A busy week for stem cells

Two bits of news from the world of stem cells this week:

First, Geron, the California company conducting the first ever official study using embryonic stem cells in humans, has suddenly terminated the study. Geron cited economic factors as the reason for stopping the trial. The study involved spine injury patients; Geron said only that the therapy was well tolerated, with no serious adverse events.

Second, a study using “adult” stem cells from patients’ own hearts to repair their own damaged heart tissue has produced promising results. The study’s purpose was not to show that the use of the cardiac stem cells was effective, but to make sure that the process is safe (the Geron study was also a test of safety); but study subjects receiving their own stem cells have already shown improvement in heart function.

Daniel Heumann, of the Christopher and Dana Reeve Foundation, said of the halted Geron study, “I’m disgusted. It makes me sick. To get people’s hopes up and then do this for financial reasons is despicable. They’re treating us like lab rats.”

The authors of the adult stem cell study, while warning that the results of the trial needed confirmation in larger trials, called the initial improvement in cardiac function “very encouraging.”

Geron has invested tens of millions of dollars in embryonic stem cell therapy in the past decade.

Even if one does not believe that it is unethical to destroy our offspring to find cures for our diseases, one should at least acknowledge that spending tens of millions of finite research dollars for an agenda that repeatedly uses reckless hype to gets people’s hopes up, only to dash them, is an unethical option when compared with funding “encouraging” research with a proven track record of producing successful treatments.

Science and a Christian worldview

Christian bioethics continuously lives at the interface of biotechnology and Christian moral values. Recently some students asked me to talk with them about whether I saw any conflicts between science and a Christian worldview. Their question took me back to the first CBHD bioethics conference that I attended in 2007 and Alvin Plantinga’s talk about that issue. He expressed things that I had understood, but had never heard expressed as well as he expressed them.
Plantinga made it clear that the conflict was not a conflict between Christian thought and science, but a conflict between the philosophy of naturalism and Christianity. He pointed out that many people assume that science, which is a method of acquiring knowledge about the physical world, was identical with philosophical naturalism which says that all that exists and all that we can know is what we can know through the empirical methods of science. However, understanding that science is a proper way to learn about the physical universe does not imply that naturalism is true, and science does not depend on supposing naturalism. In fact Plantinga showed that naturalism forms a very poor foundation for science, because the unguided evolution that must be assumed by the naturalist as the process by which human cognitive processes were formed does not give us reason to believe that those cognitive processes would be reliable sources for truth. (I always knew there was some reason why I liked epistemology.)
It is actually a Christian worldview that provides the foundation that science needs to function. We believe that God has created the universe so that it is rationally understandable and has given human beings the ability to accurately perceive the universe and cognitive faculties that are designed to comprehend truth. Those are the presuppositions needed to expect science to be a valid method for discovering the nature of our universe.
The problem is not that there is a conflict between science and a Christian world view. The problem is why someone without a Christian worldview would think that science is a reliable source of truth.

The ethics of PSA testing

 

The humble little PSA test has become a hot-button ethical issue.

The PSA (prostate-specific antigen) test is a blood test that can detect prostate cancer at an earlier stage than can physical exam. It is not a perfect test; it misses about 25% of cancers. But it is the best thing we have for detecting prostate cancer early.

The United States Preventive Services Task Force (USPSTF) reviews all of the available evidence regarding screening tests for various conditions, and makes recommendations based on the scientific evidence. Earlier this month, the USPSTF posted a draft of its update to its 2008 prostate cancer screening guidelines. The earlier guidelines had recommended that men over 75 not be screened with a PSA test, and said that there wasn’t enough evidence to make a recommendation one way or the other for younger men. The proposed new guidelines, based on more recent studies, go further, giving screening a “D” recommendation, which means that there is moderate or high certainty that the service has no net benefit, or that the harms outweigh the benefits, and the task force discourages use of the service.

But how can a PSA cause harm? It’s just a poke in the arm, right?

It is not the test itself that causes harm, but what we do with it. 90% of men with PSA-detected prostate cancer undergo radiation and/or surgical treatments that have considerable risks and side effects. The chair of the USPSTF said that for every 1,000 men treated for prostate cancer, five die of perioperative complications; 10-70 suffer significant complications but survive; and 200-300 suffer long-term problems, including urinary incontinence, impotence or both.

These numbers might be acceptable if there were evidence that treating early prostate cancer did some good. But, counterintuitive as it may seem, studies have shown little if any positive benefit from treating prostate cancer early. When men diagnosed and treated by PSA screening are compared with those who are not treated, there is virtually no reduction in prostate cancer mortality at 10 years.

J. A. Muir Gray wrote, “All screening programmes do harm; some do good as well.”

For a profession that takes seriously Primum non nocere, “FIrst, do no harm,” it seems, with what we know at the present time, that this particular screening test may contravene our first ethical principle.

Human cloning “breakthrough?”

 

Last week, Joe Gibes commented on the BBC’s report on the scientific “breakthrough” of  Dieter Egli and his colleagues at the New York Stem Cell Laboratory. As the BBC and other news agencies presented it, Egli et al derived human embryonic stem cells through a “cloning” technique, but as Joe correctly noted, no clones were produced. In transferring the nucleus of an adult skin cell to a nucleated human egg and retaining both sets of DNA during subsequent embryonic development, the researchers had actually  created not clones but  genomic hybrids with, I would add, a generally lethal defect (triploidy).

I see nothing sinister behind the imprecise language, and I don’t think Joe does either. It is, in fact, understandable as the method employed was essentially a modification of the technique (“somatic cell nuclear transfer”) that Ian Wilmut and his colleagues at the Roslin Institute used 15 years ago to create “Dolly” the sheep, the world’s first clone of an adult mammal. The chief difference is that Wilmut et al transferred the donor nucleus to an enucleated egg.

Cloning adult mammals is, to put it gently, no piece of cake. In their ground-breaking publication that introduced Dolly to the world, Wilmut et al reported making 434 attempts to fuse a nucleated donor cell  to an enucleated egg. That effort yielded 277 (63.8%)  zygotes (“fused couplets”) which they then transferred to ligated sheep oviducts for culture. Of those 277,  247 (89.2%) were recovered and of those, only 29 (11.7%) developed to a transferable stage (morula/balstocyst). As a fraction of the original 434 eggs, that represents 6.7%. Now, 14 years after the initial report of Wilmut et al, the process of producing clones from adult mammalian cells remains highly inefficient.

The “Holy Grail” of cloning, as Joe and others have put it, is not a cute little lamb, but a human embryo. Most researchers in the field recoil at the idea of cloning to reproduce full-sized copies of ourselves, but they salivate at the prospect of creating disposable, embryonic miniatures whose genomic identity would purportedly constitute for their “parents” the key to great medical benefit. Human biology, however, has proven quite resistant  to such designs, and that, I would submit, is the “story behind the story” of Egli et al. The whole reason these researchers moved to the hybrid model was because of their inability, and that of many others before them, to produce an embryonic human clone using techniques that, albeit with great inefficiency, have proven successful in animals.[1] What the BBC and others tout as a “breakthrough” is, in fact, little more than an affirmation of the status quo in human cloning research.

Whether human biology will continue to frustrate the dogged efforts of Egli and others to produce a human clone, only time will tell. But at this stage, reality certainly mirrors fiction as the quest for the “Grail” remains exactly that – a quest. Sadly, this quest to clone ourselves exacts a great toll as it drains finite resources and, more concernedly, does great violence to human dignity with its reduction of human life to an object of mere utility.  That we would dump the quest and focus our health resources elsewhere seems a right and sensible thing to do, but I’m not banking on that happening soon as many a policy-maker and researcher are “all-in”  in the gamble on so-called “therapeutic” cloning. That researchers have already discovered a method for re-programming adult human cells to a pluripotent state that requires neither a human egg donor nor an embryonic intermediate reveals the ongoing quest to produce a human clone to be less about advancing good science and medical therapy and more about satisfying a prior agenda.


[1] Sheep (1997), Mouse (1998), Gaur (2000), Pig (2000), Mouflon Sheep (2001), Cat (2002), Cow (2002), Goat (2002), Rabbit (2002), Deer (2003), Horse (2003), Mule (2003), Rat (2003), Wildcat (2003), Dog (2005), Banteng (2005), Ferret (2006), Swamp Buffalo (2006), Gray Wolf (2007).  See the US Food and Drug Administration online publication “Technology Overview: Somatic Cell Nuclear Transfer and Other Assisted Reproductive Technologies” at http://www.fda.gov/animalveterinary/safetyhealth/animalcloning/ucm124765.htm

Embryos and antioxidants

 

My heart almost stopped when I read the headline on Wednesday’s BBC article, “Human ‘cloning’ makes embryonic stem cells.” At first glance, I thought that the Holy Grail of embryonic stem cell research had been found: a way to generate personalized stem cells by cloning a person, then destroying (killing) the clone at the early embryonic stage in order to retrieve the stem cells that are oh, so tantalizing for the cures that they might hold: fixing everything from diabetes to heart disease to Alzheimer’s to aging itself.

However, a closer read of the story shows that we are no nearer the Grail than before. Cloning involves removing the DNA from a donated egg cell and replacing it with the DNA from the somatic cell of another person, making that egg cell into a genetic duplicate or clone of the person; the clone can then grow and develop stem cells. But what the scientists actually did here was to create a genetic hybrid: an embryo that contains both the DNA of the woman who donated the egg cell, and the  DNA of the person to be “cloned.” This means that each cell of the resulting embryo has three copies of each chromosome, rather than the two that each of our cells normally carry. Leaving aside for the moment the ethical questions surrounding deliberately creating something/someone so abnormal (there’s a whole book to be written there) and deliberately killing embryonic human beings, the insurmountable problems of using stem cells that are so genetically abnormal make them useless for any “cures.”

Meanwhile, a story in yesterday’s Chicago Tribune reports on antioxidants, “one of the hottest buzzwords in the health and wellness industry. Manufacturers have emblazoned it on everything from water and cereal to alcoholic drinks.” Theoretically, antioxidants, by cleaning up free radicals, can help slow the processes associated with damage caused by free radicals such as heart disease, cancer, stroke, and even aging.

The problem, of course, is that there is little to no evidence that antioxidants actually do anything of the sort, and there is good evidence that in some circumstances they may be harmful. Nevertheless, hundreds of products with antioxidant claims are developed yearly.

What’s the connection between the two stories? Two therapies that don’t work , but for which the public is willing to spend gazillions of dollars. Two therapies that promise, as an antidote to degenerative diseases, regeneration — restoration — to some, the hope of eternal youth, even eternal life.

From the numbers of people who buy into these forms of snake oil, it appears that the longings for regeneration and eternal life run deep in our race. As Christians who have experienced regeneration, and who have met the only true source of Eternal Life, we just might be able to offer some true hope in place of the hucksters’ hope to which so many cling.

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

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.

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?

From IVF to human trafficking, and how liberal bioethics led the way (actually, it followed)

 

Ross Douthat of The New York Times wrote recently of The Failure of Liberal Bioethics to provide any ethical guidance in the area of reproductive technologies. He recounts how liberal bioethicists, for all their eloquence about monitoring and controlling new reproductive technologies, really just act as a rubber stamp for whatever anybody wants to do, finding reasons “to embrace each new technological leap while promising to resist the next one . . . You can always count on them to worry, often perceptively, about hypothetical evils, potential slips down the bioethical slope.  But they’re either ineffectual or accommodating once an evil actually arrives. Tomorrow, they always say — tomorrow, we’ll draw the line. But tomorrow never comes.”

This marked failure in line-drawing in years past is bearing grim fruit today. In the August 4th New England Journal of Medicine, George Annas wrote of Canadian legal efforts to regulate the international trade in reproductive medicine. In order to bypass local regulations and expenses, people buy sperm from one country, ova harvested from women in another country, and rent a woman to act as a gestational surrogate from a third country, to try to have a child. These are just the sort of practices against which “conservative” bioethicists, those concerned with human dignity, the meaning of procreation, and the commodification of children, have warned; and about which “liberal” bioethicists have opined, “Well, there’s a theoretical risk here, we’ll have to watch that —” and then watched as theory became practice and practice became madness. Annas writes of the fear of many that reproductive medicine is “becoming a branch of international trafficking in women and children.”

This fear is reality. Last winter the Wall Street Journal ran an article featuring PlanetHospital.com LLC, a California company that scours the globe to find the “components” for its “business line” of internationally trafficked reproductive materiel and technology. ”PlanetHospital’s most affordable package, the ‘India bundle,’ buys an egg donor, four embryo transfers into four separate surrogate mothers, room and board for the surrogate, and a car and driver for the parents-to-be when they travel to India to pick up the baby.” The international nature of this enterprise places it under the radar of any governmental regulation that might interfere with the “business line,” and there does not appear to be much internal ethical regulation on the part of the company itself; anything goes, even when an apparent pedophile wants to have a child. As chief executive of PlanetHospital Mr. Rupak says, “Our ethics are agnostic. How do you prevent a pedophile from having a baby? If they’re a pedophile then I will leave that to the U.S. government to decide, not me.”

If liberal bioethicists continue to have their way, the unthinkable practices of today will become the commonplaces of next week. Annas bears disquieting witness to this when he writes of ”acts that were once thought to be so universally condemned that prohibitions against them could be incorporated in an international treaty.  These prohibitions include the knowing creation of a human clone, the creation of an embryo from the cell of a human fetus or from another embryo, the maintenance of an embryo ex utero for more than 14 days after fertilization, the use of sex-selection techniques for a reason other than the diagnosis of a sex-linked disorder, the performance of germline genetic engineering, the use of nonhuman life forms with human gametes, the creation of chimeras for any purpose, and the creation of hybrids for reproduction.”

How many of these “acts that were once thought to be so universally condemned” are already standard procedure today? If liberal bioethics continues to have its way, which of today’s unthinkables will be the next California company’s “business line?”

 

(If you have time, read all three articles.  They are very disturbing. If you think that the work of CBHD is unimportant, you may just change your mind.)

Of Machines and Men (Part I)

 

As part of my job, I have the privilege of participating in the delivery of many babies.  I was at one such blessed event earlier this week.  There were several medical personnel and the father standing around the bed of the expectant mother. Due to the wonders of epidural anesthesia, she was quite comfortable, despite the fact that she was in the final stages of labor.

Suddenly I became aware of what all of us were doing — myself, my residents, the nurse, even the father: we were watching a machine. The mother was hooked up to a machine that monitored both the baby’s heart rate and her own contractions. The rest of us stood and stared at the machine. When the machine showed she was having a contraction, we would all turn towards her and encourage her to push, cheerleaders for her and the little life that she was bringing into the world.  But we kept one eye on the machine, and as soon as it indicated the contraction was over, we turned away from the mother and towards the machine again, waiting expectantly for it to tell us when the next contraction was coming.

With a sense of deja vu I realized that I had observed a similar phenomenon in the ICU: doctors, therapists, nurses, even family and visitors who had no idea what the little multi-colored squiggly lines on the monitor meant, nonetheless staring expectantly at the monitor on the wall instead of at the patient in the bed.  And in my training of resident physicians, I have watched videotaped patient encounters showing them sitting in the office with the patient, staring deeply into the computer screen instead of at the patient who has come to see them.  Similarly, in their inpatient work, the residents spend a few minutes on the hospital floor seeing their patients, and the remaining hours of the day (and night) staring into a computer screen, tending to the computerized chart — the “iPatient,” as Abraham Verghese called it here.

The practice of medicine has historically been founded on the physician-patient relationship;  on that foundation has been erected an edifice of techniques and technologies, tools for medical practitioners to use in serving their patients. However, it seems that in our time the tools are beginning to attack the foundation of medicine rather than just being used by it. For a variety of reasons, the tools and technologies increasingly become the center of the physician’s attention. Instead of medical practitioners defining how the tools are used, the tools begin to define what medicine is. We are becoming what Neil Postman called a Technoloply: our tools change and determine our practice’s purpose and meaning, our very way of knowing and thinking and relating to our patients.

 

Edmund Pellegrino once wrote, “Men have always sensed that the more they forged and the more machines they built, the more they were forced to know, to love, and to serve these devices.” (From Humanism and the Physician.)

 

Next week:  Some thoughts on what we can do about the ascendancy of the machine in medicine.