support provided for building biotech structures, but new initiatives are emerging. We should not be pessimistic—everything is open to improvement. There is a fascinating line from Saint-Exupéry that goes: “Failures strengthen efforts.” If we recognize our shortcomings in certain areas, as long as the desire to progress remains and our fundamental research is sound, there’s no reason not to create new companies.

I want to emphasize two fundamental points. The history of science shows us that major discoveries have never been predictable. Their inventors did not work to order. We cannot blame immunology or biology and research as a whole for failing to meet societal expectations for products: discovery yield doesn’t work this way. Yield applies to development, which is an entirely different matter. Some discoveries also arise by "serendipity" (no suitable French translation exists)—accidental discoveries made unintentionally but with enough awareness. The famous example is Fleming, who discovered something in the trash. This is not mere luck. Basic research has sometimes, through serendipity, led to significant discoveries in public health. In immunology, just look at what is available today to treat autoimmune diseases. Specifically in the field of rheumatoid arthritis and soon for Crohn's disease, it is worth noting that the compounds that inhibit TNF (Tumor Necrosis Factor) are a major revolution for managing these autoimmune diseases. This is an interesting example: TNF was isolated in the 1970s, discovered as a tumor-killing factor, and today it's used for autoimmune diseases! This is a true discovery from fundamental research that now benefits patients, without a predetermined goal. Another example is the discovery of tyrosine kinase inhibitors in oncology in the late 1980s, which allow for the treatment of certain tumors (chronic myeloid leukemia).

Regarding major advances in fundamental immunology, the most important discovery since 1989 concerns Toll-like receptors. These are receptors on innate immune cells that specifically recognize pathogenic agents. They identify bacterial markers and structures conserved in bacteria. Today, there are many biotech companies, including Innate Pharma, focusing on modulating Toll-like receptors. This is truly a hot topic! Regulatory T cells have also been rediscovered, and for 20 years, immunologists thought they were useless! From an evolutionary standpoint, there is also the discovery of immune responses in lower animals. In the lamprey, for instance, there exists an immune system that resembles human B lymphocytes.

There are many important discoveries in immunology with numerous applications in sight. Each team contributes its own discoveries; we ourselves recently demonstrated the role of NK cells in fighting malaria.