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Beyond the ban on human embryo research: An Italian way?

In the context of a heated debate on human embryo research, some Italian researchers are looking for a scientific way through the moral and ethical minefield.

By | September 20, 2000

MILAN, September 20. The Catholic Church has taken a strong stance against human embryo research. Now, research by an Italian team is being cited as evidence that human embryonic stem cell research is unnecessary. In a paper published in the current issue of NatureNeuroscience (Nat Neurosci 2000, 3:986-991), Angelo Vescovi and colleagues at the Istituto Scientifico H San Raffaele in Milan, describe a new discovery: neural stem cells can give rise to skeletal muscle. As reported by the researchers, "we show that acutely isolated and clonally derived neural stem cells from mice and humans could produce skeletal myotubes in vitro and in vivo, the latter following transplantation into adult animals… we conclude that neural stem cells, that generate neurons, glia and blood cells, can also produce skeletal muscle cells, and can undergo various patterns of differentiation depending on exposure to appropriate epigenetic signals in mature tissues."

The Catholic Church, which in recent years has been defeated by popular referenda on two critical issues — divorce and abortion, is keen to influence public opinion and scientific endeavour by voicing its concerns on this key issue.

On 29 August, Pope John Paul II reaffirmed the point of view of the Catholic Church on human embryo research in an address to more than 4,000 scientists at the XVIII International Congress of the Transplantation Society in Rome. At the end of his speech, he reiterated that halting the human cloning project is a moral duty that must be translated into cultural, social and legislative terms. In particular, the Pope condemned "the attempts at human cloning with a view to obtaining organs for transplants: these techniques, insofar as they involve the manipulation and destruction of human embryos, are not morally acceptable, even when their proposed goal is good in itself."

In addition to expressing the Church's opposition to the use of human embryos, the Pope's speech presented two important openings on the approaches that the Catholic Church regards as "acceptable forms of therapeutic intervention."

First, the Pope cited xenotransplantation — organ transplant from other animal species. The legitimacy of this practice has a long history in Catholic thought: as long ago as 1956, Pope Pius XII, speaking to the Italian Association of Cornea Donors, stated that "a xenotransplant would be licit if the transplanted organ didn't impair the integrity of the psychological or genetic identity of the person receiving it, and there was a proven biological possibility that the transplant will be successful and will not expose the recipient to inordinate risk."

But the second opening is more important. "Science itself," said the Pope, "points to other forms of therapeutic intervention which would not involve cloning or the use of embryonic cells, but rather would make use of stem cells taken from adults. This is the direction the research must follow, if it wishes to respect the dignity of each and every human being, even at the embryonic stage."

In fact, xenotransplantation and differentiation of adult stem cells are the fields where Italian biological researchers have produced some of their best results. So, some commentators have written of an "Italian way" in cell research.

Raffaello Cortesini, professor at La Sapienza University of Rome, who was also the Chairman of the local organising committee of the XVIII International Congress of the Transplantation Society, is the author of significant papers on the genetic mechanisms of graft rejection, the biggest problem limiting the development of organ transplants. The most recent achievements of his team, which works in collaboration with a group at the College of Physicians and Surgeons of Columbia University, New York, have been the location within the human genome of a gene responsible for the transcription of ILT (immunoglobulin-like transcript) receptors, a family of proteins playing a major part in the suppression of immune response to transplants. Besides the possibility of developing new gene therapies that mimic natural pathways and so reduce unwanted reactions due to pharmacological treatments (such as cyclosporin), the discovery offers the possibility of creating transgenic pigs in which human genes control the immune system.

Another group — led by Cesare Peschle, head of the Department of Haematology and Oncology at the Istituto Superiore di Sanità, Rome, and professor at the Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia — has discovered the KDR receptor, a key marker defining haematopoietic stem cells (Science 1999, 285:1553-1558). Only one in 100,000 cells produced by the bone marrow is a true pluripotent haematopoietic stem cell, capable of generating a uninterrupted chain of haematopoietic progenitor cells, the 'mothers' of the red and white blood cells and the platelets. The KDR receptor, isolated by the Peschle group, is a functional marker, defining stem cells and distinguishing them from progenitors.

Edoardo Boncinelli at the Istituto Scientifico H San Raffaele, Milan, and his team, has published a series of outstanding studies on the regulating mechanisms of the genes of the Emx and Otx families. These genes control the development of the cerebral cortex, the last stage of the evolution of the brain. By switching on and off these homeogenes in adult mice, Boncinelli has shown a possible way for isolating and reprogramming the brain cells.

But the most astounding results in the field are coming from a young scientist, Angelo Vescovi, now head of the Stem Cell Research Institute at the H San Raffaele and previously at the National Neurological Institute 'C. Besta', Milan. The paper that the Italian and Canadian group led by Vescovi published in Science last year (Science 1999, 283:534-537) exploded like a firework in the sky of cell research.

The authors transplanted adult stem cells from the brains of adult mice into the bone marrow of new mice, whose haematopoietic stem cells had been destroyed by a near-lethal dose of radiation. Once in the blood stream, the transplanted neural stem cells changed their behaviour and began generating blood cells. "It took us a while to believe our own data," Vescovi said. "This tissue of the body has always been seen as unchangeable."

Commenting on the achievements of his colleague, Edoardo Boncinelli said: "We are yet debating about the ethical acceptability of the research on the human embryos and foetuses, and in the meantime the research in molecular biology is carrying out some achievements that will allow to get round the problem of the human embryos. We are beginning to understand that a brain of an 80 years old man contains about a thousand stem cells: we have to recognize them, to extract and multiply them, and finally to reprogram them to obtain the tissues we need."

But Vescovi "completely disagrees" with this interpretation of his findings and, as reported in Nature Neuroscience, argues that with the jury still out on the relative benefits of embryonic and adult stem cells for transplantation therapy, research should be pursued on both.

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