7
Sep

Daniel Ramón: “Science offers you logical explanations of topics on which you had not realized, and people like that”

ANA SERRA// Within the framework of the ESMODA-ECO project, ScienceFlows interviews Daniel Ramón, PhD in biotechnology and vice president of R&D in nutrition and health at Archer Daniels Midland Co (ADM-Biópolis), a multinational dedicated to massive genomic sequencing, to talk about the social perception of food science and technology and of the latest advances in nutrition and dietetics. Daniel Ramón is committed to research and the transfer of knowledge to society. He was a full-professor of Food Technology at the University of Valencia (2002-07) and Research Professor at the Higher Council for Scientific Research (2008-10). In 2011, he created Biópolis, a pioneering company in Spain that develops microorganisms for the food and health industry and since then he has been working in biotechnology companies. In addition, he has dedicated part of his work to disseminating research results.

Image provided by Daniel Ramón

The WHO is already talking about a malnutrition pandemic that manifests itself in two extremes: malnutrition and obesity. How can biotechnology help curb malnutrition?

This problem, in the first instance, does not require scientific measures, it requires political and social measures. We must become aware as a society that there are people livingin countries close to ours who are having a very bad time and that in some way we must help them. Among other reasons because in those areas there will be a great demographic growth in the future. This is a problem that requires social and political measures in the first place and after that, if those measures are taken, biotechnology can also be an important help. For example, it can allow, in areas like the African continent, where there are obvious water-problems, plants that are resistant to drought and salinity can be obtained that can grow in those environments. You can also use food development strategies for children that prevent the contagion of a virus, by simply adding probiotics or adding other types of compounds of the virus infection, which cause a tremendous mortality. Biotechnology can offer solutions, but if these social and political measures are given first, if not, no.

And at the other extreme, obesity … can biotechnology help curb obesity?

With regard to obesity, happens something similar, but not identical. Obesity is a multifactorial disorder where, on the one hand, diet and a healthy lifestyle obviously intervene and, on the other, there is a very important genetic component and then there is a component of the bugs that we have inside our body, what we call the microbiome. But there is a component, from my point of view, very important, which is the educational one. And it is that, either we educate our youth to follow some lifestyle habits and a healthy lifestyle or things will get much worse. This is clearly seen in a country like ours: obesity has skyrocketed in the last 50 years in an aberrational way and, above all, in children. And why do these children eat more and become obese? Because they don’t have an example from their parents. These measures are necessary and from there, again biotechnology can do a lot. Because with biotechnology we can see the genetic predisposition for someone to develop obesity. More than 300 genes related to obesity predisposition have already been identified, and if you know you have some of these mutations, you have to take a lot of precautions.

“Obesity is a multifactorial disorder where diet and a healthy lifestyle intervene on the one hand, and the genetic component and the microbiome on the other.”

Do genetic mutations influence that much in obesity?

Look, a clear example. Most people believe that the country with the highest rate of obesity and overweight is the United States, but it’s not, the one is Mexico. Why is the Mexican population so prone to obesity? What has been seen when studying the genome of many Mexicans is that there is a genome that is called the Mayan residue that is quite conserved, where mutations that are in the insulin signaling pathway accumulate, these mutations predispose to develop obesity. What has happened to the Mexican population? Until 40 years ago they had formulated a diet that in a way balanced that, they led a healthy lifestyle. But two things happen to them: on the one hand, they emigrate to countries where diet changes and lifestyle changes too – and obesity skyrockets. And, on the other, that they are subjected to other types of diets that come from abroad, other lifestyle habits that they accept but are not the ones they need to maintain that balance between their genome and their predisposition to obesity. There, for example, biotechnology can play a very important role in the early detection of obesity and, on the other hand, it can play a brutal role in the development of ingredients and diets that help prevent obesity from progressing. But, again, either you keep in mind that you have to educate the population that they have to follow an adequate diet and healthy lifestyles, or that is of little use.

One of the great discoveries in recent years and with great implications for people’s health has been the microbiome. How does it influence obesity?

One of the first scientific relationships that has been found between bugs and the digestive tract is precisely this, the influence they have on being obese or thin. About 10 years ago, researcher Jeff Gordon, from the University of Washington, began working with mice that are genetically homogeneous, but in which there are two varieties: a thin variety and an obese variety. The obese is like that because a transgenic has caused a mutation in the system that recognizes the hormone that satiates us, leptin. Those mice, although they have the hormone, they don’t have the receptor. Therefore, they eat and weigh instead of 200-300 grams up to 800 grams or one kilo.

Gordon realized that these mice were genetically the same and even with the same diet, some were thin and others fat. When he analyzed the digestive microbiome, he saw that in fat people there were more of a group of bacteria that we call fimicutes and less of a group of bacteria that we call bacteroidetes. This caught his attention a lot, it caught the attention of all of us. The question was, well, is this a cause or a consequence? In other words, why are there more of some and less of others, is that the origin of obesity or does that happen to them because they are fat?

In addition, he then analyzed the microbiome of obese and thin humans, and saw that the same thing happened: in obese humans there were more fimicutes and fewer bacteroidetes, just as in the rats with which he had worked before. And of course, he was surprised, because that showed that it was something that is quite conserved in the animal kingdom.

And is it cause or consequence?

The experiment that showed him that it was a cause and not a consequence was the following. He raised rats in a sterile environment, this is quite easy to do. You only have them in cages, in a room, where you filter all the air that enters and everything that enters and the food that you give them is sterilized, so that there are no microorganisms. After you cross the parents in that sterile environment, and there a litter is born that is sterile from the start and you feed it in that same environment. Well, when he had those mice free of microorganisms – which have many health problems – what he did was a fecal transplant. It consists of giving the mice feces from obese humans or from thin humans. What happened was that when it gave it feces from obese humans, with that microbiota that I have counted before, the mouse became obese and if it gave it feces from thin humans, no. This was the first evidence that the microorganisms in our body can play a role in obesity.

This would have great implications in the knowledge of the importance of the microbiota …

This fact, to all of us who work in nutrition, put us in the position of saying, wow, I can vary the microorganisms that I have in my stomach through diet. Because, in addition, it was found that when people with obesity followed a hypocaloric regimen and lost weight, their microbiota readjusted. So, what we thought was, if I find something that these can recover those imbalances… Well, we have found that in Biópolis … in our company we have found a probiotic, a strain from a child less than three years old, healthy and subjected to breastfeeding that is capable of giving that change and, in addition, reduces the deposit of visceral fat.

Are these products intended for the general market or for very specific circumstances?

This probiotic in particular, for example, it is thought to avoid the obesity that appears in late ages. You already know that as we get old we have a certain predisposition to gain weight, something that is very evident in women when menopause begins. And that is a problem because it is the starting point for women to have health problems, such cardiovascular risk or diabetes. We call it metabolic syndrome. This probiotic is designed as a preventative one, to avoid the problem of fat accumulation around the viscera, as this leads to obesity and then leads to much worse problems. In the end, what we are looking for in our case is healthy aging. But this probiotic also works for children who have Willi-Pradrer syndrome, a rare disease that, among other things, suffer from a genetic problem, which causes them to be obese.

¿Cómo ha incorporado la industria de la alimentación los avances en el conocimiento de la microbiota?

Portadas de las revistas Nature y Science con la publicación de las dos primeras secuenciaciones del genoma

Thanks to the publication of the first two genomes in Nature and Science, 15 years ago, the doctores began to demand that more genomes be sequenced, faster, and cheaper. Massive sequencing platforms began to be developed, machines capable of sequencing very quickly, and very cheaply.

And from there they began to be used to study microbial populations. In Biópolis we acquired the first massive sequencer in Spain – 18 years ago – and began to collect samples. We realized that everything was plagued with bacteria that we could not recover in the laboratory. In fact, mind you, you took a sample from the respiratory tract and discovered that it was riddled with bacteria, more than 500 bacterial species. And at that time the concept of pulmonologists was “this is sterile, because as it is contaminated you have an infection”.

We have collaborated with the IVI and you go and take an endometrial sample: in theory there should be nothing here. Surprise. This is riddled with bacteria, there are like 200 bacterial species. In the end the conclusion is that for 10 years we have known that if you weigh 70 kilos, 1.5 kilos or two kilos it is not you, it is the bacteria that make up your body. And these are mainly concentrated in your digestive tract. This attracted a lot of attention. Ir was suspected that a healthy eating was the foundation of a good health. But of course, that started to make sense. Yhat kilo and a half or two kilos of bacteria lives off what I eat. And what it does is transform what I eat into energy and probably a series of remote metabolites do things. And then, we started investigating …

In the end the conclusion is that for 10 years we have known that if you weigh 70 kilos, 1.5 kilos or two kilos it is not you, it is the bacteria that make up your body. And these are mainly concentrated in your digestive tract. This attracted a lot of attention. Eating well was suspected of being the foundation of good health. But of course, it was starting to make sense. Sure, but that kilo and a half or two kilos lives off what I eat. And what it does is transform what I eat to transform energy and probably a series of remote metabolites do things. And we started investigating …

What practical applications does this have?

Look, an example: we have invest a lot of time on research on skin problems. Atopic dermatitis in children and psoriasis in adults, because we suspected that the origin was not in the skin, but in the digestive microbiome. We began to analyze the microbiome of the digestive tract of children with atopic dermatitis who had recurrence of dermatitis a few days before the peak of skin inflammation and after skin inflammation. What we discovered is that within days of the peak of inflammation, the digestive microbiome changes and, furthermore, it correlates with certain bacterial species rising and falling. And there we realized that these changes produced intestinal inflammation. Normally the intestine is wrinkled in shape, you do not have to let anything out. But when there is inflammation what happens is that it opens. Then the contents of the intestine leak out and can cause inflammation at a distance. So we started to think that maybe if we could feed probiotics that lower intestinal inflammation, that would not happen and they would not have recurrences. The result of this research is a product that is being sold all over the world and that we produce in Biópolis, which only has a strong anti-inflammatory effect. What it does is prevent this inflammation from appearing and maintains the permeability of the intestine. Of course, when you have problems you have to use corticosteroids, because it is the drug to reduce skin inflammation, but if in addition to that you take our probiotic, the corticosteroid, instead of taking effect after two or three months, takes effect at four weeks. And the most important thing is that after you stop taking corticosteroids and probiotics, you do not have recurrences because you have already fixed the problem. And it takes like 6 or 7 months to come back, if he does come back. That is the perspective that we have of nutritional supplementation and functional nutrition.

What other research lines are opened in the investigation of the microbiota?

Look, an example: we have spent a lot of time on skin problems. Atopic dermatitis in children and psoriasis in adults, because we suspected that the origin was not in the skin, but in the digestive microbiome. We began to analyze the microbiome of the digestive tract of children with atopic dermatitis who had recurrence of dermatitis a few days before the peak of skin inflammation and after skin inflammation. What we discovered is that within days of the peak of inflammation, the digestive microbiome changed and, in addition, it was correlated with that certain bacterial species rose and fell. And there we realized that these changes produced intestinal inflammation. Normally the intestine is wrinkled in shape, you do not have to let anything out. But when there is inflammation what happens is that it opens. Then the contents of the intestine leak out and can cause inflammation at a distance. So we started to think that maybe if we could feed probiotics that lower intestinal inflammation, that would not happen and they would not have recurrences. The result of this research is a product that is being sold all over the world and that we produce in Biópolis, which only has a strong anti-inflammatory effect. What it does is prevent this inflammation from appearing and maintains the permeability of the intestine. Of course, when you have problems you have to use corticosteroids, because it is the drug to reduce skin inflammation, but if in addition to that you take our probiotic, the corticosteroid, instead of taking effect after two or three months, takes effect at four weeks. And the most important thing is that after you stop taking the corticosteroids and probiotics, you do not have recurrences because you have already fixed the problem. And it takes like 6 or 7 months to come back, if he does come back. That is the perspective that we have of nutritional supplementation and functional nutrition.

Personalised nutrition

How close are we of making genomic analysis for optimal nutrition a reality?

February 15 and 16, 2021 marked the 20th anniversary of the appearance of the first publication describing the first two human genomes. Those two articles cost 3 billion dollars and the work of 3,000 scientists for 10 years. Today Beijing Chinese Institute, which is the Chinese company that is dedicated to massive genomic sequencing, offers to sequence the genome for 600 dollars. That is what we have advanced in this time. The progress in genomics and data interpretation is impressive. The reality is that we are at a point in history in which I do not see any problem so that when my grandchildren are born, their genome is sequenced and their parents know all the mutations that can predispose them to develop certain pathologies.

This can have many implications …

As everything in life, it can have a positive and a negative aspect. If these data are accessible to anyone, there may be a misinterpretation of that data, or a misuse of that data, but that is what the laws and the protection of information are for. What is the positive aspect of it? Well, if my grandson has a gene that predisposes him to develop colon cancer, it is very hard, but I want to know it as soon as possible, because I know that, if I detect it at birth, simply if throughout his life he has a diet that does not promote constipation, the possibility of developing colon cancer is reduced by 80%. And so we could put more examples. I believe that we are already very close and that this is something that today may seem difficult, dangerous, etc., but I imagine it is the same as when 50 years ago they told you that they were going to put you in a device that told you if you had a tumor or not and people would also think “now what is going to happen, that the insurance companies are going to do an X-ray analysis of me before they tell me how much I have to pay in fee”. I believe that in a few years we will face the same thing. The companies will say, give me your genomic data and depending on what you have I am going to put a monthly fee or another … that will happen, that is for sure

Social perception of biotechnology

Daniel Ramón, in addition to leading a biotechnology research project, has dedicated part of his career to scientific dissemination. In fact, he has received the European Prize for Scientific Dissemination for the book “Los genes que comemos”

Portada del libro Los genes que comemos editado por Algar Ediciones

Japan is the country with the highest degree of acceptance of functional foods. Some argue that this is due to its population pyramid. Europe, and specifically Spain, has a fairly similar inverted pyramid, why isn’t there that degree of acceptance?

In just four generations life expectancy of the Spanish population went from 40.2 for women and 39.1 for men to 86.1 for women and 81.2 for men. We are the fifth country in the world in life expectancy, and being a country for the elderly has brutal repercussions. The most important will be that health spending will be brutal. In Japan they developed functional food because it is a necessity, so that the system would not break. What’s more, a report from the Hospital del Mar in Barcelona from about a year ago calculates that if the trend of increasing obesity in Spain continues as it has been up to now, in 2025, healthcare spending linked to obesity will be 3 billion euros per year. We cannot bear that, but people do not perceive it. Now with the covid-19 pandemic, it has begun to be perceived: in all countries, including Spain, the sale of nutritional supplements that trigger the immune system have exploded.

The book “Los genes que comemos” collects a study on consumer acceptance of GMOs that ensures “Consumers do not have a clear idea about accepting or rejecting the new biotechnology. It will depend on the food they put in their hands” Do you think this is still the case?

Note that the book you mention is 25 years old and things have not improved. When I wrote that book I was very shocked … I had the opportunity to speak with some science teachers working at high-school at the Valencian Community and I realized that the vast majority of teachers were chemists. This doesn’t matter at all, except for the fact that when they studied at the Faculty of Chemistry, they didn’t talk about DNA, they didn’t talk about genes, or anything like that. They hadn’t been given a DNA recycling program. With which, none of them knew very well what this transgenics was about. We began to look at the books with which they taught their students … not a single content … we only found something in a book for preparation of oppositions for teachers of Training and Labor Orientation in Vocational Training and what it said verbatim was: “Transgenic foods produced by radioactive emissions are being developed.” But my impression is that we have not improved anything since then …

Where do you think the origin of this bad perception is?

The social perception of biotechnology is bad for many reasons, but fundamentally for two: scientists have not disclosed enough so that people understand what we do and, on the other hand, the public media should be disclosing about the magnificent scientific community that there are working in the public investigation organisms that there are in this country. And that also happens because there is no structure that puts science in value, because the leaders remember the scientific community the two weeks prior to the electoral debate saying, I support innovation, I support R&D, but when they come to power they forget. Society is not informed about the advances of biotechnology because there is a strong ideological debate. It is not a technical debate, if it was technical it would have been resolved long ago, but it is an ideological debate where everyone has their interests. The multinationals have their interest, like the company I work for now, but just as the food multinationals have them. Obviously, we want to sell and get benefits, we are not the brown beasts that want to starve to death, but we are not the nuns of the charity, either… But another thing is that there are also environmental multinationals like Greenpeace, that have a structure like ours, but instead of selling food, they sell other things … and you just have to browse a little on the Internet to realize that Greenpeace finances are not as transparent as they seem. And, in the end, what life has taught me is that there is an ideological component. Then you sit down with the politicians and depending on the times they support one point or another depending on how the times take them.

“La sociedad no está informada sobre los avances de la biotecnología porque en todo esto hay un debate ideológico fuerte. No es un debate técnico, si fuera un debate técnico estaría ya resuelto hace tiempo, pero es un debate ideológico donde todo el mundo tiene sus intereses”

“La sociedad no está informada sobre los avances de la biotecnología porque en todo esto hay un debate ideológico fuerte. No es un debate técnico, si fuera un debate técnico estaría ya resuelto hace tiempo, pero es un debate ideológico donde todo el mundo tiene sus intereses”

Up to what extent scientists are also responsible for this?

Scientists have not dedicated ourselves to that, in fact, when a scientist has disseminated, the scientific community, what he said was “if they disseminate, they can’t be very good scientists…”. And, on the other hand, it is also true that public administration has not made it easy either.

People are not interested in science?

In general, it seems to society that science is a very boring thing, and we have a good part to blame for this… we have not made it easy. And we have not taught science in a nice way so people can perceive with interest scientific developments. This leads to a spiral in which scientific community is ignored. But when you explain science appealingly, then people enjoy it. I live in L’Eliana and it has been almost 20 years since several residents of L’Eliana began to organise in order to get people interested in science, and we also got the support of the City Council. We proposed an initiative called Tardes de Ciencia, which ended up later being called Al voltant de la ciència. Every two months, on a Friday, we would bring one or two scientists to L’Eliana and they would talk about a specific topic. I assure you that the House of Culture was full. And you realize that science is not boring. That’s a lie. Science offers you logical explanations for topics that you had not realized about, and people like that.