Neanderthal Research Subjects?

If we could clone Neanderthals, should we? Why or why not? What would the ethical pitfalls be? Would the consequences of doing of it be the problem, or would the research leading to the cloning be problematic in its own right?

Here's the article inspiring the questions, by Zach Zorich, in Archaeology, Should We Clone Neanderthals?

If Neanderthals ever walk the earth again, the primordial ooze from which they will rise is an emulsion of oil, water, and DNA capture beads engineered in the laboratory of 454 Life Sciences in Branford, Connecticut. Over the past 4 years those beads have been gathering tiny fragments of DNA from samples of dissolved organic materials, including pieces of Neanderthal bone....

There are still technical obstacles, but soon it could be possible to use that long-extinct genome to safely create a healthy, living Neanderthal clone. Should it be done?....

Two main thoughts occurred to me, reading this article.

1) Do (or would) Neanderthals fall, as a matter of jurisdiction, into the domain of regulations established to protect human research subjects? Whether Neanderthals ought to count as human is controversial among scientists (according to the Wikipedia page on Neanderthals, "Neanderthals are either classified as a subspecies of humans (Homo sapiens neanderthalensis) or as a separate species (Homo neanderthalensis)." Given such scientific controversy, it's at least not obvious that laws & guidelines set up to protect specifically human research subjects would apply. Research on non-human research subjects is covered by the laws & guidelines for animal research.

Now, the article has some interesting stuff about human rights law, which suggests that interpretation of the term "human" in that regard might be broad enough to include Neanderthals. But then, it might not — depending on the jurisdiction and the decision-maker. Also, it's not clear that the standard applied under human rights law would automatically be the standard taken up by those who administer the rules of research ethics. And even if it were, that leaves open interesting questions about just how far from homo sapiens you have to stray before you leave the domain of "human" research, for either ethical or regulatory purposes.

2) The article points to a number of technical obstacles to cloning a Neanderthal. It points out, for example, that getting Neanderthal DNA isn't enough — the DNA needs to be formed into chromosomes and situated inside an egg, for starters. But the article leaves out one other, ethically crucial part of the equation: Mom. To create a living, breathing Neanderthal, you'd need not just an egg loaded with Neanderthal DNA, you need to implant that egg in the uterus of a female of a closely-related species. In other words, a woman. So, even setting aside the question of whether a genetically-Neanderthal fetus would be a "human fetus", such an experiment would still clearly fall into the category of research on human subjects. Would an ethics board approve it?

Fitter, Faster and Stronger: Olympics Athletes as Research Subjects

While the Olympics don't officially start until tomorrow, the "anti-doping" investigation clinics are open and working well before the games begin. But this year, those who test athletes for "doping" are faced with another possible way for athletes to enhance performance: gene therapy.

Here is a link to the story, from CBC news: Gene Doping Risky for Athletes

"Some athletes and coaches will be tempted, prematurely and unwisely, to take advantage of results packaged by some as performance-enhancement 'breakthroughs,' even if they are untested in humans and the only 'breakthrough' is faster or stronger mice," the researchers wrote. The article says gene therapy has complicated international competitions like the Olympics. Online marketing campaigns target athletes with ads focusing on how treatments can "alter muscle genes … activating your genetic machinery."

Already, scientists doing experiments in lab animals have been approached by athletes volunteering themselves as human test subjects. The athletes want to be like the "Schwarzenegger mice" that have an extra copy of a gene that led the critters to become 30 per cent stronger.

Gene therapy isn't new. It's been used in a number of therapeutic ways, but in many contexts, it remains highly experimental. As a performance-enhancing agent, gene therapy has been used in animal experiments with baboons and the famous "Schwarzenegger mice" but has yet to be safely or thoroughly tested on humans.

The risk to athletes is considered potentially deadly. One of the most interesting aspects of this kind of performance-enhancing gene therapy is also the most lethal: the kinds of physiological processes that are "turned on" when this kind of gene product is injected into a person can't be simply turned off. This lack of control over the physiological processes can lead to deadly consequences, clearly demonstrated in animal studies.

A few thoughts:

In terms of gene therapy, science is moving quickly. However, not quickly enough, it seems. The vision and hope for the science are racing ahead of even the most efficient research. And this clearly can lead to unethical and, in this case, potentially deadly consequences as athletes are being used as research subjects exposed to very high-risk experimentation.

The potential for profit creates even more pressure to use the products of scientific inquiry prematurely. The interest in using experimental gene-based enhancements on athletes is quickly growing. As noted in the CBC report, an article that will appear in Science on Feb 12 will cite an Associated Press report that gene therapy products were being surreptitiously offered to athletes at the 2008 Beijing Olympics.

One of the take-away messages here is that potential profit and great hope for a product of research creates pressure to advance the science as quickly as possible, often, much too quickly. Earlier this month, we blogged about the
Wakefield case. While this is very different, there is one similarity. The strong desire for a quick answer to the question What causes autism? and the possibility for profit from such an answer meant that unethical and unsafe science was advanced overzealously, resulting in significant harm to many. In this case, the hope to make athletes as fit, fast and strong as possible (and the subsequent potential for profit from their achievements) is driving the science of gene therapy much faster than any safe, ethical lab or researcher.

[Chris has also written about this over on the Biotech Ethics Blog
- I highly recommend reading his analysis as well]

The Tragedy of the Wakefield Case

Here's an update to a troubling story I published here almost a year ago. Dr. Andrew Wakefield was a senior lecturer in the Departments of Medicine and Histopathology at The Royal Free Hospital (a teaching hospital in London) and a consultant in experimental Gastroenterology. Last year, when I published the original blog entry, Dr. Wakefield was in the midst of being investigated for medical misconduct, in a "fitness to practice" panel hearing of The General Medical Council in the UK. The hearing was centered around a Feb 1998 Lancet article in which Wakefield made various claims about autism, the MMR vaccine and inflammatory bowel diseases. Since the publication of that Lancet article (which, as of today, has been retracted by the journal), vaccination rates in the UK have plummeted and Wakefield has been viewed as the scientist "poster-boy" of sorts for the supposed link between autism and vaccination. You can read more about it in my initial blog entry here.

The longest medical misconduct inquiry ever conducted by the General Medical Council has now come to an end, and as Brian Deer of the Sunday Times reports, they confirmed more than 30 charges against Wakefield.

Here is a link to the Sunday Times story: ‘Callous, unethical and dishonest’: Dr Andrew Wakefield

The panel’s findings were astounding, both in their number and substance. More than 30 charges were found proven against Wakefield. For him alone they ran across 52 pages. Embracing four counts of dishonesty — including money, research and public statements — they painted a picture of a man not to be trusted. Other proven charges included nine of mistreating developmentally challenged children: causing invasive “high-risk” research to be carried out without ethical approval and against their best clinical interests.

The panel ruled that Wakefield caused three children to undergo lumbar punctures without clinical reason. Three more rulings said he had breached his employment contract at the hospital’s medical school which forbade him from involvement in patient care. He was also found to have shown “a callous disregard” for the “distress and pain” of children to whom he paid £5 in return for blood samples at his son’s fifth birthday party.

This is arguably one of the "worst case scenarios" we imagine in the field of research ethics. While we're appropriately concerned with a myriad of ethical problems such as ghostwriting, undeclared conflicts of interest, breaches of confidentiality and the like, conducting research on vulnerable children without ethics approval is clearly one of the worst and most tragic cases we can think of. The resultant harm in this case, however, is not limited to the children and families Wakefield used in his "research". I'm thinking of two additional harms that may well have resulted, surely in part, from the Wakefield case.

First, there is the societal effect that the condemned research has had. Vaccination rates in the UK (and other countries) have significantly decreased. The lack of clarity about this issue has polarized communities of parents with autistic children, creating "us" and "them" camps of parents and families. Serious misunderstandings abound, both about autism and about vaccination. As I said in my original posting last year, it's difficult to hold Wakefield solely responsible for these problems. However, in part, his research spearheaded this movement for many (especially in the UK) and he has continued to promote his findings, despite considerable objections and serious questions from the scientific community.

The second kind of harm I'm thinking of is harm to the research community in general. It's challenging enough for highly trained researchers and clinicians to sort through the vast collection of research articles and findings on this topic, that range from high-quality, valid, reliable and trustworthy to questionable, unreliable, invalid and simply untrue. For a lay person or concerned parent to try to sort through this topic and figure out what constitutes "good" versus "bad" data is beyond challenging. Now, this case may result in discredit and distrust of researchers, thus further "muddying the waters" for lay persons trying to figure out whose data to trust and whose to dismiss.