Volume VII Issue ii

Volume VII Issue ii

NanomedicineConcerns and Potentials

Also inside:Personalized Health CareOrgan Donation Policies

Archived editions of the Journal and information about the submission process can be found on our website: http://bioethicsjournal.com

The editorial staff also focuses on expanding boundaries of Penn undergraduates by hosting campus-wide events through the Penn Bioethics Society. These include formal lectures, case study presentations, public debates, debriefing of current bioethical issues and student-led conversations.

To receive our weekly newsletter, apply to join our editorial staff, or make any inquiries, please email [email protected]

Penn Bioethics Journal and Society

Email [email protected] to get more information about bioethics at Penn.

The Penn Bioethics Journal (PBJ) is the nation’s premier peer-reviewed, undergraduate bioethics journal. Established in 2004, the Journal features and provides a venue for the contributions of undergraduates to bioethics. The PBJ, embracing the interdisciplinary focus of bioethics, reviews and publishes reports of empirical research and analysis of previous work -- addressing debates in medicine, technology, philosophy, public policy, law, theology and ethics among other disciplines. The biannual Journal also features news briefs and editorials reviewing current bioethical issues, as summarized by our undergraduate editorial staff. Undergraduate editors and authors have a unique opportunity to get involved with the peer-review process through the collaborative and rigorous review and preparation of the PBJ. With an audience ranging from scholars in the field to a broader public seeking unbiased information, the Penn Bioethics Journal scholastically involves all undergraduates interested in the extensive field of bioethics.

The Penn Bioethics Journal is published twice a year by the University of Pennsylvania, Philadelphia, PA.

All business correspondence, including subscriptions, renewals, and address changes, should be addressed to the Penn Bioethics Journal, 3401 Market Street, Suite 320, Philadelphia, PA 19104. www.bioethicsjournal.com

Manuscripts for publication should be submitted according to the submission rules on the website: www.bioethicsjournal.com/submit.html

Subscription rates are by request. Permission must be requested for any kind of copying, such as copying for general distribution, advertising or promotional purposes, creating new collective works, or for resale. Requests for these permissions or further information should be addressed to [email protected]

Copyright © 2012 Penn Bioethics Journal, Philadelphia, PA.

ISSN: 2150-5462

www.bioethicsjournal.comwww.dolphin.upenn.edu/bioethics

EDITOR IN CHIEFAndrew Jakubowski

PUBLISHERYunica Jiang

MANAGING EDITORSMegan DwyerVinayak Kumar

Sofia LiouAnand Muthusamy

Aditi VermaAbby Worthen

ASSOCIATE EDITORSSinead Benyaminov

Cammy Brandfield-HarveyKlyde BreittonIlana Dreyfuss

Jiayi FanJames Feuereisen

Elana FurmanJacqui Kemmer

Alia LahrAmy Li

Robin LoTiffany Lu

Raquel MacgregorMeghna Mann

Brittany MayweatherSarah McKennaLilian McKinley

Loren MillerRina MossVitcoria Ng

Shelby RosarioMarc-Anthony Serrano

Chintav ShahRupali Singhai

Andrew WadleyTali Warburg

Nikolai Zapertov

ASSOCIATE PUBLISHERSSiyuan CaoZach Costa

Eileen MayroRina Moss

Zaina Naeem

BUSINESS MANAGERDara Bakar

FACULTY ADVISORJonathan Moreno, Ph.D.

Questions or Comments?Please direct all inquiries to the

Editor in Chief [email protected]

Contents

Articles

Letter from the Editor Andrew Jakubowski

PBJPe n n B i o e t h i c s J o u r n a l

Nanomedicine: Small Particles, Big Concerns Jonpaul Wright, University of Colorado

Discussing the Issue of Informed Consent in Relation to Surrogacy ContractsAndrew Molas, University of Toronto

4

6

7

8

9

10

12

16

22

Public Consultation on Brain Technologies

Vaccine Against Heroin Addiction

Growing Taller Through Surgery

Personalized Health Care: The Future of Health Care?

Israel Implements New Policy on Organ Donation

New Mutant H5N1 Avian Flu Strain Sparks Debate about Bioterrorism Risk

Bioethics in Brief

The Future of Nanomedicine: Potential Technologies, Current Research and Necessary RegulationsAnand Muthusamy and Aditi Verma, University of Pennsylvania

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

4

Thank you for picking up the thirteenth issue of the Penn Bioethics Journal: Volume

VII, Issue ii. Our Journal features scholarly articles addressing ethical debates in medi-cine, technology, genetics, philosophy, public policy, law, and theology. This particular issue features pieces on a diverse range of topics, including nanomedicine, organ dona-tion, surrogacy contracts, and heroin addiction. Its diversity of topics is what makes the field of bioethics so dynamic and intricate

As a staff, we aim to develop a publication in which students can showcase thought-

provoking papers and subsequently formulate their opinions on relevant bioethical is-sues. We also hope to create a publication that engages readers and encourages new persons to explore the field of bioethics.

We invite you to become an active participant in the rapidly growing field of bioeth-ics. Submit an article, an editorial, or a news brief.

Until then, enjoy your next bite of PBJ.

Letter from the Editor Andrew Jakubowski

Editor in Chief

Andrew JakubowskiEditor in Chief

University of Pennsylvania C’13

Dear Readers,

Master’s Track in MEDICAL HUMANITIES, COMPASSIONATE CARE

AND BIOETHICS

Stony Brook University/SUNY is an affirmative action, equal opportunity educator and employer. 12031335

Not just for health care professionals, this innovative, interdisciplinary program willserve students from a wide range of disciplines and professional backgrounds seekingfurther expertise and career development. Our world-class clinical faculty integrate perspectives from the humanities with their experience as health care providers.Upon completion, students will be awarded a Master of Arts in the Biological Sciences.

APPLICATION DEADLINES FOR FALL 2012:International Students — May 15

All Other Students — July 1

For more information or to apply to the program, visitstonybrook.edu/bioethics/masters

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

6

Public Consultation on Brain TechnologiesIn the international field of bioethics, the Nuffield CRe-

cently, the Nuffield Council on Bioethics has begun consult-ing with the public on technologies that interact directly with the brain (Gallagher, 2012). This UK-based, independent body examines various bioethical issues and advises policy makers on how to react to such dilemmas (Nuffield 2012).

This emerging field of technology currently being re-viewed has applications in both medicine and warfare be-cause the brain-computer interface may allow humans to command machines directly through thoughts. For exam-ple, a research group in Switzerland has already developed a wheelchair that is controlled entirely through brainwave readings (Gallagher, 2012). The user can control the direc-tion of the wheelchair’s motion by thinking about moving the right hand or the left hand. The chair turns based on the hand movements. The mind-controlled wheelchair clearly holds great promise for the disabled.

However, as one may imagine, the ability to control ma-chines with the mind has tremendous applications in war. This is particularly true in the growing field of robot drone technology. Eventually, a solider may be able to control mul-tiple war machines at a distance. Such technology would give more power to the developed countries that can afford it. Also, it would further dehumanize warfare.

Interestingly, besides reading brainwaves, the emerging technology has also been used to “write” brainwaves. This raises questions about altering one’s personality and thoughts, whether deliberately or as an unintended side effect. Further-more, Oxford University scientists have claimed that apply-ing a small current to the brain improves arithmetic abilities in subjects by stimulating the parietal lobe (Walsh, 2010). This holds promise in helping struggling students overcome their mathematical limitations, but it has also “triggered de-bates about human enhancement and whether the technol-ogy should be used in schools” (Gallagher, 2012).

Before the described forms of technology advance any further, the Nuffield Council on Bioethics has decided to work with the public in order to provide recommendations on policy and research within the next year.

-Vinayak Kumar, University of Pennsylvania

Gallagher, J. (2012, Feb 29). Consultation on brain technologies from medicine to warfare. British Broadcasting Corporation. Retrieved from http://www.bbc.co.uk/news/health-17208667

Nuffield Council on Bioethics. (2012). Retrieved from http://www.nuff-ieldbioethics.org/about

Walsh, F. (2010, Nov 4). Electric current to the brain . British Broad-casting Corporation. Retrieved from http://www.bbc.co.uk/news/health-11692799

Bioethics in BriefBioethics in Brief

Vaccine Against Heroin AddictionMexican scientists have patented a treatment heralded

as a “vaccine” against heroin addiction. Heroin, a highly ad-dictive opiate that induces euphoria in users, is a highly-regulated narcotic whose related medicinal forms are used as powerful pain treatment. Heroin dependency, however, is a debilitating and devastating disorder. The vaccine func-tions to reduce the pleasure derived from heroin use and, therefore, reduce cravings.

The vaccine reduces the euphoria experienced by users by preventing the drug from breaching the blood-brain barrier. The molecules that cause euphoria are prevented from ac-cessing opioid receptors in the central nervous system, and the user therefore feels none of the effects of use when they smoke or inject it. In clinical trials, mice addicted to heroin showed a significant decrease in dependency after adminis-tered the vaccine. Human trials will begin soon, and scien-tists hope that the vaccine will have equivalently significant influence on humans.

Currently, the primary methods for treating heroin ad-

diction are gradual replacement of heroin with other opiates like methadone. This substitution, though, is not without its problems, and users still suffer from the side effects typical of opiate usage. Should the vaccine prove to be effective in humans, it may be in use within five years and may reduce the potential long-term consequences of opiate addiction.

-Abby Worthen, University of Pennsylvania

Mexican scientists successfully test vaccine that could cut heroin addic-tion. (2012). Retrieved March 17, 2012 from http://www.guardian.co.uk/world/2012/feb/24/mexican-scientists-test-heroin-vaccine

Mexico Patents “Vaccine” Against Heroin Addiction. (2012). Retrieved March 17, 2012 from http://www.laht.com/article.asp?ArticleId=468167&CategoryId=14091

Heroin addiction vaccine ready for human trial. (2012). Retrieved March 16, 2012 from http://health.india.com/news/heroin-addiction-vac-cine-ready-for-human-trial/

Sandle, Tim. (2012). Potential heroin vaccine close to development. Re-trieved March 17, 2012 from http://digitaljournal.com/article/321240

flickr.com/digitalbob8

Penn Bioethics Journal Volume VII Issue ii

7

Growing Taller Through SurgeryAlthough limb-lengthening procedures were once exclu-

sively used to correct developmental deformities and injuries, doctors are beginning to use them more often for cosmetic reasons. Limb-lengthening patients – mostly individuals who wish to grow taller – can “grow” up to six inches over a period of a few months. Orthopedic surgeons carry out this procedure, which commonly involves breaking the leg bones and attaching a steel frame to the outside of the limbs. Patients are responsible for turning the screws on the frame, which pulls apart their leg bones a few millimeters at a time. Bone constantly regenerates to fill in the gap created by the surgery, meaning there is new bone formation, or osteogene-sis, at the site of the lengthening. In an alternative procedure, surgeons can implant a state-of-the-art telescopic rod into the broken bones, which slowly pulls apart the bones on its own. This procedure, while still painful and lengthy, does not require as much discipline from the patient. In both cases, the regenerated bone is normal, permanent, and does not wear out, and the surrounding muscles, nerves, and blood vessels also grow in response to the gradual stretch.

Because the procedure is described as excruciating and extensive, patients must often undergo psychological test-ing to ensure that they are appropriate candidates for the procedure. People who seek limb-lengthening treatments may suffer from a condition called short stature dysphoria or deep dissatisfaction with their heights. Aside from evaluat-ing the patient’s reasons for undergoing this procedure, psy-chological testing also ensures that the patient is mentally

prepared and positively spirited for a successful recovery. Recovery from the procedure can last anywhere from half a year to a full year, and the lengthening process is followed by intensive physical therapy.

In the United States, limb lengthening can cost anywhere from $85,000 to $120,000 and is not covered by insurance. Because of the financial burden and the limited number of

doctors who perform this procedure, an increasing number of people have opted to undergo the procedure overseas. In China, Germany, Egypt, Greece, Russia, and Iran, for ex-ample, the surgery can cost as little as $20,000 – granted that clinical standards are sometimes lower abroad relative to those in the United States.

Although limb lengthening is still met with skepticism, there is evidence that it is becoming more acceptable and routine. In 2011, Dr. Dror Paley, a renowned osteopathic surgeon at St. Mary’s Medical Center in Florida, performed 650 leg-lengthening surgeries. The procedure itself “is safe and effective and it can make a big difference in someone’s life,” said Dr. Robert Rozbruch, director of the Institute for Limb Lengthening and Reconstruction in New York. Dr. Rozbruch says he agrees to do the procedure because he can see how unhappy his patients are when they first come to him for a consultation. The intention of the procedure is then to alter one’s life – not just to improve one’s appearance.

-Sofia Liou, University of Pennsylvania

Dorning, Anne Marie. “Controversial and Grueling Procedure Lengthens Limbs, Risks Lives.” ABC News.<http://abcnews.go.com/Health/BeautySecrets/story?id=3948348&page=1>.

Martinez-Ramundo, Denise and B. Ritter. “New York Man “Grows” Six Inches Through Surgery.” ABC News.<http://abcnews.go.com/Health/york-man-grows-inches-surgery/story?id=15776730#.T1o-6TEgeSo>.

United States. National Institutes of Health.Leg lengthening and shortening.<http://www.nlm.nih.gov/medlineplus/ency/arti-cle/002965.

Bioethics in Brief

flickr.com/ Hamface

“The regenerated bone is normal, perma-nent, and does not wear out, and the sur-rounding muscles, nerves, and blood vessels also grow in response to the gradual stretch.”

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

8

Personalized Health Care: The Future of Health Care?Current trends indicate that online personal health re-

cords have grown in popularity. Several commercial compa-nies have created online health records that allow for more patient control. These companies have also allowed patients to share their information with other medical experts and individuals through online databases.

While this may lead to improved medical feedback, there are several ethical concerns for personalized medi-cine and these online medical databases. Primarily, these forms may infringe upon the privacy of personal informa-tion. Currently, doctor-patient confidentiality is held with extremely high regard; however, uploading personal health information online compromises such privacy. Furthermore, implementing personalized healthcare could increase the tendency to profile people from a specific group. The secu-rity of online information has minimal support.

In addition, it may be risk for people to trust an online source of medical advice . Dr. Kaikerwal says that online records could be “dangerous if patients ha[ve] drug allergies or were given incorrect medication dosages.” Once there is

online interaction, the face has disappeared and the reli-ability is questionable. The potential misuse of this stored

information could prove disastrous to hundreds of people whose private information is potentially compromised. The danger associated with storage of online personal informa-tion is of extreme ethical concern.

However, despite these caveats, one cannot ignore the growth of the Internet and its impact on society, especially in terms of health care. Online health records allow patients with unknown diseases to reach out to an international community to promote better treatment. This not only in-creases the odds of helping a person become healthier but it also encourages international collaboration efforts. There-fore, while society still perceives the Internet as a possibly dangerous unknown, society should also acknowledge the internet’s incredible untapped potential.

-Aditi Verma, University of Pennsylvania

Nuffield Council on Bioethics. (2010). Retrieved from http://www.nuff-ieldbioethics.org/personalised-healthcare-0

(2012, April 18).Doctors Warn on Electronic Health Records Security. ABC News. Retrieved from http://www.abc.net.au/news/2012 04-18/electronic-health-recordsmedical-journal/3957596

Bioethics in Brief

The University of Pennsylvania MBE is a world renowned degree highlighting clinical, reproductive, neuro, and research ethics, and the ethical implications of rationing and allocation, genetics research, vaccines and public health, and end-of-life care.

MasterofBioethics UNIVERSITY OF PENNSYLVANIA

DEPARTMENT OF MEDICAL ETHICS & HEALTH POLICY

Have you considered the Penn MBE degree?

FOR MORE INFORMATION:Web: www.med.upenn.edu/mbe

Email: [email protected]: 215.898.7136

Diverse graduate student communityBe a peer in the classroom with current and future doctors, surgeons, researchers, lawyers, dentists, and veterinarians

Dual degree opportunitiesPenn is the only Master of Bioethics program that offers dual degrees with prestigious medical, dental, and law schools

Interdisciplinary programOur faculty come from philosophy, sociology, anthropology, the medical and legal professions, and the pharmaceutical industry

Active alumni organizationJoin an expansive and powerful alumni network


9

Israel Implements New Policy for Organ Donation Living with a failing organ is perhaps one of the most

frightening health conditions a person can face. Organ transplantation is never predictable, routine, or assured and many transplant candidates wait years for an organ. The dis-parity between organ availability and patients needing or-gans causes over 4,000 deaths annually in the United States (Caplan, 2008). Many solutions, including monetary in-centives, paired organ exchanges, tax breaks, and presumed consent have been widely discussed to alleviate the problem (Statz, 2006). However, an alternate solution often disre-garded in the United States has been implemented recently in Israel: a new law specifying transplant priority for pa-tients that are listed as organ donors is due to take effect this year.

The Israeli law was introduced by Dr. Jacob Lavee, head of the heart transplant program in the Sheba Medi-cal Center in Israel. It has been implemented in response to the significant population of ultra-orthodox Jews in Is-rael that refuse to donate organs on religious grounds but still receive organs (Ofri, 2012). Judaism, although on the whole supportive of organ donation, has contradictory stat-utes that can be interpreted to forbid organ donation. Dr. Lavee points to this unfairness of the current system. The law is lauded by most as reasonable, but critics point to the discriminatory aspect of unequal access based on religious grounds.

Operating under a system of presumed consent in which patients are assumed donors unless they choose to opt-out,

Singapore also employs organ priority for donors in an ef-fort to encourage people not to opt-out of the system (Teo, 1991). However, such a two-fold system raises questions of coercion.

Coercive or not, the change in policy in Israel seems to be demonstrating fruitful results. The average number of processed donation cards per month has gone from to an average of 3,000 cards to 70,000 cards. Furthermore, trans-plants have increased by more than 60 percent this year (Ofri, 2012). Such success prompts discussion on perhaps whether this law should be implemented in other countries such as the United States.

-Raquel Macgregor, University of Pennsylvania

Caplan, A. (2008). Organ Transplantation. From Birth to Death and Bench to Clinic: The Hastings Center Bioethics Briefing Book for Journalists, Policymakers, and Campaigns. M. Crowley, (Ed.). (pp. 129-132). Garrison, NY: Hastings Center. 129-132.

Ofri, D. (2012, February 16). In Israel, a New Approach to Organ Dona-tion.The New York Times. Retrieved from http://well.blogs.nytimes.com/2012/02/16/in-israel-a-new-approach-to-organ-donation/

Stratz, S.A. (2006). Finding the Winning Combination: How Blending Organ Procurement Systems Used Internationally Can Reduce the Organ Shortage. Vanderbilt Journal of Transnational Law.

Teo, B. (1991). Organs for Transplantation The Singapore Experience. The Hastings Center Report, 21(6), 10-13. Retrieved from http://www.jstor.org/stable/3562357

Bioethics in Brief

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

10

New Mutant H5N1 Avian Flu Strain Sparks Debate about Bioterrorism RiskResearchers studying the H5N1 avian flu virus have

identified exact mutations that allow this deadly virus to be transmitted between mammals through the air. Previ-ously, this virus could only spread among people in close contact with infected bird populations. When studying the virus, Ron Fouchier of Erasmus Medical Center and Yoshi-hiro Kawaoka of the University of Wisconsin engineered a pathogen that is both lethal and highly contagious. Their research was to be published in the prominent journals Sci-ence and Nature, but the National Science Advisory Board for Biosecurity asked the journals to withhold publishing the information (Specter). The Advisory Board cited fears that others could reproduce these mutations for militarized use of the H5N1 virus. Interestingly, the National Institutes of Health recommended that the findings be published but without the methodology of how the strain was created (NIH).

The controversy over the publication of these findings and over the continuation of the research itself has brought the concept of “dual use research” into the spotlight. Dual use research is concerning because it can be exploited for the purpose of causing harm to the public in addition to potential benefits (Ram). Responding to institutional pres-sure, Kawaoka and Fouchier pledged to halt their research on the virulent strain for 60 days. During that time period, policy makers debated how the research and findings should be handled in the future (Specter).

Many individuals in the scientific community contend that enough information about the mutant strains has al-ready been released to the public for scientists to recreate the mutations. Fouchier and Kawaoka presented

preliminary findings at various research conferences. Still, others scientists note that creating mutant viruses is diffi-cult even with all the pertinent information. Similarly, they argue that there are easier methods of bioterrorism than creating viruses and thus the research findings should be published (Specter).

Other groups worry that the main threat lies in the strain accidentally being released from the laboratory into the public. The question policy makers face now is whether the knowledge to be gained from studying what Fouchier calls, “probably one of the most dangerous viruses you can make,” is worth the risk to public health (Enserink).

-Megan Dwyer, University of Pennsylvania

Carvajal, D. (2011, Dec 21). Security in Flu Study Was Paramount, Scientist Says. New York Times. Retrieved from http://www.nytimes.com/2011/12/22/health/security-in-h5n1-bird-flu-study-was-para-mount-scientist-says.html?_r=1&scp=2&sq=avian%20flu&st=cse

Enserink, M. (2011, Dec 2). Controversial Studies Give a Deadly Flu Virus Wings. Science, 334.

NIH (Ed.). (2011, December 20). Press Statement on the NSABB Review of H5N1 Research. Retrieved from http://www.nih.gov/news/health/dec2011/od-20.htm

Ram, R. (2012, March 26). Research, the Avian Flue, and Bioterrorism.Health Reform Watch. Retrieved from http://www.healthreform-watch.com/2012/01/26/research-the-avian-flu-and-bioterrorism/

Specter, M. (2012, March 12). The Deadliest Virus.The New Yorker. Retrieved from http://www.newyorker.com/reporting/2012/03/12/120312fa_fact_specter

Specter, M. (2011, Dec 22). The Trouble with Scientific Secrets.The New Yorker. Retrieved from http://www.newyorker.com/online/blogs/newsdesk/2011/12/the-trouble-with-scientific-secrets.html

Bioethics in Brief

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

12

Discussing the Issue of Informed Con-sent in Relation to Surrogacy Contracts Andrew Molas‡

In “Surrogate Motherhood: The Challenge for Femi-nists,” Lori B. Andrews (1988) defends the legitimacy of surrogacy contracts. She argues that the New Jersey Su-preme Court ruled incorrectly In re Baby M case by ac-cepting the view that Mary Beth Whitehead did not give her full and informed consent when she agreed to become a surrogate mother. The purpose of this paper is to exam-ine Andrews’ claim that an agreement to a surrogacy con-tract is sufficiently similar to consent required for other medical procedures. First, I will describe the argument that Andrews refutes and show how her objection attempts to overcome it. I will then argue that the most serious dissimi-larity between consent in surrogacy contracts and any other medical procedures is that, in cases other than surrogacy, one does not have an obligation to provide a service for someone else because the procedure is being done solely for the person’s benefit. But despite this dissimilarity, I will conclude by arguing that Andrews is justified in claiming that surrogacy contracts should be legally upheld because the kinds of concerns that are raised by informed consent, such as the potentiality for regret, are not sufficient for disallowing surrogacy. Because surrogacy is a choice that a woman must make for herself, she is fully aware of what she is doing and has thus given her consent.

In February 1985, Mary Beth Whitehead and Bill Stern entered into a surrogacy contract brokered by the Infertil-ity Clinic of New York. A surrogacy contract refers to an arrangement made between a couple (often infertile) and a surrogate mother (a fertile woman), “who agrees to un-dergo pregnancy for the couple and undertakes in advance that at birth she will surrender the child and relinquish all parental rights to the commissioning couple” (Erin & Har-ris, 1991, p. 611). The contract in the Baby M case outlined that Whitehead would receive financial compensation in the sum of $10,000, plus coverage for all medical expenses. In exchange, she would be artificially inseminated with Bill’s sperm, carrying any resulting pregnancy to term and

relinquishing all of her parental rights to the Sterns (Bill, and his wife, Elizabeth) once the baby is born (Scott, 2009, p. 113). But after giving birth to a baby girl named Me-lissa in March 1986, Whitehead refused to give her up and fled to Florida for several months with the baby until she was eventually apprehended by the police, and Melissa was returned to the Sterns (Scott, 2009, p. 113). In response, Whitehead sought legal action against the Sterns, but Judge Harold Sorkow of the New Jersey Superior Court ruled against her, claiming that the surrogacy contract held that she agreed to relinquish her parental rights upon entering the contract, and that full custody was to be granted to Bill Stern, which allowed the Sterns to legally adopt Melissa. However, upon appeal, the New Jersey Supreme Court re-versed the lower court’s initial ruling, claiming that “the pre-birth agreement by the mother to relinquish parental rights was explicitly prohibited under the adoption statute” and that surrogacy contracts could never be voluntary or properly informed because “a woman could not know what it would mean to give up her baby” (Scott, 2009, p. 114).

According to Andrews, the New Jersey Supreme Court picks up the strong element of the argument against sur-rogacy, namely that women “cannot give informed consent until they have had the experience of giving birth” (An-drews, 1988, p. 210). The argument that was put forth against the legal enforceability of the surrogacy contract in the Baby M case is that, because the agreement to en-ter in a surrogacy contract happens long before the fetus is even conceived, “any decision prior to the baby’s birth is, in the most important sense, uninformed” (Andrews, 1988, p. 210). The reason for this is since the agreement is made so far in advance, the surrogate mother’s actual desires regarding how she will feel about the child cannot reasonably be thought to be her ideal desires. If they were, she would know how she would feel after giving birth and would never have consented to surrogacy in the first place. And because contracts based on the non-ideal desires of

This paper explores the nature of the legal doctrine of informed consent, particularly, in relation to the legitimacy of surrogacy contracts. By focusing on the Baby M case, it examines Lori B. Andrews’ argument that the doctrine of informed consent should apply to surrogacy contracts since, like other medical procedures, a woman’s consent to becoming a surrogate mother ecessitates her awareness of the potential risks so that she can make an informed, con-scientious decision. Andrews feels that surrogacy contracts should be upheld legally—contrary to the New Jersey Su-preme Court’s ruling in February 1988—since the kind of consent involved is sufficiently similar to the consent involved in other medical procedures.

Article

‡ University of Toronto, [email protected]


13

the individual are unfair to her (as she is not fully aware of what she is actually agreeing to), it would be morally unacceptable to try and uphold the terms of the agreement. Therefore, the contract cannot be legally upheld.

Andrews argues that the Supreme Court’s decision, based on the premise that Whitehead did not give her full consent to the terms of the surrogacy contract, is at odds with the legal doctrine of informed consent. She believes that the decision to ban surrogacy conflicts with the general legal policy “of allowing competent individuals to engage in potentially risky behavior so long as they have given their voluntary, informed consent” (Andrews, 1988, p. 209). She argues that the court erred in the Baby M case because under the legal doctrine of informed consent, nowhere is it expected that “one have the experience first before one can make an informed judgment about whether to agree to the experience.” If such a requirement were necessary, it would “preclude people from ever giving informed consent to sterilizations, abortions, sex change operations, heart surgery, and so forth” (Andrews, 1988, p. 210). She feels that the court’s decision is wrong because the legal doctrine of informed consent “presupposes that people will predict in advance whether a particular course will be beneficial to them” (Andrews, 1988, p. 210).

But is Andrews correct in saying that an agreement to enter a surrogacy contract is sufficiently similar to these other kinds of medical procedures that require our full un-derstanding of the consequences? Or does the nature of surrogacy itself differ so greatly from other procedures that the same concept does not apply?

One of the most serious dissimilarities between an agreement to a surrogacy contract and consenting to an-other medical procedure is that, by the nature of surrogacy itself, you are performing a task that is intended to ben-efit and secure the interests of someone else, not simply of yourself. To understand this distinction more clearly, take heart surgery as an example. Suppose that you have been scheduled to undergo routine heart surgery in order to maintain your health by removing excess plaque from your arteries. At the last moment, you change your mind and decide not to go through with the operation. In this situation, although you had previously consented to the procedure and were fully informed of all the potential risks and benefits involved, your decision to opt out does not significantly affect anyone else except yourself. You have no one else to answer to because your decision only affects your livelihood.

But contrast this with a surrogacy contract: in a tradi-tional surrogacy contract, you are consenting to allow an in-fertile couple the opportunity to use your body in order for them to produce a genetically-related child. By agreeing to become a surrogate, your decisions invariably do affect oth-ers—namely, the couple—because they are relying on you to uphold your end of an agreement. Surrogacy “is designed and intended to do what is almost universally considered to be not only a good in itself but part of the very meaning and purpose of life” which is “to bring into existence chil-

dren who are wanted, who will be loved, and who have every prospect of being cared for, protected and successfully reared to adulthood” (Erin & Harris, 1991, p. 629).

Now, suppose that you initially agree to carry the child to term, but, after three months of pregnancy, you do not wish to continue and you decide to abort the fetus. Setting finan-cial compensation aside for a moment (since most surrogacy arrangements provide the surrogate mother with compensa-tion for her time, effort and medical expenses), if you decide to abort the fetus and terminate the surrogacy contract, you are negatively impacting the livelihoods of the infertile cou-ple. You are depriving them of the opportunity to have the genetically-related child that you initially promised them. Even if someone wishes to forego any financial compensa-tion for their time and effort and decides to become a sur-rogate purely due to altruism, there still remains a degree of obligation that she has towards others in the surrogacy contract—not only toward the couple, but also to their child as it is growing inside of her—that is absent in the other kinds of medical procedures mentioned that are consistent with informed consent. These additional responsibilities are quite significant because we may feel compelled, perhaps out of obligation to the promise made to the infertile couple, to remain in these contracts. Although there may be an obliga-tion to remain in the contract, the obligation does not affect the informed nature of consent. This is because the nature of consent, in general, is a completely voluntary and willful decision made by an individual, without coercion or external influence (Fiore, 2007). As I will argue, this is precisely what we agree to in the first place. The consent given when we decide to enter a surrogacy contract is as sufficient as the consent given in other procedures.

While there are important differences between entering a surrogacy contract and consenting to other kinds of medical procedures, Andrews is justified in thinking that surrogacy contracts should be legally upheld. When one agrees to enter into this kind of contract, one is having the child with the in-tention of giving it up as soon as it is born. It is not as if one is asked to give up one’s own baby to a childless couple, nor is one’s baby taken away against one’s will while recuperating in the recovery room. There are no surprises when it comes to surrogacy. One of the reasons why critics of surrogacy would wish to ban it all together is because the potential for regret is thought to be enormously high since it is unnatural for a mother to give up her child (Andrews, 1988). Andrews notes that because some birth mothers who give up their child for adoption later regret that decision, it is assumed that sur-rogates will feel that same feeling of regret (Andrews, 1988). As she explains, reproductive choices are difficult choices to make, and any decision made in regards to procedures re-lated to sexual reproductive health—such as sterilization, abortion, sex-change operations, hysterectomies, vasecto-mies, and surrogacy—might later be regretted. However, she is correct in saying that that just because these procedures have the potential for regrets, this potential is “usually not thought to be a valid reason to ban the right to choose the procedure in the first place” (Andrews, 1988, p. 209).

Discussing the Issue of Informed Consent

13

13

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

14

She asks us to consider the circumstances under which a mother puts up her child for adoption and a surrogate mother relinquishes the child to the infertile couple. In tra-ditional adoption cases, Andrews argues that the biological mother “is already pregnant as part of a personal relation-ship of her own” (Andrews, 1988, p. 209). For the most part, the biological mother has a strong desire to keep her child but simply cannot “because the relationship [she is in] is not supportive or she cannot afford to raise the child.” Because of this, “[s]he generally feels that the relinquish-ment was forced upon her” either by her parents or her lover or a counselor (Andrews, 1988, p. 209). In a surrogacy ar-rangement, however, the biological mother, or the surrogate, “seeks out the opportunity to carry a child that would not exist were it not for the couple’s desire to create a child as a part of their relationship. She makes her decision in ad-vance of pregnancy for internal, not externally enforced rea-sons” (Andrews, 1988, p. 209). There is no external pressure forcing her into entering this agreement with an infertile couple. If anything, the potential surrogate wants to do this as a gesture for the infertile couple because she knows that she can have a positive influence on their lives. Even if she regrets her decision later on, she did what she thought was best at that time given the information that was available to her, and in that sense, her decision was informed. Andrews is justified in arguing that part of being individual, respon-sible agents is the freedom to make our own choices and ac-cept the consequences. If the potential surrogate made the decision to help this couple, it should be allowed and the contract should therefore be enforced.

While roughly 75 percent of biological mothers who give a child up for adoption later change their minds, Andrews maintains that “only around 1 percent of the surrogates have similar changes of heart” (Andrews, 1988, p. 209). Perhaps the reason why adoption rates are much higher is because the mother feels she really has no choice except to give up her baby for adoption after it is born. But with all cases of surrogacy, the woman does have choice in the mat-ter because she knows that the reason why she is pregnant is so she can provide a baby to an infertile couple. It is very unlikely that a woman would intentionally get pregnant just so she can place her baby up for adoption. This difference between adoption and surrogacy is extremely important, yet we would not ban adoption or find it legally unenforceable. For the most part, however, the women who agree to be-come surrogates know what they are getting into. Unlike women who feel forced to put up their babies for adoption, surrogates have more time to think about whether the sur-rogacy route is optimal.

The issue of time is relevant because it deals with the process of reaching an informed decision. In essence, An-drews and the lower court’s initial decision on the Baby M case is correct because a woman who has that much time prior to her insemination to reflect on the options available to her and their consequences should be considered properly informed. As Andrews mentions in her article, women who consent to putting their children up for adoption may feel

that they are being rushed or pressured into that decision by external factors (perhaps we can imagine a pregnant woman who is pressured into giving her child up for adoption at a late stage in her pregnancy, after she has grown attached to it with the supposition that she is keeping it). But when it comes to surrogacy, there is no hurried-decision making or unexpectedness because she is consenting precisely to the fact that she will be relinquishing the infant after it is born.

In her article, Andrews also discusses the experiences of other surrogate mothers, including Donna Regan, who testi-fied in court that her will was not overborne when she made her decision to become a surrogate mother, nor was she over-whelmed by external pressure to enter into a surrogacy con-tract to begin with. Regan explains that “[n]o one came to ask [her] to be a surrogate mother. [She] went to them and asked them to allow [her] to be a surrogate mother” (An-drews, 1988, p. 213, emphasis added). Similar to other medi-cal procedures that are consistent with the legal doctrine of informed consent, surrogacy is a completely voluntary act. As Andrews explains, part of the feminist movement was to ensure that all women have a right to reproductive choice, which includes the choice of getting pregnant, having an abortion, or becoming a surrogate mother (Andrews, 1988). No one forced Mary Beth Whitehead to become a surrogate mother; she chose to become one. And if she has the abil-ity to make these kinds of difficult decisions for herself—in particular, a decision that directly impacts the lives of oth-ers—then she must also accept the responsibilities that the decisions entail, including potential risks.

It seems very difficult to motivate the claim that a woman is unaware of what she is doing when she agrees to become a surrogate mother. To claim that a potential surrogate is not fully informed when she consents to the surrogacy contract is wrong because surrogacy contracts “contain lengthy riders detailing the myriad of risks of pregnancy.” “Potential surro-gates are much better informed on that topic than are most women who get pregnant in a more traditional fashion” (An-drews, 1988, p. 210). Furthermore, as a result of the amount of publicity generated by the Baby M case, Andrews argues that “all potential surrogates are now aware of the possibility that they may later regret their decisions. So, at that level, the decision is informed” (Andrews, 1988, p. 210).

In essence, consent to surrogacy is consent to pregnancy. The only difference is that the biological mother is relin-quishing her custodial rights to the biological father and his spouse. The need to relinquish her custodial rights is the rel-evant difference between surrogacy and normal pregnancy. Indeed, what else is surrogacy if not the willful consent to pregnancy on condition that one relinquishes one’s custo-dial rights to the infertile couple? The surrogate consents to perform a specific task for the couple, which is to help them conceive a child that is biologically related to them. She also relinquishes any claim rights she may have on the child in exchange for financial compensation. And because surrogacy is basically consent to voluntary pregnancy, con-trary to the Supreme Court’s ruling, there is no need for a woman to have to experience being pregnant first in order to

Article


15

About the AuthorAndrew Molas is a recent graduate from the University of Toronto, where he majored in English and Philosophy.

Dr. Thomas Berry is the faculty sponsor for this submis-sion. He is an Assistant Professor of Philosophy at the University of Toronto.

understand or be properly informed about the potential harms of pregnancy. If the potential surrogate has never experienced pregnancy or childbirth, these contracts out-line the risks and expected changes that her body will go through so she can be reasonably informed and in the position to decide whether or not surrogacy is the right decision for her. And furthermore, if the surrogate has had prior experience with pregnancy—perhaps she is a mother with children of her own—then she would know what to expect after she has given birth, and in that sense, she would be informed when consenting to the surrogacy contract.

Moreover, Andrews seems to indicate in her article that Mary Beth Whitehead had already gone through pregnancy before because her decision to be a surrogate was “to pay for her children’s education” (Andrews, 1988, p. 211). In fact, the vast majority of surrogates “have already had two or three children and completed their families,” and the payment they receive for their gesta-tional services “allows these women to work part-time or to remain at home to raise young children . . . [and] supplement their family’s income” (DiFonzo & Stern, 2011, p. 357-358). If this is the case, then the Supreme Court’s ruling that she cannot be fully informed until she has the experience does not hold. If she has been pregnant and given birth before, she is fully aware of how her body would react to the gestational bond with the fetus. If that bond was too strong to be underestimated, then she would never have become a surrogate in the first place. Someone may object and claim that what the Supreme Court meant was that she would have to ex-perience being a surrogate first before her consent could be informed. But a woman certainly does not need to experience pregnancy first in order to make a rationally informed and conscientious decision on whether or not to become pregnant.

Discussing the Issue of Informed Consent

References

Andrews, L.B. (1988). Surrogate Motherhood: The Challenge for Feminists. Law, Medicine and Health Care, 16, 205-219.

DiFonzo, J.H., & Stern, R.C. (2011) The Children of Baby M. Capi-tal University Law Review, 39:2, 345-411.

Erin, C.A., Harris, J. (1991) Surrogacy. Baillière’s Clinical Obstetrics and Gynaecology, 5:3, 611-635.

Fiore, R.N. (2007). Informed Consent. In S. Ayers, A. Baum, C. Mc-Manus, S. Newman, K.

Wallston, J. Weinman, & R. West (Eds.), Cambridge Handbook of Psychology Health and Medicine (2nd ed.). (pp. 444-448). New York, NY: Cambridge University Press.

Scott, E. S. (2009). Surrogacy and the Politics of Commodification. Journal of Law and Contemporary Problems, 72:3, 109-146.

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

16

Nanomedicine: Small Particles, Big Concerns

Nanotechnology deals with molecules very near the atomic scale. Particles at this scale exhibit exotic proper-ties that are not present in their bulk form, allowing radical new medical treatments. Nanomedicine, the application of nanotechnology in medicine and biomedical science, is a burgeoning field – and one that is hotly debated. Perhaps the most contentious aspect of the debate centers on the potential toxicity of nanomedicine and its resultant ability to impact people and the environment alike through pol-lution.

These issues present both scientific and ethical dilem-mas about the use of nanomedicine and the production of the nanoparticles of which it is composed. This paper ex-amines these problems by investigating how nanomedicine behaves in our bodies when administered intravenously, and how conflicting research results suggest existing mea-sures of pharmaceutical efficacy are inadequate for gauging the long-term safety of nanomedicine. Through inhalation and ingestion, such nanopollution could subject people to further exposure to nanoparticles and their potentially harmful long-term effects.

Nanomedicine’s benefit is grounded in its use of nano-

compounds that have novel properties that can interact in our bodies in a manner previously deemed impossible. Some classes of nanoparticles used in nanomedical appli-cations include carbon nanotubes, carbon fullerenes, and

metal oxides. For example, given that they are vastly small-er than human cells, many nanoparticles can be engineered to enter cells readily. Some nanomedicines enhance drug delivery by using nanoparticles to house existing pharma-ceuticals. These medicine-carrying nanoparticles can be encased in biological molecules, such as antibodies, which bind with and permeate cells through an otherwise nor-mal process. These targeted nanoparticles can then release their medicinal payload in a particular cell or region with-out affecting neighboring cells in the body. Nanomedicine makes use of properties like these to treat, diagnose, and monitor illnesses in novel ways.

Other nanomedicines use the nanoparticles themselves as part of the actual treatment. For example, nanomedicine holds the promise of better cancer treatments. Certain gold nanoparticles have the ability to aggregate in cancerous tu-mors, resulting in a phenomenon called enhanced perme-ability and retention (EPR) (Rhyner, 2008). When specific wavelengths of light are shone on the area of the tumor, the nanoparticles heat up, which selectively kill tumor cells while leaving nearby healthy cells unharmed (Bland, 2009). However this treatment is only in the earliest stage of de-velopment, and, as will be discussed below, much of nano-medicine’s behavior in our bodies is still poorly understood.

Even though nanomedicine’s potential in the future of medicine is unquestioned, investigators are unable to ac-

Jonpaul Wright‡

The advancement of medicine has been closely associated with advancements in science. This trend continues into the 21st century with the introduction of nanomedicine. A novel technology, nanomedicine gives the hope that previously impossible treatments, such as a non-debilitating remedy for cancer, may become a reality. The discussion surround-ing nanomedicine has been understandably optimistic. But, while many commentators pay substantial attention to nanomedicine’s far-off science fiction possibilities (i.e. post-humanist modifications), few individuals focus on more pressing issues concerning the long-term health of patients and the pollution of our environment. This paper presents evidence that suggests nanomedicines and the nanoparticles that comprise them are genuine long-term threats to patients and to the environment; it also asserts that, through the general public’s subsequent unintended exposure to them, nanoparticles are dangerous to society at large. This paper aims to illuminate these issues by showing that traditional protocols for judging the safety of pharmaceuticals and evaluating the potential danger of pollutants must be amended to respond to the unique and unpredictable properties of nanoparticles.

Keywords: nanomedicine, nanotechnology, nanoparticles, nanopollution.

Article

‡ University of Colorado, [email protected]

Introduction

What Makes Nanoparticles Useful in Medicine?

The Behavior of Nanoparticles in Our Bodies


17

curately evaluate the potential health risks of the technol-ogy. The unique challenges presented by nanomedicine are compounded by its recent inception. While there is no exact birth date for nanomedicine, if we consider its rise as a function of research funding, it is reasonable to say nanomedicine began at the turn of the millennium (May-nard, 2007). Consequently there is a limited amount of research data from which to draw. In theory, we can use pre-clinical animal research to predict how nanoparticles travel through the human body, which organs they avoid, and in which organs they are metabolized. But relying on a theoretical forecast is potentially dangerous when the technology is so new. This risk was best illuminated in the only clinical trial of nanomedicine yet conducted, and has also been observed in multiple laboratory research studies involving the long-term fate of nanoparticles in mice.

As with all new treatments, nanomedicine first under-went extensive animal research before any clinical trials were attempted. The first clinical trial occurred in 2006 with a nanomedicine called TGN1412, an anti-CD28 monoclonal antibody developed to treat arthritis and leukemia designed by German pharmaceutical company TeGenero. After pre-clinical results for TGN1412 showed the drug was capable of inhibiting symptoms “in a well-tolerated fashion” (TeGenero, 2006, p. 2), a clinical trial was scheduled in London, where TGN1412 was to be admin-istered intravenously to six “healthy young male volunteers” (Suntharalingam, 2006, p. 1018). The nanomedicine fared poorly. Within an hour of administration, all six volun-teers began to be ill with headaches, nausea and diarrhea. Eventually the men suffered serious complications includ-ing convulsions, loss of blood pressure, and systemic organ failure. Fortunately, all six volunteers survived after emer-gency medical treatment and hospitalization, though two remained in intensive care for over a week (Suntharalin-gam, 2006).

The physician leading the treatment, Dr. Ganesh Sun-tharalingam, rendered an official diagnosis of systemic in-flammatory response syndrome (SIRS) characterized by a “cytokine storm.” (Suntharalingam, 2006, p. 1026). Cy-tokines are small proteins excreted by immune cells that recruit more immune cells, essentially serving as an inter-cellular whistle to alert other immune cells of an invader or targeted cell. During a cytokine storm, overwhelming numbers of cytokines are released, causing a deluge of im-mune cells to be produced and leading to excessive inflam-mation. While inflammation is a fundamental immune response, the level observed during a cytokine storm can lead to organ failure and subsequent death.

This outcome was largely a result of having insubstantial research from which to draw, which itself is a result of nano-medicine’s young age. The inability to review a long history of similar experiments in hopes of designing a better clini-cal trial is a problem faced by all revolutionary treatments,

and TGN1412 is no exception. Most importantly, no cy-tokine storm occurred during the substantial pre-clinical animal research that had been performed before the trial, and the trial itself had received the necessary approval from UK regulatory agencies (Suntharalingam, 2006). Yet the results were concerning, demonstrating just how frustrat-ingly different the science behind nanomedicine is. Not all new drugs are faced with this scenario. Eventually, clinical trials of nanomedicine will need to be conducted so we can begin to build a valuable database of knowledge, but the failure of TGN1412 – and the drastic difference between animal and human responses – confirms that the novelty of nanomedicine must be weighed carefully when considering the ethical implications of the science for future patients.

While the failed trial of TGN1412 resulted in acute danger to the volunteers, perhaps the more worrisome aspect of nanomedicine remains its potential long-term health consequences. As the clinical trial above demon-strated, predicting nanoparticle behavior in vivo has proven a difficult endeavor. In addition to redesigning testing procedures that properly evaluate the unique qualities of nanomedicine for short-term safety, we must also focus on the lasting effects of having nanoparticles in the human body. Unfortunately, anticipating the long-range outcomes of nanomedicine has proven equally frustrating.

Early experiments studying nanoparticles’ impact on health have frequently used carbon nanotubes; hollow tubes composed only of carbon atoms that typically are less than 10 nm long. These tubes are thought to present a dan-ger to people in a manner similar to the microfiber asbestos, a once commercially-prevalent but now federally-banned carcinogen which cuts and clogs the lungs of individuals who breathe the microfibers, causing inflammation that can lead to respiratory ailments and cancer (Pichot, 2008). For example, a 2008 study that injected carbon nanotubes into mice found some mice to have internal swelling and cuts – the same symptoms of asbestos damage (O’Mathuna, 2009).

This particular study, however, demonstrates the diffi-culty of establishing a testing standard for nanomedicine. In a separate 2008 experiment that tracked carbon nanotubes injected into mice’s bloodstreams for over four months, the mice’s livers and spleens were dissected and found to have large aggregations of the carbon nanotubes, even though the mice were symptom-free during the duration of the study. Subsequent trials failed to find this same accumula-tion (O’Mathuna, 2009). It was then found that only cer-tain shapes and lengths of carbon nanotubes caused harm. This discovery further illustrates how the novel aspects of nanomedicine create novel challenges. Overall, the size of nanoparticles as well as the various shapes of nanoparticle sublcasses cause unknown behavior in our bodies.

While the lack of acute symptoms in the particle-harboring mice is puzzling, their long-term well-being re-


Clinical Trial of TGN1412

Nanoparticle Infection

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

18

mains unknown. Given what other much larger particles such as asbestos cause in cancer by gathering and remaining in vital organs, it is plausible that nanoparticles, which can infiltrate organs much more easily because of their smaller size, could have a similarly harmful long-term effect. The need to predict the long-range safety of medicine is at the core of reliable treatment, and, as the above studies show, existing procedures used to test the long-term outcomes of a medicine are proving to be insufficient for judging the safety of nanomedicine.

While the state of nanomedicine will progress as the safety and regulatory protocols are developed to accom-modate its unique qualities, a potentially greater danger is nanoparticles polluting our environment. Like nanomedi-cine in our bodies, the behavior of nanoparticles in our en-vironment is poorly understood, as are the risks nanopol-lution poses to both animals and people. Research so far suggests that nanopollution presents fundamentally new challenges to efforts to remediate long-term health hazards. Exposure to nanopollution is primarily through contami-nated air and water.

While there have been some promising early results regarding inhalative nanomedicine, such as improved bio-availability of inhaled insulin, inhaled nanoparticles can also enter the body in an unintended fashion, through pollution (Bur, 2009). Nanoparticles primarily enter the atmosphere as a result of combustion engine exhaust, but they also are a product of industrial processes. Once airborne, they can pose a health hazard through inhalation and subsequent translocation (Maynard & Kuempel, 2005). And unlike larger particulate pollutants, because of their size, airborne nanoparticles en masse behave more like a gas in the open environment than they do microscale particulate matter, meaning that nanoparticles see increased exposure to the general population compared to larger particles (Clough, 2009).

The heightened exposure to nanopollutants places an increased importance on understanding the health effects of inhaled nanoparticles. Early studies of nanoparticle inhalation have focused on the path and resting location of the inhaled particles and their potential toxicity to the inhabited organs. When nanoparticles are inhaled, their final resting place in our body is determined predominantly by their size. Particles ranging from 10-50 nm end up in our alveoli, while particles outside this range tend to rest in the upper respiratory tract (Hoet, 2007). Physiologically, alveolar pollutants are not easily removed and require the immune system to intervene. But nanoparticles’ small size makes it hard for immune cells, specifically macrophages, to remove them (Hoet, 2007). Macrophages, white blood

cells normally responsible for helping reduce inflamma-tion, have been revealed to also play a part in proliferating cancer by releasing inflammatory compounds in the body. Because nanoparticles are not easily cleared by the mac-rophages, they may contribute to increased inflammation and nanoparticles are thus being investigated as possible carcinogens (Rhyner, 2009). In addition, long-term expo-sure to inhaled nanoparticles has also been associated with emphysema and chronic bronchitis (Baughman, 2010).

Nanoparticles’ behavior inside of our lungs is unique in another way: they can translocate from one organ to an-other. For example, inhaled nanoparticles smaller than 6 nm have demonstrated the ability to cross through our lung tissue into the bloodstream, travel through the body, and be excreted through the kidneys (Tsuda, 2010). Other find-ings, too, have shown inhaled nanoparticles to cause prob-lems in blood clotting and even to enter our brain, prompt-ing further investigation into the relationship between nanoparticles and neurological disorders (Hoet, 2007). Medically, nanoparticles’ ability to cross the blood-brain barrier may one day “[open] up new possibilities for treat-ment” (Allhoff, 2009, p. 8), but current research suggests this could be ethically questionable. These findings reiter-ate that current safety protocols are inadequate for dealing with the new hurdles presented by nanoparticles.

Nanopollution also affects sources of water, which can be contaminated by previously airborne nanoparticles set-tling and industrial waste. It has also been suggested that nanoparticles flushed out in urine might accumulate in our water supply, just as estrogen from oral contraceptives have been found to harm fish ( Jobling, 2006). Once nanopar-ticles enter water they exhibit unexpected properties that complicate their removal. This difficulty of extracting nanoparticles from water is made more pressing by early findings indicating that ingested nanoparticles present seri-ous health risks.

Current research has shown that nanoparticle behavior in water depends on a multitude of factors, some intrin-sic to the particle itself, others contingent upon the aque-ous environment (Mackay & Henry, 2009). A three-year study funded by the National Center for Environmental Research (NCER) examined the difficulty of removing nanoparticles, specifically metal oxides, from drinking wa-ter. The study concluded that “removal of nanomaterials by coagulation, flocculation, and sedimentation processes was relatively difficult” (Henry, 2009, p. 162). The drinking wa-ter still had over 20 percent of the original nanoparticles in it after purification. Metal oxide nanoparticles are already being tested in medical applications, including drug deliv-ery, and if they are this difficult to remove from water us-ing industrial purification techniques, their introduction to natural water sources could pose a serious problem to both regulators and citizens (He, 2010; Henry, 2009).

Similar experiments found that carbon nanotubes,

The Danger of Nanoparticles in Our Environment

Nanoparticle Inhalation Nanoparticle Ingestion

Article


19

which are hydrophobic and should clump together in wa-ter, bonded to soil and other “organic material that occurs naturally in river water” (Henry, 2009, p. 162) and remained suspended in the water for over a month. This unpredict-able affinity for naturally-occurring organic matter also held true for another subclass of nanoparticle, known as buckyballs, which are spherical fullerenes reminiscent of soccer balls. This phenomenon directly affects particle re-moval from water by influencing their flow rate. Normally particles in water are expected to travel through saturated soil with a frequency in some degree proportional to the flow velocity of the stream. But the fullerenes were unaf-fected by the flow rate, which led to increased deposition. It was also discovered that fullerenes acted like magnets to each other, so that once one was deposited in soil it would attract other fullerenes (Mackay & Henry, 2009). The aqueous environment itself has also influenced the particles’ behavior, with particle deposition changing at certain pH levels (Mackay & Henry, 2009).

Unfortunately, the failure of traditional remediation techniques to cleanse drinking water of nanoparticles could directly lead to deleterious health conditions for people who consume the contaminated water. A 2010 study of earthworms exposed to nanoparticles suspended in water revealed that the particles had harmful effects, ranging from pronounced cellular damage to death (Lapied, 2010). Like long-term exposure to air polluted with nanoparticles, exposure to contaminated drinking water seems likely to lead to lasting health problems. Until a viable solution to the problem of nanopollution is found, we are faced with a difficult situation in which we may be creating greater health problems, such as contaminated drinking water, that affect society as a whole for the sake of short-term medical treatments for a select few in need.

A systematic protocol for testing nanoparticle behav-ior in water seems an obvious answer to the contamination problem; however, none exist because classes of nanopar-ticles are so intrinsically different that attempts to general-ize conclusions from one study to overall particle behavior have failed . The perplexing unpredictability of nanopar-ticles’ reactions in something as chemically fundamental as water has left researchers frustrated and regulatory agencies at a standstill. Nanoparticles have defied easy classification thus far. Kim Henry, a hydrogeologist from Harvard Uni-versity who has studied nanoparticle behavior, asserts that at present, “the fate and transport of nanomaterials must be considered on a case-by-case basis” (Mackay & Henry, 2009, p. 151).

When considering nanomedicine it is important to remember that nanotechnology is still in its infancy. The genuinely novel features of nanotechnology present new and unique dilemmas to society. As the arguments of this paper show, bioethicists and scientists alike would benefit from a more comprehensive approach to understanding

the scientific and ethical problems posed by nanomedicine. Currently, nanomedicine has yet to be successfully used in a patient. But once it has, we must continue to focus on the long-term effects nanoparticles may cause in our bodies and environments. The ethical quandary created by nanoparticles centers on the concept of nonmaleficence. If nanomedicine offers an immediate treatment for ailing patients but subjects them to future suffering, it would be hard to justify approving the treatment. As a society, we have an obligation to better our quality of life by using new medical treatments when they are available, but we also have an ethical duty to protect ourselves, and future gen-erations, from potential harm.

Undeniably, nanomedicine should be an unqualified success: society at large should only benefit from its suc-cessful incorporation into modern medicine. Our under-standing of the basic behavior of nanoparticles, both in our bodies and in our environment, and the regulatory proto-cols that result, must advance in order to properly account for the novel qualities of this new science. Until we can determine that nanomedicine is safe for long-term use and that nanopollution can be resolved with new and effective remediation techniques, employing nanoparticles in medi-cal applications is more of a danger than a solution.


Balancing the Future of Nanomedicine

About the AuthorJonpaul Wright is a senior at the University of Colorado at Boulder, where he is majoring in Chemistry.

Mr. Donald Wilkerson is the faculty sponsor for this submission. He is a Senior Instructor in the Program for Writing and Rhetoric at the University of Colorado at Boulder.

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

20

Allhoff, Fritz. (2009) The Coming Era of Nanomedicine. The American Journal of Bioethics, 9: 10, 3-11, first Published on: 01 October 2009 (iFirst).

Bland, Eric. (2009, April 1). Gold nanospheres sear cancer cells to death: Discovery News.

Discovery Channel : Science, History, Space, Tech, Sharks, News. Web. Accessed on 17 Nov. 2010 from <http://dsc.discovery.com/news/2009/04/01/gold-nanospheres.html>.

Baughman, R., Pirozynski, M. (2010). Health Effects of Nanoparticles (Inhalation) from Medical Point of View/Type of Diseases. Nanopar-ticles in Medicine and Environment. Marijnissen, J. C. M., and Gradon, L. (Eds.) Springer Science + Business Media.

Bur, M., Henning, A., Hein, S., Schneider, M., Lehr, C.M. (2009). Inhalative nanomedicine – Opportunities and challenges. Inhalation Toxicology, 21: (S1), 137–143.

Clough, S. (2009). The potential ecological hazard of nanomaterials. Nanotechnology and the environment. Sellers, K., (Ed.). Boca Raton, Florida: CRC Press, Print.

He, J., Qi, X., Miao, Y., Wu, H.-L., He, N., Zu, J.-J. (2010). Application of smart nanostructures in medicine. Nanomedicine, 5(7): 1129–1138.

Henry, K. (2009). Treatment of nanoparticles in wastewater. Nanotech-nology and the environment. Sellers, K. (Ed.). Boca Raton, Florida: CRC Press, 2009. Print.

Hoet, P.H.M. (2007). Inhalation of nanomaterials: Short overview of the local and systemic effects. Nanotechnology - toxicology issues and environmental safety. Simeonova, P.P. (Ed.). Boca Dordrecht, The Netherlands: Springer, Print.

Jobling, S., Williams, R., Johnson, A., Taylor, A., Gross-Sorokin, M., Nolan, M., Tyler, C. R., van Aerle, R., Santos, E., Brighty, G. (2006). Predicted Exposures to Steroid Estrogens in U.K. Rivers Correlate with Widespread Sexual Disruption in Wild Fish Populations. Envi-ronmental Health Perspectives. 114, 32-39.

Lapied, E., Moudilou, E., Exbrayat, J.-M., Oughton, D. H., Joner, E. J. (2010). Silver nanoparticle exposure causes apoptotic response in the earthworm Lumbricus terrestris (Oligochaeta). Nanomedicine, 5(6): 975-984.

Mackay, C., Henry, K. (2009). Environmental fate and transport. Nanotechnology and the environment. Sellers, K. (Ed.). Boca Raton, Florida: CRC Press, 2009. Print.

Maynard, A. D. (2007). Nanoparticle safety -- A perspective from the United States. Nanotechnology: Consequences for human health and the environment. Hester, R.E., Harrison, R.M. (Eds.). Cambridge, UK: The Royal Society of Chemistry, Print.

Maynard, A. D., Kuempel, E. D. (2005). Airborne nanostructured par-ticles and occupational health. Journal of Nanoparticle Research, 7: 587-614.

O’Mathuna, D.P. (2009). Nanoethics: Big ethical issues with small tech-nology. London: Continuum International Publishing Company.

Pichot, C. (2008). Reactive nanocolloids for nanotechnologies and micro-systems. Colloidal nanoparticles in biotechnology. Elaissari, A. (Ed.). Hoboken, NJ: John Wiley & Sons, Inc., Print.

Rhyner, M. (2008). Quantum dots and targeted nanoparticle probes for in vivo tumor imaging. Nanoparticles in biomedical imaging: Emerg-ing technologies and applications. Bulte, J.W.M. (Ed.). New York: Springer Science+Business Media, LLC, Print.

Roller, M. (2009). Carcinogenicity of inhaled nanoparticles. Inhalation Toxicology, 21(S1): 144–157.

Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D., Panoskaltsis, N. (2006). “Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412”, The New England Journal of Medicine, 355: 10, 1018-1028, first Published on: 07 September 2006 (Massachusetts Medical Society).

TeGenero (2006, February 20). Research and Development: Drug De-velopment. TeGenero Immuno Therapeutics. Accessed 6 Nov. 2011 at http://web.archive.org/web/20060412052458/http://www.tegenero.com/research__development/drug_development/index.php

Tsuda, A. (2010, November 16). What happens when you breathe in nanoparticles. Technology Review. Chu, J. (Ed.). MIT Press. Ac-cessed 7 Dec. 2010 at http://www.technologyreview.com/biomedi-cine/26719/page2/

References

Article

Program Features Open enrollment Can enroll in one course or

multiple courses Each course only 3 hrs/day

over 5 days Week-long intensive format Basic and advanced courses

taught by global leaders in bioethics

Multi-course and JHU student tuition discounts available

JHU employee tuition remission available

Courses Offered

Foundations of Bioethics Reinvigorating Clinical Ethics:

From Theory to Practice Ethics of Human Subject

Research Emerging Biotechnologies,

Ethics & Policy Public Health Ethics Bodies, Boundaries &

Bioethics Foundations of Law &

Bioethics Ethical, Legal & Social Issues

in Genetics & Genomics Justice & Health

Week-long Summer Courses In Bioethics

June 4-8 & 11-15, 2012

Join the Johns Hopkins Berman Institute of Bioethics this

summer for introductory and advanced courses in Bioethics,

offered through the Berman Institute Bioethics Intensives

(BI2) program. BI2 provides an engaging bioethics

educational opportunity for current students, medical/legal/

policy professionals, researchers, scholars, and others.

FOR MORE INFORMATION

Email [email protected] with “Summer Intensives” as the subject

or visit www.bioethicsinstitute.org/intensives

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

22

The Future of Nanomedicine: Poten-tial Technologies, Current Research and Necessary Regulations

‡ University of Pennsylvania, [email protected] and [email protected]

Anand Muthusamy and Aditi Verma‡

Article

The emerging field of nanomedicine bridges nanotechnol-ogy’s powerful atomic and molecular tools with medicine’s pathological framework to detect illnesses, delivers treat-ments, and engineer synthetic systems for use in vivo. The physicist Richard Feynman is credited as the first scientist to articulate a future of nanotechnology (Drexler, 2004). Feyn-man envisioned nano-scale tools that could create smaller tools that could in turn iteratively make smaller tools down to the atomic scale. These tools together constitute nanotech-nology and can be applied in various fields such as medicine. Today, nanotechnologies are considered to consist of particles and assemblages of particles ranging from 1-250 nanometers (Moghimi et al., 2005).

Nanomedicine harbors the potential to both open new therapeutic possibilities and improve the effectiveness of ex-isting treatments. Before using nanotechnologies in the clinic, much work must be done to understand the risks associated with this strategy of treatment. This paper first describes cur-rent nanomedical technologies and existing regulatory bod-ies in the United States. Four major ethical criteria relevant to nanomedicine are then considered: 1) minimizing risk in clinical trials and later general use, 2) prima facie objections to nanomedicine, 3) the environmental impact of nanotechnolo-gies, and 4) the value of new technologies in medicine and their accessibility to patients. Because nanomedicine consti-tutes a wide variety of technologies and medical strategies and has not yet fully developed as a field, it is not possible to deter-mine if nanomedicine, an entity and practice itself, is “ethical”. Instead, this paper considers general obstacles in determining the effects of nanomedicines, the ethicality of specific prac-tices, and areas that require more research.

We find that there are no novel ethical problems with nanomedicines themselves; nanotechnologies are often ve-hicles for therapies that must be considered individually (e.g. gene therapy). Still, risks and health outcomes must be evaluated which can only be done through empirical research. We find that current scientific research can overcome several obstacles nanomedicine poses to collecting this information. Even if considered “ethical”, nanomedicine should fit into a

framework of care that optimizes health outcomes. We find Annemarie Mol’s “logic of care” useful to think about inte-grating technology into the clinic.

On the horizon are many potentially useful and varying technologies that should be considered individually. This sec-tion considers only the most prominent applications of nano-technologies in medicine. The major advances in nanotech-nology consist of extending the logic and practice of existing therapeutic strategies.

The nanotechnologies that facilitate drug delivery encap-sulate a drug to carry it to a specific location and only then release the drug. This subset of nanomedicine alone comprises 78% of sales and 58% of approved patents for nanomedi-cines throughout the world (Resnik and Tinkle, 2007). Of-ten, potent drugs are not effective because of their solubility in water or their charge that prevents them from crossing cell membranes. Nanocarriers are molecules whose structure has a pocket to carry the drug and has surface properties amicable to physiological environments. The outer surface of nanocarri-ers can be configured with synthetic polymers and ligands to confer affinity between the nanocarrier and a certain structure in the cell (Moghimi et al., 2005). This specificity in target-ing can reduce the side effects of drugs. The clearance of the carriers from the body can be verified experimentally using a method such as radionuclide labeling. The drug is then re-leased when the nanocarrier is degraded by the cell or when the carrier enters the environment of a target that is not suit-able for the linkage between drug and carrier (the carrier is engineered beforehand with this target environment in mind).

One class of nanomedicine can be distinguished by its use of technology in vitro to facilitate research. Here, diagnostic nanotechnologies are used in the lab to conduct experiments

Nanotechnology in medicine

Major categories of nanomedical technologies

Nanomaterials assisting in targeting drug delivery

Diagnostic tools used in vitro


23

and help develop treatments. Two examples of diagnos-tic nanomedical technology are DNA sequencing tech-nologies and “labs on chips” (Freitas, 2005). The pore of an alpha-hemolysin protein channel can be anchored in a membrane and read through the sequence of DNA bases (Meller, 2000). Current work is focused on altering the size and geometry of the pore to enhance accuracy of the se-quencing. Secondly, “labs on chips” function as small scale laboratories in that they receive a small sample and produce measurements (e.g. concentrations of particular cells or proteins). This technology allows a quick determination of the state of a patient’s body near the point-of-care (Srini-vasan, 2004).

The “lab on a chip” introduced above is one example of a microelectromechanical system (MEMS). BioMEMS is a class of nano-scale sensors that includes both diagnostic equipment for the lab and sensors and prosthetics implant-able in the body (Bashir, 2004). For example, researchers have begun to develop electrode arrays fixed on a flex-ible material to serve as a retinal implant to restore vision (Meyer, 2001). Both nanosensors and nanoprosthetics can be safer than their larger counterparts insofar they are less invasive and can be more easily engineered to be biocom-patible.

Synthetic materials can be implanted into the body to provide for new bodily functions or enable other therapeu-tic agents to carry out their function safely. As an example of the first type, nanoparticles with certain electrical prop-erties have been incorporated into retinal implants to im-prove charge transfer and make vision possible. An example of the second type is a nanoparticle coating with certain magnetic properties that has allowed certain implants to safely undergo MRI imaging. (Wagner et al., 2006).

Nanopores can be used in vivo to separate or isolate dif-ferent biological components. Immunoisolation is one ap-plication where a functioning cell can be enclosed in a kind of nano-cage that allows nutrients from the patient to enter but keeps out the host’s cells implicated in immune system functioning that target and destroy foreign bodies. For ex-ample, pig islet cells may be placed into an array of cham-bers that offer this selective isolation and allowed to help restore a diabetic patient’s “glucose-feedback loop” (Freitas, 2005). Nanosieves are electric gates that can be installed in a membrane and switch its polarity to keep out a certain charged ionic species (Freitas, 2005).

With the advancement of materials science comes the potential to create molecular machines that can carry out therapeutic tasks. For example, a “microbivore” is a mi-crometer scale robot that uses roughly 200 picowatts to specifically bind and encapsulate harmful bacterial and me-chanically and chemically degrade the bacterial into harm-less building blocks (Frietas, 2005). This nanorobot would augment a patient’s existing immune system and help fight infections in less time. Nanorobots can not only restore normal bodily functions, but also create possibilities for new therapeutic strategies. For example, in chromosome replacement therapy, surgical nanorobots could excise dam-aged chromosomes and replace them with fully functioning chromosomes synthesized in the lab (Frietas, 2005). In the case of nanorobots, technologies that promote “naturally occurring” processes such as immunological defense are probably not ethically problematic. Technologies that al-low for certain molecular interventions open doors to larger debates linked to the end goal of the treatment. In the case of chromosomal therapy, the nanorobot itself is not prob-lematic but rather the end to which it is used raises issues.

The United States has an established research and regu-latory framework for nanomedicine. Currently the Envi-ronmental Protection Agency (EPA), National Institute of Environmental Health Sciences, the National Science Foundation, and the National Institute of Occupational Safety and Health maintain studies of the uses and risks of nanomaterials (Resnik & Tinkle, 2007). The National Can-cer Institute continues to conduct research into the use of nanomaterials in cancer therapy. The National Nanotech-nology Initiative (NNI) began with Bill Clinton in 2000. Clinton brought the NNI into Congress to bring federal involvement in the development process of Nanotechnolo-gy. He hoped this would stimulate research in this area and increased United States competitiveness. There are thirteen Federal agencies within the NNI focused on research and development; there are twelve for health, regulation, and environmental safety. From its initiation to present day, the NNI has been funded 12.4 billion US dollars, and with that it has become invaluable to helping many government or-ganizations come up to date with the most recent knowl-edge. Studying the impact of nanotechnology on society and the environment, this organization became central to federal government’s knowledge of potential of nanotech-nologies which informed regulations.

On the most general level, the FDA has very strict oversight on eight basic products that utilize nanoparticles: new drugs’ and biological Drug Products, over the counter drugs, animal products, devices, food additives, cosmetics, and dietary supplements. Manufacturers are required to submit to the FDA a report for each product detailing the chemistry, manufacturing, active ingredients, structural for-mula, pharmacological toxicological data, and particle size

BioMEMS

Active Implants

Nanopores

Nanopores

Existing regulatory frameworks

The Future of Nanomedicine

Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

24

Congress also continues to update and fine tune the coun-try’s regulatory framework. Bill S. 1662 has been introduced in Congress and seeks to “amend the Federal Food, Drug, and Cosmetic Act to establish a nanotechnology regulatory sci-ence program” (S. 1662: Nanotechnology Regulatory Science Act of 2011). Specifically, this program would be responsible for keeping up with scientific literature, disseminating knowl-edge internationally, and promoting research needed to inform regulations on nanotechnology. This program would focus on the effects of nanotechnology on biological systems and the properties of nanotechnology that may contribute to toxicity.

In order for any therapy to be translated from the lab to the clinic, it must first receive approval from an institutional review board (IRB) overseen by Health and Human Services housed in the executive branch of the federal government (HHS, 1993). Proposed research must minimize risk to par-ticipants, match risk accrued with benefits for participants, keep record of the experiments and results, seek and document informed consent, select subjects equitably, protect vulnerable populations, and maintain privacy and confidentiality (Resnik & Tinkle, 2007). After proving the concept of a therapy in vitro and in vivo in animals, the FDA may allow for human clinical trials. Phase I trials test a therapy in a group of 25-100 research subjects. If deemed safe, the test next enters phase II trials if deemed with 100-500 subjects where efficacy of the drug is better understood. Phase III trials ultimately confirm the safety and effectiveness of the therapy. Although not re-quired, some manufactures may conduct phase IV trials, also known as “post-marketing trials” to follow up to use by the general public (Resnik & Tinkle, 2007).

For any new technology, the process of carrying out clini-cal trials poses significant ethical issues surrounding consent, sharing of information, risks, and compensation. Nanotech-nology does not present many novel problems in clinical trials but communication between doctors and patients, the time frame of trials, and minimization of risk each deserve discus-sion.

First, in order for research subjects to have meaningful agency in consenting to and participating in clinical trials, they must have adequate information about the risks and benefits of participating in the trial. Information about new life science technologies however is obfuscated by the marketing of the technologies. Kaushik Sundar Rajan has framed “biocapital” through the intersection of the market and emerging life sci-ence technologies. Biocapital constitutes the market value as-signed to therapeutics and technologies, the symbolic values attached to product, the ideologies that ground these symbolic

values, and the governance of populations needed to gener-ate value in clinical trials (Rajan, 2006). Rajan argues that life science companies must generate hype and hope surrounding their technologies to attract interest and investments.

In the case of nanomedicine, this rhetoric may take on spe-cial force with the idea of “personalized medicine” and “fine-tuned therapies” that could mean the difference between life and death. This artificially positive message spills over into the public sphere and largely colors public understanding of the biotechnology. While these marketing strategies are not unique to nanomedicine or even the medical industry, the possible distortion of information has particular acute conse-quences in the area of healthcare. Patients and research sub-jects may agree to treatments thinking that they are receiving better care than they actually will receive (Resnik & Tinkle, 2007). Like for most therapies, the issues of communication can be dealt with by countering excessive hype and hope with sound information. The exact nature of the ideal doctor-pa-tient relationship in the age of biocapital may differ between therapies (because chromosomal therapy may have a different significance than restoring immune system functioning, for example) and is beyond the scope of this paper.

Second, nanomedicine is unique in that it introduces compounds and engineered materials not like other thera-pies already tested in vivo. From the current understanding of pathology and nanotechnology however, experts argue that many potential side effects of nanomedical therapies may be evident only much later in a patient’s lifetime (Resnik & Tin-kle, 2007). As in the case of many therapies, longer studies of patients may be necessary to evaluate the true magnitude of side effects. Such studies may not only be expensive but impractical (and misleading) because patients may need to use other therapies over time that muddles the results of the initial treatment. If clear results can be obtained, then longer trials ought to be conducted for these new materials to build an intuition of they interact with the body. This requirement would necessitate amending current FDA regulation to either lengthen at least the phase III trials.

Third, nanomedicine presents new challenges to meeting the “minimizing risk for research subjects” criterion because the field is in its infancy. Extending the length of trials as dis-cussed above and addressing experimental obstacles discussed in the next section are prerequisites to determining how to minimize risk.

There exist several interlinked areas where researchers must improve their understanding of nanotechnology if they hope to continue to translate this technology to the clinic (Sanhai et al., 2008). These obstacles are generally present in the applica-tion of any potential nanotechnology agents in vivo and can be grouped into three general areas: understanding distribu-tion of agents in vivo, understanding the relationship between differently configurations of agents and their behavior, and developing models to simulate the relationship between this

data. Guiding the physical regulation process are three main components to FDA regulation: pre-market view and post-market surveillance, communication with agency in the first steps of the development process, and public input on the ad-equacy of the agency policies and procedures.

Clinical trials, communicating information, and care

Potential issues in experimental knowledge

Article


25

behavior and health outcomes. These three areas mark neces-sary conditions to begin to answer the ethical criteria listed above. Given that there are standards of care, the burden of proof in ethical considerations is on proponents of nanomed-icine. Therefore, if it were not possible to prove the safety and efficacy of the technologies, nanomedicine, by default would most likely be ethically suspect.

First, understanding how agents become distributed in the body is critical to determining all possible effects of nanomedical interventions. In order to understand this dis-tribution, imaging technologies must be developed. Imaging techniques must not just locate agents but also should be able to confirm that all particles in a given dosage are accounted (Sanhai et al., 2008). Currently, radionuclide imaging is the major technology that provides this level of detail. A radio-nuclide, an unstable nucleus that emits radiation of a specific frequency (a kind of signature), is attached to the agent be-fore they enter the body. Once in the body, the emission of radiation can be detected to locate the agents and measure what amount of the agent builds up in certain areas of the body. The link chemical bond between the radionuclide and nanoparticle however may be unstable in physiological con-ditions; these nanoparticles that lose their radionuclide can-not be tracked, introducing error into experiments (Sanhai et al., 2008).

Second, the function of an agent is highly dependent on how the agent interacts with barriers in the body (i.e. cell membranes) and different microenvironments (e.g. areas of high hydrostatic pressure) (Sanhai et al., 2008). These interactions, in turn, are dependent on the chemical and physical properties of the agent. Because each agent will be engineered for a specific function, each will have different properties and require unique experiments to determine their behavior in vivo.

Third, models and simulations must be constructed to help understand how different behaviors of nanotechnolo-gies will lead to health outcomes. A computational model can account for the perturbation of an agent and then detail the resulting state of the cell or organism. This kind of mod-eling can help researchers and physicians consider when a certain intervention is appropriate, develop a sense of risk, and weigh the health benefits against side effects (Sanhai et al., 2008).

Although these three areas represent challenges for al-most all nanotechnologies applied in vivo, there is a wide continuum of risk and benefit among these technologies. Because the landscape of nanomedicine is so varied, differ-ent technologies deserve individual attention. These current limitations on knowledge clearly indicate a need for further scientific research but do not demonstrate a certain level of indeterminacy in scientific knowledge yet. The issue of im-aging technologies can be tackled with the development of compounds and bonds that are very stable in physiologically conditions and use non-toxic constitutive materials. This emergent strategy of “bioorthogonal chemistry” is growing and shows promise for applications in nanomedicine (Algar

et al., 2011). The issue of specificity necessitates screening several nanoparticles in different environments is a problem of creating high-throughput screenings experiments. This technique is being developed in labs in the National Cancer Institute (NCI, 2012). Finally, addressing the first two prob-lems can help build an intuition of nanomedicines to assist in building better computer models.

Nanomedicine presents some prima facie ethical concerns about its practice regardless of the outcome of ther-apy. First, nanomedicine may present a new and problem-atic kind of human engineering. From the discussion of the various types of nanomedicines it should be evident that for the most part these technologies extend existing therapeutic strategies. Criticism may either be leveled at biomedicine in general or at specific practices made possible by nanotech-nologies. The former comprises very general arguments not specific to nanotechnology which are beyond the scope of the paper. The latter require debates not about nanotechnolo-gies themselves but rather about the end to which they are directed. For example, ethical issues about the chromosomal therapy robots are probably not concerns about nanorobots per se but rather the broader debates surrounding genetic modification. These cases present important ethical questions that should begin at the vehicle of the therapy but rather at the purpose and end achieved through the therapy.

Second, the effect of nanomedicine cannot be reduced to the clinic; problems of equity in healthcare may be exacer-bated by emphasis on nanomedical technologies (Resnik & Tinkle, 2007). Not enough nanotechnology has been trans-lated into the clinic to understand how the regime of “per-sonalized medicine” will affect healthcare outcomes. Equity must be delivered on two levels: prioritization of nanomedi-cines targeting needs of the general population and equity in access and care outcomes. For the former, “public value mapping” (PVM) can serve to ensure the primary needs and desires of the general public are accounted for. Specifically, PVM researches the views of researchers, government offi-cials, patient interest groups, and the general public to ‘map’ public values (Bozeman, undated). PVM ought to be applied to nanomedicine to better guide research priorities (Cozzens, 2010). A limitation to the PVM model is that it presumes that people have sufficiently information and can make rea-soned choices. As explained above, public understanding of health technologies can be especially distorted though the rhetoric of hop and marketing strategies. For this reason, the second plank of equitable outcomes should be evaluated. On face, nanomedicines will be relatively expensive at first and may not be completely accessible. However, like any new medical technology, costs should decrease over time. Equity in access and care outcomes therefore is not made impossible by anything inherent in nanomedicines. In other words, eq-uity is not a prima facie concern but rather is a concern with how nanomedicine is used by institutions and actors.

Prima facie ethical concerns


Penn

Bio

ethi

cs Jo

urna

l

V

olum

e VI

I Iss

ue ii

26

Again, different kinds of nanotechnologies have differ-ent environmental impacts. The main concern in this area is the uncontrolled exit of nanoparticles from the human body into the environment where they may then enter other organ-isms. First, it should be noted that this concern applies only to therapies that enter the body; the waste from diagnostic tools can be controlled in the lab setting. Second, much more work must be done to determine environmental effects; this knowledge will rely on the needed advances mentioned at the end of the previous section. Third, with a better understanding of the behavior of nanomedicines, experts can input this infor-mation into existing models of our environment. Specifically, the analytical technique of “environmental impact assessment” assembles several quantitative proxies of environmental health into a model, treats the model with a perturbation such as in-troduction of nanoparticles, and evaluates the resultant effects (Kessler and Dorp, 1998).

Of primary concern for experts is how nanoparticles re-leased into the environment may interact with other humans. Studies have shown that rodents that inhale multi-walled carbon nanotubes develop respiratory problems and dam-age to tissues as seen in asbestos exposure (Orberdoster, 2009). Nanoparticles directly absorbed through ingestion or uptake through skin leads to aggregations of particles local-ized in different tissues that can disrupt regular functioning (Orberdoster, 2009). Nanoparticles have even been observed to indirectly affect DNA stability through initiating cell sig-naling pathways (Myllenen, 2005). Since nanoparticles can engage in complex biochemical pathways at different con-centrations, empirical evidence must be collected to verify the safety of each nanomedicine individually.

To this end, in vitro assays can simulate an organism’s envi-ronmental exposure to nanoparticles. The general principle of these experiments is to isolate the mechanisms implicated in the beginnings of deleterious biochemical pathways and see if exposure to the nanoparticle triggers the first step in the path-way. In this way, experiments do not need to rely on testing a drug on a human to assess possible toxicity. For example, the lymph node proliferation assay is a standard test to determine if a nanoparticle triggers immune system response (Dobrovol-skaia et al., 2009). These kinds of assays can create an intuition of how nanoparticles may interact with the body but cannot replace clinical trials and empirical research.

There are currently many nanomedical technologies in development; many are even in clinical trials and could be approved for clinical use. Here, VivaGel and Abraxane are presented as examples of cases of how nanomedicines can be ethically developed and delivered in clinical research and be-yond. At such an early stage in both the technologies and the field, there is currently little research on larger social and envi-ronmental impacts of nanomedicines.

VivaGel contains the active ingredient SPL7013, a den-drimer designed with the specific purpose of human protec-tion from HIV and HSV. Using in vitro studies with tissue culture as well as animal studies, VivaGel demonstrates an ef-ficacy for not only being an effective nanotech treatment in the long run application but also maintaining a safety conscious-ness for the development of Nanotechnologies. Recognizing the potential of VivaGel, the US Food and Drug Association granted VivaGel Fast Track status in 2006 (Rupp, 563). The safety and efficacy of VivaGel in its application form as well as in its developmental process meets the bioethical standards that one would most expect.

VivaGel was proceeded through to the clinical trials pro-cess using a variety of different controls and systematic meth-odology. There were several factors that needed to be coined down before the final product. The primary concern was the safety of the active ingredient. Based on a series of tests on in vitro tissue cultures as well as animal studies, the irritation of the skin and the reactivity of the cells determined to what ex-tent the active ingredient was harmful to the epidermis. Once the safety of the ingredient was determined, the concentration necessary had to be determined. Again, using a variety of cel-lular tissue cultures and animal testing, the concentrations of 5%, 3%, and 1% were tested. The translation to the final gel required further studies on the efficacy against HIV and HSV. By controlling the concentrations of both the active ingredient in the gel and the concentration of the HIV virus, qualitative inhibitory effects were observed. In addition, post-infection alleviation was also observed, demonstrating the ability for the VivaGel to act as a treatment after infection. After this back-ground of data was collected, the final process of clinical trials yielded histological tissue results emphasizing the dearth of gel absorption and skin irritation

Abraxane is an albumin-bound nanocarrier that encapsu-lates drugs to reach a very specific targeted area before releas-ing the drug. Once again, this drug underwent several Phase I, Phase II, and Phase III trials. From the standpoint of bioeth-ics, there is no literature that emphasizes a bioethical viola-tion. However, there is literature for trials in the Phase III stage emphasizing the conscious desire to maintain bioethical standards. In various parts of the Phase III process, developers emphasized the considerations that were taken to maintain bioethical purity.

Developers carefully selected a population size while main-taining bioethical standards. The population size of 43 patients consisted of men and non-pregnant women over the age of 18. These patients had an expected survival of over 12 weeks with strong hematologic, hepatic, and renal functions (Green, 2006). In addition, patients were not included from the study if they exhibited brain metastasis or any other type of injury.

The administration of the procedure further demonstrated consciousness of ethical standards. The treatment was admin-

Environmental effects VivaGel

Drugs currently in trial

Drugs currently in trial

Article


27

istered every three weeks at a certain dosage, but ensured that a reduction in dosage concentration was acceptable un-der flexible circumstances. If there were any adverse effects after the first administration, the dosage was decreased to half its initial concentration, and if any further problems persisted, the patient was withdrawn from the study. This further demonstrated concern for the patients’ safety. The structure was very orderly through the close checkup from expert physicians.

Using this methodology, developers collected an ex-tremely large and thorough database for the effects of this treatment allowed manufactures and consumers to have strong certainty regarding the effects of Abraxane. Using a variety of imaging techniques, scientists categorized the tu-mor length in a wide spectrum of margins: from complete disappearance to 30% decrease to increase in the lesion size in any area.

Overall the treatment was very well tolerated. Almost all cycles, 98%, were administered at the full dosage. Che-motherapy improves the survival of cancer patients. How-ever, this treatment demonstrates the effectiveness of tar-geted drug delivery. These nanocarriers not only improve the efficiency of drug delivery but also reduce resources on expensive drugs and decrease the risk healthy areas face when being exposed to intensive chemotherapy.

With such varied and exciting technologies, it is easy to lose sight of the fact that functional technology is not syn-onymous with effective healthcare. In The Logic of Care: Health and the Problem of Patient Choice, Annemarie Mol demonstrates that patient choice and cutting-edge technologies are not sufficient to secure the optimal health-care outcomes (Mol 2008). Of concern is how a patient un-derstands the technology, makes use of the technology and how the process of care enables or disables the patient. Al-though it is too early to determine the healthcare outcomes of nanomedicines, due attention should be paid to the pa-tient experience in the use of new technologies. For exam-ple, an anti-HIV gel could rest sound nanotechnology, but the general principle of a gel therapeutic may or may not be effective in certain environments. Previous work with such gels has shown that economic inequities and mistrust of anti-HIV campaigns shape health outcomes (AIDS Unit-ed). Mol describes the “logic of care” as one where healing is conducted through an iterative process of understanding the patient’s needs, offering tailored therapies, and review-ing how well the patient is able to live with the therapy. The “logic of care” is contrasted with the “logic of choice” where patients are treated as consumers of pre-packaged technol-ogies and therapies. While these kinds of issues are by no means unique to nanomedicine, they must be considered whenever implementing new technologies in the clinic.

Nanotechnology and care outcomes

References

Algar, W. R., Duane Prasuhn, MIchael Stuart, Travis Jennings, Juan Blanco-Canosa, Phillip Dawson, and Igor Medintz. “The Con-trolled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry.” Bioconjugate Chemistry 22 (2011): 825-58. American Chemical Society. Web.

Bashir, Rashid. “BioMEMS: State-of-the-art in Detection, Oppor-tunities and Prospects.” Advanced Drug Delivery Reviews 56.11 (2004): 1565-586. Web.

Bozeman, Barry. “Public Value Mapping of Science Outcomes: Theory and Method.” Center for Science, Policy, and Outcomes at Columbia University (Undated). Web.

Cozzens, Sussan E. Nanotechnology and the Challenges of Equity, Equality and Development. New York: Springer, 2011. Print.

Dobrovolskaia, Marina A., Dori R. Germolec, and James L. Weaver. “Evaluation of Nanoparticle Immunotoxicity.” Nature Nano-technology 4 (2009): 411-14. Web.

Drexler, K. E. “Nanotechnology: From Feynman to Funding.” Bulle-tin of Science, Technology, and Society 24.1 (2004): 21-27. Web.

Frietas, Robert A. “What Is Nanomedicine?” Nanomedicine: Nano-technology, Biology, and Medicine 1 (2005): 2-9. Elsevier. Web.

Green, M. R. “Abraxane(R), a Novel Cremophor(R)-free, Albumin-bound Particle Form of Paclitaxel for the Treatment of Advanced Non-small-cell Lung Cancer.” Annals of Oncology 17.8 (2006): 1263-268. Print.

Meller, A., L. Nivon, E. Brandin, J. Golovchenko, and D. Branton. “Rapid Nanopore Discrimination between Single Polynucleo-tide Molecules.” Proceedings of the National Academy of Sci-ences of the United States of America 97.3 (2000): 1079-084. Web.

Meyer, Jorg-Uwe. “Retina Implant - A BioMEMS Challenge.” Sen-sors and Actuators (2002): 2-9. Elsevier. Web.

Moghimi, S. M., A. C. Hunter, and J. C. Murray. “Nanomedicine: Current Status and Future Prospects.” Journal of the Federa-tion of American Societies for Experimental Biology 19 (2005): 311-30. Web.

Mol, Annemarie. The Logic of Care: Health and the Problem of Patient Choice. New York: Routledge, 2008. Print.

Nanotechnology Regulatory Science Act of 2011, S. 1662, 112 Cong., Govtrack.us (2011). Print.

Oberdorster, G. “Safety Assessment for Nanotechnology and Nano-medicine: Concepts of Nanotoxicology.” Journal of Internal Medicine 267 (2009): 89-105. Web.

Resnik, David B., and Sally S. Tinkle. “Ethical Issues in Clinical Tri-als Involving Nanomedicine.” Contemporary Clinical Trials 28 (2007): 433-41. Web.

Resnik, David B., and Sally S. Tinkle. “Ethics in Nanomedicine.” Nanomedicine (Lond) 2 (2007): 345-50. Web.

Rupp, Richard, Susan L. Rosenthal, and Lawrence R. Stanberry. “VivaGel (SPL7013 Gel): A Candidate Dendrimer - Microbicide for the Prevention of HIV and HSV Infection.” International Journal of Nanomedicine 2.4 (2007): 561-66. Print

Sanhai, Wendy R., Jason H. Sakamoto, Richard Canaday, and Mauro Ferrari. “Seven Challenges for Nanomedicine.” Nature 3 (2008): 242-44. Web.

Srinivasan, Vijay, Vamsee K. Pamula, and Richard B. Fair. “An Integrated Digital Microfluidic Lab-on-a-chip for Clinical Diagnostics on Human Physiological Fluids.” Lab on a Chip 4 (2004): 310-15. Web.

United States of America. Health and Human Services. Office for Human Research Protections. IRB Guidebook. 1993. Print.

Wagner, Volker, Anwyn Dullaart, Anne-Katrin Bock, and Axel Zweck. “The Emerging Nanomedicine Landscape.” Nature Biotechnology 24.10 (2006): 1211-217.


28

bioethicsjournal.com

Volume VII Issue ii

Documents

Transcript of Volume VII Issue ii