Vaccines: Modern Trolley Car Dilemmas

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 safety concern with gene editing

Hat-tip to Dr. Joe Kelley for bring this to my attention…

As readers of this blog will recall, there is keen interest in exploiting recent discoveries in genetic engineering to “edit” disease-causing gene mutations and develop treatments for various diseases.  Initially, such treatments would likely use a patient’s own cells—removed from the body, edited to change the cells’ genes in a potentially therapeutic way, then return the altered cells to the patient’s bloodstream to find their way to the appropriate place and work to treat the disease.  How that would work could differ—make the cells do something they wouldn’t normally do, or make them do something better than they otherwise do (as in altering immune cells to treat cancer); or maybe make them work normally so that the normal function would replace the patient’s diseased function (as in altering blood cells for people with sickle cell anemia so that the altered cells make normal hemoglobin to replace the person’s diseased hemoglobin).

Or maybe we could even edit out a gene that causes disease (sickle cell anemia, Huntington’s disease) or increases the risk of disease (e.g., BRCA and cancer) so that future generations wouldn’t inherit it.  Or maybe we could edit genes to enhance certain health-promoting or other desirable qualities.

The recent scientific enthusiasm for gene editing is fueled by the discovery of the relatively slick and easy-to-use (if you’re a scientist, anyway) CRISPR-Cas9 system, which is a sort of immune system for bacteria but can be used to edit/alter genes in a lot of different kinds of cells.

It turns out that cells’ normal system to repair gene damage can and does thwart this, reducing the efficiency of the process.  The key component to this is something called p53, a critical protein that, if abnormal, may not do its repair job so well.  When that happens, the risk of cancer increases, often dramatically.  In cancer research, abnormal p53 is high on the list of culprits to look out for.

Two groups of scientists, one from the drug company Novartis and one from the Karolinska Institute in Sweden, have published on this.  P53’s thwarting of gene editing is particularly active in pluripotent stem cells, that are some, but not the only, candidate cells to be edited to create treatments.  These cells are also constituent cells of human embryos.  If the CRISPR-Cas9 process is used on these cells, p53 usually kills them off—unless it’s lacking or deficient, in which case it doesn’t, but also in which case it means that the altered cells could themselves become cancers, later on.

This is something that has to be monitored carefully in developing cells as medicines, so to speak, with genetic editing.  One does not want the patient to appear to be healed, only to develop a cancer, or a new cancer, later on.  One certainly would want to know the risk of that before editing an embryo—an unborn human, a future baby if placed in the right environment—to create a gene-edited human being.

Yet, as I’ve written here in the past, it appears that experimentation in heritable gene editing is pressing on.  I’ve argued, and continue to argue, that heritable human gene editing is a line that must not be crossed, that would place too much trust in the providence of the scientists/technologists who are the “actors” exerting power over fellow humans who become “subjects” in a deep sense of the term; that the risks to the subjects are undefinable; that it would enable perception of humans as “engineering projects”; that the gift of life would tend to be replaced by seeking to limit birth to “the people we want”; that the people acted upon are unable to provide consent or know what risks have been chosen for them by others, even before birth.  Rather than press ahead, we in the human race should exercise a “presumption to forbear.”

A counter argument is that, in limited cases where the genetic defect is limited and known, the disease is terrible, treatment alternatives are few or none, that the risks are worth it.  The recent papers seem to expose that line as a bit too facile.  How many embryos created (and destroyed) to develop the technique before “taking it live?”  Could we work things out in animals—monkeys, maybe?  How many generations to alter, create, and follow to be sure that a late risk—such as cancer—does not emerge?  Or maybe our animal rights sensibilities stop us from putting monkeys at such risk—maybe mice will do?

The new papers are dense science.  Frankly, I can grasp the topline story but have trouble digesting all the details.  More sophisticated readers will not be so impaired.  The news report, in the English of the general public, can be read here, the Novartis and Karolinska reports read (but not downloaded or printed) here and here, respectively.

More on physician-assisted suicide

Recently, Dr. Arthur Caplan of NYU, on the Medscape service (subscription required), took on the question of whether physician-assisted suicide (PAS) should be allowed for old folks just because they are old, or because they want to die together.  There have been reports of just that.  While he supports PAS for terminal illness but objects that PAS for “suffering” in general is just too fuzzy, and therefore rejects broadening it.  An accompanying poll of doctors reported:  64-36% against PAS for old age, but 69-31% in favor of PAS for terminal illness.  As some advocates of PAS, like the editors of The Economist, have pointed out in the past, however, this distinction is highly difficult to sustain:  if someone is suffering “intolerably,” who are we to overrule that person’s wishes based on a diagnosis of the cause of said suffering?

Better is to recognize, as Neil Skojdlal noted this week, that real palliative care is not PAS, but is the ethical alternative.  And as Mark McQuain noted this week, changing the terminology confuses, rather than clarifies, the issues.  At least Dr. Lo, whose New England Journal of Medicine editorial Mark reviewed, accepted that not all physicians will accept PAS or be willing to offer it or refer for it.  He seemed to make room for that—unlike some advocates.

In a related item, Hastings center president Mildred Solomon “Calls for ‘Moral Leadership’ to Improve End-of-Life Care.”  In essence, she argues that over-emphasis on “autonomy” can be a way for doctors to abdicate their responsibility, and leave patients out to dry without guidance in end of life decision making.  She argues for a more relational approach, rethinking social supports to provide people with broader help in late life.  Makes sense.  She doesn’t address PAS in the brief piece I’m citing here, but I would certainly leave that out of the list of recommendations.

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.”

Physician Assisted Suicide, Again

Last month, I sat through a presentation on the ethics of Physician Assisted Suicide (PAS) in a local hospital.  I attended the presentation, not because I am unfamiliar with the arguments on the subject and ambivalent about my feelings on it, but because I wanted to observe how it was presented, what the reaction of the audience was to the presentation, and how it might affect my work as a hospital chaplain.

For some context, the state where I reside, Florida, does not have a PAS law on the books, nor, according to the “Death with Dignity” website, is it even considering one.

I found the presentation to be disappointing, in part because the participants talked past each other as if they were on a cable news program, repeating the typical talking points that have become so common over the years.  It was also disappointing because it used the classic example of a sad, horrible death story to advocate the use of PAS with the highly manipulative question, “You wouldn’t want your loved one to experience this, would you?”  No one ever seems to respond that we cannot build a law out of such experiences because hard cases make bad law, nor does anyone ever take the time to wonder what else could have been done to make the suffering patient more comfortable.  It simply is an elevation of human autonomy to a staggering height.

At the end of the presentation, the PAS advocate asked for a show of hands on people’s support/non-support of PAS.  I didn’t have the heart to count the hands, but the speakers said it was about 65%-35% in favor of PAS.  My worst fears had been confirmed.  After what I witnessed in that presentation, I have no doubt that we are headed full-speed ahead towards a civilization that will in some way systematically encourage its elderly, its weak, its sick, and its disabled citizens to make a “compassionate choice” and choose “death with dignity.”  Those of us who think otherwise are firmly entrenched in the minority.

I understand that I am not the first person to have had this experience, and in some ways I have anticipated this day for some time, but because I saw it so close to home, it still was somewhat shocking to me.   When filling out the seminar evaluation, I found the question, “How will apply what you have learned today to your current practice?”  I’m not sure what the reviewers thought, but my response was simple: “I will continue to advocate strongly against PAS, affirming God’s gift of life whenever and wherever I can.”

Coming home to roost

Hoo boy.

Scientists who want to study human embryonic development have heretofore been self-limited by a 14-day rule:  embryos can only be experimented on up to 14 days of age, when they start to develop a nervous system.  This is an attempt to avoid censure for unethical experimentation on human subjects, and is seen as something of a concession, since it does not accept that human life begins at conception.

And, inevitably, they seek work-arounds.  One reported this week by Nature is the creation of human chicken hybrid embryos.  Why would someone want to do this?  (Jokes about the San Diego Chicken are NOT called for here.)

Well, apparently 14 days of embryo age is when critical organization takes place, directed by “organizer cells” that don’t appear before then.  So a group of researches did this:  they took embryonic stem cells (which itself might well require creating and destroying an embryo), and made “embryo-like structures” that had cells that either were, or were just like, these “organizer” cells.  (Apparently these structures were not capable of growing into babies, but even if not, ethical issues remain.)  Then they transplanted these cells into chicken embryos, and watched the resulting hybrid grow, and learned something about how human embryos develop.  They figure this is less of an ethical problem than trying to experiment on a fully human embryo older than 14 days, and that hybrids like this might be able to take the place of experimenting on human embryos to answer many of their questions.

Other scientists disagree with this last statement, and still think they must experiment on fully human embryos to get their answers.

Either way, at a minimum it seems that this work will require creating embryos solely for research, and there is in principle no limit on manipulating the human organism in the name of knowledge.  Work is common on some kinds of “hybrid” animals with human cells, such as immune-deficient mice who have human cells transplanted to reconstitute their immune systems.  But that work usually is done with human cells transplanted into fully-formed mice, which appears different from early, hybrid embryos.

The article describing this work says that the hybrid embryos “didn’t live long enough to hatch.”  Wonder what they would have been like if they had.

Care Dis-integration

The May 3rd edition of the New England Journal of Medicine brings us a powerful story. It is a tale of a patient, named Kenneth, written by his physician brother.

Central to the story is a delay in diagnosis, brought on by unfamiliarity with the patient as a whole person, biases against those with mental illness, presumptions and other errors familiar to those of us with an inside view of what can go wrong. The healthcare system allows these to occur through its “dis-integration.” From the story:

Rosenbaum highlights the larger problem: “Care integration is an attitude.” But this “attitude problem” affects countless U.S. patients, not just those with mental illness (or severe physical disabilities, like quadriplegia).Whose attitude, then, needs adjustment? Many doctors and nurses seethe about the profit-driven dis-integration of our health care “market” yet insist they can’t fix this mess themselves. Kenneth, no stranger to cognitive dissonance, said, Well, if they can’t fix it, who the hell can? This question becomes more urgent as our health care system’s balkanization becomes increasingly “normalized.”

I have just seen this up close. A friend of mine has a terminal illness. While he has long been well-served by his family physician, the onset of the illness brought specialty care, extensive and repeated imaging, hospitalizations, a rehabilitation facility, and no more contact with his physician. It also brought delayed diagnoses which seemed avoidable had he been seen regularly by someone who knew his story and his usual condition.

Wasn’t such familiarity what we always had hoped would come from the “specialty” of family medicine? And that years of familiarity would lead to an understanding no stranger could have? Such an understanding would give us what we longed for in medicine, such as more efficiency, avoidance of excessive and intrusive testing, smoother transitions of care, more acute perception of changes (and quicker diagnoses), and better advice.

Increasingly, however, the family physician of today can no longer fulfill the promise of the profession from decades past. Financial constraints keep him in the clinic exam room, efficiently churning through patients within a narrowing scope of practice— no longer on the wards, or in the nursing home, or performing obstetrics, or even seeing children under two. Unable to venture out because time (equals money) would be lost, he is no longer involved in the care of his patients when they need something beyond his clinic. And it is in those intense moments that he is needed the most.

I would like to have a simple answer. Kenneth’s question stings: “Well, if they can’t fix it, who the hell can?” The financial pressures are enormous, however. Costs are up for countless reasons, and to keep the money flowing, a physician becomes the engine that must keep running… inside the engine room that is the modern day clinic.

Perhaps nothing short of a major disassembling of our medical system will change that. Such change may only come from catastrophe; even then any rebuilding would take a level of insight and courage…and preparation…that are unlikely to appear in future leadership under modern pressures. If we’re ever to move toward a dream of “care integration,” however, we’ll have to start somewhere– with understanding where we are, how we got here, and where we ought to go.

A pause for doctor-assisted suicide in California

Readers of this blog probably saw this week’s news that a California judge blocked the state’s End of Life Options Act, the one that legalized doctor-assisted suicide in California.  The law passed after apparent failure in a regular California Legislature session, when its sponsors brought it up again in a special session that was supposed to be about Medicaid funding.  The judge said that inserting the assisted suicide law into that session violated the California state constitution.  So doctor-aided suicide is on hold in the state, for the moment.

Sort of a technicality, and celebration of the decision by folks (like me) who are staunch opponents of assisted suicide is likely to be short-lived.  Supporters will certainly challenge the ruling on appeal, perhaps win, perhaps also bring up the law anew in the Legislature, with (re)passage all but certain.

Legal assisted suicide is still bad policy, and assisting another’s suicide is still unethical.  But efforts against it have to address the attitudes and perspectives of our fellow citizens.  Allowing doctors and others to aid suicide poisons the central calling of medicine to protect life and to address human suffering accordingly.  It risks undermining proper palliative care.  It creates a “duty to kill” that someone has to step up to fill—or to be conscripted to fill, against moral objections that will be rejected as “inconsistent with standards of medical practice.”  It cannot logically be limited to the terminally ill (see Steve Phillips’s May 9 post on this blog) and cannot be reliably limited to those who freely and willingly choose death.  And it opens the idea of “rights” to misuse by those who desire death and to misappropriation by those who have reason to think that someone else should desire death.

Opposing assisted suicide is a longer undertaking, more than one vote or even series of votes, more than a court case with appeals.  It requires the cultivation of moral virtue by ourselves and our posterity.  It requires humble compassion subject to valuing the sanctity of human life.  It requires changed hearts.

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.

Choosing to die

When people present an argument for the moral permissibility of euthanasia they commonly start with a case in which a person is suffering from a terminal illness and has uncontrolled pain. They say that we should have no moral reason to say that it is wrong to assist those in such a condition who choose to end their life as a means of ending their suffering. This is a combination of two arguments. One is the argument from compassion that says that we have a moral obligation to minimize suffering and that euthanasia should be used if it is the most effective way to eliminate a person’s suffering. The other is the argument from respect for autonomy that says that people should be able to make decisions about their own lives, which should include the decision to end their lives, and that their physicians should respect those decisions. It has been pointed out by many who take the position that euthanasia is wrong that if these are good arguments for the permissibility of euthanasia they should be able to stand on their own. If we take these arguments individually, they lead places we should not want to go.

A couple of weeks ago I wrote about the concerns that many who live with disabilities have regarding the argument from compassion. It says that it can be the right thing to do to end a person’s life when that life is no longer worth living. They are concerned that if they become unable to make their own decisions someone will decide their lives are not worth living and they will be euthanized nonvoluntarily.

A recent case of joint euthanasia by a married couple in their mid-nineties in Canada reported in the Globe and Mail shows what can happen when the argument from respect for autonomy is taken by itself. George and Shirley Brickenden, who had been married for nearly 73 years, choose to die together. They died by lethal injection while lying on their bed holding hands in the presence of their children and clergyman. There was question about whether they both met the criteria of the Canadian law, which requires that the person receiving assisted death be suffering intolerably from a grievous and irremediable condition and that death is reasonably foreseeable. Even though Shirley suffered from long-standing rheumatoid arthritis and heart problems and George had recently begun having fainting spells from a heart rhythm problem, the primary reason for choosing euthanasia was that they did not want one of them to die and leave the other behind.

If the argument from compassion is a reason to accept euthanasia then we must accept nonvoluntary euthanasia in spite of the concerns of those with disabilities. If the argument from respect for autonomy is a reason to accept euthanasia then we must accept euthanasia for any reason given by a rational person including the desire of a married couple not to have one spouse survive longer than the other.

Rather than going to these extremes it seems reasonable to accept that there are limits to the things we ought to do to diminish suffering and there are limits to how far we should go in respecting a person’s autonomy. The intentional killing of an innocent person lies outside those limits.