I currently work on Next Generation Sequencing and thought I would share a report I wrote recently concerning NGS, its purpose (mostly in cancer research) and some of the ethical issues surrounding it that have been raised in the recent years. For more general questions regarding cancer and how it evolves, check one of my older posts: Uncovering Cancer.
Next-generation sequencing is one
of the most recent and exciting technological advances that are gradually
transforming the way both research laboratories and clinics work. Medicine is
taking a leap forward by unlocking the secrets carried in our DNA, in order to
provide a better understanding of our bodies and the diseases attacking it. However,
as with all leaps in technology and medicine, care needs to be taken with
socio-economic and ethical issues that arise, so as to ensure that the benefits
outweigh any risks and dangers.
DNA carries all the genetic
information required for the development and function of each and every
organism. Genetic information is encoded as a sequence of molecules and any
biological sample (e.g. blood) can provide the genetic material necessary for
full genome sequencing. Sequencing is the laboratory process by which an
organism’s complete DNA sequence can be unravelled and determined. This DNA
sequence is unique for every person and its decoding is used in a broad range
of applications, including forensics, disease screening and cancer research.
The Human Genome Project,
completed in 2003, whose goal was to determine the sequence of human DNA and
identify all the genes encoded, involved 3000 scientists and 13 years of work,
at a cost of about $3 billion. Next-generation sequencing (NGS) is the latest
advance in DNA sequencing and is advancing rapidly, producing remarkable data
that range from the sequencing of the 5,000-year old Iceman found in the Alps
to clinically available disease-targeted tests, including (but not limited to)
Alzheimer’s disease, cystic fibrosis, muscular dystrophy, cardiomyopathies and
cancer.
Cancer is a disease that arises
and progresses due to genetic variations in the human body. Mutations in the
DNA, i.e. changes in its sequence, can lead to uncontrollable growth of tumour
cells. NGS is helping sequence genomes of patients faster and more accurately
than ever, leading to earlier prognosis and diagnosis, but also to
better-targeted treatments. Cancer is thought to be more than one disease,
depending on a cancer’s location in the body, its stage and the mutations it
has accumulated. Current treatments are limited due to our incomplete
understanding of what drives cancer and due to the shortage of effective drugs
available. By sequencing the DNA, the genes that hold the key to cancer
development can be unmasked.
Besides earlier diagnosis, NGS
can be beneficial in monitoring the development of resistance to drugs and lead
to personalised medicine that better suits each cancer patient. NGS is also
vital in identifying key genes that drive certain cancer types, so as to create
a “cocktail” of drugs that will specifically kill them.
However, since the emergence of sequencing, certain ethical
and socio-economic dilemmas have arisen as well. The protection of patients’ identity holds main priority. Regulations
and laws need to be set into motion to protect the identity of participants,
whilst patients need to be made aware of the risks of linking data to them.
Data is and must be de-identified before any testing takes place. Governments
need to consider the possibility of enforced regulation to make it illegal for
an unauthorized party to attempt to establish the identity of an individual
from publicly accessible de-identified data.
Concerns are often raised about the cost of sequencing. Over
the past few years, the cost of NGS has been dropping exponentially, whilst the
benefits have been increasing. NGS has made possible to cost-effectively find
mutations in hundreds of diseases in children, diagnose highly genetically heterogeneous disorders, such
as congenital muscular dystrophies, detect carrier status for rare genetic
disorders and identify key genes responsible for driving different types of
cancer. Soon, the reduction in cost on all the inefficient treatments and the
beneficial results generated by NGS will outweigh the cost of running NGS
itself.
One of
the greatest obstacles to the advance of NGS is the massive amount of data
generated and its interpretation. Questions arise as to how much information
should be returned to the patient and at what cost. Providing the whole list of
discovered mutations to the participant can possibly lead to unnecessary testing
and consequent financial, physical and mental stress. A large percentage of
mutations will not have any impact at all on a person during his/her lifetime,
yet there are many whose effects still remain undiscovered. Mass Genomics suggest that only results with well-established clinical significance and with
a bearing on the participant’s and the family’s health should be returned.
Personally, if I had my genome sequenced, I would wish for the entire list to
be handed to me. Therefore, it is
essential that both prior and post-sequencing, the patient is made aware of these
risks and limitations.
Due to the complexity of results
generated by NGS and the uncertainty of benefits, it is vital that detailed
counselling and informed consent are also primary aspects of the process. The
patients and their families should be closely monitored and counselled by a
panel of experts, including their doctor and a genetics counsellor. More
ethical issues arise though when it comes to underage patients. Screening newborns
and children for certain diseases gives rise to new concerns such as the
possibility of false positives and the confusion surrounding asymptomatic
carriers of a disease, subsequently leading to stigma and discrimination. Similar concerns also
arise in patients with mental disorders, yet measures should be taken as
with any other medical tests concerning these patients.
Next-generation sequencing is a vital link between laboratory research
and the clinic. Certain concerns arise about ethical and socio-economical
impacts. The science world is still uncertain as to what NGS may unlock in the
next few years. However, NGS is a powerful tool in personalising medicine for
the treatment of many diseases and, in particular, cancer. To halt any advances
in medical technology would perhaps be unethical, considering the promise that
they hold. We need regulations to restrain any abuse using NGS technology and
we need trained medical personnel to be able to deal with the data generated
and to pass it on to patients in a manner that will only be beneficial to them.
