Experimental embryonic stem cell “treatment” for Down syndrome–any ethical issues here?

In New Delhi, India a baby received multiple injections of human embryonic stem cells as an experimental treatment for Down syndrome. Any ethical issues here? 

They are legion.

Case study

The case involved a two-month old boy who was born with Down syndrome. He also was born pre-term, kept in the ICU for two days for respiratory distress, and had cardiac atrial septal defects (ASDs).

Between September and November 2014, he received injections of human embryonic stem cells (hESCs) via intravenous, subcutaneous, and intramuscular injection.  He received another round of injections of hESCs between March and April 2015 before being discharged.

After eight months of the treatment, the open-sourced paper reports that “the child was coherent, babbling, and crawling, and eating ability was better.” It further reports “an improvement was observed in the condition of the patient such as better understanding, better muscle tone of limbs and ability to recognize nearby placed objects.”

“No adverse events (AEs) were reported.”

The report concludes by positing that the hESCs may have “induced normal neurogenesis in the brain” and that “it could be hypothesized that in our case hESCs might have activated XIST gene, helping in silencing the extra 21 chromosome.” (More on theoretical XIST treatment at this post).

Critical analysis of treatment

Before exploring the abundant ethical issues, first a critical analysis of just what was reported.

The report does not state whether or to what extent the injections of hESCs did anything or did not do.

It seems just as plausible that any claimed delay the child experienced could have been due to being born pre-term, being in ICU for two days, and/or for having ASDs, the treatment of which the reader is left to guess.

Similarly, the observed improvements following the hESC injections could be simply a matter that the child was around 18 months old, and not a two month old when he started the treatments. Babies experience dramatic milestone growth during those early months. Plus, while the article notes that supplemental therapies such as occupational and speech can minimize the delays associated with Down syndrome, it is not reported whether and to what extent the child received those therapies.

Finally, the report states that no adverse events were reported. But, really, shouldn’t that sentence end with “… yet”? For, there is no way of knowing whether the injection of human embryonic stem cells may adversely effect this child years later.

Ethical analysis

• Informed Consent

The article states that the parents provided written informed consent prior to treatment. But, what were the parents counseled about?

First, for any parent of any child, I think most people would agree any parent is challenged in providing informed consent about anything for the first two weeks of the child’s life–we’re all too sleep deprived.

Second, if these parents experience was like many other parents of children with Down syndrome, my own experience included, at two months, when this child began treatment, is only the beginning of when one or both parents are starting to move forward, having begun the process of acceptance and moving past the grieving for the child they thought they were going to have.

Compounding these parents’ experience were the associated health complications the child had. Again, for most parents of children with Down syndrome that have heart conditions like ASDs, the focus is on the treatment of that condition, then, once it’s assured that the child is going to live, the parents begin processing what their life will be like raising a child that has Down syndrome.

Lastly, discussed further below, what effort, if any, was given in counseling to address the cultural and historical stigmatization of Down syndrome and intellectual disabilities in order for the parents’ decision to be truly the result of informed consent, and not societal normative pressure to accept an experimental treatment that promised the possibility of “curing” their child with Down syndrome.

• Mengele-Tuskegee Guinea Pig Dynamic

As just mentioned, Down syndrome remains a stigmatized condition. One that headlines regarding prenatal testing and potential treatments write about as “genetic defects” and “fetal flaws.” In the report, itself, it describes how those with Down syndrome “suffer from several congenital and progressive medical conditions such as mental retardation, congenital heart disease, gastrointestinal anomalies, skeletal anomalies, leukemia and Alzheimer’s disease (AD).” This is not exactly correct, since only a minority will have the anatomical conditions and, while all will show physical symptoms of AD, not all will actually develop the actual condition.

This pejorative view of the condition itself, and therefore of those with the condition, raises the specter of historical atrocities committed against those historically segregated and oppressed in the name of medical experimentation and “progress.”

Two commonly known such atrocities were the gross medical experiments performed by Nazi Doctor (term used only technically) Mengele on concentration camp inmates and the U.S. Government’s monitoring of the disease progression of syphilis in African Americans at the Tuskegee Institute, despite those patients having been promised treatment.

These atrocities occurred because the patients were ostracized, out of sight, and considered of a lower class than those experimenting on them.

This case bears many similarities given the negative view of Down syndrome still by most societies, and particularly in India, where gender, class, and disabilities remain reasons for considering some fellow human beings as less than others who are male, of a higher caste, and not as obviously disabled.

• Impact on Prenatal Counseling

On the other hand, if hECG injections do prove to be a treatment for Down syndrome that closes developmental gaps, then that would have a tremendous impact on the administration of prenatal testing.

As written at other posts on other possible treatments, the main missing link in the medical logic of prenatal testing for Down syndrome is that it offers no treatment. In most all other medical testing, tests are performed in order to identify a condition for which then there is a treatment. Such is not the case with Down syndrome.

But, if hECG injections proved to be a viable treatment, then that would radically change the ethical justifications for prenatal testing.

Currently, prenatal testing is justified by most commentators out of respect for the woman’s autonomy to receive information upon which she can then decide whether to continue or terminate her pregnancy. If there were a viable treatment for the condition, the ethical argument could then be made that prenatal testing was justified based on beneficence for the child, by identifying a treatable condition.

But that then raises a larger ethical issue.

• Hubris of Presumption/Universal Challenge

To argue that a viable treatment that minimizes the developmental delay associated with Down syndrome would be “beneficent” presumes that those who have Down syndrome should be “improved” by medical treatment. Put another way, that there’s something “wrong” with those who have Down syndrome that is in need of “fixing.”

It has been the case in human history, that those with Down syndrome were ostracized, considered evolutionary regressions, segregated, and cast off. They were among the first targets of eugenic efforts, both in the United States and the more notorious Final Solution of the Third Reich.

It has only been in my lifetime (i.e. ~40 years), through public policy measures and a greater acceptance of those considered “others” that individuals with Down syndrome are only now being viewed as fully human, endowed and entitled to the same inalienable rights that each of us are born with, and living now fully realized lives of their own choosing.

As the report details, Down syndrome is caused by an extra copy of the 21st Chromosome. So, it is simply a genetic condition. In a large part, who each of us is, is based on our unique genetic conditions. Which of those conditions are “wrong” and in need of “fixing” and which are, instead, respected as genetic diversity that adds to the abundance of life?

In wrestling with this question, one ethical test is Kant’s “universal” test: is the proposed action something that you would apply to yourself? If it is ethically justified to inject hESCs into an individual with Down syndrome to theoretically possibly treat neurologic or genetic manifestations of the extra 21st Chromosome, would you inject hESCs (or whatever biological/pharmaceutical means) to “fix” a condition that you have?

Like I said, the ethical issues with this simple case study are abundant. This post merely scratches the surface.

I’d be interested in your thoughts on this issue of treating Down syndrome. Please leave a comment with your thoughts or concerns over whether this experiment on a child can be justified, whether Down syndrome is a condition to be treated, or any other idea you may have relevant to this post.

UPDATE: The number of patients with Down syndrome treated with this experimental hESC method is now up to 14. Comments from the report:

“There’s no obvious way in which this treatment would have worked,” says Victor Tybulewicz at the Francis Crick Institute in London. To have any effect, neural stem cells would need to be injected into the brain, he says.

“The author appears to have no idea of where [the cells] are going, or what they’re doing,” says Fisher. “It’s even worse now we know they’ve treated 14 patients, not just one.”