Researchers at the startup Kallistem announced last week that they have succeeded in obtaining sperm from tissue taken from the bodies of infertile men wishing to have a biological child. Sperm manufactured in vitro? The announcement caused a great deal of media noise, immediately generating enthusiasm and controversy.
Cor 30 years, teams of researchers from around the world have been working on this extraordinarily complicated subject. Indeed, the CNRS Journal recalls that human spermatogenesis is a physiological process that takes place over a period of 72 to 74 days and is one of the most complex physiological processes in nature. It begins with immature germ cells, the spermatogonia, nested in the seminal tubes of the testes. During three successive major stages (mitosis, meiotic stage and spermiogenesis), these round cells rich in 46 chromosomes undergo a series of multiplications and transformations to produce spermatozoa, elongated cells with 23 chromosomes. In men, the process begins at puberty and continues throughout adult life.
The project to reproduce spermatogenesis in vitro dates back to the early 1990s. It was at this time that teams from INSERM and INRA led by biologist Philippe Durand, the current scientific director of the company Kallistem at the origin of the announcement, are embarking on the adventure. They quickly succeeded in their first culture system and in 2000 they carried out the entire meiotic process of spermatogenesis in rats. Their system was validated by some twenty scientific publications. The problem is that, in this process, spermatogenesis only occurs at 80 % and is blocked from the start of the final stage. According to the researchers, the difficulty lies in the containment solution, which is not stable enough to allow the process to go all the way to the end.
A biotech feat?
To solve this problem, Philippe Durand's team is getting closer to another team from the Claude Bernard University in Lyon, which, under the leadership of Laurent David, has made good progress on hydrogels. These are biomaterials consisting essentially of water, perfect for cell culture. And these materials are fulfilling their promise. They allow the device to perfectly reproduce the confinement of tissue in the testicles. It is this device that was officially presented last week by researchers at Kallistem. The researchers claim that " This bioreactor ensures a perfect containment of the seminal tubes, conducive to complete spermatogenesis. Its hydrogel wall allows the diffusion of nutrients from the culture medium to the interior of the seminal tubes and maintains a sufficient concentration of hormones inside the tubes. ".
At this point, we can talk about a biotech feat. Indeed, Marie-Hélène Perrard, the head of Kallistem, is enthusiastic about the results of the first tests carried out on rat and monkey tissues: "The results are very encouraging. After opening the bioreactor and fragmenting the semen tubes, sperm was observed under the microscope. ». This success story is presented in a scientific article that is currently being validated. This is where enthusiasm must be tempered to avoid raising false hopes among infertility patients. Indeed, the validation has not yet been accepted by the entire scientific community and one wonders about the haste with which this announcement was made.
Announcement effect or scientific reality?
The Kallistem startup is a spin-off from the Lyon Functional Genomics Institute; it has a strong team of researchers from CNRS and INRA. We can therefore quite legitimately give them credit for the quality and seriousness of their work. What is at issue is the chosen communication strategy. Indeed, the company has chosen to create a buzz in the media, without waiting for the approval of the scientific community. As early as May 5, the company announced in a press release that it had succeeded in manufacturing complete human spermatozoa, in vitro. « A world first! ». However, no scientific evidence accompanied this announcement. And the researchers were wary of responding to media solicitations that were necessarily attracted by this information. The reason given is understandable: the researchers could not talk because their patent application filed in 2013 was pending. So be it. This patent for the Artistem process was made public at the end of May last year, freeing up the speech of the researchers who were in a hurry to communicate. Why so fast?
The Kallistem company is hosted by the Ecole Normale Supérieure de Lyon and is not yet earning money; on the contrary, it is currently in the middle of fundraising, researching, according to Les Echos2 million to complete its work. Isabelle Cuoc, the CEO of Kallistem, does not hesitate to declare frankly: " We are a start-up and we certainly have a research agenda, but we also have a financial agenda. We need to reconcile the two, but we are currently in a fund-raising period and our investors needed us to communicate about our project. "
The company therefore publishes some details on the technology used but not yet any tangible results that could be submitted for validation by scientists. The scientists are therefore, on the whole, relatively circumspect. Professor Louis Bujan, a specialist in reproduction, interviewed by the Worldsays " We look forward to a peer-reviewed scientific publication. But until then, it is difficult to make a judgment ». The same is true of Professor Isabelle Rives, who has been working on the same themes for a long time and expresses her embarrassment: "The same is true of Professor Isabelle Rives, who has been working on the same themes for a long time and expresses her embarrassment: " They gave some explanations about the matrix used, but no statistics, no details about the number of experiments performed... It's scientifically boring. ".
This haste is a symptom of the competition between the world's laboratories in the race for biotechnologies, with one major challenge: the search for funding. Biotechnology is a booming field that is the subject of considerable economic and financial battles. And the field of male infertility is an important market that represents, according to figures put forward by Les Echos2.3 billion worldwide. Researchers are caught between the pace and practice of science on the one hand and the need to move fast to finance themselves and gain market share on the other.
There's still a long way to go
Yet there is still a long way to go from test tube to patient reality. The long journey of clinical trials remains to be done; it is still necessary to verify that the spermatozoa obtained in vitro are functional and of good quality, that they are capable of being fertilized and of giving birth to viable and normal organisms. These steps are fraught with scientific as well as regulatory hurdles. It is not yet known how the National Agency for the Safety of Medicines and Health Products or the authorities responsible for ensuring the bioethics of this type of research will decide in this regard.
