Are Chimeras For Human Organs a Chimera?

The word "chimera" originally referred to a creature in Greek mythology.  It had a lion's head and body, a goat's head growing out of its back, a serpent's tail, and it breathed fire.  Also, it was female.  Seeing a chimera was generally regarded as a bad omen, leading to earthquakes or famines. 

The other use of the word, as in "the chimera of peace in the Middle East" is to mean something that's probably never going to happen.  Recent experiments at the Salk Institute and elsewhere show that while mice may be able to grow organs for transplantation into sick rats, the hope that pigs may be able to grow human organs for transplants have receded into the future, and may never be realized.  What I'd like to know is, should we even be doing this stuff at all?

First, the background.

Human organ transplants from either cadavers or live donors are plagued by the problem of rejection.  The body recognizes foreign tissue and mounts an attack on it, leading to complications in organ transplants such as graft-versus-host disease, which can ultimately lead to the failure of the transplanted organ and other chronic and acute problems.  So medical researchers would like to develop replacement organs from the patient's own body using the patient's own adult stem cells, which can be potentially made to become a wide variety of organs.  The problem is that for a desired organ such as a pancreas to develop from stem cells, it needs to be in an embryo, or an embryo-like environment that is similar enough to a human embryo to encourage the proper development and growth. 

Pigs turn out to be one of the closest animals to humans physiologically, in terms of weight, size of organs, and other factors.  So Juan Carlos Izpisúa Belmonte and Jun Wu of San Diego's Salk Institute inserted adult human stem cells in 2000 pig embryos and implanted the embryos in a number of female pigs.  The yield wasn't very good—only 186 embryos lived as long as a month, at which time the pigs were "sacrificed."  Many of the modified pig embryos were smaller than normal, and the human stem cells that survived were mostly just scattered around in the embryos rather than forming specific human organs.  Wu views this setback as temporary, calling it "a technical problem that can be tackled in a targeted and rational way."

At a recent workshop sponsored by the U. S. National Institutes of Health (NIH), that federal agency reviewed the ethics of chimera research and said it would reconsider its current ban on federal funding of such work.  But it is not clear now that a new administration has taken charge whether the ban will be lifted or not.  The Salk Institute researchers got around the ban by using private funds for their research.

It's easy to think of arguments against chimera experiments involving human cells.  The NIH people seem especially worried about the brain of a pig getting human brain cells, or the germ line (eggs and sperm) of a pig receiving human DNA.  The thought that a candidate for transformation into pork chops has a family tree that includes your Uncle Jack is indeed a disquieting notion.  And what about a human brain growing in a pig's body?  Would that make the pig-chimera human?  Obviously, to answer this question requires that one have a robust definition of what it means to be human.  And it's not clear to me that the NIH has such a definition, at least not one that can be coherently defended.

If possession of a human brain is all you need to be human, U. S. law currently allows humans to be aborted up to nearly the time of birth, under some circumstances.  While the question of human-chimera research does not at first seem relevant to the issue of abortion, both issues involve treating living beings as instruments of someone's will. 

Bioethicist Leon Kass used the phrase "the wisdom of repugnance" to describe certain reactions that people have which cannot necessarily be articulated into finely honed arguments, but which nevertheless deserve attention.  A more pungent term for the same idea is "yuck factor."  If the idea of growing a human brain inside a pig's body fills us with revulsion, maybe we should pay attention to the revulsion even if we can't say exactly why we are revolted. 

Proponents of animal rights are probably not rejoicing over the prospect of pigs that grow human organs either.  Their reasons are different in some ways, but go back to the question of whether living beings—human or animal—should be used as instruments for another's will.  There is near-universal agreement that one human should not use another as an instrument, a sentiment that goes back at least to Kant.  But there is disagreement about whether humans can use other animals as instruments, a practice that also has a long-standing tradition in favor of it. 

For now, the debate about human chimeras is largely still academic, as it appears that pigs are not yet a good candidate for this sort of thing.  Maybe they'll try monkeys next, but that raises the same sort of issues as experiments with pigs. 

God gave us human beings minds that are capable of devising plans for great good and also for great evil.  Most religious traditions hold that people also have a moral sense that gives rise to such things as the yuck factor, and that we ignore this sense at our peril.  It's probably a good thing that the NIH has refrained from supporting human chimera research, but obviously that hasn't stopped its progress.  If someone told me I had a fatal disease that could be cured with a transplant from a specially grown pig, or monkey, I don't know what I would decide.  But I'm not sure we should even contemplate asking people to make such a decision, especially if, in the process, we risk creating monstrosities who might be human and might not be.  And only the chimera would know for sure.

Sources:  I referred to two news sources for information about the Salk chimera research.  CNN carried a story entitled, "First human-pig embryos made, then destroyed," on Jan. 26 at http://www.cnn.com/2017/01/26/health/human-pig-embryo/, and Science Magazine (published by the American Association for the Advancement of Science) carried "Human organs grown in pigs?  Not so fast," on Jan. 26 at http://www.sciencemag.org/news/2017/01/human-organs-grown-pigs-not-so-fast.  I also referred to Wikipedia articles on chimeras, the Salk Institute, and the wisdom of repugnance.

Is Bioscience Spinning Its Wheels?

Each year, the U. S. National Institutes of Health (NIH) alone spends over $30 billion on medical research.  The people who decide which scientists get this money are, unsurprisingly, scientists.  Daniel Sarewitz, a professor of science and society at Arizona State University, thinks that we are no longer getting the bangs we should get for all these bucks.  In an article in the spring/summer 2016 issue of The New Atlantis, he explains why.

First off, he admits that spending lots of money on scientific research and development has historically been a great idea.  If you compare how most people in the U. S. lived in 1900 with the way things are done in 2000, most of the good differences—modern medicine, jet aircraft, cars, air conditioning, the Internet, wireless devices, computers, down to electric toothbrushes—are due to technological innovations that grew out of research directed at certain goals.  And Sarewitz has no problem with that.  The federal government was not a big player in research prior to World War II, but the lessons we learned then about how heavy investments in military technologies such as radar and nuclear weapons could pay off led to the creation of the National Science Foundation (NSF). 

The NSF was the brainchild of MIT engineer Vannevar Bush, who directed most government-funded research during the war.  Sarewitz says that in order to get his idea enacted, Bush told "a beautiful lie," and summarizes the lie this way:  "Scientific progress on a broad front results from the free play of free intellects, working on subjects of their own choice, in the manner dictated by their curiosity for exploration of the unknown."  Sarewitz spends the rest of his article showing just what was wrong about this "lie," and how it has led to inefficient and often simply incorrect research that taxpayers (and corporations too, for that matter) are paying billions for today.

In support of his thesis, he cites studies showing the increasing rate of retractions from peer-reviewed research journal in recent years.  Another source indicates that between 75 and 90 percent of all basic and preclinical biomedical studies are not reproducible. 

These are indicators of a general trend or pattern that goes something like this.  A newly minted Ph. D. in one of the softer sciences (economics, sociology, psychology, biology) gets an academic job and has to produce new and original results that are published in peer-reviewed journals or get fired in five or six years.  (That part I'm very familiar with.)  So he writes tons of proposals to NIH or wherever he can get funding, gets ten to fifteen percent of his proposals funded, and sets to work being novel.  Novel about what?  Well, that almost doesn't matter.  As long as you can show you did something that nobody's done before, and it has some remote tenuous connection with reality, you can find a journal and willing referees to publish it.  There's more Internet-based journals popping up every year, and it's almost to the point that you can get anything published if you send it to enough journals.  Multiply this picture by the thousands of Ph. D.'s we produce every year, and bear in mind that their proposals and papers are being reviewed by people who went through the very same system, and you can see how the situation described by Sarewitz can happen. 

So what should we be doing with all that money?  Sarewitz says it should be spent on highly directed research targeted at specific time-limited goals.  He cites several examples of the way it ought to be done, including a program in the 1990s directed by the U. S. Department of Defense (DOD) to develop a new treatment for breast cancer.  It led to the development of the drug herceptin, one of the most important treatment innovations in years.  The point here is that useful innovations based on science typically happen not when some isolated scientist pursues his or her private dream, but when a team of smart people use both existing and new science and engineering to pursue a specific socially profitable goal. 

Sarewitz congratulates the DOD for its no-nonsense approach to getting such things done, and for including in its project planning people without academic qualifications, but with a strong interest in the goal.  One of the sparkplugs that got the herceptin project going was an activist named Fran Visco, herself a breast cancer survivor, who founded the National Breast Cancer Coalition to do something about better treatments.  She was a lawyer, not a biologist, but the DOD welcomed her as a participant and her vision was essential in getting things done. 

In pointing out that much research today, especially in the biomedical area, doesn't seem to accomplish much more than paying for a lot of expensive professors, postdocs, grad students, and equipment, I think Sarewitz is on the money, so to speak.  However, I disagree with him that Vannevar Bush told "a beautiful lie" to get the NSF going. 

If you genuinely believe that what you say at the time is true, it isn't a lie, morally speaking.  You may be guilty of self-deception or not informing yourself sufficiently, but not of lying.  Bush was a creature of his time, and most of the people he had hired to develop things like radar and nuclear bombs had in fact spent most of their careers indulging the "free play of their free intellects," because that was the main way basic science was pursued before huge amounts of federal dollars showed up after World War II.  Most scientists before 1941 operated more or less in the style of Albert Einstein, who single-handedly revolutionized physics in his spare time that his job at the Swiss patent office provided him.  Back then, the exception was a scientist who did good science while working for industry, such as Irving Langmuir, the first industrial scientist to win a Nobel Prize.  So although the phrase "beautiful lie" is an attention-getting rhetorical device, I think Sarewitz is a little anachronistic in his accusation that Bush was lying at the time.

On the other hand, Sarewitz is probably right in pointing out that the foxes-guarding-the-henhouse pattern of handing money over to scientists who give it to other scientists may not be the right way to do things anymore, at least with the majority of federal research funds.  There's a reason that government funding for science is declining as a percent of GNP, and the public may be right in thinking that their federal research dollars are not being spent as wisely as they could be.  If the powers that are or will be listen to Sarewitz's advice, maybe things will be reorganized so that even fewer dollars can accomplish more, both in the way of pure basic science and in practical applications that improve the lives of millions.

Sources:  Daniel Sarewitz's article "Saving Science" appeared in the Spring/Summer issue of The New Atlantis, and online at http://www.thenewatlantis.com/publications/saving-science.  For the statistic on NIH spending, I referred to the NIH website at https://www.nih.gov/about-nih/what-we-do/budget.  Full disclosure:  my wife had breast cancer over a decade ago, and is now cancer-free