Pioneer of epigenetics speaks about the environment and genomes

Moshe Szyf, of McGill University, participates in an international symposium organized by FAPESP and Natura. Discussions from the event will inform the calls for proposals to create research centers.

By Karina Toledo

Agência FAPESP – One of the first scientists to suggest that the habits and social environment to which a person is exposed modulate gene function was Moshe Szyf, professor of Pharmacology and Therapy at McGill University in Canada.

Szyf was a pioneer in affirming that this genome programming – which occurs through biochemical processes known as epigenetic mechanisms – are a physiological process, a type of adaptive response to the environment that begins in utero. 

Among the known epigenetic mechanisms, the most common and most studied by Szyf is DNA methylation, which occurs when certain compounds containing hydrogen and carbon attach to the base of certain genes and hamper the expression of others. 

Although this process is physiological, it can become pathological if it occurs in the wrong context. For example, pathological results can develop if the genes that should protect us from cancer are turned off.

Research conducted by Szyf’s group and collaborators in the past few years has shown that the pattern of DNA methylation can be altered by factors such as the quality of maternal care in the first years of life or exposure to maltreatment in childhood, creating epigenetic scars that last a lifetime. 

The results of several of these studies were presented by Szyf during the International Symposium on Body-Mind-Environment Integration, held at FAPESP’s headquarters on March 12, 2013, in partnership with Natura.

A 2004 study, conducted with neuroscientist Michael Meaney, also of McGill University, compared two groups of rats: those that had been licked frequently by their mother when they were still babies and those that had not received maternal care.

The results showed that the licked animals grew into calmer adults. The reason for this difference is that maternal care changed the levels of methylation in the regions of the hippocampus that regulate the receptor gene of glucocorticoids, or, rather, altered the regulation of stress hormone levels throughout adult life.

To show that this logic also applies to humans, the McGill researcher joined with the Douglas Mental Health University Institute, also in Canada, and the Institute of Clinical Sciences in Singapore to analyze the brains of suicide victims. Through medical records and interviews with family members, the team was able to identify which suicide victims had suffered severe abuse during childhood – verbal, sexual or physical. 

In the group that had a difficult childhood, the researchers discovered that glucocorticoids were 40% less active in comparison to those who committed suicide but had not suffered abuse and also in comparison to the control group (people who died of other causes such as car accidents).

The results suggest, therefore, that the childhood abuse left these people more sensitive to the damage caused by stress in the brain; the study was published in Nature Neuroscience in 2009.

In other studies presented during the event, the scientist showed that the pattern of gene expression can also be influenced by socioeconomic conditions in childhood and by the stress endured by the mother during gestation.

“The advance in knowledge about the relationship between environment and the genome helps to combat genetic determinism, or, rather, the idea that if you are born with intelligence genes, you will be intelligent, and if you are born with healthy genes, you will be healthy, it does not matter what you do. This gives our choices more weight. It shows that we have control as parents, as public policy makers and as societies. This could define the new models for public policies,” commented Szyf to Agência FAPESP.

For the researcher, many aspects of medical practice and day-to-day life are conducted without considering their future consequences, but advances in the knowledge of epigenetics should change people’s attitudes.

“When I was a young father, the prevailing idea was to let a child cry so it could learn to be alone. Today, we don’t do this because we are afraid of the stress that this will cause and its consequences. In the same manner, we have used in vitro fertilization, surrogate mothers, and unnecessary caesarian sections without thinking very much about the consequences of this for the child. We need to begin to evaluate the cost-benefit and make conscious decisions based on information,” he maintained.

In the medical field, epigenetics has other major implications. One of them is the possibility of identifying biomarkers that would allow the identification of populations that are especially vulnerable to diseases such as cancer, heart attacks, high blood pressure and mental disturbances.

“The biggest challenge is to find forms of intervention before the clinical signs appear and the situation deteriorates. That is why it so important to understand what makes people vulnerable. This knowledge will also guide us regarding what type of intervention is most appropriate,” he commented.

Among the possible epigenetic interventions, affirmed Szyf, are drugs capable of reversing changes in the pattern of gene expression – an approach that is already used in oncology and has begun to be tested in psychiatry.

Epigenetic interventions can also be made through psychotherapy or public policies that promote changes in behavior. “The major revolution will come when we learn how to behave to obtain the same effects as the drugs capable of promoting them, discovering how to intervene in the system so that adverse epigenetic adaptations can be reversed solely by behavior,” he affirmed.

Paul Rozin, of the University of Pennsylvania, also spoke at the International Symposium on Body-Mind-Environment Integration, discussing prospects in the area of Positive Psychology – defined as the study of the forces and virtues that allow individuals and communities to prosper.

Other participants included Brazilians Silvia Koller, of Universidade Federal do Rio Grande do Sul (UFRGS), Mirian Galvonas Jasiulionis, of Universidade Federal de São Paulo (Unifesp), and Edson Amaro Júnior, of Universidade de São Paulo’s Medical School (FMUSP). They presented the national research scenarios in Positive Psychology, Epigenetics and Neurosciences, respectively.

According to FAPESP Scientific Director Carlos Henrique de Brito Cruz, the discussions during the event will be the basis of a call for proposals that will be jointly launched by the Foundation and Natura to create one or more research centers along the lines of Research, Innovation and Dissemination Centers (CEPID), in which case the two sources would provide support for up to 10 years. 

“We want to learn more about the challenges related to these topics so that we can define how the funding will be, what is the best manner to create a center for knowledge and obtain good results. It is not always easy to manage the relationship between people in universities and people in companies. Their objectives do not always match up. Our task is to find the possible convergences,” affirmed Brito Cruz.

In addition to FAPESP’s scientific director, Victor Fernandes, Natura’s science and technology director, also opened the event. “We are here attempting to understand what is the interface between three very relevant fields of science: Behavioral Neuroscience, Positive Psychology and Epigenetics. The objective is to understand how behavior and day-to-day life influence biological behavior and on top of this seek funding opportunities for science and innovation,” he underscored.