Embryonics Anonymous: Does Embryonic Stem Cell Research Require Consent?

Embryonic stem cell (ESC) research is undoubtedly one of the most heated bioethical issues in America today. While proponents of ESC research maintain that it will lead to considerable medical advances, detractors of the project contend that the practice is unethical in principle since it involves the deliberate destruction of human embryos, which they argue are humans who possess moral worth. While this controversy probably will not subside any time soon, another difficulty for current ESC research in the United States has arisen based on the possible lack of consent in certain cell lines.

In 2009, President Obama issued an executive order to the National Institutes of Health allowing for the federal funding of research on 198 human ESC lines approved by the National Institutes of Health. According to Rockefeller University researcher administrators Amy Wilkerson, Kathaliya Wongsatittham, and bioethicist Josephine Johnston in letter to the publication Cell Stem Cell, however, there is no evidence that any consent was given by the gamete donors for the use of their egg and sperm in originating 50 of these cell lines.

While Wilkerson has expressed that neither she nor her co-authors think that these cell lines should be removed from the registry due to this discovery, I think that a good argument can be made to the contrary using principles widely accepted by medical researchers. For instance, The Declaration of Helsinki of 1964 states in paragraph 25:

“For medical research using identifiable human material or data, physicians must normally seek consent for the collection, analysis, storage and/or reuse. There may be situations where consent would be impossible or impractical to obtain for such research or would pose a threat to the validity of the research. In such situations the research may be done only after consideration and approval of a research ethics committee.”

From this paragraph, it can be plausibly inferred a fortiori that experimentation and manipulation of identifiable human material requires consent as well since it is required for less important uses such as collection, analysis, and so on. Moreover, it is unlikely that obtaining consent for the use of gametes to produce embryos would have been impossible or impractical as it had been done for a number of other cell lines. Hence, as the ethics committee overseeing ESC research at Rockefeller University and two related institutions has also concluded. this appears to be a clear case of an ethical violation on part of the cell line providers involved, which warrants prohibiting future usage of these lines by researchers. I would advocate going further and simply removing these lines from the registry in order to eliminate the possibility any potential misuses of the cell lines in the future.

Wilkerson and her co-authors have indicated that their goal has been to inform other research ethics committees about the lack of evidence for consent in the origination of these cell lines. Hopefully, then, these other committees will take a harder stance against the use of these lines and the breach of ethics behind their creation.

It's not about ethics. It's about being smart.

There is no questioning the fact that the pros and cons of human experimentation has been one of the most important debates of the twenty-first century. While thousands of people involved in clinical trials, legal or illegal, have suffered from severe health deterioration including instant death, millions of people have received vaccinations for arguably incurable ailments such as polio, now on the verge of eradication. And the issue is becoming increasingly complex with time, as indicated by the following recent examples.

On 12^th April 2006, six volunteers at the North-wick Park Hospital in London were administered weakened doses of a drug called TGN1412 in the first human clinical trial conducted by researchers at a leading biotechnology firm called TeGenero. The drug was being explored as a potential treatment to auto-immune diseases like multiple sclerosis, in which the body's own immune system causes harm to the body's organs. Minutes after the infusion, all volunteers had to be transferred to intensive care as they faced life-threatening conditions which involved multi-organ failure. The United Kingdom’s Medicines and Healthcare Products Regulatory Agency immediately conducted an investigation, but did not find any flaws in the execution of the procedures in the research protocol initially submitted by TeGenero. Hence, it was ruled that this disaster was the result of unexpected behavior of the drug.

On the other hand, on 16^th July 2012, the U.S. Food and Drug Administration approved the market use of Truvada, a drug that reduces the risk of HIV infection in uninfected individuals who are at a high risk of catching the disease due to being engaged in sexual activity with HIV-infected partners. One of the events that lead to the eventual approval of this drug was a large, randomized clinical trial conducted by Gilead Sciences, the manufacturer of the drug, in 4,758 heterosexual couples where exactly one partner was HIV-infected. Truvada's safety and efficacy was demonstrated by the fact that the drug reduced the risk of being infected by 75 percent, with only mild side-effects such as diarrhea, nausea, headache etc.

The primary reason behind narrating these examples is to highlight the fact that human experimentation has 'huge' advantages and 'huge' disadvantages. Hence, an intelligent and powerful framework is essential to control the approval of these experiments. Intelligent, because the greater the expertise of the people who comprise this framework, the better the decisions made while reviewing experiments for approval. Powerful, because unless the framework has the authority to force its laws upon research groups/individuals, it cannot control the experimentation that takes place.

One way of implementing such a framework, as observed in many countries, is the establishment of government-funded agencies that adhere to a strict cost-benefit-analysis approach when evaluating experiments. Research without informed consent should not be permitted, not because it is ethically wrong, but because it would cause uncontrollable public unrest, resulting in people losing faith in their government. On the other hand, research which offers monetary benefits to volunteers should not be discarded without any further consideration based on ethical grounds, because the benefits of the same research to the society, if successful, might far outweigh the costs to the volunteers. Policies such as these might sound too radical at first, but the fact remains that the job of the government is to look after the betterment of the public. Experiments for which expected social benefit outweighs expected social cost, as determined after meticulous evaluation by experts (from fields beyond biology if necessary), must be approved and vice versa, because this is the only way of reducing the future occurrence of events such as the TGN1412 tragedy while also increasing the future occurrence of events such as the Truvada breakthrough. 

Sources:

1. http://www.nature.com/nature/journal/v440/n7086/full/440855a.html

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964774/

3. http://seattletimes.com/html/businesstechnology/2018699860_apushivdrugfda.html

4. http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/hivandaidsactivities/ucm312264.htm

Untested and Unproven Treatments: Would you risk it to save someone's life?

Outrage erupted after the terminally ill Terri Bradley was given an untested treatment in a desperate attempt to save her life. Terri, who is now deceased, was suffering from a life-threatening brain tumor. UC Davis doctors presented her with a consent form to receive treatment that had not been proven at all – the process had not even been carried out on animals. The procedure was “highly experimental, untested, unproven, and likely to be highly risky.”

The patient was informed of the risks involved and nonetheless consented to receiving the treatment. It must be noted, however, that Terri was dying, which must have played a huge role when she was making her decision. Patients who have little hope left of survival become desperate, and as a result, are easier to manipulate into doing crazy and absurd things. To capitalize on this is a highly unethical act from the doctors. Terri was willing to participate in the experimental procedure, partly because, irrespective of the result, she believed she could help further medical research in this field. However, consent from a patient does not automatically make a treatment ethical. According to clause 16 in the Declaration of Helsinki, the “responsibility for the protection of research subject must always rest with the physician, … even though [the patients] have given consent.”

The doctors claim that they were purely trying to provide an “innovative treatment”, rather than researching and performing experiments on their patients. However, is this defense even ethical? It is shocking that doctors find it acceptable to operate on a patient’s brain, unaware of what the after effects could be!

In the consent form given to Terri, the doctors even confessed that “there is no proof that such treatment might be beneficial” and that “the ensuing infection might cause further harm to the patient”. Does this not clearly violate one of the main ideas expressed in The Belmont Report: “do not harm”? The doctors may have been trying to respect Terri’s dignity by trying to save her valuable life, but this calls another aspect of human dignity into question – will Terri have a dignified life is she is completely miserable and in pain for the remainder of it? Terri’s daughter, Janet, said that her mother became a “vacant shell” following the operation, becoming depressed, apathetic and moody. While “she lived 18 months, … [it] was 18 months of hell.”

I disagree with the doctors’ decision to provide Terri with a treatment that was previously completely untested. Performing an experiment where the outcome is unknown is risky. When the experiment involves a human life, it is downright irresponsible. Yes, the doctors were trying to save Terri’s life. But they ended up causing her discomfort and suffering – something they were always well aware could happen.

Source:

http://www.sacbee.com/2013/02/11/5180237/impact-ethics-of-surgery-slammed.html

The Doomsday Virus: Should Research be Done on one of the Most Dangerous Virus in Existence?

A massive bio-ethical debate has been sparked surrounding a mutant strain of the H5N1 virus, or avian flu, was taken out of storage to resume research on the strain of the flu. The avian bird flu is one of the highest death rates of any pandemic. It has a death rate of nearly 60 percent while the flu of 1918, which killed 50 million people, had a death rate of only 2.5 percent. The only reason H5N1 hasn’t claimed many lives, only 364, is because it does not transmit well between humans due to the fact that it is not an airborne virus.

            The reason this H5N1 strain is such a controversy is because it has been genetically altered to become airborne and thus transmit between mammals much more effectively. At this point the U.S. National Science Advisory Board for Biosecurity (NSABB) asked the researches who developed this to do something unprecedented, they asked for the portions of the research paper that described how to make the virus more contagious to be removed to prevent the risks of bioterrorists learning how to make this virus into a weapon. This outraged other researchers because the sharing of research is the only way to progress the science.

            Eventually the researchers who created the virus decided to do something that was again unheard of, they stopped their research all together and put the last of the virus on ice. They wanted there to be a halt in research so they could explain their work. Just recently this moratorium was lifted and research started again but the debate still continues. Do the risks of bioterrorists or accidental releases of the virus outweigh the potential benefits of further research on the virus?

            In my opinion the virus should be released to a limited group of respected researchers for further study. This is because of a few key aspects. First of all if you limit who has access to the process of making the virus airborne to respected scientists you severely reduce the risk of the virus being used as a bio weapon. Also the mutations that make the virus airborne also make the virus much less lethal, the ferrets infected with the virus in the lab did not die. Lastly the mutations in the virus were not man made, they are all found in nature just not in the same strain of the virus. This means that it is incredibly plausible that the virus could naturally evolve to be transmitted thorough the air.

            The benefit of research outweighs the dangers in my opinion. If a vaccine could be created for H5N1 then it would no longer be a danger at all, like polio. If a vaccine cannot be made much more will be known about the virus and if an natural outbreak does occur it will be much easier to deal with anyway. Any of these benefits will be nullified if the virus is destroyed and research is completely halted. Then if a natural outbreak does occur the human population will be at a loss with what to do about the pandemic.

http://www.thestar.com/news/world/2013/02/10/mutant_virus_sparks_bioethics_debate.html

Unprepared to Protect Our Children: Pediatric Anthrax Vaccinations

If a widespread bioterrorism anthrax attack were to occur, the US would be able to vaccinate adults but would be unable to protect children, as proper pediatric vaccination dosages are not known. With this in mind, should the US government involve healthy children in clinical trials to develop an appropriate, and potentially crucial, pediatric anthrax vaccination?

The Presidential Commission for the Study of Bioethical Issues has been engaging in yearlong deliberation on this issue. The Commission was charged with balancing the risk to healthy children who would participate in the study with the devastating danger of being unprepared in case of a widespread anthrax attack.

This issue diverges from other pediatric research dilemmas. The Belmont Report states, “Medical research…is only justified if…there is a reasonable likelihood that this population…stands to benefit from the results.” While it is clear that anthrax could be used as a biological weapon, an attack might (and hopefully would not) ever occur. Thus, while treatment developed from research is, with time, generally put to good use, the results of this research could (and hopefully would) never prove necessary or beneficial to the participants. Since biological warfare is not naturally occurring like the diseases upon which most studies focus, the likelihood that children would eventually require and benefit from the results of the research cannot be predicted, which complicates the justification of the study.

 Furthermore, children participating in other clinical trials often stand to directly benefit from the study, as, through the research, subjects might receive experimental treatment for a disease from which they suffer. In contrast, an anthrax study that involves healthy children would most likely not provide any direct benefit to the participants. Thus, it is unclear whether or not involving these healthy children is ethically wrong.

While anthrax research differs from other studies because the results may never be needed, as with all research, not completing the project could potentially cause far more harm than does the study itself. If an attack was to occur and proper dosages were not available, the results could be devastating.

Can the United States in good conscience remain unprepared to protect its children—essentially sentence its youngest citizens to a terrible fate—in case of an anthrax attack? Or, knowing that the results of the study may never be needed and that the risk to potential subjects might, thus, never be justified, can the US really subject healthy children to the risks of participating in this research? And, if so, which parents would volunteer their children as subjects? How could the government ensure that the most vulnerable children (foster children, impoverished children, juvenile delinquents, etc.) are not targeted as subjects due to their easy availability? Children whose cancer is not responding to treatment might participate in an experimental study. In contrast, what would be the incentive for children to participate in this study? If the incentive must be compensation, how would the researchers ensure that subjects are not self-selected by financial desperation?

At the end of deliberations on this multifaceted ethical issue, the commission will complete an advising report for the President and Secretary of Health, who will then decide whether or not to pursue the pediatric anthrax vaccination research.

Sources:

http://www.miamiherald.com/2013/01/22/3187334/bioethics-commission-meets-at.html

http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html

Just One More Risk: Russian Enthusiasm for Participation in Medical Research

In the United States, participants in medical studies reported to the Economic Cycle Research Institute that they were motivated to take part in research based on trust in their physicians, the potential to aid future patients, or because they believed the study provided the best available treatment.  In Russia, the basis for participation is different.  A recent New York Times article, “Russians Eagerly Participate in Medical Experiments, Despite Risks,” describes how Russian citizens are increasingly enduring the dangerous side effects of drug trials.  Why do Russians undergo this ordeal?  It is the only means to access any form of medical care. 

            Sometimes, the outcome proves to be worth the risk, or at least according to the participant.  Galina I. Malinina injected herself daily with an experimental weight loss serum, and then enthusiastically tolerated two weeks of intense vomiting as a result.  However, at the conclusion of the study, she related the pleasant results of increased energy, fitness, and even quality of life.  While this case demonstrates a positive example, there are all-too-often serious side effects and no results to show for it.  On various occasions, the ingestion of experimental antibiotics by Russian research subjects has resulted in allergic reactions, loss of bowel control, vomiting, dizziness and various of other negative side effects.

            While pharmaceutical companies maintain that these trials are intended to be experiments rather than treatments, Russians readily offer their voluntary consent to act as guinea pigs and hope for the best.  The Russian government has encouraged the practice by signing a 2010 law that mandates that foreign drugs must be tested on Russians before entering the domestic market.  Though there are undeniable economic benefits of conducting medical studies locally, the participants’ motives and the possible side effects raise the question of whether or not the benefits outweigh the risks.

            The vast majority of these trials involve significant risks to the patients’ health.  However, in the eyes of Russian participants, the benefits seem to far exceed any potential risk of harm.  Americans generally have alternative means to seek treatment, and thus predominantly focus on side effects and the potential negative consequences.  In contrast, Russians do not dwell on the risks, and instead place precedence on the benefits.  To them, medical research is just one more risk in life, and the chance of a positive outcome will virtually always trump the risk.

To a Westerner, there is obviously something that seems wrong with this Russian phenomenon of eager research participants.  But is there truly an ethical problem?  Principle 16 of the Helsinki Declaration states that “The responsibility for the protection of research subjects must always rest with the physician or other health care professional and never the research subjects, even though they have given consent.”  Based on this notion, the physicians and medical personnel who are conducting the studies are at fault for not exhibiting adequate concern for the research subjects, even if the participants have provided voluntary informed consent.  Nevertheless, there seems to be no clear-cut solution.  Russian citizens cannot simply be prevented from participating without being provided with a reasonable alternative means to access medical care.  Furthermore, there is no authority that is willing and able to implement a change in policy.  Unless the Russian state or society as a whole can come up with a better option for these citizens, it seems that each individual is entitled to make an autonomous decision as to whether or not to participate in a potentially dangerous medical study.

https://www.ecri.org/Documents/Clinical_Trials_Patient_Guide_Evidence_Report.pdf

http://www.nytimes.com/2012/09/27/business/global/russians-eagerly-participating-in-medical-experiments-despite-risks.html?pagewanted=all