The failure of
If inherited genes
are not to blame for our most common illnesses, how can we find out
Since the human genome was sequenced, over 10 years
ago, hardly a week has gone by without some new genetic
"breakthrough" being reported. Last week five new
"genes for Alzheimer's disease" generated sometimes
front-page coverage across the globe. But take a closer look and
the reality is very different.
Among all the genetic findings
for common illnesses, such as heart disease, cancer and mental
illnesses, only a handful are of genuine significance for human
health. Faulty genes rarely cause, or even
mildly predispose us, to disease, and as a consequence the science of
human genetics is in deep crisis.
The human genome
sequencing project was based on a huge, but calculated, gamble.
The then leaders-to-be of the project believed that faulty genes
inherited from our parents were probably the cause of most disease.
After all, many rarer diseases were already known to be genetic.
So it seemed a small leap to suppose that inherited faulty genes would
underlie common diseases, too.
There was, however, a problem with the basis for their
confidence. The best scientific evidence in humans for genes as
causes of common disease was based on comparing disease rates in
genetically identical twins against rates in non-identical twins (who
share 50% of their DNA). These comparisons, called
heritability studies, aimed to measure the relative contributions
of genetic variation versus environmental variation.
Although extremely widely used and cited, these studies were
considered worthless by some geneticists. Richard
Harvard University, for instance, called in 1974 "for an end to the measurement of
useless quantities". Other critics pointed out that these
experiments relied on the proposition that identical twins experienced
no more identical environments than did non-identical twins, when it
was abundantly clear that parents were treating their identical
offspring more similarly than their non-identical twins. These
arguments constituted a threat to the genome project. Ultimately they
were swept aside and all but forgotten.
In 2009, one of the few
remaining scientifically active leaders of the original genome
project, Francis Collins, published a review paper in the scientific
journal Nature, along with 26 other prominent geneticists. It
was titled Finding the Missing Heritability of Complex
Diseases. In it, the authors acknowledged that, despite more
than 700 genome-scanning publications and nearly $100bn spent,
geneticists still had not found more than a fractional genetic basis
for human disease.
Since the Collins paper was published nothing
has happened to change that conclusion. It now seems that the
original twin-study critics were more right than they imagined.
The most likely explanation for why genes for common diseases have not
been found is that, with few exceptions, they do not exist.
to find meaningful inherited genetic predispositions is likely to
become the most profound crisis that science has faced. Not only
has the most expensive scientific project ever conceived failed to
reach a goal it assured the world it would achieve, but there is also
the ticklish problem of why the headlines have been so consistently
discrepant with reality. As the failures to find significant
genes have accumulated, geneticists have remained silent.
There are still important decisions
to be made. The Collins paper proposed a no doubt expensive and
open-ended search among hitherto disregarded genetic locations.
We should be under no illusions, however. The likelihood that
further searching might rescue the day appears slim. A much
better use of that money would be to ask: if inherited genes are not
to blame for our commonest illnesses, can we find out what
- to which
this comment (inter alia) was posted:
* Jonathan Latham
asks: "If inherited genes are not to blame for our commonest
illnesses, can we find out what is?" The answers have been known
for decades, but are not genetic and have been largely unacknowledged:
poor nutrition, lack of exercise, chemical pollution of our bodies and
the environment, electromagnetic pollution, and the stress of living
in an economically driven society. There is good reason why people who
have had little contact with western ways rarely suffer from western
diseases; however, if such people adopt our ways, they too become
subject to our common illnesses.
Dr Eva Novotny