Brave New Chimeras

Tampering with human embryonic stem cells has been at the forefront of ethical debates for a decade.  Behind it, though, lurks an even more alarming prospect: the creation of human-animal hybrids.  As with embryos, the appeal has been to improve human health.  But ethicists ask if there is any benefit worth blurring the line between humans and animals.  Pro-chimera advocates admit there is a certain “disgust” factor that could arouse public anxiety, and agree that experimentation would need to be regulated.  But who would regulate the regulators, and on what moral grounds?

Meanwhile, tensions between advocates of embryonic stem cells (ESC) and adult stem cells (ASC) continue.  ESC advocates received an unexpected boost this week when an appeals court reversed an earlier ruling that halted federal funding of ESC research (New Scientist, PhysOrg).  A 2009 lawsuit had been brought by two ASC researchers who claimed that “who argued that Obama’s expansion [of ESC research funding] jeopardized their ability to win government funding for research using adult stem cells – ones that have already matured to create specific types of tissues – because it will mean extra competition”  (02/13/2011).  The appeals court overturned Judge Lamberth’s argument that such funding violated the Dickey-Wicker amendment that prohibits federal funding of research that destroys human embryos.  The surprise reversal pretty much ended the plaintiffs’ case, and gives a green light for federally-funded ESC research.  According to PhysOrg, “the scientific community applauded the ruling” as did NIH Director Francis Collins, who said, “This ruling will help ensure this groundbreaking research can continue to move forward.”  From the coverage by both New Scientist and PhysOrg, it appears that the ethical concerns so prominent in the George Bush era have been almost forgotten.

Adult stem cell research continues to offer promising treatments, while news about embryonic stem cell progress is notable for its absence.  In just the last ten days, these gains were reported for ASC research:

• Researchers improve method to create induced pluripotent stem cells (PhysOrg).
• Researchers create reprogrammed stem cells for disease studies (PhysOrg).
• Patients’ own kidney cells could cure kidney disease (Medical Xpress).
• Fibroblast Growth Factor-2 Primes Human Mesenchymal Stem Cells for Enhanced Chondrogenesis (PLoS One).
• Gladstone scientist converts human skin cells into functional brain cells (Medical Xpress).
• Doctors begin major bone marrow stem cell trial for Multiple Sclerosis patients (BBC News).

But even before ESC research has brought its first cure for anything, after a decade of promises, some scientific institutions are arguing that we need chimeras.  A Nature editorial this week¹ said we need to get past the legacy of Dr. Moreau:

The science-fiction author H. G. Wells coined the term humanized animals in his 1896 novel The Island of Doctor Moreau. The book invited readers to consider the ethical limits of curiosity-driven research and to ponder the moral value of the distinction between humans and animals. The book’s evil protagonist creates, through a vaguely defined process of ‘vivisection’, a colony of half-human ‘beast folk’, unhappy in themselves and frightening to others.

Dr Moreau’s humanized animals evoke visceral disgust. Thankfully, more than a century later, they remain science fiction. However, the ethical dilemmas presented by Wells do not.

What ethical dilemmas did the editors entertain as valid?  The public might get past the disgust of seeing a mouse created with human skin, and may express concern about the suffering of animals involved, but “One of the biggest horrors – although technically unlikely – could be a self-aware monkey, a creature with human thought trapped in the body of an animal, unable to express itself.”

Prompted by the possibilities, scientists around the world have begun to discuss the ethical consequences of taking to extremes the frontier technologies that allow mixing of species. These include the introduction of human stem cells into animals, where they could integrate into the animal’s body; or the formation of hybrid or chimaeric embryos that mix the DNA of humans and animals.

Nevertheless, the editors promulgated limited experimentation, short of “extensive humanization of the monkey brain or the development of embryos that mix DNA from humans and non-human primates” which they agreed crossed ethical boundaries.  They referred to guidelines advanced by the UK Academy of Sciences that are “likely to lead to pioneering legislation specifically geared towards regulating research on animals containing human material.”  This “timely and important” step in the early stages can pre-empt “future calls for outright bans, should public anxiety grow,” while reinforcing “Britain’s reputation as an attractive research environment, strictly controlled but without unwarranted hindrances.”

The editors opined that the UK has “some of the world’s most stringent laws on the welfare of research animals, but also some of the most rational regulations for research using human embryonic stem cells,” (by rational meaning liberal).  Given its progressive, liberalized treading over the ethics of ESCs, why not progress even further?  “It allows the creation of hybrid embryos that are predominantly human – forbidden in many countries – as long as they are destroyed before they develop beyond the two-cell stage,” the editors said.  “Now the country seems ready to regulate hybrid embryos that are mainly animal, as well as chimaeric animals.”

In the same issue of Nature,² Martin Bobrow (former Cambridge professor) argued that regulations are needed for chimeric research, because today’s rules can’t handle the upcoming possibilities with (get ready for another acronym) ACHM (animals that contain human material).  Already, he said, the Chinese have introduced human stem cells into goat fetuses, and “US scientists have examined the ethics of creating a mouse that has some human-derived brain cells (although they have not done the experiment).”  Thousands of rodents with grafted human tissue have already been created worldwide, he said, “But few countries have specifically considered the governance of research involving animals that contain human material (ACHM), and the topic has had little public discussion.” 

How does one regulate a sliding scale?  Is 49.9% human material permissible, but 50.1% not?  Bobrow describes the “regulatory discontinuity” created by the lack of a consensus ethical principle:

Research with embryos that contain animal material but are judged by regulators to be ‘predominantly human’, is subject to stringent scrutiny and authorization by the Human Fertilisation and Embryology Authority (HFEA). The HFEA takes account of scientific, medical, ethical and social issues, and frequently consults the public on emerging techniques. A similar chimaeric embryo with marginally less human material judged ‘predominantly animal’, however, is regulated by the Home Office in consultation with the Animal Procedures Committee under legislation intended to protect animal welfare. In mammals, this regulation becomes applicable at the midpoint of gestation.

The lack of a formal working interface between these two systems creates uncertainty for scientists requiring regulatory approval for their work. It could also allow sensitive experiments to be done legally but without expert ethical scrutiny.

Britain has an enviable position of rational debate in Parliament with public involvement; “However, violent opposition to animal research has sometimes hampered open discussion,” Bobrow noted.  “We hope that era is behind us, and the opportunity for inclusive discussion of these more subtle issues can be grasped” (by inclusive certainly referring to the scientists who want the research).  Bobrow discussed his involvement with a working group that produced a report that “recommends where the ethical limits of such methods may lie, and what governance is needed.”  The working group garnered input from a thousand members of the public.  They supported ACHM research but found disgust with three possibilities:

• Modifications of the animal brain that are likely to lead to human-like cerebral function.
• Experiments that could lead to functional human gametes in an animal (especially if the gametes might be fertilized).
• Modifications to an animal that create features perceived as uniquely human, such as facial shape, skin texture or speech.

Bobrow proposed an international regulatory body, “a similar regulatory structure to that proposed internationally for human stem-cell research,” be formed to monitor experiments on chimeras, with power to (1) review the expected many uncontentious experiments, (2) scrutinize those encroaching on the above “areas of sensitivity” and (3) ban others: “a very limited number of studies should not currently be undertaken because they raise very strong ethical concerns or lack sufficient scientific justification.”  He mentioned “ethically and socially sensitive kinds of research,” but did not mention whose ethics, or which sensitivity – ethical or social – should have the upper hand.  It doesn’t really matter, though, because sensitivity is sure to evolve: “Recognizing that an effective regulatory system must not needlessly hamper potentially beneficial science, we recommend that this body should be sufficiently flexible and consultative to adapt to evolving scientific knowledge and social attitudes.”

Will future regulators and courts, though, find today’s regulations “unwarranted hindrances”?  After the disgust factor is overcome in the public by desensitization of the creeping unthinkable, why not continue to push the ethical boundaries further and further?  Nature’s editors presented surprisingly little, beyond empty promises, in the way of evidence that chimera research might advance human health.  They said, “instinctive revulsion should not automatically block future research that will undoubtedly pave the way for therapies for currently incurable diseases.”  Instead, more emphasis was placed on reinforcing “Britain’s reputation as an attractive research environment” – a familiar argument for those who remember the pleas for unlimited ESC research (03/12/2004, 09/07/2004, 09/26/2007, 10/15/2008, 04/07/2009).  Bobrow’s priorities agreed; “Securing a robust, forward-looking regulatory framework for ACHM would promote Britain’s position as a responsible home for cutting-edge science.”

1. Editorial, “The Legacy of Dr. Moreau,” Nature 475 (28 July 2011), p. 423; doi:10.1038/475423a.

2. Martin Bobrow, “Regulate research at the animal–human interface,” Nature 475 (28 July 2011), p. 448, doi:10.1038/475448a.

The international scientific community, by rejecting creation and embracing evolution, has rejected any hope for a stable foundation for ethics.  Instead, it has an ethics that evolves and floats on nothing.  Whoever controls the jets of hot air directs the craft, and the ones with the most hot air are the ones seeking fame and reward – perhaps a Nobel prize or national prestige.  Ethicists on board point in all directions with little more to guide their opinions than disgust (an echo from the tarnished Imago Dei). 

What horrors lie ahead with people like this at the controls?  Nature’s editors could not deny that “The ethical questions raised by H. G. Wells are as valid today as they ever were.” [Historical note: H.G. Wells was an apostate Christian young man who embraced evolution in college under Thomas Huxley, ending up denouncing Christianity and helping found the social-Darwinist Fabian Society.]  Then the editors subtly hinted that we can overcome those concerns: “But as facts and fiction converge, the answers have become more complex.” Never fear; we’ll get the answers.  Appoint a working group.  Get public involvement.  Form an internationally regulatory panel.  Set up ground rules and let them evolve.  Man can do it.  We can appease the ethicists and teach the public not to respond in disgust by promising them health benefits they will forget a decade later.  We did it with embryos; we can do it with chimeras.  More important is national prestige, money, and human pride.

Suggested Reading:  C. S. Lewis’s prescient novel That Hideous Strength should be re-read for our time.  Lewis shows how human scientific pride becomes corrupted and ends up being demonic.  A similar theme emerges in Jon Saboe’s new novel The Days of Lamech.  The world of his protagonist includes an institution of elitists who, while promising to improve mankind, shows utter disdain for the individual people they work on.