Medical research ethics

In today's NYTimes, there is an OpEd column by bioethicist Carl Elliott about biomedical ethics (or its lack) at the University of Minnesota.  It outlines many what sound like very serious ethical violations and a lack of ethics-approval (Institutional Review Board, or IRB) scrutiny for research.    IRBs don't oversee the actual research, they just review proposals.  So, their job is to identify unethical aspects, such as lack of adequate informed consent, unnecessary pain or stress to animals, control of confidential information, and so on, so that the proposal can be adjusted before it can go forward.

As Elliott writes, the current iteration of IRBs, that each institution set up a self-based review system to approve or disapprove any research proposal that some faculty or staff member wishes to do, was established in the 1970's. The problem, he writes, is that this is basically just a self-monitored, institution-specific honor system, and honor systems are voluntary, subjective, and can be subverted.  More ongoing monitoring, with teeth, would be called for if abuses are to be spotted and prevented.  The commentary names many in the psychiatry department at Minnesota alone that seem to have been rather horrific.

But there are generalizable problems.  Over the years we have seen all sorts of projects approved, especially those involving animals (usually, lab mice).  We're not in our medical school, which has a distant campus, so we can't say anything about human subjects there or generally, beyond that occasionally one gets the impression that approval is pretty lax.  We were once told by a high-placed university administrator at a major medical campus (not ours), an IRB committee member there, that s/he regularly tried to persuade the IRB to approve things they were hesitant about....because the university wanted the overhead funds from the grant, which they'd not get if the project were not approved.

There are community members on these boards, not just the institution's insiders, but how often or effective they are (given that they are not specialists and for the other usual social-pressure reasons) at stopping questionable projects is something we cannot comment on--but should be studied carefully (perhaps it has been).

What's right to do to them?  From Wikimedia Commons

The things that are permitted to be done to animals are often of a kind that the animal-rights people have every reason to object to.  Not only is much done that does cause serious distress (e.g., making animals genetically transformed to develop abnormally or get disease, or surgeries of all sorts, or monitoring function intrusively in live animals), but much is done that is essentially trivial relative to the life and death of a sentient organism.  Should we personally have been allowed to study countless embryos to see how genes were used in patterning their teeth and tooth-cusps?  Our work was to understand basic genetic processes that led to complexly, nested patterning of many traits of which teeth were an accessible example.  Should students be allowed to practice procedures such as euthanizing mice who otherwise would not be killed?

The issues are daunting, because at present many things we would want to know (generally for selfish human-oriented reasons) can't really be studied except in lab animals. Humans may be irrelevant if the work is not about disease, and even for disease-related problems cell culture is, so far, only a partial substitute.  So how do you draw the line? Don't we have good reason to want to 'practice' on animals before, say, costly and rare transgenic animals are used for some procedure that may take skill and experience (even if just to minimize the animal's distress)?  With faculty careers depending on research productivity and, one must be frank, that means universities' interest in getting the grants with their overhead as well as consequent publication productivity their office can spin about, how much or how often is research on humans or animals done in ways that, really, are almost wholly about our careers, not theirs?

We raise animals, often under miserable conditions, to slaughter and eat them.  Lab animals often have protected, safe conditions until we decide to end their lives, and then we do that mostly without pain or terror to them.  They would have no life at all, no awareness experience, without our breeding them.  Where is the line to be drawn?

Similar issues apply to human subjects, even those involved in social or psychological surveys that really involve no risk except, perhaps, possible breach of confidentiality about sensitive issues related to them. And medical procedures really do need to be tested to see if they work, and working on animals can only take this so far. We may have to 'experiment' on humans in disease-related settings by exploring things we really can't promise will work, or that the test subjects will not be worse off.

More disturbing to us is that the idea that subjects are really 'informed' when they sign informed consent is inevitably far off the mark.  Subjects may be desperate, dependent on the investigator, or volunteer because they are good-willed and socially responsible, but they rarely understand the small print of their informedness, no matter how educated they are or how sincere the investigators are. More profoundly, if the investigators actually knew all the benefits and risks, they wouldn't need to do the research.  So even they themselves aren't fully 'informed'.  That's not the same as serious or draconian malpractice, and the situation is far from clear-cut, which is in a sense why some sort of review board is needed.  But how do we make sure that it works effectively, if honor is not sufficient?

What are this chimp's proper civil 'rights'?  From the linked BBC story.

Then there are questions about the more human-like animals.  Chimps have received some protections.  They are so human-like that they have been preferred or even required model systems for human problems.  We personally don't know about restrictions that may apply to other great apes. But monkeys are now being brought into the where-are-the-limits question.  A good journalistic treatment of the issue of animal 'human' rights is on today's BBC website. In some ways, this seems silly, but in many ways it is absolutely something serious to think about.  And what about cloning Neanderthals (or even mammoths)?  Where is the ethical line to be drawn?

These are serious moral issues, but morals have a tendency to be rationalized, and cruelty to be euphemized.  When and where are we being too loose, and how can we decide what is right, or at least acceptable, to do as we work through our careers, hoping to leave the world, or at least humankind, better off as a result?

Where are the limits of human-animal rights?

How far should we extend consideration for animal rights, in particular with regard to chimpanzees or other 'higher' primates?  Views on this vary from people who argue about the necessity of using non-human primates to understand human disease, or behavior, or evolution, to the those who argue that as our nearest relatives, chimpanzees should enjoy the same rights that humans enjoy.  In fact, the New York Times had a story on Sunday about the first chimp suing its owner for abuse.  Federal regulations have changed on this over the years, currently erring on the side of more rights than fewer, but this hasn't always been so.

Now, Svante Paabo, a pioneer of sequencing ancient DNA (from fossils) and the first and one of the major sequencers of Neanderthal fossil DNA, has written a thoughtful NY Times piece about the rather culpably casual rhetoric about 'cloning' a Neanderthal that has followed the sequencing of several Neanderthal genomes.  The  widespread headlines by promoters of this sexy idea usually omit some important technical details that clearly show that the idea is not actually cloning a Neanderthal (Svante briefly itemizes some of this), but that's not our point here.

Neanderthal; BBC website

The Neanderthal is treated in the usual stories, even by prominent investigators who should know better, as some object of study, as an 'it'.  But we know that Neanderthals and other populations that once existed, or at least are identified as populations by some sample fossil finds, could interbreed with the direct ancestors of us modern humans, or is that the way to put it?

If 'they' bred with early 'us', then what makes them 'they' rather than others of 'us'?  The answer is that this is a misrepresentation of the population dynamics.  What happened, based on current knowledge and interpretation, is that two groups of our ancestors met and inter-bred.  The only reason one is called 'them' and the other 'us' is that the vast majority of the DNA you and we carry around seems  to have come from the ancestors being referred to as our own, and only minority from the Neanderthals who are often treated as a truly different kind of life--a different species.  This shows some modern arrogance on our part, as if they were some sort of strange interlopers into our noble lineage.  Instead, they were just part of our lineage.

Is old-fashioned racism lurking beneath the jolly stories here?
Of course, in our current scientific system, including news and other attention-seeking media, we quickly see evaluations of what functionally important genes 'they' gave to 'us'?  (Anything we gave to them must have been rather devastating, if the interpretation that they all died out is correct).  Whether the list is of 'good' or 'bad' genes, does the assignment of such genes as being owned by one or the other ancestral group an unmixed scientific assessment?

Or, by classifying the groups as us and them, and then saying 'they' had this or that genetic variant that they gave to 'us', are we carelessly indulging in just another form of group generalization, another form or value-judgment racism?  Do we blame their inferior nature for the 'bad' genes, for type 2 diabetes, say, that we got by some careless intermixture with 'them'?  If genes they gave us were superior (say, high-IQ genes such as found in certain racial groups today--you can fill in the blanks, we're sure), then why did they die out and we persevere?  If we won but they had the superior genes at the time of encounters, then why doesn't this make people think twice about ritualized Darwinist assertions of how who adapted to what?

If it was a few of their good genes mixing with our overall-better genomes, then why didn't the offspring, who were 50-50 in terms of ancestry, lend superiority to their part of the interacting groups?  Of course, you can make up any story you want, especially if you believe that the 'disease' or 'superior' variants really are so--we readily know how vulnerable GWAS and other genetic value assessments are proving to be, to over-generalization.

So perhaps there's the additional issue not just of animal/human distinctions, but of careless talk reinforcing the racism always latent in the human heart.

But even that is not our point today.

What about the clones?
Let's suppose that the modern Dr Frankensteins can bring the Neanderthal 'It' to life.  How will that be done?  First, with present-day technology, there will have to be a very low-tech participant besides the Neanderthal DNA: some woman to carry the fetus.  It probably can't be a chimp, should one 'volunteer', because Neanderthals were so essentially human that a human uterus,  pelvis, and physiology would be needed to carry the new baby.  Well, there are probably plenty of people who'd volunteer for the job.  So, forgetting that minor obstacle, what will occur once the venerable Dr F has the bundle of joy in his lab?

Will it be 'human'?  Svante likens the cloning to doing that with his deceased grandparent's DNA and points out how rather spooky and wrong that would be.  Here, there would be no personally known relative involved.  But would the cloner, our kindly Dr F, have ownership of the baby?  Would the baby be considered an animal or a person?

So, would the beneficent Dr F have the right to keep little It in a cage?  Or, say, put It on display in his lab or in the (say, naming no names) nearby Boston zoo?  Would It be housed alone, or with some other animals.....and if so, which, and which type of animals as It's roommate(s)?

Would scientists have the right to poke, probe, and experiment with Neando?  To draw blood or even snip out a few tissue biopsies when they wanted to (often enough to generate a stream of Nature papers)?   Subject it to CT or fMRI scans?  Why not?  After all, this is science! 

Or, alternatively, would little Neando automatically have civil rights as a human?  Born in some august university's city here, would it have citizenship?  Would it have the right to a real foster home, with human parents?  To be taught language (not as an experiment by some always-well-meaning NIH-funded psychology professors, but by a real adoptive parent)?  Would it have the expectation, indeed the right, to go to school?

When it reached adulthood, assuming it wasn't so immunologically vulnerable that it would quickly die of some sort of infection, or malnutrition by being fed our typical diabetogenic diet, would it have the right to vote?

The real test of ethics
The real test of ethics, indeed the basic core of ethics, is when it restrains you from doing something you'd really like to do.  Otherwise, it's basically a feel-good game.  So, how seriously, no matter how many ethics seminars we may have been certified as having attended, do we take human rights?  On which side of the sadism line do our views lie?  When is it time to stop superficial speculation or even joking about all of this, even in major news and journal media, instead to take a stand and draw the line, a line that one simply may not cross?