• Carrying trauma to the next generation

New evidence suggests that the trauma is not just psychological, but
biological and even heritable. By altering the chemical mechanisms regulating
gene expression, these modifications may become embedded in the male germ line,
and can be passed down to the victim's children.

The July 7 bombings and heritability: carrying trauma to the next generation
The offspring of male survivors of the July 7 bombings may inherit anxiety and
depression.
By Michael Stewart
The Telegraph

23 Nov 2010

It is often said of a particularly dramatic event – such as the September 11
attacks or the July 7 bombings – that its consequences will "reverberate for
generations". It can seem like hyperbole, yet new evidence suggests that
traumatic events can affect the genes, and lives, of children as yet unborn.
Take the July 7 London bombings. As the harrowing evidence continues to emerge,
the psychological impact on the survivors has been all too clear.

As many as 30 per cent of those directly caught up in the atrocities have gone
on to develop full post-traumatic stress disorder (PTSD). This is in line with
similar incidents: after the Oklahoma City bombing in 1995, 41 per cent of
survivors were diagnosed with PTSD after six months, and 26 per cent were still
suffering after seven years. Among soldiers returning from Iraq and Afghanistan,
the British Armed Forces reckon that 10 per cent develop PTSD. However, an
American study gave a figure as high as 30 per cent.

Yet new evidence suggests that the trauma is not just psychological, but
biological and even heritable. By altering the chemical mechanisms regulating
gene expression, these modifications may become embedded in the male germ line,
and can be passed down to the victim's children.

This idea is deeply controversial, not least because it seems to cast doubt on
one of the key principles of modern evolutionary theory. The doctrine of natural
selection holds that it is our DNA alone that is passed down to our children –
and that this remains unaffected by our actual experiences.

Conventional biologists groan with horror at the spectre of the 18th-century
French biologist Jean-Baptiste Lamarck rising from the grave.His theory – that
characteristics acquired during a creature's lifetime can be passed on to its
offspring – is intuitively appealing, but it is rank heresy.

According to the scientific orthodoxy, our only genetic inheritance from our
parents is our DNA. Yet this, it now appears, is not entirely the case. Embedded
within the DNA sequence are epigenetic regulators, chemical marks that control
which genes are expressed and which are not. This is a crucial function, given
that every cell in our bodies contains our entire lexicon of DNA. It is the
regulators that selectively silence some genes so that particular cells become,
say, skin or brain cells, and stay like that when they divide.

The heretical proposition here is that these epigenetic marks can be transmitted
along with the DNA. It is the result of intensive research into how these
mechanisms work. The best understood is DNA methylation, in which methyl
molecules latch on to some areas of the DNA strand and act as switches that
render a gene active or inactive.

Too much or too little methylation, and a host of problems occur, from fragile X
syndrome to a variety of cancers. The latest findings, however, indicate that
psychological conditions, such as trauma and stress, also leave an epigenetic
mark. Professor David Sweatt and his colleagues at the University of Alabama
have found that maltreating rat pups for just one week is enough to trigger
epigenetic changes that deactivate the gene for a protein important in memory
formation and emotional balance. This same agent – brain-derived neurotrophic
factor – is often abnormally low in schizophrenics and those with bipolar disorder.

In a similar experiment, Professor Eric Richards at Washington University, St
Louis, showed that the way rats are nurtured affects the methylation of a
crucial receptor in the hippocampus. After a positive nurturing experience, the
appropriate gene gets turned on at a vital early stage; after a bad one, the
gene remains unused. The same is found in humans. A study of women in Holland
who were pregnant during a prolonged famine after the Second World War found
that their daughters had twice the normal risk of developing schizophrenia.
Again, the causes were epigenetic, the result of changes in the expression of a
gene linked with embryonic growth.

But can these effects be inherited? Can nurture in one generation affect nature
in the next? It's becoming increasingly clear that the answer is yes. Take
Holocaust survivors, for example. A high proportion show abnormally low levels
of the hormone cortisol, a deficit of which is associated with PTSD.

What is surprising, though, is that their offspring have equally abnormal levels
– and this has been shown to be a biological trait, rather than an effect of the
parent-child relationship.

All told, Professor Eva Jablonka and Gal Raz of Tel Aviv University have cited
more than 100 cases of inherited epigenetic variation, ranging from bacteria and
fungi to plants and animals. But how does it happen? The conventional view is
that epigenetic marks are "wiped" at fertilisation, but crucial new evidence
shows that this is not always the case. In a seminal recent experiment,
Professor Isabelle Mansuy and her colleagues at the University of Zurich exposed
male mice to stress and maternal neglect during the first two weeks after birth.

Predictably, the mice became anxious and depressed – but so did two generations
of their descendants, despite being reared with normal levels of maternal care
and attention. Key genes were incorrectly methylated not only in the sperm of
the fathers, but also in the brain cells and germ lines of their children.

It is important to point out that such a mechanism can be beneficial, at least
in a biological sense: in times of stress, it provides a way to generate rapid
variation in a population and help offspring cope with changing environmental
demands. Even the challenge to natural selection is not as severe as it might
be. Epigenetic marks are ultimately reversible and would only become a permanent
part of the genome if they afforded an adaptive advantage. Evolution by natural
selection is therefore not threatened: all we are seeing is a broader
understanding of what, in Professor Richard Dawkins's phrase, constitutes the
"selfish replicator".

As our understanding develops, this phenomenon will open the way towards a host
of epigenetic therapies, and even enhancements. Yet it will also have profound
social implications: it suggests that depression might breed depression, or that
impaired brain function due to a difficult upbringing on a sink estate could be
perpetuated down the generations. It also implies that much of our behaviour
lies outside the power of the individual or society to control.

For the male survivors of the July 7 bombings, the implications must be acutely
personal. Yet the good news is that adverse epigenetic effects are reversible.
With science in this field progressing, we are sure to develop ways to mitigate
the consequences for future generations. That should help ease the minds of
those who have more than enough to cope with already.

http://www.telegraph.co.uk/science/evolution/8153276/The-July-7-bombings...