Consumer’s Guide to Genetic Testing

Google-owned company 23andMe is launching a new program called Exome 80x, where a select few individuals can receive a data readout of their genome at a very high accuracy for the price of $999. According to the company’s promotional web site the benefits include:

A person’s physical structure, their body’s chemical reactions and the expression of their genes are controlled by the proteins encoded in the exome. The vast majority of genetic diseases also hinge on variations in the exome. For these reasons, exome data may be useful for those exploring their personal sequence data.

And

In contrast, the exome sequencing pilot provides users with raw variant data for about 50 million bases of DNA, without reports. Over time, 23andMe will add a limited set of tools and content that utilize exome sequence data.

Instead of the report that 23andMe offers its current clientele, Exome80x will provide clients with the raw data consisting of a list of nucleotides. Think of it as the difference between reading the results of an opinion poll and seeing every responder’s individual answer. The web site says that this test is not for everyone. For example, if you are unsure what the difference is between an exon and intron, then you are probably not a good candidate for this test. (See the report in Forbes, here).

DNA has “active” chunks and “inactive” chunks known as exons and introns, respectively. The active chunks code for proteins while the inactive chunks have been dubbed “junk DNA” because of their apparent lack of function. The DNA is “read” by proteins that go over every letter (or sets of three letters) and translate those letters into an amino acid chain. The amino acids are strung together and form a protein, molecular machines that conduct cellular function.

So the question is, if I had $999, would I get the test? The answer is no, for the following reasons:

  • Introns are not inactive. Several articles have appeared in the literature over the past few years that indicate introns are actually important segments of DNA and are anything but inactive. Introns may not code for proteins directly, but they probably assist in regulation and folding. See The Myth of Junk DNA for a summary of recent literature on this issue. So, for $999, I’d like the whole kit and caboodle, please, not just exons.
  • A parts list probably will not be helpful. A read-out of raw data means that for $999 you receive a parts list without an instruction book. This doesn’t mean it is useless for everyone in every case. For example, Matthew Herper from Forbes reports on a child that was suffering from severe and unknown complications in his intestinal tract. The doctors sequenced his DNA as a last-ditch effort to try to understand his mysterious disease. In most cases, all a DNA test can tell the doctors is if a person has markers for some diseases (not all diseases are genetic, so this is limited to genetic disease), but does not necessarily offer a solution. In this child’s case, the doctors found that he had a rare mutation that they decided to try and treat with umbilical cord stem cells. The treatment seemed to have worked well. However, this is not the norm. So, while the DNA test was a good idea for this child, I don’t know that it is a necessary procedure for someone who is healthy.
  • Ethical implications of knowing your genetics: The guilt. In the story above, the mother of the boy carries a lot of guilt because the gene was passed to him from her. She has made the decision to not have any more children. Her decision to not have children is a personal one. Genetic probability is not the same thing as certainty, but obviously she does not want to risk putting another child through this disease. However, the guilt poses another ethical concern. I do not believe this is a burden that this woman must bear. For now, we are not responsible for passing “healthy” genes, and we are not culpable for passing “unhealthy” genes. Perhaps this poses a larger bioethical question: With the advent of genetic testing, will people be held responsible (or hold themselves responsible) for genetic mutations? This seems to be treading down a eugenic-type path and mind-set that should be carefully examined.
  • Ethical implications of knowing: The inevitability and helplessness. In the book, DNA, by James Watson (with Andrew Berry), they report on a woman named Nancy Wexler, who has been a pioneer in the search for the genetic markers of Huntington’s Disease. Huntington’s Disease is a genetic degenerative disease. Nancy’s mother and uncles died of Huntington’s Disease, which means that she and her sister have a 50-50 chance of dying from it. Usually death occurs before age 60, and after a severe physical and mental decline. Even though she helped find the genetic markers for the disease, Nancy would rather not know whether she has the marker or not until a cure can be found (DNA, page 324, 325).

DNA sequencing is not a bad thing, and it has illuminated many areas of research, although it has not been the panacea that was hoped for during the years of the Human Genome Project. There are times and cases where looking for a mutation might be helpful, and thankfully it is an option for those difficult cases where doctors are dealing with mutations that wreak havoc on the body. But DNA sequencing is probably not something that everyone needs on his or her medical file. The bottom line: This consumer guide says that for most of us, your $999 would better serve your future health if you used it to buy a 3-year gym membership.

Reflections from the Front: End-of-Life Care

Reflections from the Front: End-of-Life Care

In the past sixteen months three members of my immediate family have died. Heart Disease, Dementia and Cancer claimed the lives of my father, my mother and my wife. If it were not for the resurrection, we would be totally bereft. As it is, we grieve, “but not as those who have no hope.”

In their last days, with each family member, we made the decision to not pursue all possible treatments at any cost, but instead only reasonable treatments, that would help mitigate pain and suffering, and whose benefits clearly outweighed the likely downsides to treatment. In regard to specific decisions, however, this may be easy to say, but not so easy to do.

Particularly for the Christian who continually prays for God’s miraculous interventional healing, it is tempting to continue to push, based on the possibility that God will intervene “soon”, if we have faith, and don’t give up the fight. Deciding when to transition care from a cure-orientation to a palliative care approach, can, at times, be especially difficult when the patient and the whole family are not at the same place at the same time.  The person who perhaps prophetically realizes that God’s healing may not come on this present earth may be perceived as being less committed, less loving, and less faith-filled. Perhaps; but perhaps they have an insight from the Lord.

Dr. John Dunlop, Internist and Geriatrician, recently wrote an outstanding, yet easy-to-read book– Finishing Well to the Glory of God, (2011, Crossway Books, Wheaton, Illinois,) covering just these issues. I highly recommend his book, which I found personally helpful. I would also recommend the website: http://www.cancer.gov/cancertopics/factsheet/Support/end-of-life-care

Discussions in the abstract, quoting probabilities of life, death, pain and disability can be almost mathematical. For populations these predictions have been found to be relatively accurate. For the patient or family member directly in front of you, they are much less helpful. When your time comes to deal with these issues as a provider, friend, or family member, I recommend Dr. Dunlop’s book, appropriate, accurate medical data, continuous prayer, and reliance on the Holy Spirit to help you walk through this minefield. I also recommend patience and love for your family circle members who aren’t where you are and a spirit of humility, forgiveness and grace as you make tough decisions.

Caring too much?

 

Is it possible to have too much care?

Apparently, a lot of primary care docs in this country think so. In a study published in Monday’s Archives of Internal Medicine, 42% of primary care doctors surveyed said that their patients were receiving too much medical care, and 28% said “they themselves were practicing more aggressively (ie, ordering more tests and referrals) than they would ideally like to be.”

But is it really possible to have too much care?

Well, it depends on how we define our terms.

If by care we mean what we usually mean by the word — sitting with someone, showing concern and empathy, listening, attending to their needs — then no, I don’t think we can have too much care.

But if we replace this humanistic definition of care with a technical definition of care, as in, “I show care by ordering something for this patient, whether it’s a test, a procedure, a pill,” then yes, we can have too much care.

Because every pill or procedure has side effects; every test carries its inherent risks. And all of these interventions cost money, and add cost to a system in which the medical costs are skyrocketing at unsustainable levels.

Interestingly, the doctors in the study gave “Inadequate time to spend with patients” as one of the top three reasons they provide too much technological care. The humanistic type of care requires time. In a system that pushes doctors to do more and more, there is less and less time to care for patients. So the time taken to provide humanistic care is replaced by techno-care: tests, studies, etc.

There are many patients who are truly underserved, who get neither enough humanistic care — time with a doctor who knows them — nor enough technological care — that is, appropriate tests and interventions. But we will never have the wherewithal to serve these patients unless we stop pouring money into inappropriate technological “care” that serves as a poor substitute for the humanistic care we can’t seem to take the time to provide.

An e-mail went around our office asking the docs what were the top three things patients came to see them for. One experienced doctor wrote, “I decided the top three are love, attention, and sympathy.”

Those things, the essence of real care, require real time. How do we change a system so that it stops encouraging the provision of expensive technological care as a replacement for time-consuming humanistic care?

As a society we need to find an answer, or we will not be able to afford either one.


Are You Sure You Want to “Stand with Planned Parenthood”?

 

Lately, my wife and I have been casually strolling around our beautiful town, Concord, NH, taking in the remarkable New England fall experience. During these strolls we are not only struck by the beauty of the leaves but by the stark contrast of the bright red signs planted in our fellow citizens’ lawns, proclaiming: “I stand with Planned Parenthood.”

This is strangely ironic given that my wife (who is now 14 months pregnant) and I often spend this time discussing life, parenthood, and our child—we are planning for parenthood.

Well, if you know anything of NH’s latest funding battles that is not at all what these signs are talking about.

Recently, NH’s Executive Council voted against Federal funding to go to Planned Parenthood because of the divisiveness of abortion and the earnings of PP officials. But “the U.S. Department of Health and Human Services announced it will provide the contract for family planning with PP directly from the federal government to the abortion business rather than routing the money through the state and letting NH officials determine who should receive the Title X grants” (Life News).

This has caused a bit of a stir around town… Especially since this is happening while Congress (Energy and Commerce Committee) has responded with action to AUL’s early July report, “The Case for Investigating Planned Parenthood”, which endeavors to expose PP’s questionable behavior (spending of Federal monies).

In response, PP has launched a series of counter statements against AUL in an effort to diffuse the accusations, question AUL’s motives, and negate the severity of the claims. To these and other counterclaims Dr. Yoest (Pres. of AUL) stated:

“Ensuring compliance with the law is not a partisan issue, and the Committee’s decision to investigate an organization that has been rocked by systematic fraud and abuse shows that Congress takes its responsibility to be good stewards of taxpayers dollars seriously.”

In the great “live free or die” state, as well as states across the US, it seems that “Standing with Planned Parenthood” may not be the best idea even if only half of the accusations in the report are true. But then again only time will tell the extent of their indiscretions…

Why do people buy snake oil?

There a lot of ethical concerns about stem cell research.  Many have to do with the destruction of embryos for embryonic stem cell research.  Those of us who oppose embryo destructive research frequently promote the potential for adult stem cell research as a better and less ethically problematic alternative.  But adult stem cell therapy has a different problem. It is becoming the most recent version of snake oil.

While legitimate research involving adult stem cells should be supported, everyone from Texas Governor Perry to Indianapolis Colts quarterback Peyton Manning have been getting unproven adult stem cell treatments outside of valid research protocols.  Why would otherwise intelligent people subject themselves to unproven and potentially risky treatments?

Part of it may have to do with our human tendency to believe that something is true when we strongly desire for it to be true.  Our desires can be so strong they cloud our ability to reason and there are plenty of people who understand they can take advantage of that for their own profit.  They sell everything from snake oil to mangosteen juice to stem cells to people whose desire for a cure makes them vulnerable.

Another part may be our society’s unrealistic belief that scientific medicine should be able to cure everything.  Researchers’ hopeful expression of what may be possible with treatments such as stem cell therapy can make people with medical problems for which there are not effective treatments susceptible to trying an unproven treatment because of that potential.

Then again there is always the possibility that an unproven treatment may work.  Snake oil was actually a traditional Chinese remedy that used the fat of the Chinese water snake that was high in a prostaglandin precursor to help relieve inflamed joints.  When used correctly it may work.  Adult stem cell therapy may turn out to be effective for some of the things it is being used for by those selling unproven treatments.  But we won’t know unless those treatments are done in properly controlled trials.

It’s Not Your Fault. You’re Just Abnormal.

BioEdge, a bioethics news source, reported on a disturbing case out of Italy. Apparently the Italian court has decided to reduce the sentence of two people due to new evidence from brain scans. The most recent one is discussed in the report: “In 2009 28-year-old Stefania Albertani pleaded guilty to murdering her sister by force-feeding her with psychotropic drugs, burning her body, and later attempting to murder her mother. She was sentenced to 30 years imprisonment.”

New evidence from fMRI scans indicates that Albertani had some discrepancies in her brain structure. The report from Nature provides the technical details:

Albertani’s grey matter volume in the imaging scans is different from that of a control group – 10 healthy women – in the Anterior Cingulate Gyrus and insula areas, among others. Changes in the Anterior Cingulate Gyrus have been linked to reduced inhibition and to the processes that regulate truth-telling; insula changes have been linked with aggressive behaviour… The genetic tests show that Albertani has low MAOA gene activity, which has been linked to violent behaviour.

To translate, her brain is not the same as ten other females who have been deemed “normal” by some set of subjective criteria. There are several issues to consider with this case. Her sentence was reduced from life to 20 years.

The criminal justice system is based on the idea that man acts as a moral agent and is therefore responsible for his actions. This system presupposes that man is more than a product of his environment and genetics, but that he has a free choice to act (or not act). In the case of Albertani, she force-fed her sister drugs, burned her corpse, and a couple of months later tried to kill her parents. Obviously anyone who commits such violent acts against another person has problems, whether those acts are due to anger issues, bitterness and vengeance, or a mental disability. The question becomes: Was the person sinning, or is her mental state such that she has no moral responsibility, similar to an animal, or does she have very little understanding of moral responsibility, like a small child? The only way to truly answer this question is to see inside the perpetrator’s head, not just her brain, but what is going on inside her head. With functional magnetic resonance imaging (fMRI), scientists can practically do that. Of course, my question for the scientists is, “Do you know what you’re looking at?”

Certainly, scientists are able to see many parts of the brain, but the brain is very complex and sometimes scientists are overly optimistic on what they actually know. For example, fMRI can show which parts of the brain are digesting or gaining water faster than other parts of the brain. Scientists say that this part of the brain is “active.” As far as structure, scientists have to arbitrarily decide who is normal, and look at his or her brain and decide that this is what a normal brain looks like. Furthermore, scientists must assume that abnormalities in structure, necessarily lead to abnormalities in behavior. In some cases this has been shown to be true; for example, people with tumors in certain locations will exhibit “odd” behavior. By “odd” this usually means behavior that is out of the norm for the particular person; tumors are usually found because there is a drastic change in the individual’s behavior.

As a bioethicist, this gives me pause. While I admit that there are ways that our bodies are designed that indicate how they are supposed to function, such as the ball-and-socket joint in the leg, there are some cases where “normal” is ambiguous. We know that people who cannot walk have a disability because we know how structures like the leg are supposed to work. The case is different with the brain and with behavior. We don’t know enough about structure-to-action correspondence to make an assessment that “abnormal behavior” corresponds to what may be an oddity in the brain. Furthermore, much of the neuroscience literature seems to indicate that there is a distinction between the mind and the brain, which is still not completely understood. With so many questions, determining what is normal can be quite subjective. Let’s take an example from Carl Elliot’s book, Better than Well. In it he describes how Americans more often than Japanese will take anti-depressants (SSRI’s) even though incidence of depression is similar as well as valuing medicine, pharmacology and health in both of these countries. Part of the reason is that American culture values extrovertism and out-going sociable behavior, while Japanese culture values very controlled, less emotional, and quieter behavior (Elliot, 75, 76). Mental disorders, much like depression, are diagnosed by behavior and mood, which is often very subjective, and may be relative to what the doctor (or jury) considers the cultural norm. I am not describing extreme examples of depression or mental disability, but the more common cases.

Stephen Morse has an interesting paper discussing this topic. He believes that while the context of the mental disorder should be considered in legal cases, for the most part, mentally ill criminals should not be treated differently except in extreme cases. He contends that by treating them differently, they are marginalized and are robbed of liberty and dignity. Morse also makes a very good argument against some of the presuppositions behind a type of determinism that can come out of looking at physical structures (brain or genetics or otherwise) and assuming that it determines behavior. He points out that if we are truly determined by the structure and function of our brain, then why not do away with the criminal justice system all together, and just have a deterrent and detention system? I believe that he makes some valid points on this topic. His insights on preserving the dignity of the mentally ill and criteria for insanity are helpful. He is very intentional in not being reductionistic or deterministic. See his paper, which can be downloaded here.

Insanity pleas were meant to be the exception, not the norm. They were meant to protect those very extreme cases where an individual truly has no conception of actions and consequences. These are rare cases. For most cases, people need to be held accountable for their actions. Not doing so treats the person who committed the crime at most, as a lower-tiered individual in society with fewer rights and liberties than “normal” people, and at worst, as something less than human, whether it is a machine determined by its parts, or an animal that was acting on instinct.

The Four Levels of Happiness

We were fortunate to have bioethicist and physician John Patrick come to our little city of Temple, Texas last night.  He reminded us that the difficulties we face in bioethics and in Western culture in general often stem from not understanding the ideas that built our society in the first place.  This most notably includes Judeo-Christian principles but also ancient Greek and Roman philosophy.  He illustrated this predicament by speaking on the Four Levels of Happiness, a concept used by Christian as well as ancient thinkers.  Those of us in medicine are familiar with the first level of happiness–food and sex–because our profession oftentimes only sees human beings in light of these animal desires.  This almost perfectly echoed a statement made days earlier by my supervising physician on my psychiatry rotation.  I wanted to speak up and say, “But isn’t there something more, something deeper?”

Dr. Patrick went on to say that, second, we find happiness by excelling in some occupation and, third, in living for other people.  Christian physicians have something critical to offer patients, whether it be while treating a depressed person in a psychiatric clinic or counseling a couple as a family practitioner.  Talking about these deeper matters touches on what it means to be human, and such ideas should be a part of any concept of health.

Dr. Patrick often leaves his audience hanging by not mentioning the fourth level of happiness, especially when speaking to a thoroughly secular group.  Sometimes he even takes a vote to see if they really want to know the rest of the story, and of course they do.  So I, too, will fill you in because the fourth level is that poignant moment when God reveals himself to us in a very personal way.  Many of us have experienced such moments, and they are certainly to be treasured.

For more on Dr. Patrick’s work on Hippocratic ideals in medicine and Augustine College where he teaches, take a look here:

The marketing of umbilical cord blood banking

 

One stem-cell success story has been the use of stem cells derived from umbilical cord blood. The list  (more here) of diseases treatable by transplants of such stem cells is impressive, even more so when compared to, say, embryonic stem cell treatments, which are currently used in therapies such as . . . well . . . hmmm . . . uh, let me get back to you on that one.

One gratifying aspect of the use of umbilical cord stem cells is that obtaining them carries none of the unethical aspects associated with embryonic stem cell use. Nobody is killed in collecting umbilical cord blood; after the delivery of a baby, blood is removed from a vein in the umbilical cord, causing no harm to mother or newborn.

This does not mean that there are no ethical issues surrounding umbilical cord blood. There are currently two ways to “bank” umbilical cord blood, either through public or commercial cord blood banks. The public banking option is free to the parents, strictly quality controlled, and the blood is available to any patient who needs it and is a correct match. Commercial banks, on the other hand, typically charge $500-$2000 to collect the blood, along with an annual storage fee of $110-$150; are not as quality-controlled; and the blood is available only for the exclusive (potential) use of the patient.

Ethical issues arise from the marketing tactics employed by some of the commercial banks. The premise underlying the marketing is, Bank your child’s cord blood for his or her own exclusive use, so that if your child gets a disease sometime in his or her life, we’ll have perfectly matched stem cells to treat their disease, and you’ll have peace of mind! It is not unusual for companies to advertise cord blood as “Life insurance,” or to warn that “This may be your one opportunity to save your child,” or to promise “Potential regenerative therapies from stem cells such as treatments for arthritis, heart disease, etc.”  — therapies which currently do not exist. (The quotes are from commercial websites.)

These ads are based on hype and fear: hype, because they seem to promise treatments that are not currently available and may never come to pass; fear, because they play on every parent’s concern about terrible diseases their child could contract.

(Hype and fear: aren’t those are the same tactics used to promote embryonic stem cell research?)

Embryonic stem cell research and umbilical cord stem cell therapies are ethical worlds apart in their practice, and we should aggressively oppose the former and actively pursue the latter. But we should also oppose unethical commercial exploitation of otherwise ethical therapies through false advertising. Commercial umbilical blood banks should be held to strict “Truth-in-advertising” standards, and stopped from falsely promising anything more than we know they can deliver. This might save a lot of parents their hard-earned cash.

And while we’re at it, we ought to hold the promoters of embryonic stem-cell research to the same standards of truth. This might save a lot of embryonic persons their lives.

Ethics and Worship

Sometimes I think evangelical Christians get confused about where ethics fits in the Christian life.  Why is it so important?  We understand that we are fallen and that there is nothing that we can do to merit God’s favor.  Salvation is a gift of God’s grace accomplished fully by Jesus’ sacrificial death.  Ethics can be seen as a set of moral laws that we are obligated to live by, but which we all fail to keep.  Why focus on the law when we have God’s grace?  Doesn’t God accept us just as we are?

The answer is worship.  While none of us can merit a relationship with a holy God through living morally perfect lives, those who have been redeemed by God’s mercy and grace desire to worship Him.  Romans 12: 1-2 tells us that we should respond to God’s mercy by presenting our lives to Him in worship.  We should desire to be transformed so that the lives we present to Him in worship are lives being lived in conformity to his good and perfect will.  Ethics is about how we should live to conform to what is good and right.  It involves living lives conformed to God’s good and perfect will.  We can’t do it on our own, but we can allow Him to transform us so that we do not conform to the immoral patterns of this world, but have our minds renewed with an understanding of what is good and right.

South Korea Takes an Ethical Step Backwards

This week (Sept. 19) it was reported that the government of South Korea will invest $89 million to recommence its pursuit of human embryonic stem cells (http://www.bbc.co.uk/news/world-asia-pacific-14968613).  You may remember the scandal that erupted in 2006 when a South Korean scientist (Hwang Woo-suk) declared that he had generated human embryonic stem cells by means of cloning.  Later it was discovered that the research had been faked.  Woo-suk, who was considered a national hero before the scandal, “caused inevitable damage to the entire stem cell research community in Korea,” according to South Korea’s president, Lee Myung-bak.  The money will be invested, proclaimed Lee, to “…restore our national fame as a stem cell powerhouse.”  The BBC report ends with the oft-cited list of all the diseases that may be treated by stem cells including, “Parkinson’s disease, heart disease, stroke, arthritis, diabetes, burns and spinal cord damage.”[i]

The announcement by President Lee troubles me on several levels:

1) there is no evidence that human embryonic stem cells (hESC) can actually treat human diseases.  Yet, the technology is touted as the panacea to all the major diseases that inflict humans today.

2) thus far, the research has produced more hype than tangible hope.  Indeed, the promises of hESC therapy entice those with money to burn in the search for a magic cure.  For example, recently it was reported that Peyton Manning traveled to Europe to seek stem cell treatment for a neck injury.  ABC News referred to Manning’s efforts as a “Stem Cell Hail Mary.”  Apparently the treatment was unsuccessful.  The ABC News article included the following statements by Dr. Ruth Macklin (bioethics professor, Albert Einstein College): “We live in an era where physicians are encouraged to practice ‘evidence-based’ medicine.  However, a sports superstar has the money… to travel anywhere in the world to receive an experimental procedure that is not based on any evidence that works for his condition.”  Another stem cell researcher, Dr. Lawrence Goldstein, noted that “he was unaware of any stem cell approach that is proven to help any sort of spinal issue.”[ii]

3) hESC research, of course, destroys human embryos.  Yet we know that zygotes formed at fertilization are genetically unique with an intrinsic capacity of self-development.  The zygote does not become a human being at some later stage (e.g., implantation); it is a human being!

4) other types of stem cell research, such as somatic stem cells and induced pluripotent stem cells, show far more promise for present and future therapy than hESCs.  Furthermore, somatic stem cells and induced pluripotent stem cell research are not ethically problematic because they do not entail the destruction of embryos.

It is unfortunate that South Korea has renewed its pursuit of the unethical practice of hESC research.  It could instead follow the example of several Japanese scientists (e.g., Shinya Yamanaka and Kazutoshi Takahashi of Kyoto University) who have researched ways to reprogram skin tissue in mice to mimic embryonic stem cells.  In the end, South Korea’s effort to become a “stem cell powerhouse” will be overshadowed by its moral compromise.


[i] http://www.bbc.co.uk/news/world-asia-pacific-14968613

[ii] http://abcnews.go.com/blogs/health/2011/09/19/peyton-mannings-stem-cell-hail-mary/

See also The Center for Bioethics and Human Dignity website for the story on Peyton Manning.  http://cbhd.org/ is an excellent source for bioethical news.