Beyond the Genome The chain of life. This too was discussed at the Meeting. A researcher sums up the current debate. Genetic determinism and the “I,” a challenge for reason By MARCO PIEROTTI*

Beyond the Genome

The chain of life. This too was discussed at the Meeting. A researcher sums up the current debate. Genetic determinism and the “I,” a challenge for reason

By MARCO PIEROTTI*

Ayear after the announcement that the human genome has been almost completely deciphered, officially published last February by the two consortia–the public one coordinated by Francis Collins and the private one guided by Craig Venter, in two articles in the two most prestigious biomedical journals, Science and Nature–it might be useful to dwell briefly on the meaning and possible consequences of this event. “The human genome underlies the fundamental unity of all members of the human family, as well as the recognition of their intrinsic dignity and diversity. In a symbolic sense, it is the heritage of humanity.”

This statement, taken from the Universal Declaration on the Human Genome and Human Rights issued by UNESCO, effectively represents the degree to which the possibility of the knowledge of the human genome can produce a highly significant impact on every stratum and component of human society. More than scientific knowledge, it is the experience of daily life that shows us how the human being is more than the mere product of his genome (Collins and Venter themselves agree in saying that “man is much greater than the sum of his genes”). Nonetheless, in a certain sense, we are biologically “defined,” both collectively and individually, within our genome. Consequently, the mapping, sequence, and analysis of the human genome represent a fundamental progress toward knowledge of ourselves. The positive aspects of this cognitive process must not make us forget the potential negative effects that might be brought about by irresponsible genetic manipulation or even just by the penetration into the biological intimacy of each of us.

In any case, a correct application of this knowledge will certainly produce, over time, material benefits for all mankind. Correct application: this is one of the crucial points of the ethical debate provoked by the technical progress of science which keeps moving its limits farther and farther ahead. In the field of genetics, where in the most unscrupulous circles (but not a minority) there is no hesitation to state that by now “we can play God,” I believe that there should be no space for weak thinking or “politically correct” positions. On the contrary, we have need of certain, unambiguous referents; in that case a correct application of knowledge of the genome cannot elude a position of morality. And true morality, Fr Giussani tells us, is charity. Charity is “the way God feels about the world and treats the world.”

Three billion letters
Knowledge of the genome, thus the complete sequence of the some 3 billion letters which make up human DNA, represents the success of the most formidable biological undertaking ever attempted by man, conceived in 1985, begun in 1990, and now accomplished. It is commonly said that in our genome is written the genetic code. In reality, the genetic code represents the instrument, the way in which the gigantic genetic message, which is the more correct definition of the contents of our genome, is translated. This message is codified in a language made up of just four letters (A,T,C,G), therefore it requires the formation of very long phrases in the three billion letters of the total. These correspond to an informational content of about 1 gigabyte that, if put in visual form, would fill about 500,000 pages of standard format. In this context, a gene is a fragment of the general message which specifies a given biological function or, if you will, a chapter of the message.

Various questions have been raised about the total number of genes contained in the human genome. The truth is that at the moment we do not know, even if it is certain that in the end we shall be able to pinpoint it with great accuracy. It is almost certain that the number will not be fewer than 10,000, nor more than 200,000 to 300,000. An estimate of 50,000 to 100,000 is closest to what we have already been able to determine. However, the problem is not in the numbers. Since 1977, in fact, we have known that a gene can build more than one protein, the entity most directly linked to a biological function. Today, we even think it is an exception when this does not occur.

Complexity of interactions
The complexity is thus dictated, more than by the number of genes, by their interactions and the reciprocal interactions of their protein products. Furthermore, we must not ignore the interactions of the genes with their environment, both inside and outside the cell, starting already from the zygote, the product of conception, which now the development of new techniques proposes in alternative forms to the natural one, that used to seem inviolably sacred. It is in this complex of interactions, in these processes still in large part unknown, that the intrinsic potential of our genes and our evolutionary heritage takes concrete form in the actuality of our being and makes every living being literally a masterpiece of biological uniqueness. This widely accepted vision already in and of itself underlines the limits and inadequacies of a position of extreme genetic determinism. Nonetheless, the central role of knowledge of the human genome in the biological universe can cause us to fall, following the tendency indicated by so-called scientific universalism, into a heavy genetic reductionism and a utopic vision of the role of science, as Hans Magnus Enzenberger recently warned in an article on the “shamans of biotechnology,” starting from the observation that today “it is no longer the priests who speak of immortality, but the researchers.” Once again, the central point of the question is constituted by the limits set by a purely materialistic view of man. Following the most widespread integrally atheistic view, which considers man to be the product of chance who evolved according to necessity and environmental logic, we can arrive at only two results: either lucid desperation (refused by the intelligence, even though recent events posit it either consciously or not as the only referent for the action of certain groups of young people), or a proud assumption of responsibility (certainly a positive outcome, but unreliable in human terms, as a realistic reading of individual and collective human history demonstrates). In this context, the question, “Who am I?,” remains unanswered. And knowledge of one’s genome does not coincide with knowledge of one’s “I.”

“Bad” genes
Returning to more general concepts about the genome, the concept is widespread of dividing genes into good and bad, in a vision that is understandable, but reductively anthropocentric. The “bad” genes determine genetic illnesses. In reality, intrinsic in the nature of DNA, in its constitution, is the possibility of error and, thus, of sometimes generating a bad gene from the modification of a good one. The frequency with which this happens has been estimated in one mistaken letter every billion letters in the genetic message. These errors create variability and thus, at times, result in a “diversity” that is more useful to the organism; but other times they can cause illness. This is the acknowledged, although not always accepted, human limit. In the post-genome era, we shall come to know our genes better and better. There may be three different categories of genes: those about which we know something or can imagine their function. Second, others that we are sure exist because of indirect evidence, but about which we know little or nothing, and which manifest themselves through phenomena of reciprocal interaction, and on which the environment, in the broadest sense of the term, has significant influence–for example, where I was born, what I have eaten, etc. Finally, it is possible, but we cannot say how probable, that there exists a third category of “genes” about which we know nothing and imagine nothing. They are the ones “hidden” in the 97% of human DNA thought to be superfluous, that is, having no use!

As for the applicative aspects of knowledge of the human genome, these will lead us ever closer to a predictive type of medicine, that is, a medicine that estimates the risk for individuals who are healthy but are “at risk” for illness. This reading of the genetic destiny considerably increases the responsibility of the doctor, not only in the professional sense, but above all in the human sense.

Genetic determinism, which is inadequate for understanding and explaining man’s essence, his feelings, and in large part his behavior, is nonetheless present to a different degree in the more than 6,600 hereditary pathologies which afflict mankind. In this context, it is in some ways paradoxical that the apex of biomedical knowledge, i.e., the capacity to predict exactly the appearance of a pathology not yet manifest, is accompanied by a therapeutic response that is still quite modest.

It is once again in this squeeze between highly refined diagnostic capacities and limited offerings in terms of therapy that the terrain of action lies for the physician-protagonist of the first era of post-genomic medicine, sharing completely the needs of the person, in whom he must see a Destiny, and not only a genetic one.

* Researcher of the National Tumor Institute (Milan, Italy)