Why is Epigenetics so sexy? And other related questions.

Giuseppe Testa

By Sara Formichetti

When I was asked to write a post about the last Science & Society talk we had at our EMBL site in Rome I was particularly excited. Science & Society lectures are all about the impact of science on society and the speakers work in fields that are of utmost relevance to the public – but often misunderstood.

Most recently, Giuseppe Testa spoke at EMBL Rome. Testa works on epigenetic regulation, cell reprogramming and disease models. His talk dealt with the impact of epigenetics on society, which is a concern for all of us working at EMBL Rome, considering that we recently chose to rename our unit “Epigenetics and Neurobiology” to focus the interests of new group leaders in these two fields.

But, what is the exact definition of epigenetics? Personally, I like a very broad definition of epigenetics: all mechanisms leading from a single genotype (DNA) to multiple cellular phenotypes (physical outcomes) that are not explained by the DNA sequence. A narrower definition is the one considering “epigenetics modifications” as those chemical modifications of chromatin or the DNA molecule itself which do not alter the DNA sequence. But according to Testa, it is not necessary to give a precise definition of epigenetics. Instead we should embrace the idea of epigenetics as a “boundary object” and exploit the possibilities offered by this imprecision.

I personally don’t like the fact that the ‘-genetics’ half of epigenetics can mislead people into thinking that we only talk about modifications which are inherited by our progeny. This is what scientists call “transgenerational epigenetics inheritance”, a phenomenon which is demonstrated only for a few epigenetics modifications, while most of them are still controversial and difficult to prove. Nevertheless, this controversial idea has already spread into society! This leads to two main questions:

  • How can we talk about our scientific discoveries and maintain a good compromise between being cautious and making things clear and simple enough?
  • Why is the controversial idea of epigenetics inheritance so appealing?

Perhaps the answer to the second question is that it suggests that the way we live our life can influence the phenotype of our children. Our destiny and the destiny of our descendants is not just what is written in our genetic code (i.e. in our DNA sequence) after all, we can actually do something to change it. Nurture, the theory seems to suggest, can affect nature. It is the revenge of will! But just because a scientific theory makes us feel better doesn’t mean that it is right. I think that we scientists should all make a bigger effort to talk about what we do to our friends, moms, brothers and sisters in terms that they can understand, but that we should also be able to explain why some results have to be treated as controversial.*

Scientific revolutions are always accompanied by a huge impact on society. We have the duty, as scientists, to take this impact into account when we choose the biological questions to research. But can we actually choose our questions to specifically address a social issue of our interest? In other words, what do you think of choosing a question BECAUSE OF its specific impact on society? When we asked Testa this question during our lunch in the small EMBL garden, he said that this is indeed what they are doing in his lab; however, Testa is also one of the organizers of the cross disciplinary program in Molecular Biology and Bioethics in the University of Milan, which combines the study of biology with the understanding of the related ethical issues. Thus, the message I got from the day spent with Testa – that I will try to keep in mind during my scientific career – is the following: it can be seen as part of our scientific freedom to choose to study particular biological questions that could lead to thorny answers, but being aware of these consequences when we start can make us better scientists.

Giuseppe Testa talking about the battle between nature (the genomic sequence) and nurture (the environment)

There is a final question that I would like to address in this post: why are epigenetics and epigenomics (i.e. the profiling of epigenetics modifications in the whole genome) so appealing for scientists?

In his paper, Testa claims that epigenetics is a “new place-holder to anchor the environment to the genome”, which makes much sense in the context of today’s digitalization of biology. Today, molecular biology has shifted from hypothesis-driven research, investigating the roles of specific molecules in a process, to analysing big-data in the search for new patterns and mechanisms. We are able to reconstruct pathways and networks in-silico, which could predict mathematically how to go from one cell line to another. This digitalisation has great pros: it makes data more standardised and easier to access for everyone (it is easier for me to trust a dataset I can re-analyse on my own than an image of a band of a Western Blot). For me, a systems biology lover, data-driven biology also allows us to look at the whole picture at once and to pick new molecules/processes with an unbiased look! Sequencing and proteomics techniques are a real revolution.

However, I cannot hide from the negatives of this fast change in how we perform biology. It has become too easy to draw conclusions based on pure data-analysis when they should of course be supported by different experiments. All “wetties” (i.e. people also working at the bench) know how each -omic technique is affected by its own artifacts and biases. However, the business of current science, willing to have “quick-and-dirty” big results, sometimes doesn’t give scientists enough time to properly prove the hypothesis suggested by their -omics data.

We are in a transitional moment: quickly spitting out gigabytes of potential new information, while many molecular biologists are still not able to analyse and deeply interpret this kind of data on their own. The danger is that researchers can trust papers which are in fact not so strong.

The situation is changing with the new generation of young scientists. And it is to them that I address my final sentence: let’s keep ourselves critical!

*The human need to create a separation between Nature and Nurture (are we sure that this separation exists?) is widely discussed in Evelyn Fox Keller’s “The Mirage of a Space between Nature and Nurture”, a book I would recommend in case you are interested in this topic 🙂

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