Medical errors and more medical errors

Last week the BMJ reported that annually, there are 251,000 hospital deaths due to preventable medical errors in the US. There’s some debate about the calculations that they used to arrive at that number, and about what exactly constitutes a medical error. However, rather than quibble over the fine points, let’s acknowledge that medical errors are an ethical problem that must be addressed. In this post I would like to widen the conversation beyond the hospital walls. Below is a sample of some deaths due to preventable medical errors that weren’t included in the BMJ calculations (most of these ones happen outside of hospitals); nevertheless, they too affect thousands of people annually. I will also attempt to provide a taxonomy of the relevant errors.

Deaths due to the inability of the patient to obtain medical care because they couldn’t afford the care or the insurance — unknown number. The medical error here is a systemic one, the rationing of health care on the basis of who can pay for it.

Deaths of patients due to their being the subjects of human research — unknown number. This is peculiarly prevalent among embryonic patients (as Jon Holmlund wrote about last week). The medical errors include the failure to extend to embryonic research subjects the protections enumerated in the Declaration of Helsinki. There is also a category error: classifying embryonic patients as something other than human beings.

Deaths of embryonic or fetal patients through elective induced abortion — 977,000 (2014 data). The same category error as previous comes into play here: the failure to recognize the humanity of the unborn human.

Deaths of patients from drugs prescribed by their physician for the purpose of suicide — the numbers data is incomplete. The number is relatively low but projected to grow as more jurisdictions legalize physician-assisted suicide. The errors here include a professionalism lapse (forgetting that the professional status of medicine was established, among other things, on the dictum that doctors do not give deadly drugs, even if asked to do so). There is also the error of hubris: the belief that doctors can decide that someone should be allowed to kill themselves.

Preventable medical errors, all.

A Step Toward Ex Vivo Gestation?

The biggest news of the week has nothing to do with the U.S. presidential election.  The bigger scoop is that scientists have grown human embryos in the lab for 13 days after fertilization.  The previous record was 9 days.  The work was stopped after 13 days’ maturation because many societies ban research on human embryos that are more than 14 days old, the latest point at which natural twinning can occur and at which, according to the reasoning behind the ban, a unique individual exists.

This work was done on embryos “donated” from an in vitro fertilization (IVF) clinic.  Potential applications include using older human embryos to text the toxicity of new drugs (pushing the dose concentration until toxicity occurs), studying birth defects, trying to understand how to grow stem cells into embryos or something like it, and improving the efficiency of IVF.  In all cases, embryos would be destroyed (that is, killed on purpose) for the sake of research, and if “donated” embryos were not available, then some would have to be created solely for research.  So the embryos are like lab animals, except that PETA wouldn’t get upset.

If, as I hold, human life begins at conception—and the recent “flash of light” observed by Northwestern University researchers at fertilization is provocative, at least—then keeping the embryos alive longer is ethical only if the subsequent intent is to bring them to term.  Turning a human stem cell into a human embryo is an unethical enterprise at its core, as is using the embryos for pharmaceutical toxicology experiments.  If insights into birth defects or IVF efficiency could be gained without killing the embryos on purpose, that could be ethical.

Of course, any ethical concern about such treatment of human embryos will be rejected by the technological community as “politics interfering with science.”  That’s always the charge when an elected official raises life issues. 

And, not surprisingly, the 14-day boundary is now being challenged because it is appearing technically feasible, in the foreseeable future, to keep embryos alive in the lab for longer, and ultimately “lead to scientists being able to study all aspects of human development with unprecedented precision.”  So it goes with any bioethics ban; agreed to only when there is no associated opportunity cost.

I expect that soon the “boundary” will be moved to some point that is deemed politically palatable—perhaps 13 weeks, the end of the first trimester—and will be moved again when that boundary is approached at some undetermined future point.  It could take a while, because beyond 14 days interaction with Mom apparently is critical for future growth.  But it will be tried, because the embryologists, without irony, are embarrassed that they can tell their students more about animal embryology than human embryology.  Also, if the aforementioned stem-cell-to-embryo-like-object work progresses, it will be unclear whether the result is really a human embryo, and therefore subject to the ban.  Maybe someday someone will bring such a construct to term in an attempt to settle the question.

Working back from the other direction, maybe work on an artificial placenta or artificial uterus will facilitate further growth and maturation of embryos outside the human womb. 

 

So much of this work seems so monstrous on its face, as the logical endpoint at least used to sound monstrous when Huxley wrote of it decades ago, but the point now seems lost.  There is no stopping this.  Leon Kass some time ago fretted that someday some religious conservatives might accept “babies born in bottles as long as no embryo is destroyed in the process,” except many will be destroyed on the way there, and the end result would be the complete replacement of human procreation with production.

Crazy?  I’m not a young man, so maybe I’m just turning into a cranky old one.  Or maybe I’m just putting politics in front of science, instead of quietly capitulating.  The 14-day limit should stay in place.

In the name of God, forbear!

A Bit More about the Minimal Genome

Earlier this week, Mark McQuain posted a nice summary of the recently-published work by J. Craig Venter’s group to identify a “minimal genome” for a type of bacterium, the mycoplasmas, which are, as the group points out, “the simplest cells capable of autonomous growth.”  Mark wondered aloud what the implications would be for our understanding of what it is to be human—how many genes do you need to be human?

A few preliminary thoughts about that:

  • ·       I would say—perhaps contra Dr. Venter—that we are not our genes.  The great technical achievement of Dr. Venter’s group is to use modern genetic methods to synthesize mycoplasma genomes on the lab bench, and implant them into the rest of an existing mycoplasma, and show that the result can thrive with characteristics driven by the synthesized genome.  But I don’t think even he, who has said that “DNA is the software that writes its own hardware,” would say that the DNA alone is the organism, even for the mycoplasmas.
  • ·       It took a lot of attempts to piece together a set of “minimally required” genes.
  • ·       The effort was not from the ground up, but was done by breaking the genome into pieces and iteratively testing the pieces to find out how essential they are.  Indeed, taking what had been thought to be known about how essential individual genes are, and “just” deleting the other ones, did not leave them with viable organisms.
  • ·       In the process, there were a lot of failures.
  • ·       One advantage of working with mycoplasmas is that their genetic simplicity is in large part because they are “fastidious” organisms, with narrow strictures on what they need to survive, and so not very adaptable to changes in environments.  Lots of genes in lots of organisms are presumably there to make the organisms adaptable and robust.
  • ·       Indeed, their work found that there were certain “quasi-essential” genes, that might leave the resulting organism “alive,” but not capable of much growth—that is, not so alive after all.  Or should we say the organism has a poor “quality of life?”

So this work is intriguing in the first case for what it might eventually tell about the life of single-celled organisms.  I want to imagine novel antibiotics someday, as a result—maybe we should hope someday soon, given the rise of antibiotic-resistant bacteria.

But I extrapolate from the same complexities and challenges of this work to argue that a search for a “minimal human genome” is a quest that ought never be attempted, because to try would be to create, on purpose, a series of critically deficient human or humanoid embryos that would have to be raised to substantial viability to determine just how “well-endowed” they were.  It seems to me this would have to be, if not the final goal of the enterprise, an intermediate goal.  Before embarking on it, humanity would require that it be the absolute scientific/technological last resort to solving a critical human need.  That might be a good sci-fi story, but not a path that I would expect ever to become illuminated.  The more likely approach of “try it and see where it leads” is, I think, morally unacceptable.  I would say the same thing about the other big goal of synthetic biology (the fusion of biology and engineering); viz., creation of a “protocell”—a cell made of only the minimum set of biomolecules necessary to function.  I could see doing that to a yeast or bacterium for production of drugs in a lab or factory, but not to human somatic cells, much less to human germ cells. 

And I have a hard time embracing the notion of ever extending minimal genome or protocell work to animals or even higher organisms, because—why?  What’s the goal of the research? 

The current minimal genome work is far from the point at which we ought to limit our tinkering, but I believe that point exists, a point at which knowledge is not a sufficient justification, at which sufficiently good ends cannot be articulated, and at which we ought to observe a “presumption to forbear.”

Genetic Prime Patterns

Last month, Science published the results of an ongoing experiment conceived to determine, among other things, the minimum number of genes necessary for viability in a mycoplasma bacterium. Calling their engineered result Syn 3.0, scientists at the J. Craig Venter Institute (JCVI) rearranged and reduced the number of genes on the single chromosome of a M. mycoides bacterium and inserted it into a different mycoplasma called M. capricolum, whose genetic material had been removed. The new genetically rearranged mycoplasma had just 473 genes, 52 fewer than the 525 found in the naturally occurring smallest cousin M. genitalium. Starting with their first artificially rearranged viable mycoplasma, Syn 1.0, which had 901 genes, the JCVI scientists divided their artificial chromosome into roughly eight sections and began trial-and-error substitution and rearrangement until they arrived at the current frugal collection of possibly necessary but certainly sufficient genes for viability. While the bacterium successfully reproduces itself, I am not sufficiently skilled in taxonomy to determine whether or not the resulting organism is still a mycoplasma or something else altogether.

Regardless, the project has many benefits, the most significant of which is to learn which genes do what in the life of this bacterium. Out of the 473 genes in Syn 3.0, scientists are confident of the function of 324 of those genes. This means that the remaining 149 genes are necessary but mysterious as to what role they play in the life of this particular mycoplasma bacterium. Efforts continue in an attempt to gain a more detailed understanding of the function of these genes and to eliminate any remaining genes to arrive at the fewest genes necessary for viability, what I am calling the genetic prime pattern for this particular mycoplasma.

Wondering out loud: Is there a similar genetic prime pattern for human viability? Humans are estimated to have between 20,000 and 25,000 genes so any process to investigate this question is going to take infinitely longer than fiddling with 473 genes of a single-celled organism, not to mention the ethical prohibitions (currently) from conducting similar experiments on human chromosomes. Regardless, what would a genetic prime pattern human look like (genotypically and phenotypically speaking)? For instance, while such a human could, by definition, reproduce, would he or she seem human?

The last question is begging for a definition of humanity. Knowledge of an organism’s genetic prime pattern gives genetic engineers a viability starting point. Experiments such as Syn 3.0 point to our growing ability to rearrange and reduce genetic material, literally creating new genetic patterns (at least in mycoplasma) that are viable. Would the equivalent human genetic prime pattern be an adequate minimal definition of humanity?

After all, aren’t we just the sum of our parts?

Doctor-Assisted Suicide in Canada: the Next Step

The general press is reporting that the Liberal majority in Canada has drafted proposed legislation to establish the conditions under which physician-assisted suicide (PAS) would be legal.  Per the Canadian Supreme Court’s order last year that PAS is allowed in Canada, the Parliament has until June 6 to pass it, or the Court’s prior order would come into force.  This would effectively leave judgments of when or how to carry out PAS in Canada to individual doctors or regional governments.  The province of Quebec had already acted separately in support of PAS.

It is reported that the proposed law:

  • ·       Would apply to people age 18 or older with “grievous and irremediable” medical conditions;
  • ·       May not be clear about whether people with dementia or degenerative diseases would be eligible;
  • ·       Would require a 15-day waiting period after review of the patient’s written request by two physicians or nurses;
  • ·       Would apply only to Canadians (those eligible for services in the Canadian health care system—no “suicide tourism” allowed;
  • ·       May not be clear about whether conscientious-objecting doctors will be allowed to opt out of participation (the Health Minister says yes, but some health-care workers worry that the law is too vague on this point, or that complicity will be unavoidable);
  • ·       Could not be used in advance to create a directive to carry out PAS at some future date.

I and other contributors to this blog have written extensively against PAS.  I will not rehearse those arguments again here.  My guess is that this provision in Canada will become law. 

Wesley Smith adds the criticism that the Canadian law, by protecting suicide-assisters from legal liability if they act in good faith, eliminates any guarantee that the process will be limited to those who freely and voluntarily request death.  There is too much wiggle room.  

I would add this worry:  active euthanasia by physicians or nurses appears to be included.  From the bill (text can be found here):  

“medical assistance in dying means

(a) the administering by a medical practitioner or nurse practitioner of a substance to a person, at their request, that causes their death; or

(b) the prescribing or providing by a medical practitioner or nurse practitioner of a substance to a person, at their request, so that they may self-administer the substance and in doing so cause their own death. (aide médicale à mourir)” [emphasis mine].

“People get ready, there’s a train a’comin…”

Experimentation on nonviable human embryos

Nature News recently reported that a second Chinese research team has done research on non-viable triploid human embryos in which they used CRISPR-Cas9 genome editing to introduce a mutation that cripples the immune cell gene CCR5 and would make individuals with the mutation resistant to HIV. This research raises a multitude of ethical concerns. Should we be pursuing such research when we have not decided whether using these techniques to create individuals who would be brought to birth would be permissible? Does the fact that only 4 of 26 human embryos targeted were modified and that those were not modified on all of their chromosomes and there were a large number of unintended mutations indicate we are nowhere near ready to try this technique on human embryos? If this could be done effectively would we want to make children with an impaired immune system, but who are resistant to HIV?

I would like to focus on a more basic ethical concern. The researchers in this and the prior Chines study reported in April 2105 justified experimenting on human embryos by using embryos that were non-viable. They obtained from a fertility clinic early human embryos that were triploid, meaning they came from eggs that were fertilized by two sperm and contain 69 chromosomes rather than the normal 46. This is a fatal condition. Most naturally occurring triploid fetuses miscarry in the first trimester and the very few who survive until birth seldom live more than a few days after birth. Embryos created during IVF that are identified as being triploid are not implanted since those doing IVF desire a healthy child, not a disabled one. The researchers contend that the fact that these embryos will not survive makes it permissible to use them for genetic research because it removes the concern that a genetically modified human being could be born.

However, does the fact that a human embryo is destined (almost always) to die prior to birth mean that it is permissible to use that embryo as a research subject? If a human embryo is a human being who has been made in the image of God, then the life that the embryo is living has value and should be respected even if that individual will never be born. When we do research on children who are not able to voluntarily consent to being research subjects we restrict that to research that either has minimal risk to the subject or is being done to try to benefit a child for whom no other treatment is available. Embryos are not able to consent to be research subjects, yet this research is being done on them with great risk to the life that they do have and with no intent to benefit them. If these two sets of researchers do not believe that human embryos deserve this type of respect, then why not use normal embryos instead of triploid ones? In both cases they would be experimenting on living human beings who are incapable of consent and are being killed and the end of the research. Why would it be more acceptable to do that with human beings who are more disabled and have a shorter life expectancy?

We have made significant ethical advances over the past century in our understanding of how we should conduct human subject research. We need to remember that human embryos are human subjects when they are used in research.

“Imago Dei” by any other name…

William Shakespeare reminded us that an object’s essence is not determined by the label we assign to it. No one has since proven Shakespeare wrong. Despite this fact, nowhere have labels been more strongly asserted than in the bioethical debate of abortion. Exactly what or who exists in the uterus of a pregnant human female? The list of labels is long and includes: “baby”, “the pregnancy”, “embryo”, “fetus”, “the products of conception”, “the unborn” and “potential future person”. These labels may honestly reflect an individual’s sincere belief or understanding of the essence of the object in question. But the labels can impede an honest discussion of and agreement upon the essence of that very object. Termination of a baby carries more moral alarm than termination of a pregnancy even though both refer to the same event. We even have different labels to identify the opposing groups on the abortion issue that avoid naming the procedure; Pro-Life and Pro-Choice.

With abortion being the third rail of social politics, it should surprise no one when we see our politicians on both sides of the aisle politically injured when mishandling the subject. When asked if a pregnant woman should be held liable for seeking an abortion in some hypothetical future where abortion is illegal, Mr. Trump eventually suggested she might be subject to “some form of punishment”(1), though later walked back the statement after realizing his assertion upset both Pro-Choice and Pro-Life groups. Since this was a legal rather than ethical question, a non-lawyer could similarly struggle to rationalize how one presently can be held criminally liable for the unintentional death of the fetus of a pregnant woman via a motor vehicle collision(2) but not held criminally liable for the intentional death of the same fetus under current (read: legal) abortion laws(3). No discussion was undertaken from an ethical standpoint to explain why punishment might be deserved in the first place.

Within a week of Mr. Trump, Ms. Clinton caused a different abortion controversy by “referring to the unborn as a person”, drawing the ire of her Pro-Choice supporters(4). The label “person” usually carries moral protection prohibiting, for instance, potentially fatal surgical procedures without informed consent, and abortion is certainly fatal, at least from the standpoint of the unborn, particularly when promoted to a person. Similar to a previous statement above, aborting a person carries more moral alarm than aborting the unborn.

For the Christian, the essence of the pregnancy, products of conception, embryo, fetus, unborn or potential future person must include the Image of God, the Imago Dei. It is this essence that provides moral boundary and ethical guidance regardless of other human attributes, whether potential or realized. See this recent blog entry for further detail.

As per Shakespeare, we cannot ignore the smell of the rose, regardless of how we choose to label it. Would that we could not ignore the essence of the Imago Dei, regardless of our ethical, social or political beliefs.

 

The pertinent portion of note 3: “If the mother can intentionally terminate the pregnancy at three months, without regard to the rights of the fetus, it becomes increasingly difficult to justify holding a third person liable to the fetus for unknowingly and unintentionally, but negligently, causing the pregnancy to end at that same stage. There would be an inherent conflict in giving the mother the right to terminate the pregnancy yet holding that an action may be brought on behalf of the same fetus under the wrongful death act.”

A Brief Comment About Our Political Moment

Some comments are prescient, but some are more prescient than others.

This is a bioethics blog, not a political opinion blog, but the general tenor of the current campaign and the headlines about the role of legal demands or prohibitions to address ethical matters seems to merit a brief general comment.  A political conservative writing some 50 years ago commented that political liberty demands an acknowledgment of a transcendent ground of morality, and I am inclined to wonder about the future of liberty itself.

To expand on it, my wife reminded me of a certain passage.  I imagine many if not most of the readers of this blog are thoughtful evangelicals.  If that describes you, see if you recognize the following:

[T]he central message of biblical Christianity…has secondary results, among them the unusual and wide freedoms which biblical Christianity gave to countries where it supplied the consensus.  When these freedoms are separated from the Christian base, however, they become a force of destruction leading to chaos.  When this happens…then, to quote Eric Hoffer (1902—), “When freedom destroys order, the yearning for order will destroy freedom.”

At this point the words left or right will make no difference. They are only two roads to the same end.  There is no difference between an authoritarian government from the right or the left: the results are the same.  [Emphasis in the original.]  An elite, an authoritarianism as such, will gradually force form on society so that it will not go on to chaos. 

Recognize this yet?  Maybe a bit more of a hint?  The author continued:

And most people will accept it—from the desire for personal peace and affluence, from apathy, and for the yearning for order to assure the functioning of some political system, business, and the affairs of daily life.  That is just what Rome did with Caesar Augustus. 

Francis Schaeffer, How Should We Then Live?, 1976, page 245.

Four things Christians need to know about ethics #3

Knowing who is a person with full moral status

In Luke 10 Luke tells the story of an expert in the law who had a conversation with Jesus. After Jesus had confirmed that he was correct that the essence of the law was to love God and to love our neighbor, the man asked Jesus another question. His motive was wrong, but the question was a good one. He asked “Who is my neighbor?” Jesus answered him with the story that we know as the parable of the Good Samaritan. Jesus’ answer was a very inclusive one, but the culture around us would suggest we should be more restrictive.

We live in a culture that gives an answer to the question that is much closer to what the man talking with Jesus was looking for. I suspect that he was wanting to narrow down the list of people who qualified as a neighbor since he was desiring to justify himself. Many in our culture would say that our neighbor is someone like us and say that we can come up with a list of characteristics or capacities that an individual needs to have to be one whom we have an obligation to treat like ourselves. Ethicists would call this defining personhood or determining who has full moral status. Western philosophical ethicists commonly have devised lists of capacities required to be a person. Mary Ann Warren’s list includes consciousness and ability to feel pain (sentience), reasoning, self-motivated activity (will), capacity to communicate, and presence of self-concepts and self-awareness.

This is not a new idea and just like the man talking with Jesus cultures have sought to justify what they wanted to do by choosing characteristics of who was a person or neighbor so that those whom they chose to mistreat would be left out. In past cultures a person has been defined as needing to have such characteristics as being white, male, or a member of a particular nation or tribe. That left out those who were black, female, Jewish, or a slave. Today the dominant culture would choose to leave out those who are not fully developed such as embryos and fetuses, those with mental disabilities such as Down syndrome or dementia, and others who are weak or frail or dying.

The Bible tells us that all human beings have dignity and value because we have been made by God in his image. That means that every member of the human family, no matter what that individual’s level of development or capacities may be, should be seen as a person with full moral status who is our neighbor. Even the weakest and most vulnerable should be included.

Recently I asked a group of senior science majors if they thought they would agree to participate in a research project that would involve the destruction of human embryos and a large majority of them said they would participate. For many of them it was because they did not see a human embryo as a person that they had an obligation not to kill. For others it was because the possible benefits of finding a treatment for a serious genetic disorder in the scenario I had given them outweighed their concern about destroying the embryos. That relates to the consequential moral reasoning I discussed in issue #2 of this series.

Those of us who claim to follow Jesus need to be careful to be as inclusive as he was regarding who is our neighbor.

I am – is it?

This past summer, researchers at RPI’s Cognitive Science Department programmed three Nao robots to see if they could pass a test of self-awareness. Modeled after the classic “Wisemen Puzzle”, the robots were asked whether or not they had been given a “dumbing pill” (in this case, a tap on their head, which muted their verbal output) or a placebo. The test not only required the robots to respond to a verbal question (“Which pill did you receive?”) but also recognize its own voice as distinct from the others and correctly respond (“I was able to prove that I was not given the dumbing pill”). For a $9500 retail robot, this is an impressive artificial intelligence (AI) test and worth watching HERE.

Dr. Selmer Bringsjord, lead investigator and chair of the Cognitive Science Department at RPI is careful to point out that these robots have been programmed to be self-conscious in a specific situation and describes his work as making progress in logical and mathematical correlates to self-consciousness. His biography page on the RPI faculty website provides a rather tongue-in-cheek assessment of the results of his research: “I figure the ultimate growth industry will be building smarter and smarter such machines on the one hand, and philosophizing about whether they are truly conscious and free on the other. Nice job security.”

I believe philosophizing about whether the robots are truly self-conscious to be the more interesting topic. In their current form, while the robot appears to a human observer to be self-aware, it is really the algorithm or program that correctly indicates (realizes?) that the robot did not receive the dumbing pill. But the algorithm itself is not aware that it correctly determined which pill the robot received. One could make the algorithm more complex, such that the algorithm tests whether the algorithm correctly determined which pill the robot received. But would that algorithm really be aware that the algorithm was aware which pill the robot received? One can see the infinite regression building. (Google: “It’s turtles all the way down”)

Perhaps the more interesting question is how we humans will react as the robot AI algorithms appear more self-aware, whether or not they actually are. Taking Dr. Bringsjord’s lead, should I invest in the domain name “spcr.org”* now or give it some more time?

 

* Society for the Prevention of Cruelty to Robots