What’s Wrong with Humanized Mice, Pig Men and Humanzees?

A federal funding ban has not stopped scientists from gestating human-animal embryos for research, including those made using aborted human baby cells.

(photo: Shutterstock/Szasz-Fabian Jozsef)

WASHINGTON — Scientists are creating human-animal chimeras at several laboratories throughout the U.S., despite a ban against federal funding of the controversial research. An article last month in MIT Technology Review revealed that the work, directed at growing human organs for transplantation inside livestock, has resulted in human cells being injected into early animal embryos that have been gestated in sheep and pigs.

Based on interviews with members of three research teams in California and Minnesota, and presentations by scientists at a National Institutes of Health “workshop” on the subject in Maryland in November, the MIT article reported that about 20 human-animal chimeras have been transplanted into female livestock in the U.S. during the past year, although none of the research is published, and none of the gestating embryos were delivered.

The prospect of lab-generated animal-human creatures raises a new quagmire of troubling ethical questions, especially as powerful new CRISPR/Cas9 gene-editing technologies have developed, which push the possibilities for intermingling species to new boundaries.

“We are not near the island of Dr. Moreau, but science moves fast,” NIH ethicist David Resnik said at the meeting in Maryland. “The specter of an intelligent mouse stuck in a laboratory somewhere screaming, ‘I want to get out’ would be very troubling to people.”

Already, other kinds of human-animal chimeras  — including “humanized mice,” created by injecting liver and thymus tissue from human aborted babies into mice soon after they are born — are widely used for creating animal models of disease and testing pharmaceuticals, though widespread practical benefits are yet to be seen. An exposé last summer of Planned Parenthood’s sale of such fetal tissues for profit to researchers has led to public awareness of the practice and vocal opposition to it.


A Step Further

But the research that is under way goes a step further, placing human cells into very early-stage animal embryos, when the tissue can multiply and potentially “differentiate” — or specialize — into any part of the body, including brain or reproductive tissue.

For example, a team of researchers under Steve Goldman at the University of Rochester Medical Center in New York made “smarter” mice by implanting brain cells from 17- to 22-week-old aborted human babies into the brains of mice pups.

Next, as reported by New Scientist, the scientists used younger brain cells from aborted fetuses that grew and multiplied to invade the space of the mouse cells. Tests showed that the humanized mice were smarter than controls, freezing a “whopping” four times as long at a sound associated with electric shock, for example, suggesting their memories were four times better.

Disturbing as these studies are, Harvard professor George Daley, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, regretted the “unflattering depictions of the nature of this science” at the NIH meeting. The “only defense against this is to speak strongly for the scientific validity and justification for the work that is being done, he said, and to “distribute the sense of how impactful this work can be for human health.”

The scientists conceded that they have a gauntlet of knowledge gaps and technological hurdles to run before they reach their objective of growing human organs, such as kidneys and hearts, within livestock. They hope it will one day counter the shortage of organs for transplant and eliminate other ethical dilemmas, such as the “brain death” controversy and trafficking in human organs. As well, the prospect of growing human organs from patients’ own cells inside farm animals might overcome the problem of immune rejection of transplants.


Government Funding

Though the NIH banned federal funding of the human-animal research in 2014, Carrie Wolinetz, the agency’s associate director for science policy, said the “pause” in funding had not resulted in any researchers being “stripped” of funds already granted.

Funding from other government sources underwrites the research, as well as private funds. For example, MIT Technology Review reported that the U.S. Army recently granted $1.4 million for a chimera project at the University of Minnesota, led by cardiologist Daniel Garry, who is trying to grow human hearts in pigs.

Hiromitsu Nakauchi, a stem-cell biologist whose work was criticized as creating a “pig man” in Japan, was lured to Stanford University with a $6-million grant from the state-run California Institute of Regenerative Medicine and the promise of little government interference. He began making human-sheep chimeras this year.

He told the NIH that, so far, only about 0.5% of the cells in his embryos are human; and at that proportion, “it’s very unlikely to get thinking pigs or standing sheep. … But if it’s large, like 40%, then we’d have to do something about that.”


Catholic Perspective

From a technical viewpoint alone, Nakauchi’s work may not transgress Catholic moral teaching regarding the sanctity of life; he used so-called “adult” stem cells adapted from his own blood cells to avoid using volunteers, which also circumvented the gravely immoral use of human embryos and fetal tissue.

Human-animal chimeras raise more than technical questions, however. “If such combinations (at whatever proportion) transgress some fundamental ethical principle, then why are they permitted at the embryonic stage?” asked David Jones, director of the Anscombe Bioethics Centre in Oxford, England, and author of Chimera’s Children. “On the other hand, if there is nothing inherently wrong with such combinations, why is it absolutely forbidden to bring such creations to term?”

“Long ago [‘Address to the Italian Association of Cornea Donors and to Clinical Oculists and Legal Medical Practitioners,’ May 14, 1956], Pius XII stated that transplantation of tissue from a non-human animal into a human being might be morally acceptable in some cases, and I would have no objection, for example, to the use of pig valves in heart surgery,” Jones told the Register.

“However, Pius XII also warned that, just because some cases are acceptable, it does not follow that all are acceptable. He identified brain tissue and reproductive tissue as especially problematic,” he added. “A problem with some of this particular research seems to be that at least some scientists are uncertain whether we can rule out the possibility of creating a mainly human mixed creature.”

“Imagine a cross between a human and a chimpanzee, if such a cross were possible. How would the newborn ‘humanzee’ be regarded?” Jones, to whom the Catholic Bishops of England and Wales refer questions on the topic, has written. “Would he be a child or a non-human animal? Should he go to special school? Should he be reared in a human environment? Should he be clothed?”

There is a “more fundamental problem” in attempting to cross human and animal species, Jones has argued. “Just as bestiality is inhuman and a travesty of human sexual union, so deliberately creating a half-human, half-non-human creature is a travesty of human procreation.”

A 2001 document from the Pontifical Academy for Life on “xenotransplantation” — the act of using animal organs or tissues for human benefit — says that Catholic theology does not preclude it within “reasonable” limits, even if it involves genetically modifying animals.

However, the document noted that “humans must also answer to the Creator for the manner in which they treat animals.”


Pope Francis

That sentiment was echoed last year in Laudato Si (The Care of Our Common Home) by Pope Francis, who said, “Every act of cruelty towards any creature is ‘contrary to human dignity.’”

But in an interview published by Scientific American on Jan. 25, Juan Carlos Izpisua Belmonte, a Spanish animal-human hybridization researcher currently working in California, claimed that the Pope Father had blessed his work.

“Even though Spain is quite open to this stem-cell research area, at the same time, Spain is a very Catholic country, so we had to go through the Pope,” Izpisua Belmonte said, in order to obtain ethical approval of his creation of human-animal chimeric embryos.

“He very nicely said Yes. … So the Vatican is behind this research and has no problem, based on the idea it is to help humankind,” the hybrid researcher added.

However, the Vatican thinks Belmonte’s claim of a papal endorsement is false information and a misunderstanding, possibly derived from something said during a private audience.

Vatican officials are now examining the matter more closely to better understand the dynamics involved in Belmonte’s research, referencing the clear positions of the Church on the experimentation with human embryos and on the dignity of the human person set forth in Dignitas Personae, a 2008 instruction from the Congregation for the Doctrine of the Faith on some bioethical questions, along with Pope Francis’ relevant statements in Laudato Si (115-119, 130-136). 

“Recently, animal oocytes have been used for reprogramming the nuclei of human somatic cells — this is generally called hybrid cloning — in order to extract embryonic stem cells from the resulting embryos without having to use human oocytes,” Dignitas Personae stated (33).

“From the ethical standpoint, such procedures represent an offense against the dignity of human beings on account of the admixture of human and animal genetic elements capable of disrupting the specific identity of man. The possible use of the stem cells, taken from these embryos, may also involve additional health risks, as yet unknown, due to the presence of animal genetic material in their cytoplasm. To consciously expose a human being to such risks is morally and ethically unacceptable.”


Unsettled issues

For his part, ethicist Resnik reminded the NIH meeting that all of the ethical issues that came to light a decade ago, as such research began to gain momentum, remain equally relevant today.  

“You seem to think that these issues were all put to bed 10 years ago,” he told the scientists. “Well, you know what? The public is still out there, and the public can change its mind, just as we saw the videos of abortion clinics have tremendous impact.”

“The moral issues have not gone anywhere,” Resnik added. “And the fact the public hasn’t said much in the last 10 years just means the public has maybe been thinking about other things. But I can guarantee you … if people were thinking about this a lot more, they would be very concerned.”

Register correspondent Celeste McGovern writes from Scotland.

Register Rome correspondent Edward Pentin contributed to this report.