Knowing too little about too much

 

With the ability to map the human genome, we find ourselves in the bewildering position of knowing too much and knowing too little at the same time.

Consider this scenario: The year is 2015. You, being the modern that you are, want to know your future, so that you can have some degree of control over it. You’re pretty sure astrology isn’t very helpful; but you’ve been keeping up with Time and Newsweek, and you’re thinking from what you’ve read there that genetic testing offers the scientific equivalent of what astrology promises. So you go down to the local Genetics-R-Us and for a mere $99 have your entire genome analyzed in 15 minutes. You then sit down with one of their genetic consultants, who reveals that you have a 64% likelihood of developing diabetes and a 43% chance of developing colon cancer. You go on a vegan diet, exercise three hours a day, and start a regular regimen of bowel cleansing and weekly colonoscopies. You have your genome analysis results sent to your primary care provider (PCP) to be part of your medical record.

Fast forward to 2025, when you are diagnosed with a rare cancer of the nose. After a little research, you discover that this particular type of cancer can be predicted by genetic testing. Genetics-R-Us went out of business, so you go to your PCP and demand to know why she didn’t warn you about the possibility of this cancer. She steps out to do a little research and comes back into the room:

“It turns out that the gene that predisposes you to this kind of cancer wasn’t discovered until 2019, and you had this test done in 2015.”

“But when that information became available, why didn’t you go back and recheck my genome?” you reply.

“That’s the responsibility of the company that tested you,” she says, as she gets her defense lawyer on the phone.

“But Genetics-R-Us went bankrupt! You’re the only one who has the data!”

“We have thousands of these genome maps in our records, each consisting of six billion base-pairs. They are encoded in various formats, none of which are compatible with each other, and some of which are so outdated we can’t access them anymore. Plus, a 200-page update of the latest new gene dicoveries is published every month. We simply don’t have the resources to go back through everybody’s individual genome and check for all of these genetic abnormalities that are constantly being discovered.”

***

With the capability to map an individual’s genome, we can gather lots of data, but we do not yet have the knowledge of how to apply that data (much less the wisdom with which to use it!). We know too little about all that we know. As genome testing becomes more affordable and widely available, some of the ethical questions that arise are, Is there an ethical obligation to go back an re-analyze data in light of new findings? If so, whose is the responsibility?

Privacy and the risks of IVF

A recent article in Toronto’s National Post tells of the experience of Dr. Rosanna Weksberg, a University of Toronto geneticist, when she presented a talk on the need to study risks associated with IVF (in vitro fertilization) to the Canadian Fertility and Andrology Society. Her talk related her experience in seeing an increased number of children with rare genetic disorders among children conceived by IVF. Some of those disorders are seen as much as 10 times more often in children born by IVF.

She expressed her concern that follow-up studies of children born by IVF are needed. The reception from the meeting of fertility specialists was polite, but no interest in her proposal for study was expressed. She said she has been trying to find fertility clinics willing to partner in studies of children born with the help of reproductive technology, but has not found any willing to work with her. A spokesman for the fertility society said they were interested, but that clinics could not afford to fund research.

In the United States assisted reproduction is a 3 billion dollar a year industry, but like in Canada there is no accurate information on the risk of genetic disorders, birth defects, or other increased health risks of the children produced by these procedures. Our culture has set apart everything having to do with sexuality and reproduction in a domain protected by privacy. That protection is so complete that it causes assisted reproductive technology to be entirely unregulated and makes any attempt to study the outcomes of the children produced exceedingly difficult. We need to recognize that, even though privacy in reproductive decisions is important, people cannot make responsible decisions without good information. Those contemplating the use of assisted reproductive technology need to know what the risks are for the children they bring into the world. They owe it to their children.

Another Promising Result Using Induced Pluripotent Stem Cells

Last Friday it was announced in Medical News Today that researchers at Johns Hopkins have discovered a means to fix the genetic defect that causes sickle cell disease with the patient’s own stem cells.  According to the announcement, “The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene.”[1]  This does not mean that a clinical application is imminent or that the procedure is safe.  As stated in the original abstract from Blood, the Journal of the American Society of Hematology, “the safety and feasibility of stem cell mobilization in individuals with sickle cell trait (SCT) has not been documented.”  However, the report added that “no untoward adverse events occurred in either group, including sickle cell crises.” [2]

The new treatment could prove to be revolutionary; at present the only existing therapy for sickle cell disease is through bone marrow transplantation.  However, the journal Blood reports that, “many patients are ineligible [for bone marrow transplantation] because of either the lack of a suitable donor or their underlying condition.”  The advantage of “peripheral blood stem cells” (PBSC) from the patient are obvious: patients don’t have to wait for a suitable donor – they are their own source of the stem cells.  The study concludes that, “Products from SCT donors require only minor changes in ex vivo cell processing, allowing for the use of mobilized peripheral blood as a potential source of stem cells for transplantation in sickle cell disease.”  Furthermore, as one researcher stated, “The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells.”[3]  In short, scientists believe they are now one step closer to successful stem cell therapy for sickle cell disease.

Of course, the word is still out on the success of PBSCs.  But ethicists should applaud any research that is as promising as embryonic stem cell research, but does not require the destruction of human embryos.


[1] http://www.medicalnewstoday.com/releases/235221.php

[2] There were two separate control groups with eight individuals in each group – one SCT group and one non-SCT group.  In the words of the research team, the study does “not permit the conclusion that G-CSF is completely without such risk. Our study, however, suggests that the risk is limited…” http://bloodjournal.hematologylibrary.org/content/99/3/850.full?sid=62767506-48e6-45f1-be88-b033f616fcc7

[3] http://www.medicalnewstoday.com/releases/235221.php

Do-it-yourself DNA Analysis for $19.95!

Well, not quite, although a very cheap version may be just around the corner.  In this month’s edition of Wired (September 2011), one article reports that it is now possible to build your own DNA research lab for just “a few hundred bucks.”  The technology promises consumers the ability to turn “small samples of DNA into quantities large enough to analyze.”  The advantages to such technology are obvious; imagine having the capability of examining and identifying DNA in your own garage or basement.  Indeed, DIYbio (http://diybio.org/) is “dedicated to creating pop-up labs and doing biology outside the traditional environments of universities and industry.”  Currently there are DIYbioer groups all over the world, especially in the U.S.

In the past, the chief obstacle was affordability; the technology was simply far too expensive for the average amateur on a shoe-string budget.  The situation is changing, however.  Wired reports that “Behind the scenes, engineers and science enthusiasts are teaming up to mod tools and technologies and sell their inventions – or simply share tips on how to build them – to anyone interested.”  For example, PCR (polymerase chain reactions) kits, described as a “copy machine for DNA,” are attracting lots of attention.  According to DIYbio, for under $600, you can purchase a PCR to diagnose diseases or explore your own genome.

As with any technology, DIY DNA analysis is a mixed bag.  Professional PCR machines range from $6,000 to $17,000.  With a small investment, individuals interested in the technology can bypass the big corporations and achieve some of the same results.  Three years ago, high school students used DNA testing in the classroom and discovered that “sushi restaurants and supermarkets were mislabeling their fish” (an event known as “Sushigate,” Wired).

Then again, there is always the dark side to technology.  Suppose it becomes viable to detect one’s own genetic defects with the technology?  Or, what if it’s possible to discover someone else’s genetic defects?  Needless to say, the technology raises a couple of ethical questions:

*what should a person do with knowledge of a future genetic disease, especially if there is a gap between diagnosis and treatment, or if there is no treatment in the foreseeable future?

*then there is the question of whether a person has a moral obligation to inform others of genetic defects, such as one’s potential spouse.

Perhaps the most worrisome aspect to pop-up labs is the lack of regulation or ethical guidelines.  Also, what else can be done with the technology, and who is going to oversee the research and monitor the results?

As humans, we have this unfortunate tendency to be self-centered, to ignore our finiteness, to press forward without caution, to abuse technology to gain greater power, and to proceed without moral guidelines.  We do well to heed the frequently quoted warning of Hans Jonas, “Modern technology has introduced actions of such novel scale, objects, and consequences that the framework of former ethics can no longer contain them.”  Where then is the ethical framework to restrict the misuse of this technology?

Of Machines and Men (Part II)

 

I observed last week that machines are increasingly shaping the nature of medicine; rather than medicine using its machines, its machines are starting to “use” medicine, to shape and direct the nature of medicine and adapt medical practice to the nature and methods of the machine. In this process, human activity absorbs the ethos and rhythms of the machine. Machines are all about efficiency, standardization, precision, data, and automation. Is this not becoming characteristic of the practice of medicine?

In medicine, “Efficiency” appears to be the watchword and underlying criterion for more and more decisions. The term “industry,” which previously one never would have used in the same sentence as the word “medical,” has become an accurate representation. Interactions between “medical consumers” and “providers” are increasingly mediated through machines. Leaders in medicine strive for standardization, automation, the effacement of individual practice variations, and centralization. Specialization is ever-increasing, and specialists with more techniques and machines to offer are valued more highly (and reimbursed more handsomely) than generalists who are the masters of less technology. Health care workers have reached the point where they can not practice without their gadgets. Practice quality is measured only by what is quantifiable; data, information, seems to have become the primary distinguishing characteristic of medicine, over and above relationship. Medical ethics is being reduced to machine-like process; content has become almost irrelevant. Technology is used more and more in an attempt to eradicate all ambiguity, imprecision, and uncertainty. Technology is used more and more simply because the technology exists. Both physicians and patients feel the increasingly machine-like nature of medical practice, even if they can not express it as such: patients complain of the impersonalization, sterilization, and dehumanization of medicine, while doctors feel more and more like cogs in a machine.

Efficiency is the end-all and be-all of machine medicine;  eliminating inefficient means becomes part of the grand project. And who in our time quibbles with eliminating inefficiency? The problem is compounded when the efficiency value system is applied not just to medicine, but to the humans it was meant to serve, when those patients who are considered “less efficient” are eliminated as blithely as last year’s smartphone. It happens now in the unborn, with prenatal genetic diagnosis identifying those “less efficient” humans who are then prevented from being born; it happens in the older and disabled, with euthanasia and physician-assisted suicide removing those who are too sick or old to be of use to themselves or others. Where will it be applied next?

To remain a human profession, medicine must regain and retain its human ethos . . . which, is why ethics is so central to its practice. In a future post I will consider some ways to resist the usurping of the essence of medicine by the efficient principle of the machine.

 

Cybrid-gate in the UK

In last week’s blog (July 26), I highlighted an article from Wired magazine (August 2011) titled “Extreme Science”  in which Wired explores seven “shocking experiments” that scientists could learn from if they were willing to set aside their ethical concerns.  One experiment involves cross-breeding humans with chimpanzees in order to better understand human development.

What I find fascinating about all of this is that the Wired article was written as if unethical experiments don’t occur; as if, in reality, scientists are guided by a moral compass.  But are they?  Just 2 days before I wrote my blog, The Daily Mail (a British publication) reported that over a 3-year span scientists “have created more than 150 human-animal hybrid embryos in British laboratories.”  So, what Wired posed as a hypothetical thought experiment was already happening (albeit secretly) in the UK.

According to The Daily Mail, “155 ‘admixed’ embryos, containing both human and animal genetic material, have been created since the introduction of the 2008 Human Fertilization Embryology Act.  This legalized the creation of a variety of hybrids, including an animal egg fertilized by a human sperm; ‘cybrids’, in which a human nucleus is implanted into an animal cell; and ‘chimeras’, in which human cells are mixed with animal embryos.”  http://www.dailymail.co.uk/sciencetech/article-2017818/Embryos-involving-genes-animals-mixed-humans-produced-secretively-past-years.html

The Human Fertilization and Embryology Act of 2008, Section 4A, contains some of the following prohibitions:

“(1) No person shall place in a woman –

(a) a human admixed embryo,

(b) any other embryo that is not a human embryo, or

(c) any gametes other than human gametes.

(2) No person shall –

(a) mix human gametes with animal gametes,

(b) bring about the creation of a human admixed embryo, or

(c) keep or use a human admixed embryo…”

So far, so good.  Or so I thought.  The Act continues:  It is illegal to do #2 above (i.e., mix human gametes) “except in pursuance of a license.

In other words, it is still possible, with government authorization, to mix human gametes with animal gametes to create an admixed embryo.  The only restriction, according to the Act, is that the admixed embryo cannot be kept or used after the first 14 days of its existence.  Indeed, it is also possible, according to the wording of the Act, to create an admixed embryo, store it (i.e., freeze it) over a period of time, and then at some future point do research on it, as long as it is not allowed to live beyond 14 days.

(To view The Human Fertilization and Embryology Act of 2008, go to:  http://www.legislation.gov.uk/ukpga/2008/22/contents)

But the story’s intrigue deepens.  The creation of the cybrids” in the UK was apparently done in secret.  As noted in a recent Christian Medical Fellowship blog (July 26): “there seems to be a murky mix of confusion and secrecy from which the true facts and figures are difficult to extract.”  But why the secrecy if research was being done within the guidelines of The Human Fertilization and Embryology Act?

Furthermore, the research was not carefully documented.  It is less than clear the exact numbers of cybrids that were created.  The Christian Medical Fellowship reports that, “According to The Independent “many more cybrid embryos were created – 278.  That large number is naturally of concern, but also of concern is that the numbers don’t match the figure of 155 released last week.  The Government has avoided answering that question.  Moreover, if all funding (apparently) stopped in 2010 and the licence was revoked from the only researcher, when were these 155 (or 278) embryos created?  Were they all created before 2010?  Or are they still being created?  If so, by whom?” http://www.cmfblog.org.uk/2011/07/26/155-animal-human-embryos-created-in-the-uk-%E2%80%93-we-think/?doing_wp_cron

In other words, in spite of government oversight, an assortment of so-called “ethical guidelines,” and the best intentions of scientists, it’s less than obvious that research is done within any firm restrictions.  The CMF concludes that “the glaring discrepancies in the figures issued by The Human Fertilization and Embryology Authority shows it is not fit for purpose when it comes to regulating the scientists.  It is incapable of keeping accurate records and is unable to keep on top of what is going on in research, either with embryos or eggs.”

I ended last week’s blog with the following observation:  “Humans have also demonstrated a natural tendency to push the moral envelope, to give priority to what can be done over what should be done.  Time will tell whether experiments that are now considered unethical will one day be the norm.”  Apparently we no longer need to wait for “time” to make this announcement.

Parental Guidance Before and After Birth

 

As I sat sipping coffee and reading articles on the moral implications of genetic interventions in the germ-line (don’t yawn), a perfect picture was painted at the table across from me.  A young and boisterous child spoke of his aspirations for the future, vehemently proclaiming to a doubting adult audience, “I want to be a teacher, a singer, a dancer, a hospital man, I want to be everything.”

 

His ambitions were a bit outlandish.

 

His father, or who I believed to be his father, responded: “Do you know how you can be all of those things? You can be an actor.  This way you can be a teacher one day, and a singer another, and…”

 

“No, I want to be them all!”– Clearly the aspirations of the father were distinct from that of the son.

 

Imagine, if you will, that your direct (active) influence on your child could begin before conception. What if you could unify your aspirations before birth? No longer would you have to squelch his dreams as he bellows across Starbucks…

 

Although this is not yet in our grasp, Gender selection and disease screening are already a possibility. What if more options become available?

 

John Harris, recognizing this future possibility in his book Enhancing Evolution, avows an ethical parity in genetic interventions before conception and parental influences after birth. Could this be true?  Are encouraging your child to play an instrument and (in some future world) fashioning an embryo to be a world-class musician morally equivalent?

 

I would say there is a distinct difference between choosing for our children potential traits in embryo and guiding our children along in life. No doubt both influences are according to parental values. However, by choosing traits we are no longer discussing influence in terms of persuasion and direction, we are discussing a new kind of coercion.

 

What do you think?

 

Kaddish “I Am Here”

This past fall, I had the privilege of attending the Houston Symphony’s production of

A prisoner in a special chamber responds to changing air pressure during high-altitude experiments. 1942. Dachau, Germany

Kaddish.  The Kaddish Project seeks to commemorate the noble struggle of individual Holocaust survivors, including four who have made their homes in Houston.  Much of my research at Trinity focused on the concept of personhood, that we are more than just biological systems but instead are “someones,” persons.  I couldn’t help but think of this as I heard the chorus sing the song of the persecuted Jews: I am someone and “I am here.”  Though mocked and beaten in the streets even in the days before World War II, the Jewish people of Europe taught their children that they were of value even though others thought otherwise.  The soloists and chorus related the story of one survivor’s recollection of a concentration camp.  When the prisoners arrived, those under 14 years of age and over 65 were separated to the left and killed.  They were less than optimal for the German labor camp, so they were eliminated.  Kaddish led me to reflect on how physicians were a significant part of the German “Final Solution.”  They were the ones who deemed the crippled and deformed, the mentally deranged and deficient economic burdens.  That’s why I think that as we look for disease and perform technical procedures, it’s important for us to remember that our patients are someones who we must relate to and care for.