CONTRIBUTION : Dr. Héléna Duval prescribes antibiotics to approximately one or two patients out of the 40 she attends each day. She explained that some tests allow us to know if an infection is bacterial or viral. But these kinds of tests are rare. She only has one for angina and always asks for a urine dipstick for urinary infections. Most of the time, the diagnosis can only be based on the clinic observation and the discussion with the patient, which constitute the most essential part. She tries to avoid prescribing antibiotics as much as possible if something else can help. And when nothing else is possible, she tries to give one with the narrowest spectrum possible. She really takes time to think before prescribing antibiotics because she knows the potential consequences, like antibiotic resistance, but also because there is a possibility that the patient will react to it, may be allergic to it, or may interact with another medicine. It's sometimes hard to know whether it's a good thing to prescribe.

"I try to be careful, but maybe sometimes I wouldn't have prescribed it if I'd had a test"

For children younger than 3 years old, for example, she doesn't prescribe antibiotics because there is usually no bacterial angina. In theory, the best for a child with otitis is to wait 48 hours before giving antibiotics to see if the patient is getting better. But in reality, it's challenging to do so, and they often return feeling even worse after 48 hours. Besides the few tests she has, she uses "AntibioClic", a tool made by the CPAM to help the doctors prescribe the best antibiotics according to the patient's clinical state.

Furthermore, she added that antibiotic resistance affects even people who haven't taken many antibiotics. They can get the bacteria from an environment where they abound, for instance, epidemics in hospitals of multiresistant bacteria. Sometimes, she also needs to prescribe a more potent antibiotic for a longer time because the first one didn't work.

"It scares me as a doctor, a wife, and a mother, because I know that there are deaths linked to antibiotic resistance".

OUTLOOK : The interview confirmed the patients are demanding antibiotics. They know what they need when they come to see the doctor. They want a quick recovery right away, no need to move, no wait, no waste of time to be reassessed. With time, this gets only worse. Antibiotics appear as THE solution for them. There is a lack of knowledge about it.

"With a virus, you're supposed to be able to escape it, but with a bacterium, if you don't have the antibacterial, you're not cured, so if they're no longer effective, I'm worried about the future".

Even if doctors in France were sensitized to antibiotic resistance by Social Security, patients need to be informed. Some education is needed. Even in medical studies, it should be more important.

Dr. Héléna Duval heard of antibiotic resistance in articles or hospital reports, and it seems to get worse because the delegate of CPAM, the French health insurance, said that their prescription of antibiotics would be checked. Before, pharmaceutical laboratories could even advertise antibiotics and pay doctors who prescribe them. Fortunately, this is not allowed now.

Moreover, CPAM also proposed a solution to avoid self-medication. Indeed, when people go to the pharmacy to get their medicines, they get a whole box with more medication than needed. After completing their treatment, they have some pills left. Many people keep them instead of returning them to the pharmacy. If they get sick later with the same kind of symptoms, they usually start taking these pills left without a new medical opinion. When antibiotics are taken for a viral infection, it has no effect at all. For a bacterial infection, if it's not the right antibiotic in the right proportion and for the proper length of time, the antibiotics don't kill enough bacteria and increase the possibility of them becoming resistant to it. That's why Dr. Duval is for this proposition to unpack the pills and give just the right amount to the patient.

CONTRIBUTION : The discussion with Doctor Le Houssel gave us a first opinion on antibiotic resistance and how the issue is perceived in the professional and public world.

First, we learned that, in the context of his job, which is to treat more urgent problems, antibiotics that could lead to resistance were predominantly prescribed for urinary, ORL, and dental infections. During his career, he noticed that many people think they are not very well healed if they don't have antibiotics. It is an education problem of the population on antibiotic use. During a certain period, there was a massive use of antibiotics. At this time, medicines were easily and automatically prescribed. But he thinks that sensibilization campaigns can change this, as it has been made in the 2000's with our famous French campaign: "Antibiotics are not automatic". For him: "It is a real work of explanation."

For him, it is the role of public power and governance of health to prevent and sensibilize the population. The doctor can do this sensibilization, but sometimes it can be challenging.

OUTLOOK : Knowing the main problems that lead to the prescription of antibiotics enabled the team to target a specific one in an attempt to solve a problem that is most common in the population. That is why we then target Carbapenemase, which is an antibiotic used as a last resort. It treats, for example, urinary infections, one of the main infections pointed out by Doctor Le Houssel.

He also pointed out the awareness-raising problem that we then took into account to create the education part of our project.

CONTRIBUTION : The interview begins with a presentation of the two leading causes of the emergence of antibiotic resistance, according to Jean Carlet: overconsumption and cross-transmission of this resistance due to hygiene. He says we must change our lifestyle habits to counter this transmission. Prevention policies on hygiene during COVID-19 have benefited the cause, but we must do even better. Therefore, the need for a change in the population's behavior is now needed, and it might be possible if the scientists share their knowledge on the subject with them. Jean Carlet then explained the unequal emergence of antibiotic resistance in Europe and Asia. Some countries, such as Greece, are seeing an explosion of resistant bacteria, but, for now, we do not know why. Jean Carlet sees "biological causes, mechanisms that we do not yet know". He explained to us his concern: no new antibiotics for more than 20 years, fewer and fewer that work, and, surely, new infections will emerge because of global warming. He told us that solutions like ours are indeed appropriate but insufficient and that he doesn't see them as sustainable.

OUTLOOK : This interview highlighted the need for much better hygiene around the world to prevent the transmission of resistance. This can be done through communication and prevention. A question about the sustainability of our tool was raised. How will we deal with new bacteria? Is SuperBugBuster really a complete solution?

CONTRIBUTION : During the interview, she evokes that the evolution of consumptions and prescriptions changed in France when the CPAM (Primary health insurance fund) diffused widely in the territory a sensibilization campaign: "Antibiotics are not automatic'. Now, this sentence is widely known by most in France: it greatly impacted people. But this was in 2002, and since then, no other campaign like this has been created for antibiotics.

She told us that people overall had confidence in their prescription and were not reluctant to consume antibiotics. On the contrary, some patients come to the pharmacy without any prescriptions to have antibiotics with sentences like : "I have the same symptoms as last time and had antibiotics. Can I have some ?"

People lack awareness about the problem related to antibiotic resistance.

To finish the interview, she discussed the fact that the agroalimentary industry uses many antibiotics, sometimes even unreasonably. Their use for animals is indeed part of the problem of antibiotic resistance because, veterinarians are not only prescribers but also users of antibiotics.

OUTLOOK : This interview permits us to have one point of view on the consumption of antibiotics. In conclusion, we can say that overall, the population doesn't really know the danger of antibiotics and their misuse. The Sensibilisation campaign worked, but it was a few years ago. People forget, indeed, the human brain works with repetition to learn, so we need to repeat the sensibilization to the general public in the hope that people change their habits. This has to be done by public organizations such as CPAM, and has to go through political authorities, industries, and other actors in the sectors. This is why we then tried to interrogate people linked to the pharmaceutical industry to have their point of view on the subject.

The evocation of the agroalimentary industry was an important point in our reflection on the problem. We wanted to have a global point of view of the issue, and this fitted totally with what we saw previously with the onion method: it is a "One Health" problem. Indeed, not only does the problem touch humans but also animals. This reflection opened a new "branch" to our tree, where we needed to go deeper and question more people in this field.

CONTRIBUTION : The discussion began on the ethics question behind a synthetic biology project like SuperBugBuster. According to Lucie Dalibert, the problem behind biotechnological progress is the closure of the debate by the scientific circle. For example, the legitimacy of a tool such as CRISPR must be discussed according to a public consensus, integrating politics, science, philosophers, and non-experts such as the population.

For a scientist, the danger of remaining isolated in the laboratory, neglecting to seek input from a diverse range of perspectives, and becoming overly fixated on their instrument is the potential failure to measure the risks and repercussions associated with their tool. Lucie Dalibert then gave us the example of the Azilomar conference in 1975, organized after a scientist realized that he planned to create a carcinogenic bacteria capable of spreading this gene within "human, bacterial, plant populations and animals", leading to unpredictable consequences. A meeting of 150 researchers was then organized: "Now we have to think about the impacts of the technology that we are developing. And define the limit to implement the technology." This was not enough to think about all the risks faced by these scientists. The discussion continued on the tool's legitimacy: a technical response to a technical problem. Lucie Dalibert then explained that it is often easier for humans to create a new technical tool rather than asking themselves "How did we get here? What do we need to change?". To avoid getting lost in a form of solutionism, it is therefore essential to explore this question of human practices in more depth.

Then we discussed the aspect of technology "for all". Lucie Dalibert then talked to us about social justice: "The challenge is not to develop a technology created by Northern, for Northern problematics and then diffuse it to all the world; it is to think in equity: we need to take into account the specificity of everyone/country." We must ask ourselves the question: "who are we to decide if a technology would be good for others?" Lucie Dalibert tells us that we must not lose sight of the colonial past of the North and that even if the intention is good, it can be very frowned upon. We must communicate with local populations and understand how they experience and perceive antibiotic resistance. We must not impose a Northern-centric vision that would be out of step with local cultures and fail (for example, the corpses incinerated during Ebola in Africa, impossible for populations needing to practice their funerary rite).

The final aspect of the discussion was on how to communicate about science. Indeed, an educational question we wanted to pursue was understanding how such a serious problem could be so silent and why the risks were so little known and understood, especially for non-experts. According to Lucie Dalibert, the issue of communication on antibiotic resistance could lie in several things: the fact of not measuring the dangerousness of such a small thing that we can't see, that we do not touch; the fact that it is a technical subject or even the fact of skepticism among populations. The solution, not miraculous but which could move things forward, would be to integrate more scientists into the public debate to recognize the wrongs of science and society on this problem. It's not a question of blaming the individual but of taking responsibility, as a scientist, for communicating about antibiotic resistance.

OUTLOOK :A lot of information and advice emerged during this interview, which was crucial during our reflection. We realized the importance of being open to everyone's opinions and criticisms (from non-scientifics, too) and even the necessity of seeking them out. Understanding our past errors and supporting our tool with in-depth human practices study and education is the only way to make it sustainable and relevant. We must still be aware of all the risks that science can bring and try to limit them by constantly questioning ourselves. As scientists, we are also responsible for understanding the past and imagining a more sustainable future, not just in terms of biotechnological progress.

One of the big questions we have here was the one about the relations between the Northern and Southern countries. We didn't appreciate the difficulty of this, and we did recognize that we positioned ourselves too much "as a savior", to use the words of Lucie Dalibert. To get out of this pattern and be able to carry out effective education, she advises us to contact Catherine Bourgain to continue this discussion more deeply and to mature our reflection.

We also reflected on the biological part, understanding that our tool would only partially be ready to be a solution. Indeed, we don't know whether it could be risky for health, its effect on health, or if it could cause some problems. We made it the safest possible, but when we talk about the health of living beings, we need more tests. Thus, our tool would need further trials regarding the degree of benefits or danger it provides to the environment, such as ecosystems, animals, or humans. Moreover, it is necessary to know if it can cause a phenomenon similar to antibiotic resistance.

CONTRIBUTION : The point of view of Dr. Olivier Alazard enlightens us on the use of antibiotics by veterinarians and the changes during his career of more than 25 years.

In his job, he tries to have a graduation in the choice of antibiotics, not to use one with a larger spectrum if it's possible to use one with a narrower one. He tries to make the most reasonable choice. Sometimes, he needs to give antibiotics in precaution, when the test's results can’t be obtained before a weekend to confirm the diagnosis. He gives antibiotics when it’s needed or if the animal won't get better otherwise. His diagnosis is established mainly by checking the animal. His experience and sample analyses are really useful. One type of them is antibiograms. He often obtains some with germs that are not sensitive anymore to any antibiotic.

"But not all skin infections require antibiotic treatment. You can treat them with local disinfection, antiseptics, creams and healing agents [...] the smallest boo-boo is not systematically treated with antibiotics, but that's been the case for a long time".

"Antibiotics are being used less and less, with use down by at least 30% in 10 years".

When antibiotics are needed, usually for infectious phenomena, it's for a short duration, and people will only get the right amount of pills, the right dose for the treatment, not the all-box. This is to prevent antibiotic resistance. We can see here that what Dr. Héléna Duval said about the CPAM's will is already being done by veterinarians. He also proposed to do it for humans to avoid self-medication. It's because of those types of practices that resistance is propagated. Decades ago, antibiotics were delivered without a prescription, so people bought them, kept them, and consumed them. They also often stopped when they got better. That's how we create resistance and the bouncing effect. But fortunately, he thinks that there is more consciousness now. Clients seem conscious of the problem, but for them, antibiotics are the basic treatment; they don't fear it. He then has to explain to them that if it's not a bacterial infection, it doesn't cure it. For him, our way of consumption also plays a significant role. After the expiration date, the drug is still active even if it's less efficient, so the industries probably produce more than we consume. Antibiotic consumption and production regulation is a key to solving this problem. But fraud is also a problem, and all countries are not on the same level about this problem.

OUTLOOK : Dr. Olivier ALAZARD confirmed that, like in human health, it's been a while since new antibiotics were discovered in animal health. The Order of Veterinarians raised awareness among veterinarians even if they learned a bit about antibiotic resistance in their studies. But, for him, they need more awareness. Education is needed for everybody.

Moreover, Dr. Olivier Alazard told us about antibiotics of long actions that are very useful for some animals when it's difficult to approach them, for example. It's just one shot with the right dose that will last in time. But most of the time, they are last-generation antibiotics, and he can't give them all the time.

Another point is that during his 25 years of practice, he noticed some changes in the use of antibiotics. For example, over the past 10 years, antibiotics he doesn’t give on surgery to prevent anymore. In addition, now, industries don't do discounts based on how many antibiotics veterinarians buy. Whereas before, there were rewards and, therefore, the lure of gain for some veterinarians. On the other hand, in the livestock and industries, treatments were planned systematically. This was unreasonable. For decades, there were systematic treatments of animals that were destined for human consumption. Some antibiotics were even withdrawn in the veterinary field because they were still present long-term in food. Before, even for a little symptom, antibiotics were given to the animal and all the other animals, just in case. There is a "charter of best practices" about it. With animals, there is more transmission for livestock, for instance. So strict hygiene is needed and enough. Antibiotics are not even necessary.

CONTRIBUTION : The discussion started with discussing the consumption of antibiotics and how it's vastly different according to the country where you live. Indeed, the rules and laws about the sale of antibiotics are different worldwide, leading to different behavior and consumption habits. For example, if you can't afford a test to determine whether it's a virus or a bacterial infection, you'll probably take an antibiotic immediately.

But the difference between countries doesn't stop there because it is also linked to how the countries will react to antibiotic resistance. Indeed, Northern and the wealthiest countries will be able to afford the newest antibiotics and research. In contrast, Southern, poorer countries, without a lot of budget, will be unable to afford many antibiotics so those countries will suffer more from this world issue.

He quoted a UK report saying: "In 2050, there will be about 50-100 million people dying of antimicrobial resistance. "

We, of course, talked about the education part, and according to him, it is working together that will permit a resolution. Science needs to speak to policymakers, to people on TV, finances, and pharma … If all people communicate, there is a chance to have something multidisciplinary.

OUTLOOK : The discussion on the difference between countries made us realize that our interview has a specific point of view: Europe and a Northern country. Indeed, this may not fully reflect the subject and may be a Europe-centric study. We wanted to open this field and this point of view, especially in the educational part, where the sensibilization campaign for France can only be applied in some places, as it is not the same culture, habits, and laws about antibiotics. It is why we decided to contact some IGEM League from other continents, such as Asia, Latin America, and Africa, for our research.

CONTRIBUTION : The interview of Astrid Duval allows us to understand the use of antibiotics for veterinarians but also what a medical secretary sees every day: the patient's demand for treatment.

She thinks that veterinarians give more antibiotics than human doctors because the patients, the animals, are usually at a more advanced stage. She observed a similarity between her two jobs: people want results. When they leave the appointment, they want their pet or themselves to be cured, or at least to receive a magic medicine to heal quickly. They see antibiotics as this kind of cure and usually ask for it. The patients are deviants and have no patience.

Sometimes, when they don't know what can cause the animal's sickness, they give antibiotics, hoping that it will help. They don't have anything else to guide them, no testimony, just the clinical aspect of the animal. Unlike for people where cures and medical consultations are refunded, there is a price for animals, so owners expect results and don't want to return.

She also joined Dr. Héléna Duval about people doing a lot of self-medication and the consequences of it.

OUTLOOK : During her experience as a food hygiene veterinarian, there was surveillance about antibiotics since they can even be integrated into the animal diet to get a bigger yield and profit. Another case of excessive use is if one animal is sick and needs antibiotics, every animal next to him will also get some in "prevention". She told us that, in her opinion, this is linked to our way of consumption. Indeed, there are more and more people on earth, and we want to eat a lot of meat. So nowadays, there is a lot of industrial breeding to obtain more meat to satisfy the demand. But with this, antibiotics are released in nature by excrement and even sometimes in the meat we eat, even if it's usually checked. So, decreasing meat consumption is not just an ecological act but also one against antibiotic resistance, as fewer antibiotics will be released in nature.

During consultations, when the animal needed antibiotics, she explained to the owners that they must follow the prescription, the dose, and the duration of treatment because otherwise, it would promote antibiotic resistance by selecting the resistant bacteria.

When we asked her if she knew how to avoid antibiotics, she first said that basic hygiene like hand washing and blowing one's nose needs to be increased at the beginning of the sickness to prevent it from worsening. She then talked about essential oils and solutions, such as magnesium chloride, which can have antibiotic properties.

"It could certainly avoid, not everything, but certain percentages of aggravations that lead to antibiotics being taken."

She observed that magnesium chloride solution is also really helping for the cicatrization of wounds. For animals, she was cautious about wound cleansing to prevent superinfection. She uses these things before taking antibiotics, even for herself, because she was aware of antibiotic resistance and its mechanisms during her studies. But if it still gets worse, then she goes to the doctor.

CONTRIBUTION : The discussion enabled us to find out more about the role of industry on the subject of antibiotic resistance. Antibiotics are a pillar of modern medicine, not only for treating infections but also for organ transplants, cancer treatment, and complicated surgery. If there is resistance, these operations will no longer be risk-free, which is the major motivation for finding ways to fight back.

Moreover, it is no longer profitable for companies to focus on the creation of new antibiotics. A lack of profit and lengthy research, for a product that sells for less than a cancer therapy, makes industries uninterested. "It costs 1 billion euros to create an antibiotic and 10 years approximately." The point now is to create new mechanisms and reinvest in the public health field by directly confronting this resistance and no longer trying to bypass it.

We have pointed out certain inequalities in this new fight against antibiotic resistance. Some countries, such as India, don't have access to the latest antibiotics, so resistance develops more quickly and becomes a real scourge. In contrast, developed countries have access to the latest innovations, which enable them to keep, as Mr. Mabilat called them, the "reserve antibiotics". The problem also stems from the fact that third-world countries don't have access to diagnostic tools, so they go more quickly and easily to treatment, even though it's not really necessary, which accentuates drug abuse.

All countries are expected to deploy an action plan against antibiotic resistance. Mr. Mabilat mentions actions grouped under the umbrella of antimicrobial stewardship. There are five stages of implementation of these measures, 1 being the drafting of these measures, and 5 being the finality of the plan, financed and deployed on a large scale. While these measures are being implemented in the Nordic countries, many countries are still stuck at stage 2 or 3, which is too low.

People's lack of awareness of the problem remains the number one factor in inaction. Awareness campaigns are needed, and not just in developed countries!

OUTLOOK : This discussion enabled us to learn more about the factors leading to antibiotic resistance and their direct consequences. Inaction towards this scourge stems from a lack of investment on the part of governments and industry, justified by a lack of revenue and interest in the subject. Inequalities in access to treatment based on a country's wealth also need to be reviewed. To be truly effective, action must be global and worldwide. The starting point should be to inform people through effective awareness-raising campaigns, which is why we've decided to deploy one.

CONTRIBUTION : Ms. Boucher's work consists mainly of training technicians to raise the breeders' awareness of antibiotic resistance. This is possible thanks to the creation and diffusion of a training course. During the training course, they explain what an antibiotic is, how it works, the disease for which it works, the good practices, antibiotic resistance, and how to prevent it. They also inform farmers of the new rules.

"It's really being at the service of breeders for sanitary issues. GDS are associations, so they are run by breeders for the benefit of breeders."

Numbers are encouraging. An apparent diminution of antibiotic use has been seen in the breeding field this past few years, especially for pork, where they were used massively as prevention. For instance, more and more breeding, particularly organic ones, have found an alternative to using antibiotics by employing plants or other natural products. It reduces their consumption of antibiotics. Even if there is a change in mentalities, some things still need to be reinforced and explained.

OUTLOOK : In this interview, Ms. Boucher explained to us the importance of a reasoned use of antibiotics in livestock and breeding because the resistant bacteria present in animals can then be transmitted to humans. More and more bacteria are becoming resistant. It is an important phenomenon that touches everyone, animals and humans. Eventually, we will find ourselves in a therapeutic impasse for several diseases.

In an effort to discourage the indiscriminate use of antibiotics, a new European regulation, known as the Animal Health Law, was implemented in 2021. It introduces, among other, new rules for antibiotics, especially for antibiotic prophylaxis. After this one, more rules were then made, and the usage was more supervised to limit the mass use of antibiotics as much as possible.

Concerning the future, according to her, we must work on biosecurity: fewer pathogens to use less medicine and reduce antibiotic resistance. But balance is necessary since you can't leave an animal sick. Animal welfare needs to be respected as well.

“Some so-called critical antibiotics will be reserved for human health because there is just too much resistance, but if we take too many antibiotics away from animal health, we'll find ourselves in a therapeutic impasse for animals too, so we have to find the right balance. That's no easy task.”

CONTRIBUTION : The interview began with the Foundation's vision of environmental issues and technological development. For example, in the context of climate issues, if techniques and solutions lead to the destruction of the biodiversity, which is the foundation of our world, these solutions are not viable and will not promote human progress in the broadest sense, i.e. including well-being and equity. Knowledge of one's own health and a global viewpoint are not shared by everyone.

Some still consider humans as a separate part, almost as if they did not belong to the “living”, as a distinct entity above everything else. This objective of increasing the overall level of understanding of the functioning of living things can be achieved through the popularization of science, associated with knowledge from the social sciences and academia, as well as the promotion and dissemination of scientific publications.

Regarding antibiotic resistance, Ms. Soubelet explained to us that the foundation has carried out a systematic review on effective solutions to combat antibiotic resistance in the environment. Unfortunately, marketing authorizations do not adequately address the fate of antibiotics and residues in the environment, but the soil contains billions of micro-organisms likely to carry a resistance gene.

She recommends that we take an interest in the SDGs, the United Nations Sustainable Development Goals, because it is not only a question of living species when we talk about biodiversity. We must also consider the services that humans derive from biological diversity and the interactions they have with it.

Take the example of dietary diversity:

11 million deaths in the world are due to a diet poor in diversity, poor in nutrition, but also very energetic (50% of human consumption is made up of rice, potatoes, corn and wheat)

Or even that of the appearance of zoonoses, due to the degradation of ecosystems:

3 to 5 new zoonoses have appeared every year since the Second World War.

Furthermore, she stressed that trying to control bacteria is utopian due to the complexity of this kingdom, its scale. She points out that antibiotic therapy was not created by man. It is one of several methods of defense of bacteria against other bacteria and predators such as phages and amoebae. In addition, we only know 1% of soil biodiversity. It is therefore very complex, even utopian, to prevent the appearance of antibiotic resistance.

All actions on the living induce a response from it, it adapts, it flees, it disappears. The phenomenon is stochastic, that is to say it is not predictable.

Another problem with soil and the environment is that we can't model everything because there are too many species and too much genetic variability. So the technical approach which consists of simplifying interactions, identifying a unitary problem and defining a general solution does not work, or not for long (conferring the appearance of resistance after use of antibiotics or pesticides). We need to think globally and take into account many points of view.

"Do we have the right to upset the great balances of life? "

For her, the factors of antibiotic resistance are multiple but the main ones are:

Excessive use of antibiotics

improper use of antibiotics

Lack of effective effluent treatment

An imbalance in biodiversity, particularly in intensive agrosystems which reduces the possibility of natural remediation (i.e. the degradation of the antibiotic, its residues, as well as the regulation of resistant bacteria)

Furthermore, we no longer have the same microbiota as before, e.g.: Finnish study: removal of concrete from schools and observation of bacterial populations on the skin, the respiratory tract of children and the digestive tract. After one year: they compared to a control group: children in contact with green spaces no longer had pathogenic bacteria on the skin and more diversity than children in schoolyards and concrete daycare centers: https: //www.sciencedirect.com/science/article/pii/S0160412021004360 We cannot solve a problem by creating new ones; engineers who develop technologies must explore their externalities before deploying them widely: there is a real need for prevention and education on this subject. “How to introduce ethics into a program, into scientific reflection on the development of a tool or technique?

OUTLOOK : The main perspective of this discussion was how we can take all issues into consideration when developing technology (having a systemic view, understanding the impacts of technological developments, understanding who will benefit, who will suffer indirect consequences ) and have an ethical reflection which is, according to her, essential. Above all, we should not consider humans as an entity superior to other species on earth, which leads us to think about their current and future impacts, the consequences of technology on other living beings and on the humans who depend on them. : releasing antibiotics, genes, genetically modified organisms into the environment without control, without understanding their fate, the threat they represent can have immeasurable consequences on soil communities, soil users, consumers .

CONTRIBUTION : The discussion began with the question of using technology to address a technical problem. Catherine Bourgain answered us, in line with Lucie Dalibert's words, that thinking that a technical solution can be miraculous is an error. Trying to repair a problem caused by an older technology with a new one is indeed tempting. But it is illusory to say that this can solve the situation as it doesn't come from the fact that we use antibiotics but from how we use them (excess…). That's why we need a real reflection when designing the technology.

Catherine Bourgain insists and goes further on the precautions that we must take in the way of thinking about our tool: "Sociologists talk about "script" embodied by technology: meaning that certain uses are possible and others not, even if the technology is not determinist and we can't be sure of how the technology will be used (depending on culture, time…)." She adds that since 40 years, that marks the beginning of the development of genetics, we need to be careful because there is always a thing that we didn't think about: "we need to integrate that we can always overlook something". According to her, the unexpected has to be a constant word occupying our minds; the more alert we are, the more we can try to prevent the risks.

We then move on to the North/South issue. Catherine Bourgain warned us: "Even with good intentions, the industrial innovation in southern countries often becomes a weapon of domination on local communities." She then gave us the example of a mosquito modified to be malaria-resistant. It was financed by Microsoft and developed in England. It was thought to be experimented on local communities in Africa, but no one wondered how this technology would affect the village. We then asked if it is truly our role to meddle in such a private matter, is it our place to intervene in other populations' lives. Catherine Bourgain answered that we could be interested in this matter but that we must take into account the locals' point of view on the subject: "Often it is linked to the local actors: Will there be any kind of dependence between actors ? What is the economy that will be established ? Who will supposedly benefit from the deal ?...". At this stage of our tool development, we can question the education provided to the southern countries. Catherine Bourgain explains its importance: "These are the types of questions that need to be asked, asked more often, since we don't have the same technological development, different technologies will be created. It's important."

Finally, we ended with a discussion about skepticism and who is "responsible" for this problem. Catherine Bourgain agrees with Lucie Dalibert on that point. People can change their practices, but it will only have an impact if done on a bigger scale. Therefore, The goal is to encourage this change by educating populations. We have to think not only about why we arrived at this point but also about how we will get out of it and what will happen in the future: "It is important to forget about the chimera that we can build/are building a miracle."

OUTLOOK : The interview with Catherine Bourgain confirmed the fact that we now have to reach out to people from developed countries in the South with different cultures from ours. The goal is then to understand others and their cultures so that we can learn from them to create an ethical and effective approach to the problem of antibiotic resistance. Furthermore, Catherine Bourgain insisted that "unpredictable" must be the keyword during our project. We should maintain a continuous state of vigilance and make every effort to anticipate future risks. It's equally important to constantly challenge our thought processes, as errors often arise from not questioning our approach.

CONTRIBUTION : Ms. Muzard started by telling us that the use and consumption of antibiotics increased during the past few years in her hospital. But she didn't associate this with unreasonable consumption. We simply treat more people, we prevent infections, like transplant stem cell patients, immunocompromised ones… However, hospitals don't have control over how patients take their medicine. Indeed, they often don't really respect their prescription on the time the prescribers gave. Moreover, hospitals face problems with the shortage of some antibiotics, which limits the use and choice of antibiotics and complicates prescriptions.

Antibiotic resistance is a genuine problem in hospitals as the number of nosocomial infections increased these past few years. Confronted with this challenge, pharmacists employ various techniques to choose the most appropriate antibiotic for treatment carefully. They utilize tools such as antibiograms to prevent indiscriminate prescriptions and determine whether the infection is bacterial or viral. But this also goes with the need to promote the proper use of antibiotics and the need for advice from specialists (pharmacists, infectiologists).

“Pluridisciplinary cooperation can be a solution to that”

When we talked about the context of antibiotic resistance, she stated that, regularly, there are national plans to teach medical personnel about its danger. Yet, the patients are not aware of it. For them, the medical field has the solution for all their medical problems. But she told us that this began to change with COVID, where we faced a wall, and people realized that sometimes science and medicine don't have solutions. She thinks that this can be changed with the education of the population.

But, antibiotic resistance appears in more than just hospitals but also in livestock feed or effluents, and finally, land in the environment.

Moreover, she told us that bacteriophage is a technique that can be a solution to replace antibiotics. But this is still in tests and is not deployed.

OUTLOOK : The interview allows us to have another pharmacist's opinion but in a different sector. The lack of education on the subject appeared to be, once again, a considerable brake in the evolution of antibiotic consumption.

Furthermore, the evocation of livestock and the environment confirms our research on antibiotic resistance to tell us that this is a One Health problem that can touch everyone and everything on our planet. We then needed to go deeper into these subjects.

It also made us think that we could use our tool to withdraw antibiotic resistance from our environment.

Thanks to this interview, we also researched bacteriophages to understand them better. We saw that this could be an alternative to antibiotics, but one phage is specific to one bacterium, and the bacterium can still develop resistance to the phage. The phages can also be vectors of tools as they transfer their genetic material to bacteria. Still, for the same reason of ultra specificity (we want our tool to fight the resistance of a wide range of bacteria) and resistance problem, we concluded that it wasn't a solution.

CONTRIBUTION : As Doctor Mollo is working on the use of antibiotics, the interviews quickly began with the problem of antibiotic use. To him, educating people on the paradox between technical advances and available treatments is the most complicated thing. Twenty years ago, we could not treat them because we did not have enough antibiotics. Now, we do have enough stocks, but we still cannot treat them because of antibiotic resistance. Before antibiotics, large spectrum were for special patient, whereas now it is like the routine and there are used a lot. Second-line antibiotics became the first line, and third-line antibiotics appeared. In 10 to 15 years, we will have more and more resistant bacteria. This is why a new job like antibiotic referents is becoming more prevalent. In MSF, it is more common to have toto-resistant bacteria, meaning bacteria resistant to all the antibiotics possible.

"It is like a silent epidemic."

MSF tries to educate people, but they cannot implement programs about the good use of antibiotics in each country; to do so, they would need all types of antibiotics, the whole pharmaceutical structure, the budget … Moreover, most of the time, these countries have other priorities than educating people about antibiotic resistance.

In his opinion, it is why we need to prevent resistance since we can't find that many new molecules anymore. In the past, scientists were racing to find new and efficient antibiotics, but nowadays, this race is put to an end. Indeed, currently, the creation of antibiotics implies creating a new antibiotic for the last remedies. But it is a niche market, so it is uninteresting for industries and companies. Sadly, it would be beneficial, even if it is only for a few patients. Even if there is a real need to create new molecules, who would want to finance that?

Moreover, if, for example, in France or the USA, systems are regulated, it is not the case in other countries like India. In those countries, there is a lot of resistance because the market is not regulated, and the population can't afford new molecules.

And even if we have a new antibiotic, there will always be resistance, a new adaptation mechanism. That is why teaching people the danger of antibiotic misuse is crucial.

When we asked him about how the population perceives antibiotics, he told us that they generally don't have any consciousness about it. However, this is not the case for professionals. For example, the Pasteur Institute in Paris opened a "One Health" course, evoking antibiotic resistance in a global approach. However, this type of complementary reflection is still missing in medicine courses.

He also evokes the phage that can be a solution to antibiotic resistance.

OUTLOOK : This interview helped us to point out other issues regarding the education and the sensibilization of other populations, with the constraint of a different budget and culture. We tried to integrate this reflection in the questionnaire that we have sent to the IGEM Leagues of other continents to have their point of view on how you can educate populations when you are not born in it, not to be seen as the miracle savior that knows everything, teaches everything to others.

Moreover, it confirms that the research around antibiotics is not cost-effective enough for the industry. That is why there are few advances in this field. It demonstrates that we need to find a solution like Super BugBuster to compensate for this lack.