26
April 2013
LEUVEN
– We may not be fully aware of it, but future generations will likely consider
our era truly historic. Never before has mankind been able to understand the
functioning of cells, tissues, and organs, the precise molecular mechanisms of
evolution, and where and how our species originated and spread throughout the
world.
The
technology that allows us to unravel cellular and subcellular processes and
mechanisms, identify the causes of diseases and develop more specific and
effective treatments, and determine who is biologically related to us and to
what degree combines knowledge from biology, computer sciences, information
technology, and material sciences. As might be expected, such a revolution in
knowledge must also have a significant societal impact, requiring answers to
questions that, until recently, were considered pure science fiction.
Today,
it is technically possible to sequence the 2.4 meters of DNA – present in
the nucleus of every cell of our body – in only a few days. And, just as the
speed of reliable sequencing continues to increase, the price of sequencing has
dropped precipitously, and will soon amount to just a few hundred dollars. Once
the function of every fragment of DNA is known, nothing will stand in the way
of routine sequencing.
Already,
variations in the composition of about 500,000 DNA building blocks (SNPs or
Single Nucleotide Polymorphisms), spread over the total length of the DNA and
shown to correlate with particular physical and behavioral characteristics or
susceptibility to diseases, are being analyzed routinely. Major errors in DNA
composition that are responsible for about 3,000 of the 7,000 known genetic
diseases can be visualized, and efforts are underway to identify the causes of
the remaining 4,000.
Meanwhile,
a growing number of companies are offering a new commercial service:
direct-to-consumer analysis of DNA for genealogical or medical purposes. While
their activities and clientele are steadily increasing, many of the results
currently are of only limited value for determining physical and behavioral
characteristics or risks of common diseases such as hypertension,
cardiovascular diseases, diabetes, and depression.
Some
people, however, claim the right to know all information pertaining to them,
including even the slightest elevated risk for these diseases. Some are even
willing to undergo preventive measures or modify their behavior to decrease or
control this risk. Others must cope with results showing that they carry
defects that significantly increase their risk of developing a hereditary form
of cancer or dementia, or of transmitting a defect to their children that
could, in turn, cause a serious defect in their grandchildren.
Some
people – so far still a minority – are fascinated by this new knowledge, and take
the results for granted. But more research is needed before we can understand
the results of sequencing correctly and apply this knowledge appropriately in
risk calculations. For example, more than 97% of our DNA contains no
information for the synthesis of proteins – that is, it contains no genes – but
nonetheless interacts with our genes to increase, decrease, or inhibit the
production of proteins.
We
also know that even if our DNA is somewhat responsible for increased risks for
common diseases, and in some cases is fully responsible for inherited diseases,
the environment in which this DNA functions can be as important as the
composition of the DNA itself. Indeed, from fertilization on, the environment
in which the fertilized egg develops – for example, what the mother eats,
whether she smokes or drinks alcohol, and whether she develops diseases or
infections – places so-called epigenetic marks on the DNA or on the proteins
surrounding it, affecting its function.
This
conditioning effect continues and increases after birth, leading to different
degrees of epigenetic marking in different organs. Individual differences in
susceptibility to diseases can be the consequence. This is nicely illustrated
in identical twins, who show as they age increasing differences in the way that
their identical DNA is marked by the environment.
Nonetheless,
the dangers implied by recent technological progress have become increasingly
obvious. For example, it is now possible to analyze the DNA of an unborn child
from the blood of its mother and determine its risk for diseases later in life.
This opens the way to full-blown eugenics – the selection (by parents,
authorities, or others) of children with characteristics considered
“appropriate.”
We
must take care that we do not become more fascinated by the composition of DNA
and what characteristics and risks it carries than we are by the human
qualities of less-than-perfect individuals, which we all are. This does not
mean that there are no applications of our knowledge that are not important,
life-saving, and even necessary. But they are more limited in number and scope
than many seem to believe. Now is a time not only to advance current research,
but also to reflect and to tread cautiously.
Jean-Jacques Cassiman
Jean-Jacques
Cassiman is Professor of Human Genetics at the Center for Human Genetics at the
Catholic University of Leuven.
