Animal health research is distinguished by particular objectives, methods, biological models and scientific questions. However, there nevertheless are areas of generic and methodological convergence with biomedical research.
3.1. Distinguishing features of the objectives, methods, and biological models
First of all, livestock farming is an economic activity whose end goal is to generate revenue. In this context, animal health is one of several factors that farmers must manage; they do so by minimizing their herds' exposure to health risks and by finding the least expensive way to limit the impact of disease . In a given livestock system, diseases are closely linked to the way livestock are managed, notably to parameters related to the quality of housing, nutrition, hygiene, and to animal production levels. The intensification of livestock systems that has taken place in agriculture over the past fifty years has accentuated the tension between limiting inputs, increasing production, and the risk of disease.
Over time, questions regarding livestock health have moved beyond a sole objective of achieving economic gains by reducing disease frequency to addressing the sanitary quality of products of animal origin, reducing the use of xenobiotics, and animal welfare in the interest of public health and sustainable development. The multiplicity of the challenges leads to the question of how the best balance may be achieved between these different parameters. To continue working in this direction, animal health stakeholders, whether from the perspective of research or development, need to establish close ties with livestock sciences and agricultural professionals.
To take into account these elements, population medicine on farms will be needed, as well as research on diseases that specifically recognizes the close connections between health and animal production science. This implies in-depth collaboration with other animal science disciplines on one hand, and with the various stakeholders in the livestock world on the other. The only pertinent research is that carried out in close contact with the actual practices of farmers and animal sectors. For example, within an integrated agriculture framework, integrated research on livestock health management implies solid understanding of the livestock world, requires close collaboration between animal production, genetics, livestock economics, sociology and animal health disciplines, and relies on a partnership with livestock health stakeholders.
A second distinguishing feature of animal health research is the overwhelming predominance of infectious and parasitic diseases, at least for livestock, with a very large diversity of pathologies and a very large repertoire of pathogens involved . Animal health research teams consequently are obliged to study a wide variety of pathogen families, developing in the process a pool of rare and precious skills in virology, bacteriology, parasitology, and medical entomology.
A third distinguishing feature of animal health research is related to the special genetic features of livestock animals. The evolution of animal species, which results in the diversity of species, takes much longer time than phases of domestication, which result in the diversity of breeds. The intensive selection practices implemented over the past fifty years has improved production considerably, but the cost has been a sharp drop in genetic diversity among livestock [19, 20]. A distinguishing feature of livestock systems effectively is the possibility of human intervention to select animals for particular genetic traits, most often production (for example, quantity of milk) but also resistance to disease (for example, against scrapie). To understand the genetic foundations of susceptibility to infectious diseases, the duration of co-evolution, genetic diversity, and the respective evolutionary dynamics of hosts and pathogens therefore must be taken into account. The genetic improvement of the immune response is a complex selection objective. It generally either is directed against a single target (pathogen) that is constantly evolving (due to its rapid evolutionary dynamic), or seeks a better overall immunocompetence; in either case, there tends to a negative correlation with the selection of production traits.
Animals of economic importance include species that belong to very distinct animal clades such as fish, bees, chicken, pigs, goats, sheep and cattle. These clades diverged from each other hundreds of millions of years ago. Even within mammals, the Laurasiatheria superorder, which includes ruminants and pigs, and the Euarchontoglires superorder, which includes humans and mice, diverged from each other around 100 million years ago, rendering mice and human phylogenetically closer to each other (so called supra-primates) than they are to ruminants and pigs . These millions of years of separated evolution generated specific anatomical, metabolic and physiological traits, as well as specific commensal-host and pathogen-host relationships. For example, fish show particularities linked to their aquatic environment with some pathogens entering via fins ; they present a more primitive immune system and their cells are highly permissive to DNA transfer, allowing highly efficient DNA vaccination .
Whereas the basic structures and the generation mechanisms of the T cell receptors and immunoglobulins are similar from teleost fish to higher mammals, each species presents particularities, such as specific isotypes (unlike humans, mice do not secrete IgD or IgG4) and specific mechanisms of antibody diversity generation (gene conversion in chicken, hyper somatic mutations in human and mice). Notably, cytokines are specific to some species; for example, those controlling the production of type I IFN in humans and probably pigs does not exist in mice. Across species, mother to offspring transmission of pathogens and of immunity is strongly dependent on developmental characteristics related to oviparity and variations in placentation modalities. Thus whereas baby mice acquire their immunoglobulin pool during pregnancy by translocation through the placenta, ruminants acquire their immunoglobulin pool at birth via the colostrum due to the relative impermeability of their placenta.
Most basic and applied research is conducted on laboratory mice, in which some human and domestic animal diseases have been experimentally adapted. In many instances, therapeutic and prophylactic treatments that are effective in laboratory mice do no work when transposed to human and veterinary species. This lack of transposition can be explained by the specific physiological traits mentioned above and by the artificial pathological mouse models used in the laboratories. It is very important for pathogen-host interactions and novel therapeutic and prophylactic treatments to be evaluated on the targeted veterinary species, thereby studying the effect in the actual host and consequently limiting a "mouse" bias as much as possible. Research and experiments on "target" species (fish, chicken, pigs, ruminants) therefore often is necessary, and presents an advantage because the research findings may be applied directly to the species without the extra step of validating an extrapolation based on an animal model, in contrast to research undertaken for biomedical applications.
Lastly, there are special features related to the types of actions taken for animal disease control and health management. Beyond vaccination and the protection of livestock, animal health rules covering contagious diseases include a range of control methods, including at times the slaughter of animals to eliminate those posing a risk for unaffected animals and humans. These practices lead to specific research questions regarding intervention mechanisms. At the top of this list is the need to update serological tools so that vaccinated animals may be distinguished from infected animals because disease control measures are different for these two categories of animals. Another priority is the set of questions regarding the comparative economic advantage of different control methods and the conditions by which they are appropriated by livestock farmers and public officials.
While the livestock world has many other distinguishing characteristics, these do not seem to have a notable impact on the manner by which animal health research is conducted.
3.2. Special features of scientific questioning
In addition to the aspects discussed in the preceding sections, one of the main distinguishing features of animal health research are the scientific questions pursued, which are posed from the perspective of animal, and not human, health. Consequently, even in the case of zoonotic agents, the questions asked by animal health teams are not the same as those asked by biomedical teams. In the case of zoonotic vector agents, for example, Bartonella or Borrelia agents of Lyme disease, animal health research would focus on the role of animals as reservoirs of agents potentially pathogenic for humans, and on the elements that allow the development of an infectious agent in its host reservoir versus a human. Biomedical research, on the other hand, would focus on the development of an infectious agent in a human. For prion diseases, an animal health perspective leads to studying the diversity of strains found in the animal and to an attempt to decipher the interactions between the infectious strain and the host species. More broadly, studies of pathogenic agent/host interactions that are pursued from an animal health angle often prove to be fruitful from both a pure and applied perspective. This is due in particular to the genetic knowledge generated on the infected host and the possibility of implementing protocols with an experimental cohort with a defined genetic status. This is, for example, the case with the demonstration in sheep of the modulation of susceptibility to scrapie in connection with the polymorphism of the protein prion coding gene .
It thus would appear that, while working on the same agents and with the same tools, the questions pursued in animal health may be different from, and complementary to, those in human biology, and lead to the production of complementary knowledge. It follows that opportunities for collaboration between animal health and biomedical teams should be pursued, each having, through the questions they pursue and their "natural" partnership networks (hospitals versus farms or the environment), access to different and complementary types of samples. For example, collaboration could focus on comparing, with an epidemiological objective, Bartonella strains sampled from humans and different animal species.
3.3. Generic and methodological areas of convergence with human health
In certain fields, research carried out in human biology and animal health use similar tools, and even the same models, to address research questions. When this is the case, notably in the framework of the study of zoonotic pathogens, the only difference lies in the nature of the questions explored.
In certain circumstances, the convergence continues up to point where the biomedical and animal health teams share the same questions, and then no evident distinguishing feature remains. The development of projects initially focused on animal health progressively may lead the teams involved to pose questions that are increasingly focussed on models shared with human biology. As an illustration, we may cite fundamental research approaches to the molecular mechanisms of the invasion of cells targeted by the influenza virus, or the biological origin of prions and the determinants of the species barrier modulating their transmission capacity. In such cases, it is easy to imagine that the same research could be conducted in research laboratories unrelated to animal health. However, an animal health perspective offers certain advantages, notably expertise for extensive experimental research in a confinement area, and special links maintained through collaborations with other scientists working notably in the fields of pathogenesis and animal genetics.
The discussion presented here was conducted in relation to human biology research work. A parallel approach could be envisioned in relation to work carried out on plant health. Such an analysis may elicit a certain community of tools and methods with animal health, an advantage of comparative biology, but apparently few shared issues at stake for the pathogens of interest.