Budny, 4:00
L09
ETHICAL IMPLICATIONS OF USING NANOPARTICLES IN THE
TREATMENT OF ALZHEIMER’S DISEASE
Rahul Rege ([email protected])
INTRODUCTION: ANALYSIS OF
ETHICAL SCENARIO INVOLVING
NANOPARTICLE USE IN TREATMENT OF
ALZHEIMER’S DISEASE
As I work as a biomedical engineer developing
nanomedicine delivery systems for Nanotech Incorporated, it
has come to my attention that while the innovative systems
that I am helping design have many benefits, they also pose
some ethical issues. Currently, I am working on
nanotechnologies that will aid in the treatment of Alzheimer’s
disease. These innovative technologies, called nanoparticles,
are able to pass through the blood-brain barrier, enabling them
to carry drugs straight to the affected regions of the cerebral
cortex. They can also be used in detecting the pathological
effects of the disease so people are better prepared to deal with
the disease [1]. These technologies, if implemented in clinical
settings, can provide more aid than the pharmacological
approach currently used to only treat symptoms of
Alzheimer’s disease.
As an attentive and inquisitive engineer, I am beginning
to think about not only the positives of the application of the
nanoparticles I develop but also about their potential
negatives. The nanoparticles that I am developing will be
better able to treat Alzheimer’s disease than the current
pharmacological methods. They will also be more cost
effective to the overall economy. However, they may also
pose a safety issue in that the brain areas that are targeted may
not respond to the nanoparticles as desired. Also, since the
nanoparticles that I am working with (iron-oxide
nanoparticles) are non-degradable, there is a risk of
neurotoxicity after they deliver the particular drug to the
affected cortical region [2].
These potential “minuses” of my design have caused me
some stress. I brought this concern to my boss, but he just
laughed it off. He told me that I should not worry about the
ethical consequences of what I am designing, as long as it will
make money for the company. My boss insisted that I do not
at any point make note of this potential problem and that I
wholeheartedly endorse the system under development.
Since I have always been a proponent of adhering to rules and
regulations, my boss’s instructions did not fit well with me.
Now, I plan on better understanding the safety and cost
effectiveness of my nanoparticulate drug-delivery system, in
regards to ethics.
As I delve into the ethical issues that deal with the
nanoparticles that I am working with, I will consult the Code
of Ethics of both the National Society of Professional
Engineers (NSPE) and the Biomedical Engineering Society
University of Pittsburgh, Swanson School of Engineering 1
Submission Date 2013-10-29
(BMES). Using these resources and other sources on
engineering ethics, I will make an ethical decision about how
to proceed in my work.
SAFETY OF NANOPARTICLES IN
TREATMENT OF ALZHEIMER’S DISEASE
As I begin my “ethical inspection” of the nanoparticles I
am developing, one of the first features that I question is their
safety to patients. Both the NSPE and BMES Codes of Ethics
hold safety as an issue of principal importance. The NSPE
Code of Ethics states, “Engineers shall hold paramount the
safety, health, and welfare of the public” [3]. Similarly, the
BMES Code of Ethics includes the statement, “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” [4]. To
be able to discuss the safety of nanoparticles, one must first
understand how they function.
The safety issues concerned with nanoparticles depend on
how the nanoparticles function within the brain.
The intravenously injected Alzheimer’s disease nanoparticles
that I am dealing with are meant to go straight to the affected
cortical region. In order to do so, these nanoparticles must be
constructed out of material that can pass through the bloodbrain barrier (BBB). Nanoparticulate systems are used as
“Trojan systems” for transporting active molecules across the
BBB. This system improves therapeutic efficacy of the drugs
that treat the impacted neural regions [5].
One of the safety issues that I have noticed is that the
potential exists that the nanoparticles may not react as
expected once they have passed through the BBB. According
to an article from the Journal of Controlled Release, “A
successful passage of the drug loaded nanoparticles across the
BBB is not fully predictive of its therapeutic effect, because
after penetration of the drug across the BBB it is equally
important to evaluate whether its biological activity is
retained or not” [1]. Just because the nanoparticle containing
the therapeutic drugs passes through the BBB does not mean
it will release the drugs. Like current medications, there are
“side effects” to using nanoparticulate systems in treating
Alzheimer’s disease.
Another safety concern of nanoparticles in treating
Alzheimer’s, and in general neurological disorders, is the
cortical impact of the materials from which nanoparticles are
made. An article from Nanomedicine: Nanotechnology,
Biology and Medicine brings up the fact that “there are a
number of unanswered questions regarding their fate in the
living body, especially if they have a size less than < 50 nm.
Rahul Rege
Nanoparticles < 100 nm have a high likelihood of
aggregation, thus forming a cluster that can embolize and
occlude blood flow. Besides this, lodging of these aggregates
in various organs may also result, in undesirable
consequences like pulmonary embolism, strokes, myocardial
infarctions, and other microinfarctions at distant sites and
organs. Furthermore, due to their particular physicochemical
properties, such as large surface area, the nanoparticles may
cause neurotoxicity after reaching the brain thus arising a
need for further investigations regarding the toxic pathways
through which nanoparticles may exert their toxic effects for
their safe and effective use” [5]. The iron-oxide nanoparticles
that I am using do not degrade easily, so their toxicity is a
concern. Using nanoparticles in the treatment of Alzheimer’s
disease results in costs in terms of safety.
Although there are some safety concerns brought up
regarding the use of nanoparticles in treatment of Alzheimer’s
disease, measures have been taken to reduce the risks.
According to Nanoscale, a journal that expertizes in critiquing
new nanotechnologies, there is an approach to deliver the
neurotransmitter acetylcholine (ACh) to the brain to “remedy
the disrupted cholinergic neurotransmission in Alzheimer’s
disease based on the use of single-wall carbon nanotubes
(SWCNTs) as the carrier” [6]. This new method allows for
nanotechnologies to carry drugs directly to the cortical areas
affected by the pathology associated with Alzheimer’s
disease. The study demonstrates that by carefully controlling
the dosages, it is possible to safely deliver ACh preferentially
to the target organelle while at the same time avoiding its
mitochondrial toxicity [6]. This study provides hope that the
current nanoparticulate system I am designing can be
improved upon to reduce safety risks.
Having considered the safety concerns of the nanoparticle
technology with which I am working, I currently realize that
although methods need to be improved upon to increase
safety, the nanoparticles are in ethically good standing. I
know that the current pharmacological methods of treating
Alzheimer’s disease are not as effective as nanoparticulate
drug delivery systems have the potential to be. If we do not
further these systems the damaging ailment which currently
affects 24.3 million people worldwide will continue to
expand. An article from Nanomedicine: Nanotechnology,
Biology, and Medicine states that, “the prevalence of
Alzheimer’s disease is about 5–10% above the age of 60 years
but increases dramatically up to 40–50% above the age 85
years”[5]. When I consider the ethics involved in
nanotechnology, as mentioned in an article in the Journal of
Law, Medicine, and Ethics, I realize that if nanoparticles can
provide better treatment of Alzheimer’s disease then current
methods, then they must be further pursued and put on
market. The journal says, “The principle of Beneficence,
which involves the necessity of providing the greatest good to
society” must be taken into context in considering the ethics
of nanotechnology [7]. Although a slight risk is posed by
nanoparticles, the upside that they will provide (Nanowerk- a
website
discussing the
latest
advancements
in
nanotechnology- projected 90% increase in successful
treatment of Alzheimer’s disease [8]) illustrates the principal
of Beneficence; making their uses ethically sound. Also, by
furthering these technologies, I would be in compliance with
the BMES Code of Ethics which states that I must, “consider
the larger consequences of my work” [4]. The larger
consequences, in this case would be that I would be improving
a more effective method of Alzheimer’s disease treatment;
which would provide most benefit to society.
COST EFFECTIVENESS OF
NANOPARTICLES IN TREATMENT OF
ALZHEIMER’S DISEASE
As I study the ethical implications of the nanoparticulate
systems with which I am dealing, I realize that cost of
medicines and availability are of the utmost importance.
Although my boss told me to only consider the money the
nanoparticles would make for the company, I know I must
consider the patients who will use the drug-delivering
nanoparticles I develop. The BMES Code of Ethics states,
“Consider the larger consequences of their work in regard to
cost, availability, and delivery of health care” [4]. In addition,
“A Portrait of Nanomedicine and Its Bioethical Implications,”
an article in the Journal of Law, Medicine, and Ethics states a
key component of nanoparticle engineering is the principle of
“Justice, the notion that equitable access to health care should
be provided to all” [7]. In order to continue my determination
of the ethical implications of the nanoparticles that I am
developing for the treatment of Alzheimer’s disease, I must
determine whether they will improve the current economical
strains caused by Alzheimer’s disease.
Current pharmacotherapy which is currently being used as
the primary form of treatment for Alzheimer’s disease is
slightly improving; however, it poses extreme financial
burdens. According to an article from The Journal of
Controlled Release, “the estimated annual cost of healthcare
is over $100 billion and is expected to be about $500 billion
by the year 2020 in the United States alone” [1]. These
estimates exemplify the economic problems that illnesses
cause. Alzheimer’s disease is a key contributor to these
financial costs due to the fact that it impacts 24.3 million
people worldwide.
Knowing that the current pharmacological methods of
treating Alzheimer’s disease are placing a major burden on
the economy, especially in terms of cost of healthcare, I will
analyze the prospective costs of the nanoparticulate systems
on which I am working. According to “Beyond Human
Subjects: Risk, Ethics, and Clinical Development
of Nanomedicines,” an article from the Journal of Law,
Medicine, and Ethics, “The first-ever cost effectiveness
analysis, directly comparing conventional cancer drugs and
nanotherapies was recently presented. This analysis
concluded that while nanodrugs are more expensive per
treatment, the reduction of costs associated with the treatment
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Rahul Rege
of side effects and the additional health benefits induced by
the nanodrugs make them overall a less costly option than
conventional treatment on the basis of a Quality-of Life-Years
adjusted analysis” [9]. This cost analysis demonstrates
nanoparticulate systems have be shown to be more cost
effective in use of treating other diseases, such as cancer. The
analysis illustrates that the nanoparticulate drug delivery
system which I am developing has a very good likelihood of
reducing the economical strain caused by Alzheimer’s
disease.
the code of ethics that binds professional engineers” [11]. He
continued to engage in a lawsuit with the company and was
able to get the hundreds of respirators recalled.
By examining this case, I realize the responsibilities that I
have as a professional engineer. I have to address the safety
concerns involved with my nanoparticulate drug-delivery
system. I will proceed with caution in developing the
nanoparticles and try my best to reduce their risk.
CONCLUSION
ETHICS OF MANAGING RISK
From my ethical investigation into the Codes of Ethics of
both the NSPE and the BMES and other sources related to
engineering ethics, I have concluded that although the
nanoparticulate drug-delivery system which I am designing
may pose risks, it will have a positive impact on society. It
would be ethically right for me to pursue its development, as
long as I take into account possible safety risks. I will
minimize these risks and make the public aware of any
potential hazard of my product. I will disregard my boss’s
instructions of ignoring the negatives of my design since his
advice is against professional engineering Code of Ethics. I
plan on informing a higher authority about the orders my boss
gave me.
Having considered all ethical implications and taking risks
into account, I believe that the greatest risk at this time may
well be in not taking advantage of the full potential of the
nanoparticulate drug delivery system which I am designing to
treat Alzheimer’s disease for the benefit of society.
Dealing with risk is an extremely important component of
engineering ethics. Up to this point in my “ethical
investigation” of the nanoparticulate drug-delivery system I
am designing, I have documented both its safety concerns and
cost effectiveness. Now, I will refer to the NSPE Code of
Ethics to understand how to deal with risk.
The NSPE Code of Ethics states under the Professional
Obligations sections, “Engineers shall acknowledge their
errors and shall not distort or alter the facts. Engineers shall
advise their clients or employers when they believe a project
will not be successful” [3]. Since I know that the drugdelivery system that I am designing will be more cost
effective than current pharmacological treatments and,
according to Nanowerk, will provide 90% more effective
treatment of Alzheimer’s disease, I know that I must continue
developing it [8]. However, I know that there is the potential
of risk involved based on my acquired knowledge of its safety
concerns. Based on the NSPE Code of Ethics, I understand
that it would be wrongful of me to hide/ ignore this risk. To
act according to this Code of Ethics, I must make all of the
safety concerns known to the public. I must also report the
actions of my boss to a higher authority since what he was
expecting of me was directly against the NSPE’s Code of
Ethics.
REFERENCES
[1] J. Sahni, S. Doggui, J. Ali, et al. (2011). “Neurotherapeutic
applications of nanoparticles in Alzheimer's disease.” Journal
of
Controlled
Release.
(Online
Article).
DOI:
10.1016/j.jconrel.2010.11.033. pp. 208-231
[2] L. Jasmin. (2011). “Alzheimer’s disease.” PubMed
Health.
(Website).
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001767/
[3] (2007). “Code of Ethics for Engineers.” National Society
of
Professional
Engineers.
(Online
Article).
http://www.nspe.org/resources/pdfs/Ethics/CodeofEthics/Co
de-2007-July.pdf
[4] (2004). “Biomedical Engineering Society Code of Ethics.”
Biomedical Engineering Society. (Online Article).
http://bmes.org/files/2004%20Approved%20%20Code%20o
f%20Ethics(2).pdf
[5] D. Brambilla, B. Droumaguet, J. Nicolas, et al. (2011).
“Nanotechnologies for Alzheimer's disease: diagnosis,
therapy, and safety issues.” Nanomedicine: Nanotechnology,
Biology and Medicine. (Online
Article). DOI:
10.1016/j.nano.2011.03.008. pp. 521-540
REFERRING TO THE PAST IN ORDER
TO BETTER THE FUTURE
In order to further aid me in making my final decision on
how to proceed under my circumstances, I have turned to a
prior case that is similar to mine and its results. This case,
entitled “Infants Under Pressure” was considered of ethical
importance by the Institute of Electrical and Electronics
Engineers. The case is about Sam Wilson, an employee of
MedTech (a company that engineers medical technology).
Mr. Wilson realized that a respirator for infants that his
company was producing had a defect that caused it to provide
too much pressure. He knew the problem could be fixed, so
he reported this problem to his boss. His boss did not pay any
attention to him. Mr. Wilson was fired for threatening to
report the boss to a higher authority. Mr. Wilson claimed “his
actions in calling attention to the problem were mandated by
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Rahul Rege
[6] A. Pietroiusti. (2012). “Health implications of engineered
nanomaterials.” Nanoscale. (Online Article). DOI:
10.1039/C2NR11688J. pp. 1231-1247
[7] R. Hall, T. Sun, M. Ferrari. (2012). “A Portrait of
Nanomedicine and Its Bioethical Implications.” Journal of
Law, Medicine, and Ethics. (Online Article). DOI:
10.1111/j.1748-720X.2012.00705.x. pp. 763-779
[8] G. Mahajan. (2011). “Fighting Alzheimer's disease with
nanotechnology.”
Nanowerk.
(Website).
http://www.nanowerk.com/spotlight/spotid=23726.php
[9] J. Kimmelman. (2012). “Beyond Human Subjects:
Risk, Ethics, and Clinical Development of Nanomedicines.”
Journal of Law, Medicine, and Ethics. (Online Article). DOI:
10.1111/j.1748-720X.2012.00712.x.
[10] R. Burgess, M. Davis, M. Dyrud, et al. (2012).
“Engineering Ethics: Looking Back, Looking Forward.”
Springer Science. (Online Article). DOI: 10.1007/s11948012-9374-7. pp. 1395-1404
[11] S. Unger. (1999). “IEEE Cases 1999 - Infants Under
Pressure.” Online Ethics Center for Engineering and
Research.
(Online
Article).
http://www.onlineethics.org/cms/19482.aspx
ACKNOLEDGEMENTS
I would like to thank my roommate, Andrew Clark, for
allowing me to discuss my thoughts with him. He helped
expand my thought process and assisted me in making this
paper the best I could make it. I would also like to thank the
librarians of Hillman Library for showing me how to use
PittCAT and other library databases. These resource gave me
further references which enabled me to write this paper.
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Written Assignment 3 - University of Pittsburgh