The $280 Better Mousetrap

The rising cost of the Mylan EpiPen has been in the news. Since 2007, Mylan has raised the cost of their two pack EpiPen from just under $100 to over $600 today. That is a cool $300 per EpiPen, substantially above the ten to twenty dollar retail cost of the raw material epinephrine. Why should I be asked to spend a $280 mark-up? Is this ethical?

Briefly, here is some background. Adrenalin, pharmacologically known as epinephrine, is a substance that your body releases in response to stress. It allows the body to handle emergencies by the so-called “fight or flight response”. Large doses can be lifesaving, as is the case with allergic reactions. Individuals with allergies to peanuts or bee stings can receive epinephrine via an injection under the skin or into a large muscle, which can delay or even eliminate a life-threatening anaphylactic reaction (allergic swelling so widespread that an individual cannot breath or maintain their blood pressure), usually allowing time to travel to the ER for further care.

The EpiPen is one method of administering the epinephrine. An individual simply grabs the device, shaped like a stick, and jabs the end of the stick against his or her thigh muscle. This causes the EpiPen to release a spring-loaded needle, extending the needle into the thigh muscle, delivering a fixed dose of epinephrine into the muscle. The device is very easy to use, so much so that a young child can be taught to use the device safely and reliably.

One does not need to use an EpiPen to self-administer epinephrine. I checked with my local pharmacist and he can set me up with a syringe, needle and vial of epinephrine, and, as long as I can draw up the correct dose, and, as long as I am not squeamish about giving myself an injection in my thigh muscle, I can administer the exact same life-saving dose of epinephrine as the EpiPen. The total cost is around ten to twenty dollars per dose. Many other drugs, most notably insulin, are both self-administered and life saving, so nothing novel is required here. Additionally, according to my pharmacist, the “purse-life” of the generic vial of epinephrine extends several months beyond the one-year limit of the epinephrine in the EpiPen.

In short, Mylan is asking you to pay $280 for the privilege and convenience of using their stick to administer epinephrine rather than doing it yourself. Presently, there are no other options. Mylan’s only other competitor, Sanofi, withdrew in October 2015 their version of the EpiPen, called Auvi-Q, after multiple reports of failing to reliably deliver the correct dose of epinephrine. The present lack of a competitor seems to suggest that Mylan has indeed built a better mousetrap. They seem to be feeling a little guilty about their market dominance, as they have just today promised an identical generic EpiPen at half the cost.

Mylan’s mea culpa aside, is it ethical for them to charge whatever the market will bear, not for the epinephrine, but for the convenience of administering the epinephrine?

Vouchers for Kidneys

An innovative voucher program has begun at the UCLA Medical Center to increase the number of live kidney donations. The program allows for an individual to donate his or her kidney in exchange for a voucher that allows the donor’s specified voucher recipient to receive a kidney in the future. See HERE for the details.

Presently the number of people needing a kidney donation far exceeds the number of available kidneys. Historically, kidneys were obtained upon the death of an individual via the United Network for Organ Sharing (UNOS) and were (and still are) dispensed via a transparent process matching donors and recipients based upon disease severity and tissue-type matching. More recently, it has become possible for a living person to donate one of their two kidneys to another individual that the donor specifies (usually a close family member). The process is managed by several organizations, such as the National Kidney Registry. The process is regulated such that donor kidneys may not be bought or sold. There are real health risks to the donor in a live kidney donation but the actual risk of death is low. Despite the addition of live kidney donations to the pool from UNOS, the number of people awaiting a kidney donation far outpaces the number of available kidneys – approximately 13 people die every day awaiting a kidney transplant.

Trusty Wikipedia defines a voucher as “a bond of the redeemable transaction type which is worth a certain monetary value and which may be spent only for specific reasons or on specific goods”. Is this voucher system going to lead to a “cash for kidneys” situation? Presently, there appear to be some good safeguards in place. The UCLA voucher is not transferable to anyone other than the five people listed on the voucher, and only the first person within the list needing a kidney can redeem that voucher. Recipients are also identified by specific tissue typing and blood typing, making it virtually impossible to transfer the voucher to a random person. As long as these restrictions remain in place, these vouchers should have no market value for anyone not listed on the voucher.

But the voucher program does abstract the act of donating a kidney, storing the value of the act in paper format, allowing its redemption (in this case, the receiving of a kidney) at some future time. Effectively, the voucher program monetizes the kidney donation. Kidneys perish and vouchers do not. This is effectively one of the benefits of using money over bartering as a basis for expanding trade. UCLA hopes the voucher program results in such an expansion of the supply of kidneys and that expansion of supply is a good thing.

However, this monetization of the kidney donation program demands we remain ever more ethically vigilant to avoid heading down the slippery slope of “cash for kidneys”.

The Bioethics in Routine Office Visits

I saw two patients last week on the same morning for identical tests whose divergent stories generated an interesting debate amongst my staff regarding healthcare rights and the cost of providing the same.

For some background pertinent to this discussion, I perform a diagnostic test in my office called an Electromyogram (EMG) which quantifies the electrical function of muscles and nerves, and is used by my surgical colleagues to assist in their decision whether or not to operate. Depending on the diagnostic question, the test can take anywhere from 30 minutes up to 2 hours to perform, interpret and generate a report, the average encounter lasting about 45 minutes. Currently, we are reimbursed via rates we negotiate with the various insurance carriers, all of which are fixed at a rate that is some percentage of Medicare reimbursement rates (generally ranging from 80% of Medicare for most state Medicaid products to 125% of Medicare for some private insurance products). Without getting into the minutia of medical cost accounting, there are real costs to our group related to my performance of the test on any given patient such that, below a certain reimbursement level, we actually lose money. Further, if a patient cancels his or her test at the last minute and I am not able to move another patient into the cancelled appointment time, no revenue is generated for that appointment.

The first patient showed up for her test and had a state Medicaid insurance plan such that she paid nothing for her insurance plan. She was not even required to pay an office “co-pay” so she had no “out-of-pocket” costs for her medical care. When my nurse explained the EMG test, including the need to use rubbing alcohol on her skin in areas where I would be inserting an electrical needle, she declined the test. When asked why, she indicated she had just spent $120 on a “spray-on-tan” the day before and did not want to cause streaking of the tan. In our region, the going rate for this type of tan is $60 per application and she required two such applications to achieve her desired result. She was rescheduled and later did complete the test and our practice was eventually reimbursed at the contract rate of 80% of the standard Medicare reimbursement rate.

The second patient was a single mother of two who worked two jobs, making just enough to fail to qualify for the state Medicaid insurance just described, but not enough to afford the cost of insurance through the PPACA exchange in our state. She determined that her monthly insurance premium and $5000 deductible was more than she could afford. She requested our “self-pay rate”, which I further reduced to 95% of our Medicare rate after hearing her situation.

Most of my staff were disgusted with the behavior of the first patient and admired the behavior of the second. A few wanted me to further reduce the charges to the second. I pointed out that if I saw only patients like the first or second patient, I would have to lay-off 30% of my current staff, this after salary reductions all around. Others noted the first patient’s behavior was very rational from the standpoint of her personal cost accounting. A $120 spray-on-tan has financial priority over a $0 EMG test, despite the fact that the subsequent test did reveal a finding that caused my partner to correctly modify his treatment plan (i.e. the test turned out to be medically beneficial to her health).

The two isolated cases presented here are an insufficient basis upon which to form healthcare policy. In both of these cases, the EMG test results caused a better surgical decision to be made for each patient, so in that sense, both tests were medically necessary. In both cases my frugal office manager argues that we lost money. The cases did generate very good questions by our staff such as: How much should a necessary test cost a patient? How much should our practice get reimbursed for performing a necessary test? Essentially, who should pay for necessary healthcare? Is healthcare a right such that someone is obligated to provide the necessary service? What makes a service necessary? Should everyone have some (financial) skin in the game? Unfortunately, we generated several more great questions but no consensus answers.

Except for one: The only consensus opinion that my staff formed after considering these two examples was that one’s co-pay should approach the local cost of a spray-on-tan, but just a single application not a double.

The Strange (Future) Case of Doctors & Mr. Hyde

On 28 June 2016, the Supreme Court declined to hear an appeal of a Ninth Circuit decision that forced a small pharmacy in Washington to dispense Plan B (a “morning after pill” that terminates a pregnancy via abortion) despite the religious objections of the pharmacist owners. In other words, the lower court ruled that the pharmacists must violate their conscience by prescribing Plan B or terminate their pharmacy business. Only three Supreme Court Justices agreed to hear the case; four are required. It can be argued that if Justice Scalia were still on the Court, The Court would have heard the case. As such, the Ninth Circuit’s ruling stands but is limited to the Ninth Circuit. Justice Alito’s dissent is worth the 15 page read. Doctors of Pharmacy no longer have religious/conscience protections in the United States within the Ninth Circuit.

Read that last sentence again.

Conscience protection for other health care providers may be more tenuous than is generally granted. Previously, multiple federal amendments provided health care workers conscience protections (Church Amendment, Public Health Service Act 245 & Weldon Amendment) A separate rider to annual omnibus bills called the Hyde Amendment actually prohibited federal Medicare and Medicaid funding of abortion specifically. The PPACA (Obamacare) changed the funding rules and arguably some of the previous conscience protections to the point where President Obama had to issue Executive Order 13535 specifically guaranteeing continuation of those protections in order to secure passage of the PPACA. The alleged tenuousness of current conscience protections mentioned above is the fact that an Executive Order can be easily be rescinded by this or any future president while overturning, even in part, the PPACA is no easy task. Additionally, efforts by those pro-abortion to eliminate amendments like the Hyde Amendment in its current form are vigorous and ongoing. (The link is presented as evidence not endorsement)

Regarding the title, the late Congressman Mr. Henry Hyde, author of the Hyde Amendment, is the antithetical homonym of the fictional Mr. Edward Hyde, the evil sociopathic alter ego of the philanthropic Dr. Henry Jekyll. Ironically, the present day Hyde (along with the other amendments listed) may be one of health care’s last protections against future violations of moral integrity by continuing to allow the unobstructed practice of medicine with one’s conscience intact.

Gender Indiscrimination

Steve Phillips has recently written in this blog about gender dysphoria and our culture’s struggle to respond consistently to it. Please see here for that discussion. North Carolina recently passed a law requiring individuals to use the bathroom of their biologic sex rather than their self-identified gender. This has resulted in claims of gender discrimination and gender phobia against those who do not wish to be in the same shower or bathroom with someone of the opposite biological sex, regardless of how that someone chooses to self-identify his or her gender.

In early June, a young high school student in Alaska, whose biological sex is male but who identifies as a female, recently placed 5th and 3rd place in the girls 100 meter and 200 meter state high school track meet. Interestingly, the cries of discrimination focused almost exclusively on the claim that this was unfair to the other women running in the same race. Said differently, there have been extremely few claims of gender discrimination or gender phobia against those who do not want to be in the same sporting event with someone of the opposite sex, regardless of how that someone chooses to self-identify his sex.

Why is there a difference?

Notice that in both cases, opposing sides agree that males and females are different, deserving different bathrooms and different sporting competitions, the latter a successful result of Title IX federal regulations beginning in the 1970’s. Both sides seem to agree that the issue is how to discriminate who belongs in which group. In both examples, one side argues that subjective self-identification is a sufficient claim to gender group membership while the other side demands objective biological criteria. So who is right?

And why is the girl who finished 6th in the 100 meter Alaska High School Track meet less likely to be called bigoted if she complains about having to race against the boy who identifies as a girl as when she complains about having to share the shower with him after the race? If the difference is one of fairness/justice in public sports competition, it is unclear why we should elevate public sports competition above private social interpersonal contact in terms of our bigotry tolerance.

But let’s say we do. Both the IOC and the Women’s Sports Foundation have position statements that effectively argue that the issue comes down to objective biological criteria, namely testosterone levels. At least in competitive sports, subjective self-indentification is not a sufficient claim to gender group membership.

But what about public bathrooms? Curiously, the Justice Department is using Title IX, that landmark federal regulation banning sex discrimination by schools that receive federal funds, to effectively require schools to be rather gender indiscriminate. Effectively, they are requiring schools to allow students to use sex-segregated bathrooms based on their self-identified gender or move away from sex segregated bathrooms altogether. As Jeannie Suk recently stated in The New Yorker: “The discomfort that some people, some sexual-assault survivors, in particular, feel at the idea of being in rest rooms with people with male sex organs, whatever their gender, is not easy to brush aside as bigotry. But having, in the past several years, directed the public toward heightened anxiety about campus sexual assault, the federal government now says that to carry that discomfort into bathrooms is illegitimate because it is discrimination. [emphasis mine]”

It seems that our culture’s response to this issue remains incoherent.

Roundup Ready® Humans

Everyone is familiar with Roundup®, arguably the most well-known of any herbicide in the world and my favorite gardening tool. What may be less well known is that Monsanto has created a line of genetically modified organisms (GMOs), which are resistant to their famous herbicide. Called Roundup Ready®, soybeans in this product line can essentially take a bath in Roundup and still grow up to be healthy soybeans. Monsanto charges a lot more for these soybean seeds but farmers apparently make up the difference in their yields, as they can use Roundup to kill off competing weeds. Farmers also agree not to use the new growth seeds without paying Monsanto a royalty for their technology or resign to simply buy new seeds the following year. As such, Monsanto effectively controls a large swath of soybean production, and the herbicide market that controls soybean weeds.

One farmer attempted to skirt Monsanto’s royalty scheme. He went to his local grain silo and cheaply and legally bought random soybean seeds, gambling that at least some of these random seeds were descendants of the Roundup Ready® soybeans. He treated his random soybean seed field with Roundup®, effectively killing off all the non Roundup Ready® soybeans. Having no contractural obligation preventing him from using the new seeds, he eventually developed a supply of Roundup Ready® soybean seeds without ever paying Monsanto for their technology, arguing that the he was not responsible for soybeans doing what soybeans do naturally – making more soybean seeds. Monsanto naturally disagreed and the patent case went all the way to the Supreme Court, with the Court siding unanimously with Monsanto. The Court’s opinion stopped short of applying their verdict to all self-replicating entities, limiting the decision in this case to preventing individuals from replicating patented products (nice NPR summary article)

Fast forward to humans. John Holmlund provided a nice summary of a recent closed-door meeting at Harvard Medical School of a group of leading genetic researchers whose reported goal would be to synthesize (make from scratch) an entire human genome in the next 10 years, perhaps even creating novel sequences of human DNA resistant to various (or all) diseases. The novel sequences come close to a Roundup Ready® human. Who will own the disease-resistant human DNA sequences?

To move this closer to the Monsanto soybean example, suppose the Harvard group formed a private company called Humansanto and they developed a human antiviral drug that effectively disabled any virus, at the cost of unavoidable continuous low-grade, flu-like symptoms in the humans that took the drug. Humansanto then invented a human genome sequence that made an individual and her descendants resistant to the side effects of their antiviral. While it seems reasonable for the individual receiving the initial genetic treatment to pay Humansanto, should all of her descendants pay as well? Following the current Monsanto ruling, the answer would be yes.

It would not take too much imagination to turn this into a good genetic terrorism novel or movie where the side effects of the antiviral drug are intentionally far worse, or the evil corporation develops the actual deadly virus, all preventable, of course, with their modestly priced DNA sequence.

It seems unfair that Monsanto (or Humansanto) is not equally obligated to pay a similar royalty to the Original Holder of the patent on soybeans (or humans).

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?

“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.”

Mitochondrial Replacement Techniques – is this Human Enhancement?

Ever since I read John Holmlund’s blog entry (HERE) on mitochondrial replacement techniques (MRT) for inherited mitochondrial diseases, I have been thinking a lot about the issue of enhancement. Almost in passing, the Institute of Medicine (IOM) stipulated that MRT would not be a meaningful example of human enhancement because of the relatively limited genetic information in mitochondria.

Recall that mitochondria are the energy power houses of cells. Dysfunctional mitochondria tend to cause significant problems in tissues that require higher energy consumption, such as muscles and nerves. MRT is being proposed to prevent the birth of an individual who could develop mitochondrial myopathy, one example of the family of very debilitating and occasionally fatal mitochondrial diseases. With MRT, we are replacing en bloc defective maternal mitochondrial DNA with presumably extremely healthy mitochondrial DNA from a separate maternal donor. The resulting child is the nuclear genetic combination of her two parents plus a third healthy mitochondrial DNA donor, hence the designation “3 parent baby”.

As to whether or not MRT represents a meaningful example of human enhancement, consider the following thought experiment. Let’s stipulate that in the not-so-distant future, MRT has become routine and safe for preventing the birth of an individual with mitochondrial myopathy. Since the critical criterion for a potential maternal mitochondrial donor is a female with no genetic history of mitochondrial disease, any female meeting this condition and willing to be a donor becomes a donor candidate. Within that group, why not select a woman who also has outstanding muscle function, such as Carmelita Jeter (currently the fastest living female world record holder for the 100 meter dash). While the parental nuclear DNA undoubtedly controls much of the development of their future child’s muscle function, having Carmelita Jeter’s mitochondrial DNA certainly can not be expected to slow the child down (for if it does slow her down, then our stipulation of MRT safety fails). But does it speed her up?

Obviously the answer to the question of whether or not MRT represents an example of enhancement is – we don’t know. The IOM’s solution to determining the answer to this question (and the many other questions related to the ethics and safety of MRT) is effectively to try MRT and see what happens.

My stipulation is that MRT represents the first approved genetic enhancement therapy, despite the relatively small amount of genetic information in mitochondria.

I also think the child speeds up.

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