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The Humane Genome fifty years after the discovery of the DNA double helix

The celebrations of the 50-year anniversary is a good moment to reflect on ethical limits and real possibilities

Mayana Zatz

In spite of the structure of the double helix having been discovered some fifty years ago, it was only in the 80s that the technology that allows an analysis of DNA began to make itself accessible. In 1990 the Human Genome Project was started with the objective of sequencing, by the year 2005, the fifty to one hundred thousand genes estimated to be responsible for human characteristics. In 2001 it was announced that the sequencing of our genome had been almost completed. The media did not tire of repeating that the knowledge generated would revolutionize medicine.

Could it be that we are finally going to understand why we get sick? Why we grow old? Why we die? Why we react differently to the same medication? How much of our personality is due to behavior and conditioned by our genes? In the mean time, while speculating about the future, little is said with respect to the immediate applications of this grand scientific feat. How can the Human Genome Project directly influence our lives? How can medicine have benefited from the study of genes? What already exists in practice? What are the ethical implications? The main objective of the Human Genome Project is understanding how our genes function when normal and why they cause illnesses when altered.

One manner of dealing with this question is to start from a study of genetic illnesses that is the focal point of research at the Studies Center for the Human Genome. Understanding genetic workings is the first step towards future treatments. Furthermore, the identification of pathogenic mutations has an immediate application in the prevention of new cases starting from genetic counseling, which includes: diagnosis of those affected, determination of genetic risks, identification of couples “at risk” of having their offspring affected and pre-natal diagnosis. The molecular study of neuromuscular illnesses (the occurrence of which is of one in every thousand individuals), which has been our research objective, has contributed considerably to an understanding of the behavior of our genes.

That is to say, how different diseases can have been caused by mutations in the same gene, or on the contrary, how mutations in distinct genes can cause the same pathology. Dynamic genes have been described, that is to say, genes that cause illnesses because there exist sequences of DNA in them that can self-expand (“grow”) and for which the greater the expansion the graver is the clinical case. To understand that some illnesses are caused by an excess of a product and other by a lack of a product will be fundamental for future treatments.

However, the more interesting thing was to discover that, for some diseases, people who carry the same mutation can have a different clinical picture, varying from a serious form to complete absence of the symptoms. This demonstrates that many mutations stated to be “pathogenic” may well not be “determinants” in themselves on their own of a pathology, but that other factors (gene modifiers, RNA interference, etc.) modulate the expression of genes. The identification of these factors that “protect” some people from the harmful effects of a gene opens up an enormous pathway for future treatments.

Besides the diagnosis in affected patients, the identification of pathogenic mutations in asymptomatic individuals contributes to the prevention of the birth of new cases, which is fundamental for serious illnesses still without a cure. However, while we act upon prevention and we search for a cure, we have also a very important ethical commitment in relation to the use of genetic tests, principally for people who are clinically normal.

Ethical questions that crop up in real situations are: when to offer tests? To what point does our right to interfere extend? How to react if the DNA analysis reveals unexpected data such as, for example, false paternity? The principle of confidentiality, which is one of the rules of genetic counseling, protects whom? We must also remember that the results of a genetic test don?t change with time, and its impact can influence the future of a person or of a complete family. Before an exam the person must be informed: what is the purpose of this test? What does a positive result signify? What does a negative result signify? What is the advantage in being tested? What can be done in this respect?

On the other hand, the possibility to analyze the DNA from a discarded cigarette butt demonstrated that the information contained in our DNA is much more accessible than what we had judged it to be, which brings up other questions: is it ethical to carry out a test on such material silently or against the wishes of a certain person? And the right to “not know”? And our privacy? Will employers and insurance/health companies have access to this information? All are questions that are relevant to all of us and that must be discussed by all of society.

Mayana Zatz is the professor of human genetics and the medical coordinator of the Studies Center for the Human Genome at the Biology Department ? Biosciences Institute /USP. This article is a summary of the author?s lecture during the round table entitled “Fifty Years of the Double Helix of DNA”, held at the Livraria Cultura in the Villa-Lobos Shopping Center on the 10th of April.