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29 October 2014

Considerations and Misunderstandings Around DNA

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The commemoration of World DNA Day last 25 April marks the announcement –on that day or thereabouts– of two scientific advances that have been instrumental in ensuring DNA’s importance in today’s society. These were Watson and Crick’s double helix in 1953, and the presentation of the draft of the human genome in 2003 by Venter and Collins, with the then president Bill Clinton as master of ceremonies. The importance of this molecule in living beings is highlighted by the ever-increasing flow of news about scientific discoveries in the field of DNA which holds out the hope that the human race can increase its understanding of the nature of living beings and what makes them work, and also that this knowledge will have useful applications in medicine, agriculture and livestock farming, the fight against pollution, and so on.

But there are numerous misunderstandings around DNA and about a number of the discoveries involving this molecule.

We have recently seen how an experiment in which the DNA of a yeast chromosome was artificially synthesized, one nucleotide at a time, washailed as having succeeded in artificially synthesizing life, or at least as being a major step in this direction. The basis for these claims (above all by the media, not the actual scientists who conducted the experiment) is the fact that this proves this artificial chromosome can substitute the yeast’s own natural one without any reduction in its functioning. Taken to an extreme, this view of living beings would mean that once we have the total DNA sequence of an organism and are capable of synthesizing its DNA sequence artificially, we will be able to manufacture and modify cells and organisms at will.

This idea fails to take into account certain basic concepts of genetics and biology in general.

  • In the first place, DNA per se is a “dead” molecule which is not even capable of self-replicating or acting on its own to synthesize the other molecules in the cells. It requires the presence of other molecules, and particularly enzymatic proteins. These molecules will therefore need to be added to the possible cocktail in order to create life “de novo”; and although these molecules can also be synthesized artificially, we still have no clear idea what has to be done to ensure they fold correctly and are functional.
  • In second place, no thought is given to the fact that the cells of an organism contain many more structures (membranes, cytoplasm, mitochondria…) in addition to DNA molecules and the chromosomes in which they are housed, which we have even less idea of how to build and synthesize. These two aspects mean that in experiments seeking to synthesize totally artificial life using synthetic chromosomes, these chromosomes will have to be inserted in a pre-existing cell “casing” already containing the molecules and structures the cell requires in order to be functional.

This misconception of the part played by DNA in the artificial “creation” of life has its origins in one of the most basic misunderstandings about the role of DNA and its functional units genes in organisms. This assumes that genes “make” or “manufacture” organisms on their own, and specifically determine their shape, size, behavior and so on. But some geneticists like Richard Lewontin rightly point out that if anything is determined by genes and their mutations it is the variations in the characteristics of the organisms, as was already demonstrated by Mendel in the 19th century. And secondly, an organism is the result of the interaction of three factors: the genes it carries, the external factors with which the organism comes into contact throughout its life, and the fortuitous molecular interactions of its cells.

In fact direct DNA analyses are highlighting the fact that the environment not only supplies the materials that enables genes and the cell machinery in general to act, but that it does something more: it can provoke alterations in the nucleotides forming the DNA (triggering gene mutations), as well as modifications “on top of” these nucleotides (which give rise to so-called epigenetic modifications; that is, in addition to genes). And although –as we said above– mutations in genes are the main causes of differences between organisms, some of these differences may also be due to epigenetic modifications, as these modifications sometimes determine changes in gene expression.

All this means that each organism even identical twins and clones is unique.

Finally, there are two major misunderstandings about the role played by DNA in human disease. It is nowadays claimed in the first place that an ever greater number of diseases have a genetic basis, and are thus to varying degrees unaffected by the environment. But very few diseases (such as cystic fibrosis or Huntington’s chorea, St. Vitus dance) are due to genetic causes acting independently of other factors such as diet, behavior, social class –in short, the environment. For this reason, we can and should act on these environmental factors (lifestyle, diet, hygiene, and so on) to prevent and combat most diseases. In other words the variations in our genes do not condemn us sometimes inevitably to suffer from certain diseases; they can be prevented by means of “environmental” measures, even when they have a clearly genetic basis. A typical example of a disease that has a genetic basis and can still be prevented with a simple modification to the environment is phenylketonuria. This is an illness where a diet low in the amino acid phenylalanine is recommended in order to avoid metabolic problems– particularly neuronal degeneration– for people with a gene mutation in the metabolic pathway for this amino acid. And generally speaking, these actions on the environment in which we live – diet, lifestyle and so on– are effective in preventing diseases with a more complex genetic basis such as neurodegenerative and heart disease, among others.

Second, another widespread misconception today is that once we have discovered the DNA sequence and the genes implicated in different diseases, we will immediately know the cause of the disease and be able to establish a therapy for it. But, unfortunately, knowing the sequence of the gene involved in a disease and the possible mutation or mutations carried by the sufferers does not tell us anything about the functional chain of which this gene is a link, or how the mutations these people carry in their DNA sequence alter these functions. This gap in our knowledge thus makes it difficult and even impossible to act on the disease with any scientific basis. However this does not matter, as many diseases have been cured without understanding their genetic-functional basis. In contrast, attempts to cure certain diseases whose genetic basis has been determined beyond a doubt by means of genetic surgery or therapy (that is, replacing the “anomalous” gene with a “normal” one) have not been widely successful, owing partly to technical problems in the substitution process, and partly to our current ignorance of the overall functioning of genes, cells and organisms.

These considerations may go some way to avoiding misunderstandings about DNA and genes, and should be included in a general program for educating our society in order to avoid giving rise to false hopes and expectations.

Access to the original text available on the website of madri+d.

Manuel Ruiz Rejón
Professor of Genetics. University of Granada

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