Getting the Best Possible Organs for the Rest of Us

By Mark McQuain

A recent September 6th Perspective in the NEJM entitled “Voluntary Euthanasia – Implications for Organ Donation” teases with the following lead-in:“Canada now permits physicians to hasten the death of a patient by means of physician-assisted suicide or voluntary euthanasia. This development creates a new pathway for organ donation – and with it, some challenges.” Kudos to the NEJM marketing department for luring me into finally buying a full subscription. I’ll summarize some key points for those without a subscription.

The article begins by summarizing some differences between the comatose patient receiving end-of-life care in a standard ICU environment and the situation of individual intending voluntary euthanasia in a hospital. Healthcare teams may rely on surrogate decision making in the first instance but require first person consent in the euthanasia instance. Also, use of sedatives and analgesics in traditional end of life care are guided by the doctrine of double effect (intending comfort but not death) whereas physicians are not legally required to titrate those same medications in the instance of voluntary euthanasia (where euthanasia is legal). These issues are effectively the non-controversial portion of the article.

The heart of the article dealt with what one ought to do in the situation of a patient who wants to donate his or her organs “in the best condition possible” while receiving voluntary euthanasia. This would involve “procuring the patient’s organs in the same way that organs are procured from brain-dead patients (with the use of general anesthesia to ensure the patient’s comfort).”

The problem is that these patients aren’t brain dead yet. The authors are frustrated that awaiting brain death, even in voluntary euthanasia, results in sub-optimal quality of the donor organs. Harvesting organs from voluntarily euthanized patients before they are brain-dead “would require an amendment to the Criminal Code of Canada, which defines medical assistance in dying as the administration of a ‘substance’ by a qualified provider. By this definition, organ retrieval is not an accepted cause of death.” (N.B.- Though it most certainly is the cause of death!)

For those unable to retrieve the NEJM article, I offer a similar article by Dominic Wilkinson and Julian Savulescu supporting the same ethical argument (that it is OK to cause the death of an individual by harvesting their organs if they wished voluntary euthanasia). They summarize Dr. Robert Truog’s bioethical position (one of the authors of the present NEJM article) in footnote 66 as follows:

“Truog’s justification for ODE [Organ Donation Euthanasia] is different from that presented here [in our paper]. He argues that current concepts of brain death and the dead-donor rule are incoherent, and he proposes an alternative based upon the principles of autonomy and non-maleficence. We find Truog’s arguments compelling. Our paper can be seen as providing a complementary argument in favour of ODE. Truog favours a narrow definition for the group of patients who may consent to this procedure: only those who will die within minutes of withdrawal of life support, or who are permanently unconscious. Our definition of LSW [Life Support Withdrawal] donors overlaps with Truog’s, but includes the larger group of patients from whom it is permissible to withdraw life support in intensive care, and whose death is highly likely to ensue (though not necessarily instantly).”

To be blunt, what both groups are arguing is that it should be OK to surgically remove organs from an individual who is not brain dead though has already consented to voluntary euthanasia, knowing that the surgical removal of the organs will cause the immediate death of the individual. The priority of marrying euthanasia and organ donation is obtaining the best possible organs for the rest of us.

As a counter argument, I again turn to Wesley Smith for his thoughts in a recent National Review article similarly entitled “Canada Conjoining Euthanasia/Organ Donation”. It is short and to the point.

I must concur with Wesley Smith: The slippery slope of euthanasia is getting more slippery. How long before we grease those skids further by paying for the organs so harvested?

Reducing Abortion Regardless of Roe v. Wade

By Mark McQuain

The selection of the next Supreme Court Justice has perhaps naturally unleashed a flurry of op-eds describing the post-apocalyptic world that will result from any partial or complete reversal of Roe v. Wade. In the July 18th, 2018 Perspective in the NEJM, Dr. Julie Ingelfinger offers the tragic case of a foreign nursing student she befriended while both were training in New York in the late 1960s. The student was finishing her final nursing year and was engaged to be married when she became pregnant despite the use of contraceptives. Per Dr. Ingelfinger, neither the student nor fiancé had “the means to provide for a baby, so they reluctantly decided that terminating the pregnancy was the only choice.” The only abortion option available at that time, pre-Roe v. Wade, was a “back-alley abortion.” After the abortion, the student developed sepsis, resulting in a hysterectomy and kidney failure. Dr. Ingelfinger oversaw the dialysis and despite appropriate medical care, the student died suddenly from complications of the dialysis. Dr. Ingelfinger’s reason for sharing this story now is to remind us that back-alley abortions resulted in similar complications in many other young women pre-Roe v. Wade and warn that if Roe v. Wade is overturned in the future, young women seeking abortion will again suffer the same fate as her nursing student friend.

In a similar vein to Dr. Ingelfinger’s editorial, there is a second op-ed on CNN website on May 5, 2018 by Danielle Campoamor entitled “Why Supporting Abortion is a Pro-Life Position”. She fears any future restrictions in Roe v. Wade will result in the suffering or death of young women seeking an abortion and wants everyone to have the “safe, affordable and relatively easy abortion” that she experienced:

“I wasn’t subjected to mandatory waiting periods, forced counseling or an abortion provider required to regurgitate state-mandated, inaccurate information. I didn’t have to travel long distances, worry I was getting there too late in the pregnancy, find money to pay for child care or walk past angry or intrusive protesters. Instead, I went in pregnant and, a few hours later, came out with my future back in my control.”

In both articles, the focus is unilaterally on the health and life of the mother. Ms. Campoamor’s position is easily challenged, if not decimated, by including the health and life of the baby in her calculus. Dr. Ingelfinger’s premise requires more unpacking.

Her position appears to be that all future unwanted pregnancies in an overturned-Roe v. Wade world would require a pre-Roe v. Wade “back-alley” surgical abortion. Many Latin American countries have never legalized abortion yet their illegal abortion fatalities have dropped as medical abortifacients (morning after pills) have replaced surgical abortion methods. Interestingly, both the author of the previously linked article on the Latin American experience and Dr. Ingelfinger cited economics (and not legality) as a main reason for choosing abortion. Analysis of the statistics on why women in the US choose to abort challenges this assertion. A clear understanding of these statistics might help identify strategies that lead to a voluntary reduction in the number of abortions, absent changes in the legal status of abortion.

There is a nearly 15-fold increased risk to carry a baby to full-term than it is to have an elective abortion. We have “successfully” divorced sexual activity from the risk and responsibility of bearing and rearing a child, as long as we are willing to use abortion as the definitive stop gap in maintaining our birth control. From my standpoint, this success and this control has come at a terrible price, namely the deaths of over 60 million babies in the US alone. Sadly, I pessimistically do not believe that there will be a meaningful change in the Federal law regarding abortion, regardless of who becomes our next Supreme Court Justice (link requires subscription). There are simply too many women and men who have come to rely upon the type of control of their future activities that abortion provides. Therefore, I ask Dr. Ingelfinger, Ms. Campoamor and all of those on the other side of the abortion divide: must all unwanted pregnancies end in abortion (medical or surgical), regardless of the status of Roe v. Wade?

The Benefits of your local Medical Ethics Committee Consultation

By Mark McQuain

No doctor or hospital system is perfect and, frankly, no one would ever claim to be. Regardless, we hold some medical facilities in very high regard simply because of the consistency of their record of care. One such place is the Mayo Clinic in Rochester, Minnesota. So, it was somewhat of a surprise to see a CNN headline featuring a complicated medical ethics issue gone awry. The story is long and admittedly somewhat one-sided, with more she said than he said. Still, the story as told is instructive by reminding everyone that medical ethics cases are complex, and it is usually best never to “go it alone”.

Briefly, in 2016, a 18-year-old young woman with a brain aneursym was transfered to the Mayo Clinic for urgent surgical treatment. Her surgery went well. The problems did not really begin until she was recovering on the inpatient rehabilitation unit. The patient and family became dissatisfied with her care. The staff believed that the patient was unable to make informed medical decisions due to alleged changes in her cognitive status as a result of treating the brain aneurysm and rather than appoint a family surrogate, began the long complicated process of trying to arrange for third-party guardianship. The mother and stepfather, in advocating for their daughter, came into conflict with the rehabilitation staff, resulting in the mother being banned from the hospital. The staff reached out to the biological father but he declined to become involved. The staff apparently believed the family to be unreliable and began a process to acquire a third party guardian to assist the patient with her medical decisions. The family and patient came to feel the patient was imprisoned against her will. The patient and her family eventually arranged “her escape” after which the rehabilitation staff called the police, claiming the patient was “abducted”. The patient has and is continuing to recover apart from Mayo. The legal issues remain.

Medical ethicists who have reviewed the details of the case agree on at least one detail: Mayo should have utilized their medical ethics committee to assist in determining how best to handle the patient’s possible lack of medical-decision-making ability, and in determining who might best serve as the patient’s surrogate if such was needed. Most medical providers have become involved in contentious medical decision making, where the patient and/or family comes to disagree with a recommended treatment plan by the medical staff. Involving the hospital’s medical ethics committee can be an excellent resource to regain dialog with the patient and family, and hopefully come to a medical decision that best benefits the patient.

The Cost of Getting RNA to Mumble

By Mark McQuain

In my previous blog entry, I crudely summarized the genetic basis for Duchenne Muscular Dystrophy (DMD) and one pharmaceutical company’s (Sarepta) current effort to research, manufacture and finance a genetic treatment that increases the production of a muscle protein missing in patients with DMD called dystrophin. Please see my previous blog entry for that summary or this article for a more detailed thorough overview of the science and investigational process to date. For this blog entry, I want to consider the bioethics of the cost of Sarepta’s treatment eteplirsen (Exondys 51), currently estimated on average to be around $300,000 per year.

DMD is a devastating disease that generally causes the patient’s death by his mid-twenties but it only affects a very small number of boys and young men worldwide, estimated to be around 400-600 newborn males in the US each year. This small number of patients places medications for DMD in a category called Orphan Drugs, those that benefit fewer than 200,00 people per year. Eteplirsen is only beneficial in the 15% of DMD patients that have the specific RNA defect in dystophin protein production that eteplirsen corrects. Back-of-the napkin calculations mean that if 15% of all 600 boys born in the US every year with DMD (90 boys per year) used Sarepta’s $300,000-per-year drug, that is a $27 million increase in revenue (not profit) to Sarepta each year. While that sounds huge, it ignores the massive expensive cost barriers to bringing such a drug to market, including research, investigational studies to gain FDA approval and legal financial risk with future adverse effects yet unknown. Inability to gain FDA approval prohibits access to capital markets necessary to fund such a process. Were it not for grants available for orphan drugs, it is unlikely that eteplirsen would exist. Better for drug makers to target their R&D to a bigger disease market for the chance of a bigger reward (consider Bayer aspirin and their $3.3 BILLION profit in 2011 alone).

There are calls for Sarepta to “give back” some of their potential future income, calls from the very organizations that were their staunchest supporters in their FDA approval process. Strong ethical arguments are made that the company did benefit early on by using federal grants and this alone should require the company to reduce a portion of their future income by lowing the cost to patients. Calls for the FDA to federalize Sarepta’s patents and take government ownership will most certainly go unheeded as that would cause every other orphan drug manufacturer to immediately discontinue any further financial risk for fear of similar confiscation.

There are, however, opportunity costs beyond the financial. Some would say that the FDA approved eteplirsen with extremely flimsy data, as less than 10 boys showed borderline promising results when the drug was approved in November 2016. That FDA approval allowed Sarepta to survive as a company. Per the editorial board at the Wall Street Journal(subscription needed):

“But if FDA had cashiered that therapy, Sarepta would have lacked the resources to continue its research and testing to treat Duchenne and develop what may be an even better drug. If eteplirsen had failed to get approval, dollars and brain power would inevitably have flowed toward treating other diseases with more promise of success. FDA has tremendous influence over private investment.”

Indeed Sarepta has new genetic treatments in the pipeline which reportedly do provide increased levels of dystrophin, even for RNA patterns beyond what eteplirsen can presently correct. Have the ends justified the means? Presently, for DMD patients, despite the $300K yearly price tag for eteplirsen, that answer may be – yes. Sadly, there are no other currently functional treatment options for DMD – yet.

From a public health standpoint (and a public funding standpoint), orphan drugs for treatment of small population diseases like DMD are non-starters. Is the only answer to provide the opportunity for great financial reward to encourage individuals to assume all of the private risk?

Forcing RNA to, at least, Mumble…

BY MARK MCQUAIN

We are at a turning point in medicine where instead of supplementing patients with proteins or enzymes that their bodies fail to manufacture due to genetic abnormalities, we soon may be able to re-engineer the abnormal DNA, restoring the DNA’s ability to instruct the body to make those same proteins or enzymes. On our way to full-fledged genetic engineering, we have learned that DNA makes something called RNA, which can be thought of as specific instructions for assembling these vital proteins, telling cells exactly how to assemble protein building blocks, called amino acids, in their proper sequence. Even a very minor disorder in a very long amino acid sequence of a protein can cause that protein to function poorly or not at all. When bad DNA makes bad RNA, or when good RNA gets subsequently damaged or misread, the protein either gets assembled in a garbled fashion, or not at all. Think of RNA as the boss of protein production who can speak clearly, mumble or say nothing at all. Recently, there is one well-known disease where it looks like it is possible to force bad RNA that presently says nothing at all to, at least, mumble.

The disease is Muscular Dystophy (MD) and the missing necessary protein is called dystrophin. Dystrophin is responsible for the structural integrity of muscle. Poorly formed or garbled dystrophin results in a mild form of MD, such as one called Becker Muscular Dystrophy (BMD) where patients can live well into their 40s or 50s. If no dystrophin is produced at all, a severe form of the disease called Duchenne MD (DMD) results, in which muscles simply fall apart over a shorter period of time, causing patients to stop walking in their teens, usually dying in their twenties from cardiac or respiratory muscle failure. While it would be great to restore normal production of dystrophin in patients with DMD, one company called Sarepta, appears to be able to cause patients with DMD, who normally do not make any dystrophin, to produce a garbled dystrophin, giving them a milder BMD-like disease.

Consider the following sentence: “The big red fat cat bit the sly fox and ate the shy jay”. The individual letters represent the RNA sequence and the three letter words represent unique amino acid protein building blocks, resulting in a meaningful protein sentence – think of this as the normal dystrophin protein in a healthy person. If the RNA was missing the 22nd through 24th letters (the 8th word “sly”), the sentence becomes: “The big red fat cat bit the fox and ate the shy jay”. It is a minimally garbled version of the first sentence but still meaningful – think of this as the dysfunctional dystrophin in milder BMD. If the original RNA sequence was missing only the 7th and 8th letters, the sentence becomes: “The big dfa tca tbi tth esl yfo xan dat eth esh yja y”. This sentence has no meaning beyond “The big” – think of this as no dystrophin in severe DMD. If we could get the RNA reader to ignore the first letter “d” in the last RNA sequence, the sentence becomes: “The big fat cat bit the sly fox and ate the shy jay”. We are back to a minimally garbled version of the first sentence but still meaningful – think of this as another dysfunctional protein in a milder “Becker-like” MD. This is how scientists at Sarepta appear to have taken an RNA sequence that originally said nothing and forced it to mumble, producing a new garbled form of dystrophin, which works better than no dystrophin at all.

I realize this has been a long walk in the weeds for some of our regular readers but hopefully it has provided some helpful background into the current treatment of MD and a sense of how much further we have yet to go. I will use this blog entry as background for my next blog entry to discuss some of the bioethics around the cost of getting RNA to mumble.

For now and for me, advancing medical knowledge like this convinces me of how fearfully and wonderfully we are made. (Psalm 139:14)

A Supreme Court of One

BY MARK MCQUAIN

Like Neil Skjoldal in yesterday’s blog entry, I, too, am a Supreme Court watcher and enjoy reading their decisions as some might enjoy watching a good sports match or listening to a beautiful symphony. Nerd that I am, I find a well-articulated argument a beautiful thing to behold, even when it runs counter to my bioethics, as it can be a learning experience to help me sharpen my counter argument. My counter argument becomes moot if five or more Justices concur with that original argument, as it is rare, though not impossible, for the Court to completely reverse itself.

Last week, the legal landscape suffered the equivalent of a San Andreas-like major tremor along its political fault-line with the announced retirement of Associate Supreme Court Justice Anthony Kennedy. Justice Kennedy has generally been considered the political center of the Court, the all-important tiebreaker, if you will, on controversial bioethical issues related to abortion, gay marriage and the death penalty. Presently, we give 9 Justices the authority to be the final interpreters of our laws, including those that determine our collective bioethics. Amazingly, we will accept a majority rule 5-4 split decision as being just as acceptable as a 9-0 unanimous decision when validating or invalidating our laws. Being the tiebreaker on previous controversial issues effectively made Justice Kennedy what I call “a Supreme Court of One”. And that is exactly how both political parties are treating the selection of Justice Kennedy’s replacement.

And they should.

In a past blog entry, I tried to make the case that it vitally matters who is interpreting our Constitution, as those individuals are grounding our secular bioethics. Allowing one tie-breaker to decide these important issues is too much power and responsibility in one individual but that has been the reality in our presently divided Court.

My favorite legal philosopher is the late Yale Law School professor Arthur Leff. He gave a lecture at the Duke University Law School in the late 1970s called “Unspeakable Ethics, Unnatural Law”. He made the case that if our source of right and wrong is anything other than a transcendental (unnatural) source, then the resulting ethics/law is always open to challenge. The U.S. Constitution is an example of a natural source of law, perhaps the best that mankind can create for itself, but, since it was created by us, it is therefore always open to challenge by us. Given its internal checks and balances, as long as “We the People” continue to agree to be governed by the Constitution (and this is by no means a permanent agreement), rulings by the Supreme Court essentially function as our collective approval of laws that determine our national bioethics.

I have shared the following quote from Leff’s lecture before but it again seems appropriate:

As long as the Constitution is accepted, or at least not overthrown, it successfully functions as a God would in a valid ethical system: its restrictions and accommodations govern. They could be other than they are, but they are what they are, and that is that. There will be, as with all divine pronouncements, a continuous controversy over what God says, but whatever the practical importance of the power to determine those questions, they are theoretically unthreatening. It is only when the Constitution ceases to be seen as fulfilling God’s normative role, ceases, that is, to be outside the normative system it totally constitutes, or when, as is impossible with a real God, it is seen to have “gaps,” that a crisis comes to exist. What “wins” when the Constitution will not say, or says two things at the same time?

Presently, the Supreme Court interprets those gaps and decides what wins and what loses in our national bioethics debates. Given our present evenly split Court, picking the next Supreme Court of One can literally make all the bioethical difference in the world.

Vaccines: Modern Trolley Car Dilemmas

BY MARK MCQUAIN

The Trolley Car dilemma is back in bioethics news. For those unfamiliar with the trolley car dilemma, you alone are responsible to operate a trolley track switch to divert an out-of-control trolley car away from five workers on one section of track only to cause the death of a lone worker on the only alternate section of track. The dilemma: someone is going to die, and you get to decide who. In a recent editorial in the June 13th New England Journal of Medicine, Dr. Lisa Rosenbaum nicely describes the utilitarian dilemma surrounding the public health risks and benefits associated with a vaccine for the dengue virus, a mosquito-borne virus that annually causes significant severe illness and death worldwide. The dengue vaccine, Dengvaxia, is a real-world trolley car dilemma. Dengvaxia presently can protect large numbers of patients from this deadly virus, but at the expense of causing severe illness and death in a much smaller number of patients, mostly children.

Dr. Rosenbaum describes our response to utilitarian thinking, correctly I think. We don’t mind utilitarian rules that negatively affect others, particularly when the rules tend to confer benefit to our group as a whole (the very definition of utilitarianism) but we resist utilitarian thinking when it threatens to affect us negatively as an individual despite overall benefit to the rest of our group. Healthy self-interest often conflicts with the utilitarian calculus that purports to determine the overall benefit to the group. In the case of Dengvaxia, if the deaths caused by the vaccine only occurred in people who would have died from the natural dengue virus anyway, there would be no problem. In other words, by golly, you all were going to die from the widespread disease anyway, and since the vaccine did save some of you from dying, there is really no new or additional loss. Net positive outcome, right?

Sadly, vaccines do not work that way. With Dengvaxia, it may be possible to create a pre-vaccine test for seropositivity for the virus. This would mean determining whether a person previously had a very mild case of the virus such that they would not suffer a catastrophic outcome from receiving the vaccine, thereby allowing them to safely receive the vaccine to prevent a more severe case of dengue in the future. Such a screening test may be possible but it would cost some unknown amount of additional money and would still not be 100% accurate. Even so, no vaccine is 100% safe.

How many lives would need to be saved and at what cost before we are satisfied with the cost/benefit ratio of Dengvaxia (or any vaccine for that matter)? Presently the World Health Organization is recommending a pre-vaccination test be developed and only vaccinate those who test positive for prior exposure. This is effectively saying that the vaccination is not only not required but not even presently recommended in endemic regions, this despite the fact that Dengvaxia clearly significantly reduces overall mortality and morbidity. If the disease were more contagious and more lethal than dengue, at what point does the vaccine, however imperfect, become mandatory? This is the ultimate trolley car switch for public health officials.

Aren’t trolley car dilemmas fun?

A Rose By Any Other Name…

Dr. Bernard Lo, professor emeritus at the University of California, San Francisco and present President and CEO of the Greenwall Foundation, a foundation that sponsors bioethics research, wrote one of the lead editorials in the May 31st NEJM entitled Beyond Legalization – Dilemmas Physicians Confront Regarding Aid in Dying. His main point was that regardless of the physician’s position, given the increasing number of jurisdictions where “Physician Aid in Dying” (his term, hereafter PAD) is now legal, at some point the physician will probably be asked about the process, as well as their position, and whether or not they are willing to participate, so it is better for physicians to have answers to those questions prior to that doctor-patient discussion. I think it is perhaps more important to understand the terminology in which these issues are presently being discussed so I encourage your review of the short editorial in the link before considering my following concerns.

I believe the lumping of all terminal care into the moniker PAD confuses the issue. Physicians have always participated in their patient’s care, including the death of their patients. What is novel is the expectation that physicians will hasten the death itself. A physician treating a dying patient has always been legal. What is becoming legal is physician-assisted suicide (PAS), specifically causing the death via suicide that the terminal illness has, at that point, failed to accomplish. A physician directly administering an agent with the intent to cause death should be physician homicide (PH) or at least physician manslaughter (PM), though it is unclear why the adjective “physician” should change the criminality of the event.

At one point, Dr. Lo appears to include Palliative Care within PAD but later clearly identifies them as distinct and separate options in his provision for patients with terminal illness. This is especially so given his statement that “perceived loss of autonomy and dignity is now a more common reason for requesting PAD than inadequate pain control.” If PAD simply was the preferred term for general end-of-life care then palliative care would obviously be one component. Since it is not, then Dr. Lo is really talking about PAS and he should use the term PAS rather than PAD and be honest about it.

Finally, Dr. Lo discusses the need to consider adverse outcomes “such as deciding whether to call 911 if distressing symptoms develop after lethal medications are ingested.” What does he expect 911 to do? I am assuming he wants their assistance in stopping the suicide process, nevermind that it was physician assisted. If a growing number of physicians are henceforth going to be expected to actively kill their patients, surely we can all agree to keep 911 as an emergency response unit of healthcare providers unambiguously dedicated to keeping their patients alive? A call to 911 seems a tacit admission that supporters of PAS aren’t exactly certain or in common agreement as to what euthanasia (“a good death”) or “Death with Dignity” is supposed to look like, and, perhaps more importantly, an admission that no one can control the dying process as well as they may believe they can. By the way, what does Dr. Lo mean by “distressing symptoms”? I thought the reason for providing PAS was that the original terminal process wasn’t going as desired and this was causing “distressing symptoms”. If the addition of PAS can cause more distressing symptoms, what has been gained through PAS? Certainly not euthanasia or “Death with Dignity”.

Discussing whether or not a physician should hasten their patient’s death for any reason is unfortunately a necessary debate given the present diversity of world views in our society. Describing that process in less specific terms such as “Physician Aid in Dying” does nothing to help that discussion. Like Neil Skjoldal said in yesterday’s blog entry, I also will “continue to advocate strongly against PAS, affirming God’s gift of life whenever and wherever I can.”

One Man’s Trash is Another Man’s DNA Treasure

Last month, investigators used big data analysis, public DNA genealogy websites and “Discarded DNA” to identify the Golden State Killer (WSJ subscription needed), an individual believed responsible for over 12 murders, greater than 50 rapes and over 100 burglaries in California between 1974 through 1986. While justice may be served if the legal case remains solid, there are some interesting bioethical issues that warrant discussion.

This blog has previously discussed the ethics of searching reportedly anonymized databases and the ability of algorithms to “unanonymize” the data (see HERE and HERE). The current technique used in the Golden State Killer case takes this one step further. Using a public genealogy database site, where individuals looking for distant relatives voluntarily share their personal DNA samples, investigators looked into these databases for partial DNA matches. A partial DNA match means that the investigators were looking for any relatives of the original suspect hoping to gain any identifying information of the relative, leading back to the original suspect. Then, using this narrower group of DNA relatives, investigators literally collected DNA samples this group of people unwittingly left behind, such as skin cells on a paper cup in the trash, so called discarded or abandoned DNA.

One man’s trash is another man’s DNA treasure.

Presently, neither the method of partial DNA search of public voluntary genealogy databases nor the collection of discarded DNA samples violates the 4th Amendment regarding unreasonable search and seizure. Neither the Health Insurance Portability and Accountability Act of 1996 (HIPAA) nor the Genetic Information Nondiscrimination Act of 2008 (GINA) provide protection as none of the data relates to health care records or employment, respectively.

Shouldn’t some law or regulation prevent my personal DNA code from becoming public, particularly if I have not taken steps to publicize it on one of the many public voluntary genealogy sites?

Since your DNA is the ultimate physical marker of personal identity, how much control do you or should you have over it? While you may wish to live a life of anonymity, your extroverted cousin who voluntarily provides her DNA to a public DNA database has just unwittingly publicized some portion of your family DNA as well as traceable personal family data that may allow others to know more about you than you desire. An energetic sleuth dumpster-diving your trash can retrieve your actual DNA. I shred my mail to avoid my social security number or other personal financial information from being obtained and used for identity theft. How do I “shred my DNA” to prevent it from being similarly recovered from my trash?

What may someone do with my DNA information obtained using these techniques. What should someone be able to do?

You could not have convinced me back in 2001 that anyone would spend money to build cars with 360 video equipment and figure out optimal routes that would eventually become what is now Google Street View. Might not someone do the same thing with trash-sourced DNA samples, perhaps Google DNA View?

We already have figured out the garbage truck routes.

Deep Brain Stimulation: the New Mood Modifier?

A patient of mine recently had a deep brain stimulator (DBS) placed to reduce her severe tremors. The stimulator has worked very well to almost eliminate her tremor but has resulted in a side effect that causes her personality to be more impulsive. Her husband notices this more than the patient. Both agree that the reduction in the tremor outweigh the change in her personality though her husband has indicated that her personality change has been more than he imagined when they were initially considering the surgery. He has commented that if her new impulsivity were any stronger, he might be inclined to reverse the process. As one might imagine, the patient sees no problem with the impulsivity and remains extremely pleased with her newfound lack of tremor.

I share the preceding clinical vignette as backdrop to a recent article in Nature describing research funded by the US military’s research agency, The Defense Advance Research Projects Agency (DARPA – the same group that sponsored the early development of the Internet), where they are looking into modifying neural activity with the goal to alter mood, and eventually cure mental health disorders. Using patients that already have DBS stimulators in place for treatment of epilepsy or movement disorders such as Parkinson’s Disease, scientists are developing algorithms that “decode” a person’s changing mood. Edward Chang, a neuroscientist at the University of California, San Francisco (UCSF) believe they have a preliminary “mood map” and further believe that they can use the DBS stimulators to stimulate the brain and modify the local brain activity to alter the patient’s mood. The UCSF group describes this as a “closed-loop” (using the stimulator to both receive and then stimulate the brain). Chang further admits that they have already “tested some closed-loop stimulation in people, but declined to provide details because the work is preliminary.”

If scientists are on the verge of changing your mood, might they not also be on the verge of creating your urges? Professor Laura Cabrera, a neuroethicist, and Professor Jennifer Carter-Johnson, a lawyer, both at Michigan State University, argue we need to begin worrying about that possibility and further that we need to begin considering who is responsible for those new urges, particularly if those urges result in actions that cause harm against other people. The article does a masterful job of the ethical-legal ramifications of just what happens when your DBS causes you to swerve your car into a crowd of people – Is it your fault or did your DBS make you do it?

Returning to my patient, the alteration in her behavior is an unwanted but not a completely surprising result of her DBS to treat her movement disorder. Despite the informed consent, her husband was not prepared for the change in her personality. The treatment to correct my patient’s movement disorder (a good thing) has altered my patient’s personality (a not-so-good thing). My patient’s husband might even argue that his wife is almost a different person post DBS.

When we modify the brain in these experiments, we are intentionally modifying behavior but also risk modifying the person’s actual identity – the “who we are”. As the DARPA experiments proceed and cascade into spin-off research arms, we need to be very clear with patient-subjects in current and future informed consents that the patient who signs the consent may end up very different from the patient who completes the experiment. How much difference in behavior or urges should we tolerate? Could the changes be significant enough that they are considered a new person by their family and friends?

And if that is true, who should consent to the experiment?