Schaub 4:00
L09
WHOLE-GENOME SEQUENCING, INCIDENTAL FINDINGS AND BRIBERY
Dipali Shah (dds33@pitt.edu)
INTRODUCTION: WHAT IS WHOLEGENOME SEQUENCING?
SUCCESSES OF WGS
WGS Statistics and Examples
Curing certain genetic diseases has become a likely
prospect via a process known as whole-genome
sequencing (WGS). This is a lab-based scientific process
for determining an organism’s DNA sequence at a
specific point in time while obtaining a systematic
assessment of any genetic deviation or obscurity.
According to an article in Time by Bonnie Rochman, to
do the testing, lab technicians need less than a teaspoon
of blood, which is chemically treated to burst open the
cells so the DNA inside them can be collected [1]. Those
miniscule strands are then fed into sophisticated
machines that read the base pairs which make up a
person's genetic alphabet [1]. Computers scan the data for
the equivalent of spelling mistakes. Some mistakes cause
disease while others don't. By studying the natural
variation of the human genome, genes that appear in
various, common diseases can be identified [2]. This is
what helps researchers find cures to certain genetic
diseases because they can figure out what the problem is
and try to decipher solutions based on their findings.
When the Human Genome Project first commenced,
scientists only knew the genetic basis of about fifty
diseases; today, close to 5,000 are known [3]. Doctors
now have the ability to test patients to see if they carry
gene mutations that increase their risk for particular
diseases and can advise them correspondingly on how
they may inhibit or postpone these disorders. “‘Knowing
more of the basic genetics that makes up an individual
has allowed us to diagnose far more genetic diseases,’
says Dr. Barbara Pober, a medical geneticist at the Frank
H. Netter, M.D. School of Medicine at Quinnipiac
University in North Haven, Conn.” [3]. When a diagnosis
is made, doctors can determine treatment for certain
diseases using gene sequencing. For example patients
with breast cancer can be tested to determine their
response to the drug Herceptin [3]. This shows how
WGS has been successfully used to test patients’
responses to drugs associated with specific disorders they
have.
HOW WGS HAS EVOLVED OVER TIME
CRITICS AND
COUNTERARGUMENTS
In 1990 scientists embarked upon an endeavor to
map human DNA, known as the Human Genome Project.
It took thirteen years and almost three billion dollars to
complete, but it was well worth it. According to Amanda
Gardner’s article from HealthDay Consumer News
Service, the Human Genome Project was acknowledged
as a significant breakthrough because researchers
“identified all of the nearly 25,000 genes in human DNA
and sequenced the 3 billion chemical base pairs
comprising that DNA” [3]. The genetic information
garnered from the project provided scientists with the
means necessary to identify how variations in particular
genes could provoke certain diseases. One of the most
substantial advantages of the project has been the
advancement of cutting-edge sequencing technology and
a remarkable reduction in cost of utilizing that
technology. Dr. Eric Green, director of the National
Human Genome Research Institute in Bethesda, Md.,
says that “‘the cost of sequencing one human genome
[today] is closer to $5,000 and can be done in a day or
two’” [3]. That means the rate of research, and its
associated innovations, has been accelerated a great deal.
University of Pittsburgh, Swanson School of Engineering 1
Submission Date 2013-10-01
Opponents of WGS services argue that agencies
could get hold of genetics information and share it with
other organizations for research purposes. Agreements
would need to be established as to how whole-genome
information should be recorded, disclosed and stored and
for how long. Present moral and legal standards require
that doctors give precedence to the welfares of their
patients so that they are not turned into research subjects
without their consent [4]. Clinics that use WGS would
require unambiguous policies to administrate decisions
about what to report.
Liam Brunham and Michael Hayden from an article
in an issue of Science have proposed to split variants into
two categories [5]. The first includes those with
“established clinical importance for which the medical
implications are clear, such as variants in the BRCA
(breast cancer)” [5]; the second category contains
“clinically important variants not associated with welldefined medical intervention, such as mutations in the
Huntington disease gene, yet requiring special precounseling and a consent form” [5]. Splitting these
variants into categories helps with deciding what data can
Dipali Shah
be reported because if researchers find what they were
initially looking for, there is no problem. However if
they find data that was not originally expected, they
would have to get permission from patients to use those
findings for research. Recently, the American College of
Medical Genetics and Genomics published a policy
statement suggesting compulsory pre- and posttest
counseling and an official consent process to address
some of the vagueness associated with what should be
reported [5]. As long as some version of this policy is
implemented, patients should have no worries about
having their results used for research purposes without
their permission.
In May 2012, the American College of Medical
Genetics and Genomics (ACMG) released a policy
statement on Points to Consider in the Clinical
Application of Genomic Sequencing in which they
cautioned that when interpreting secondary findings it is
crucial that the standards for what is reportable be high
to avoid burdening consumers with what could be very
large numbers of false results [10]. As a result, ACMG
convened a working group to offer recommendations on
handling incidental findings in clinical sequencing. The
Working Group recommends against patients choosing
whether to receive incidental findings, because clinicians
and laboratory personnel have a fiduciary duty to prevent
harm by warning patients and their families about certain
incidental findings [10]. If this recommendation had been
implemented, Dr. Shah would not be in this dilemma
because she could have just told Adams about her
incidental findings.
ENGINEERING MEETS ETHICS
Incidental Findings
Riley Adams’s family has a strong history of ovarian
and breast cancer. She partook in a study trying to
discover cancer genes that, when mutated, significantly
escalate the risk of developing breast cancer. But Adams,
frightened by her family history, also intended to get a
mastectomy. On her consent form, she checked off the
box that said she was not to be contacted by the
researchers with the results of the study. Consent forms
are generally written like this because the purpose of such
studies is not to supply medical care but to acquire new
insight [6]. But the researchers knew about Riley’s plan,
and they realized their study revealed that she did not
have her family’s breast cancer gene, but instead found a
gene mutation that showed she had an increased risk for
Alzheimer’s disease which is untreatable and
unpreventable.
Consulting Sources on Ethics in Engineering
Dr. Shah did not know what to do. She had three
ethical dilemmas all surrounding this one woman and her
decisions would alter Riley Adams’s life forever. So she
decided to look to the Biomedical Engineering Society
Code of Ethics and the Engineering Code of Ethics as
guides to help her decision-making process. The quality
of life for all people is directly impacted by engineering;
“accordingly, the services provided by engineers require
honesty, impartiality, fairness, and equity, and must be
dedicated to the protection of the public health, safety,
and welfare” [7]. Engineers must always perform under
a standard of professional behavior that necessitates
adherence to the highest principles of ethical conduct [7].
The Biomedical Engineering Society Code of Ethics
has a canon which states that “biomedical engineers in
the fulfillment of their professional engineering duties
shall use their knowledge, skills, and abilities to enhance
the safety, health, and welfare of the public” [8]. The
Code of Ethics for Engineers has a code that says “if
engineers' judgment is overruled under circumstances
that endanger life or property, they shall notify their …
client … as may be appropriate” [7]. According to these
codes, Dr. Shah should inform Adams about the lack of
her family’s breast cancer gene because getting a
mastectomy for no reason could endanger her safety and
welfare if something were to go wrong with the surgery.
Based on these codes, she should also inform Riley about
the gene mutation she has that increases her risk of
Alzheimer’s disease because that may affect her health at
some point in her life.
Dr. Shah decided to do more research and found
other resources that conflicted with the two engineering
codes.
Inadequate information can make people
irrational—or broke—by chasing after threats that may
never become a reality [1]. Probabilities are not the same
Bribery
A few days later, as the researchers were debating
whether to breach Adams’s consent form, the headresearcher, Dr. Shah, was approached by editors of
Biotechnology and Bioengineering. They heard about
Riley’s study results and wanted to publish an article on
her story with real statistics from the study. Dr. Shah told
the representatives from the magazine that Adams
indicated on her consent form that she did not give
permission for her results to be published in any way.
The reps then said they would be willing to pay $500,000
to get their hands on the results that Dr. Shah and her
team had gathered. She knew accepting this bribe would
be ethically wrong, but half of a million dollars was a lot
to pass up, so she told the magazine she would think
about it and contact them later with her response.
ACMG Policy Statement and Recommendations
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Dipali Shah
CONCLUSION: DR. SHAH’S FINAL
DECISIONS
as certifications; all genetic mutations that researchers
may find in a participant will not guarantee that the
person will have genetic diseases corresponding to those
mutations in the future. If participants of WGS studies
become anxious and confused due to test results, or if
they are wrongly reassured by false-negative test results,
this may adversely impact their health [9]. Lack of
adequate information and informed consent could harm
consumers via the receipt of unsolicited and potentially
detrimental information like finding out that one is at
increased risk for an unpreventable or untreatable
disease.
Geneticists trip over incidental findings often, but
Dr. Shah started to wonder whether patients should be
told about the risk of diseases for which there are not yet
cures. A majority of bioethicists agree on the idea that
only results which can be immediately acted upon should
be shared with patients and study participants [1]. So
according to these sources, there would not really be a
point in telling Riley about her gene mutation that
increases her risk of getting Alzheimer’s disease since
there is no current treatment or cure for the disease.
After consulting all of these resourceful guides, Dr.
Shah had somewhat of an idea on how to deal with the
incidental findings from Riley’s study, but now she had
to think about whether she should give the results of the
study to the editors of Biotechnology and
Bioengineering. She decided to go back to the
Biomedical Engineering Society Code of Ethics and the
Engineering Code of Ethics to help her with making a
decision. The Biomedical Engineering Society Code of
Ethics has a canon which states that “Biomedical
engineers … shall regard responsibility toward and rights
of patients, including those of confidentiality and
privacy, as their primary concern” [8]. So this is saying
that Dr. Shah should not give the Riley’s data to the
magazine because that would breech her confidentiality
and privacy rights.
According to the Engineering Code of Ethics,
“engineers shall not reveal facts, data, or information
without the prior consent of the client” [7]. Another
canon says that “engineers shall be guided in all their
relations by the highest standards of honesty and
integrity” [7]. The last relevant canon from the Code
states that “engineers shall not be influenced in their
professional duties by conflicting interests” [7]. So
basically if Dr. Shah wants to follow the ethical code that
engineers need to follow, she cannot reveal the results of
Adams’s trial to anyone because that would be breeching
her privacy rights. On top of that Dr. Shah would not be
acting with honesty and integrity and her professional
duties would be influenced by conflicting interests if she
accepted the offer.
Dr. Shah and her research team ran a study, with
Riley Adams as the participant, to discover cancer genes
that, when mutated, significantly escalate the risk of
developing breast cancer. Riley’s family has a strong
history of breast cancer so she planned to get a
mastectomy on top of participating in the study. After
running the tests however the researchers found out that
Adams in fact did not have that gene, but instead had a
genetic mutation that is correlated with an increased risk
of Alzheimer’s disease. “Currently, there are no
evidence-based guidelines for return of incidental
findings from clinical sequencing” [11]. This means that
there is no clear-cut answer to Dr. Shah’s problem. So
she decided to do a little research. She found two
engineering codes of ethics which pointed her in the
direction of telling Riley about the lack of one gene and
the incidental finding of another one. However, after
consulting other resources, Dr. Shah has decided to tell
Adams about the absence of her family’s breast cancer
gene, but not about the presence of the Alzheimer’s gene
because there is no cure and it might just make her worry
for no reason. Finally, Dr. Shah has decided not to give
Riley’s private information to the magazine. Even though
the editors are offering a lot of money, she realized after
looking at the Engineering Code of Ethics that it would
be ethically wrong of her to gain a profit by breeching the
privacy rights of an innocent person.
REFERENCES
[1] B. Rochman. (2012). “The DNA Dilemma: A Test
That Could Change Your Life.” Time. (Online Article).
http://web.ebscohost.com/ehost/detail?sid=2ef9932ccd65-46bf-9fdae3e05ed3c24b%40sessionmgr111&vid=11&bk=1&hid
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[2] H. Howard. (2013). “Whole-genome sequencing in
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(Blog
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[3] M. Stremlau. (2010). “Message in a Genome.” Wilson
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[4] K. Smith. (2013). “Think You Know Human Genome
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[5] D. Miller. (2012). “Whole-Genome Sequencing:
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[6] G. Kolata. (2012). “Genes Now Tell Doctors Secrets
They Can’t Utter.” The New York Times. (Online
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http://www.nytimes.com/2012/08/26/health/research/wit
h-rise-of-gene-sequencing-ethical-puzzles.html?_r=2&
[7] (2007). “NSPE Code of Ethics for Engineers.” NSPE.
(Online
Article).
http://www.nspe.org/Ethics/CodeofEthics/index.html
[8] (2004). “Biomedical Engineering Society Code of
Ethics.”
BMES.
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http://bmes.org/files/2004%20Approved%20%20Code
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[9] E. Bunnik. (2013) “The New Genetics and Informed
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[10] M. Allyse. (2013). “Not-so-incidental findings: the
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[11] J. Wiley. (2012). “Perspectives of Clinical Genetics
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bject
I would like to thank my 0011 instructor, Dr. Rick Schaub,
for allowing me to research this topic in which I have so much
interest and to write a paper about it for his Introduction to
Engineering class. I also want to thank Mr. Jack Giles, from
the Writing Resource Center at the University of Pittsburgh,
for taking the time to help me edit my paper. This paper could
not have been written without the substantial inspiration and
support of my friends Mary Jess Heddinger and Nina Obwald.
ACKNOWLEDGEMENTS
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Dipali Shah
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