Marco Corrao

Period 6

Oct 17th, 2015

Ghost in Your Genes

1. Might genes not be the all story?
In the early 1990s, the largest project ever taken in biology fascinated the
whole world. The Human Genome Project (HGP) started with the aim of
mapping the whole human genome, with the idea that this would help
understanding why human are so complex and find solutions to many
conditions and diseases. Results, however, did not meet the original
expectations. It turned out that human genome contains about 30,000
genes, which is the same number or even lower- of many other species.
Even more startling, chimpanzees genome matches ours for 98.9 %:
clearly, this cannot explain the incredible complexity that characterize us.
A key question is then arisen: Might genes not be the all story?

2. Same sequence, different syndrome

A first prove that something other than genes is passed through
generations, came long before that the human genome was mapped.
Geneticists like Marcus Pambrey (University College of London) stumbled in
a bizarre genetic case. Angelman syndrome (characterized by many
symptoms, including a continuous smile and laughter) is caused by the
deletion of a part of the chromosome 15. Yet, the same deletion could also
lead to a totally different condition: Prader-Willi syndrome.
Further
research shown that if the chromosome was inherited by the mother, the
patient would suffer by the Angelman Syndrome, whereas if the
chromosome was related to the father, the deletion would result in the
Prader-Willi syndrome. Scientists were stunned: it was like if the
chromosome knew where it came from, but how could this happen?
Apparently, there must be something like a tag, an imprint placed on the
chromosome when the sperm or the egg is created in the previous
generation. This tags can be inherited and are able to affect directly a
gene, switching them on or off.

3. Above the genome

This tags have been studied, and resulted to be chemicals such as methyl
molecule, which can affix near to a gene, shutting it on or off. Other
molecules can grab the histones proteins around which the DNA is
wrapped- and tighten or loosen them, controlling the activity of the genes.
A common example of this process can be seen in the differentiation of our
cells. All cells in our body share in fact the same genome. Yet, it is clear
that an eye cell appears and work differently from a blood cell or a skin
one. This variety in aspect function is the result of these imprint that,
controlling the genes expression are able to differentiate the different cells

Marco Corrao

Period 6

Oct 17th, 2015

activities. These tags are also very stable, and can be passed through
generations so that a skin cell, reproducing itself, give origin to other
identical skin cells, with the same function. This direct control on the gene
activity is known as epigenome, literally: above the genome.

4. The identical twins

Further prove of the epigenetic role came up as a result of a study involving

40 pairs of identical twins across a wide range of ages. The case was raised
after some considerations about the reason why, even if two twins share
100% of their genome, one developed cancer and not the other. The study
of the DNA of these pairs of twins led to startling conclusions. Although
having the same sequence of DNA many genes resulted to work differently
in the same couple of twins. Furthermore, the oldest the twins were, the
more marked was this difference. It is clear, then that our genes play just
one part in the way we work, the other part being our epigenome, which is
affected by the environment and change throughout our lives

5. Nature vs Nurture

Another interesting evidence in the study of epigenetics came from a study

on mice concerning the way parental care affect the offspring in the long
term. The study involved both high licking (high caring) and low licking (low
caring) mothers. The less nurtured babies shown a greater increase in blood
pressure and stress hormones while reacting to stressful situations. The low
licking mothers babies were then exchanged with the other mothers ones.
Again, the mice who were less licked shown a worst response to stress. It is
clear, so, that the parental care affect directly the mice in a way that is
somehow remembered by their bodies. Studies on the gene responsible for
lowering the level of stress hormones (found in the hippocampus) revealed
that this was active in the high nurtured mice, whereas it was epigenetically
silenced in the low licked ones.

6. Choosing diplomacy

The experiment on mice had not, however, reached its best part. The low
nurtured rats were in fact treated with a drug, which was known to remove
the tags diming that gene. The behavior of these mice utterly changed: they
now responded to stress as normal rats. Scientists were, so, able to invert
this process and reactivate that gene. This surprising result led to a further
step in the study of epigenetics. Is it possible that epigenetics markers are
also responsible for some human diseases, such as cancer? Experimental
treatments were tried on some patients suffering from some forms of
cancer, like M.D.S. These patients were treated with drugs trying to
eliminate those Methyl tags which were thought to be responsible for
silencing some particular genes. Scientists thought the diming of these

Marco Corrao

Period 6

Oct 17th, 2015

genes may lead to an abnormal functioning of steam cells and, therefore, to

cancer. Although this did not represent a cure for cancer, results were still
startling. Many patient shown great improvements and other became also
cancer-free for a certain period. The aim of this experiment was, instead of
killing the cancer cells, to teach them how to work properly by
reactivating the genes responsible for their abnormal behavior. This can,
somehow, be considered a diplomatic way of facing diseases and,
although these are just the first steps, results are not discouraging at all.

7. The Swedish village study

Swedish researcher Olov Bygren, with the collaboration of the English

geneticist Marcus Pambrey, conducted a study on a Swedish village, which
was particularly isolated in the 20 th century. Furthermore, extremely detailed
record allowed the scientists to trace birth and deaths back to many
generations and to analyze this data comparing it to the periods of famine
and good harvest. The results were incredible. If a men were exposed to
famine in his late childhood, his paternal grandsons were four times less
likely to die of diabetes-related diseases. On the other hand, if the
grandfather had plenty of food during the same period, his grandsons would
have a shorter life average. A similar pattern appeared to occur with
women. However, the process was reversed. If a woman was exposed to
famine while being in the womb (the sensitive period is therefore different),
her granddaughters were likely to die earlier than the average and vice
versa.

8. Ethical consideration on the study

The results of this study clearly show ow an environmental exposure can

trigger a transgenerational response. These results appear, therefore, to be
as startling as scaring. If these correlation will be proven to be scientifically
true and explainable (and epigenetics may offer an approach), then our
conception regarding how we live our lives. This study suggests in fact that
way we behave now (think about smoking, drinking, obesity, drugs) may
not harm us, but could have consequences in our grandsons or
granddaughters. It actually brings over us an incredible responsibility and,
no doubts, raises a wide range of ethical questions and issues.

9. Experimentation on environmental exposure

A scientific prove of this phenomenon was studied by the American Michael

Skninner. He exposed some rats with toxic agents and observed how they
developed a wide range of diseases, including cancer. He also ensured that
the DNA of the animals had not mutated. He then proceeded breeding the
mice and studied the offspring of a few generations. Skinner shown how
even many generation after, a large percentage of the mice still developed

Marco Corrao

Oct 17th, 2015

Period 6

those conditions, proving this way that environmental exposure to toxins

may imprint our sperm or eggs, passing that message through generations.
This study easily related to the problem of pesticides, which still today
represent an incredible threat to our health and, apparently, to the one of
our sons, grandsons and so on.

10.
epigenome project

Towards

The overall conclusions about these studies and discoveries are extremely
important. We came across a scientific evidence that the way our genes act
express themselves- is regulated by the epigenome and is as important as
our actual genome. This discoveries bring about the incredible relevance of
the environmental exposure in the determining who we are, giving nurture
an incredible power, enhanced by the fact that these changes are often
inheritable. Overall, we can say that the study of epigenetics may open to a
prosperous future and hope regarding the way we study and treat diseases,
as well as raising ethical questions on the way we should live our lives. The
mapping of the human genome was, accordingly, just the first step in
understanding our complexity. Now, we should aim further, toward a Human
Epigenome Project.