Whole WGS, the established norms pertaining to ethical research

Whole genome sequencing (WGS) are
relatively new, incredibly potent tools in the quest for human gene discovery
and in furthering putative genetic epidemiological association. Until very
recently, the limiting factor in any sequencing project was the cost and
throughput of Sanger sequencing. The Human Genome project, completed in 2004,
cost approximately $300 million and was completed over several years, utilizing
several hundred capillary sequencers (Tabor et al., 2011). The cost of
sequencing per base is decreasing in what is best described by a logarithmic function,
and as a result it didn’t take long to complete the $10 million genome. Now, we
are closing in on the $1000 genome (Robertson, 2003). Given that the cost of
human WGS is dwindling rapidly, we are going to see a proportionally large surge
in the amount of genomes being sequenced. At this time, the genomes of several
dozen persons have been sequenced, predominantly ensuing testing different
computational methodologies, analytical methods and sequencing platforms (Tabor
et al., 2011).  In this nascent stage, we
have not yet reached maturity in the field of pharmacogenomics. Despite this,
WGS have been used to identify causal variants for certain monogenic syndromes.

Additionally, WGS are now being utilized in studying variants underlying more
common, mundane phenotypes like diabetes and autism. Here in the United
Kingdom, the Wellcome Trust are creating large genomic databases with a clear
aim to provide context in the linkage between phenotypic traits and the
underlying genotype. As a consequence of the departure from targeted genetic
studies and the torrent of data produced in WGS, the established norms
pertaining to ethical research conduct are being strained – consequently,
concerns of privacy and consent have to be brought up again (Lunshof et al.,

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The development and subsequent
application of novel sequencing techniques marks a paradigm shift in the long-standing
status-quo of human genetic research, with the arrival of the next generation
of sequencers and computational analysis tools, a considerably greater quantity
of data is produced. “There are no conditions under which an offer of
disclosure of research results should not be made” (Fernandez et. al., 2003).

The former quote is dangerous as it conveys a sense of absolutism, and indeed
ignorance in the perceived capabilities of pioneering researchers. Since the
norm has long been for research participants to receive clinical trial results,
a departure from this model is going to be difficult and policy-ridden. If participants
were to receive probabilistic disease results, they may be misled to overestimate
their significance (Bookman et al., 2006) (Trikalinos et al., 2004). Traditional

“the difficulty in deciding whether
to return research results lies in the fact that exploratory genetic factors
have not yet reached the point of general clinical acceptance”


based approaches may have generated
hundreds, thousands or even millions of polymorphisms, most of these are for
non-coding regions of DNA, and impose next to none functional implication. In a
juxtaposition, WGS offer functional information on effectively all
protein-coding gene variants in the genome of the subject. However, the
information gathered is probabilistic and hard conclusions should not be drawn,
neither by researchers nor by participants. As one group so eloquently puts it “the
difficulty in deciding whether to return research results lies in the fact that
exploratory genetic factors have not yet reached the point of general clinical
acceptance” (Renegar et al., 2006). This quote is now over eleven years old – and
we have to consider that significant technological advances have been made, the
bioethical norms, on the other hand, have remained relatively stable in a small
range of flux.


Since the international ethical
consensus, and subsequent statutes is based on the foregone paradigm of human
genetic research; this essay aims to describe how WGS studies puts the long-standing
ethical framework used by geneticists to a test. We devote distinctive emphasis
to certain integral segments of this framework: X, Y and Z. It is not our goal
to criticize the ethical practices of present WGS studies, but rather to
elucidate the current state of these studies and technologies with an ethically
inclined viewpoint –  and to consider where
further development in the field of human genomic research might lead us so
that future ethical qualms may be prevented.





In the month of May, 2007, Nobel
laureate James Watson peered into his own genome for the very first time. The
hard drive he was endowed with, contained the first genome to be sequenced for
less than $1 million. Although Dr. Watson is a renowned scientist with a deep
academic connection to the personal genome project, at that time he was also a
subject in a genomic research initiative. In a stark contrast to Dr. Watson,
whose strong academic background allows him to make sense of the contents of
the hard drive, is the vast majority of those that will have their genomes
sequenced for medical purposes.


In literature, it has been
stipulated that the responsibility researchers bear regarding disclosure of
genetic research results varies depending on “the type of study, the clinical
significance and reliability of the information, and whether the study involves
patients, genetically ‘at-risk’ families for a tested predisposition or healthy
volunteers” (Knoppers et. al., 2006). Although the former statement is
informative, it is ridden with ambiguity. Additionally, at present time there
are many jurisdictions in which there are no clear policies pertaining to
ethical research conduct. There is a strong plea from the international
genomics community to create standardized approach to issues concerning
consent, disclosure of results and eventual obligations to genetic relatives.