Nuno Henrique Franco's entry into research wasn't typical. A biology and geology teacher, he started an outreach project that gave elementary school children the opportunity to observe and experiment with the behavior of laboratory rats. Run by the Institute for Molecular and Cell Biology (IBMC) in Porto, Portugal, the project emphasized both the scientific method and animal welfare. "I liked it because it allowed me to integrate what I knew from biology and from the education field," Franco says. The experience prompted Franco to start a Ph.D. in laboratory animal science; he's now about halfway through a program at IBMC.

Franco's research aims to find ways to improve science and increase knowledge by treating research animals better. He says he is, fundamentally, a scientist. But laboratory animal scientists also “have this consideration for animal welfare, this ethical consideration," he says. It's a consideration increasingly shared by European policymakers; new European legislation, to be voted on by parliament next September, would put in place stricter rules regulating animal welfare and better harmonize practices across Europe.

From teaching science ...

"I always wanted to be a scientist, but I didn’t have a realistic idea of what a scientist was," Franco says. A high school biology teacher inspired him to pursue a teaching career. Franco graduated in 2003 from the Universidade de Trás-os-Montes e Alto Douro (UTAD), in his native Portugal, with a 5-year degree in biology and geology teaching. By 2002, at 22, he was teaching pupils not much younger than he was.

After he'd been teaching for a couple of years, Franco came across a booklet intended for secondary school students; the booklet's theme was what it means to be a scientist. "I really enjoyed teaching science," he says -- but learning about the life of biologists made him want to do science, too. "I was just telling other people’s stories, and I realized I wanted to live these stories." So he decided to go back to studying -- initially for a first degree in general and animal biology, also at UTAD. Because he had already taken some of the subjects, he was able to finish in just 2 years while continuing to teach, which he did "out of interest and out of need," he says.

For the final year of his new degree, Franco did a 1-year internship in the Laboratory Animal Science group at IBMC, led by Anna Olsson. His job was to implement an outreach program called Rodentia. The program aimed literally to turn lab rats into school pets. "Like many outreach activities, the main idea is to engage children into science," Franco says. Rodentia went further, using the animals to teach the scientific method to children and make them aware of the need to ensure animal welfare, he says.

Franco was responsible for designing an enriched living habitat for the rats and overseeing their welfare, while also teaching the scientific method to the children. In order to properly learn and apply the scientific method, "one has to develop a scientific mind: be curious, study hard, be healthily skeptical, don’t be afraid to make mistakes, always rethink your steps, and never be too sure of anything, including your own assumptions," Franco says. "At first, they needed a lot of guidance, but at the end of the project they were fully autonomous, asking the questions, looking at the results, and asking other questions," he adds. They became adept at thinking about factors that could influence the results, and controlling for them.

In one experiment, carried out at the French School of Porto, the children experimented to see whether a rat was able to find a piece of cheese hidden in a labyrinth. When their rat, called Cuca, didn't fulfill their expectations -- the rat showed no interest in the cheese -- the children decided to sensitize her, to the labyrinth and the cheese, and try again. In that second experiment, the rat found, and ate, the cheese. "They became very critical of their own work," Franco says. "We were not expecting children that young to be so good ... at very complex skills." The project team presented their findings -- about the children's learning, not the rat's -- at national and international meetings.

Yet the rats, too, won Franco's admiration. "People usually dislike wild rats because they live in sewage and carry disease." But they are able to "solve very complex problems. They show cooperation between themselves, empathy," he says. "I loved these rats." A class he took the year before had sensitized him to the bioethical issues surrounding animal research, and as he worked directly with rats, his interest in the topic grew. When his internship came to an end, Olsson invited Franco to apply for a grant from the Portuguese ministry's Foundation for Science and Technology to do a Ph.D. in her lab. The application succeeded.


(Courtesy of Nuno Franco)
Schoolchildren in Portugal were taught the scientific method using laboratory rats as school pets.

... to improving science

For his Ph.D., Franco has been researching the application of the "three R's" of animal experimentation -- ethical principles first proposed in 1959 that include, where possible, "replacement" of the use of animals, "reduction" in the numbers of animals used, and "refinement" of animal husbandry and experimental procedures so that they are less painful and distressful to the animals.

Franco has a particular focus on the last "R": refinement. He studies what scientists can do to improve not just the welfare of animals used but also the resulting science. There is scientific evidence that stress affects immunological responses and can skew results. Yet it is not rare for scientists to ignore such factors when designing experiments, Franco says. He cites one published study in which researchers compared the efficiency of an injected antibiotic with an orally administered agent, and with their combination, in treating tuberculosis-infected mice. They found that two of the groups, which had received the lowest doses of the oral agent, were significantly worse off than the controls, which received no treatment, Franco says. His hypothesis: force-feeding is stressful for animals, and the induced stress worsens the disease.

By studying the literature, Franco has assessed techniques aimed at improved animal welfare in infectious disease and neurodegenerative disorder research. Another aspect of his work is to look at researchers' attitudes toward animal use. Franco believes that the new European legislation -- which would require systematic evaluation of all research involving laboratory animals in all E.U. countries, with ethical considerations a big part of the assessment -- makes now a good time "to assess what [researchers] think about using animals, what effect training can have not only about their knowledge of the three R's but also how it affects their attitudes."


Nuno Franco (Courtesy of Nuno Franco)

Franco is also collaborating with a researcher who came to his lab seeking help in refining his mouse models for diabetes. "I find it very cool that a PI [principal investigator] looks at his own work and questions, ... 'Couldn't I improve this animal's life?' " Franco says.

Such collaborations are nonetheless challenging, because it's necessary to take into account the science and the animals' welfare and try to improve both, Franco says. "That's difficult because I am not an immunologist, a diabetes researcher, a neuroscientist, and I have to know a lot about these fields."

Not all researchers are accepting of Franco's proposals. "I have heard from scientists, 'We have used animals this way and we will continue using animals this way because we publish and didn't have any problems so far,' " Franco says. There can even be some "condescendence, until they hear what I have to say and then realize that I am a scientist, [that] I am science-driven." At the other extreme, many animal activists reject the notion of refinement, which they see as granting legitimacy to animal use. "We want to improve science and improve [animal] welfare, but sometimes we are disregarded by both sides."

Franco believes the new legislation is a step forward. But what is most needed, he says, is raised consciousness and a change in attitudes. "If the scientist is not aware and doesn't acknowledge the need to improve animal welfare, he won't do it, because you won't be there all the time," Franco says. "Ultimately, it is the scientist who is responsible, and that" -- responsibility -- "is the fourth "R'"."

If scientists are convinced that animal welfare is better not just for animals but also for science, acceptance is much more likely, Franco says. "With the new legislation, with this new generation of researchers, we will watch a paradigm shift. I don't know whether it will be enough, but it will be much better."

More on Laboratory Animal Science

The American Association for Laboratory Animal Science defines laboratory animal science as "a field of science devoted to the production, care, and study of laboratory animals used in biomedical research and education. It is a large field comprised of professionals from many scientific and educational disciplines such as anatomy, animal science, comparative biology, engineering, environmental science, ethics, genetics, microbiology, pharmacology, physiology, and toxicology. Professionals within this field have a deep sense of purpose and are dedicated to helping society and improving the lives of people and animals alike."

You can find more information, training courses, and conferences announcements on the Web sites of the following associations:

• The European Commission's section on laboratory animals

• The Federation of European Laboratory Animal Science Associations

• The European Society of Laboratory Animal Veterinarians

• The U.K.-based Universities Federation for Animal Welfare

• The European Biomedical Research Association

Altweb, the Alternatives to Animal Testing Web Site at the Johns Hopkins Bloomberg School of Public Health

• The World Organisation for Animal Health

Elisabeth Pain is contributing editor for Europe.

Elisabeth Pain is contributing editor for Europe.

10.1126/science.caredit.a1000079