“In the summer of 1998, a young South American scientist named Jose Cibelli worked at Advanced Cell Technology [ACT] where [Michael] West had agreed to serve as president. He was due to arrive in Worcester full-time in October, but several months earlier Cibelli was dispatched to Haifa with the express intent of trying to clone human embryonic stem cells –in the same lab as one of [Jamie] Thomson’s collaborators…Itskovitz-Eldor…[p165]
“In the spring of 1998, exiled from Geron and divorced from the stem cell race he had personally organized, Michael West was wandering the world like an entreprenurial nomad, searching for a way to become a player again… West traveled to Scotland specifically to ask [Ian] Wilmut [‘main architect of Dolly, the cloned sheep’] based at the Roslin Institute near Edinburgh, if he would like to collaborate in an effort to create human stem cells through cloning. [p166] West continued to talk to anyone who would listen… He became infatuated with ‘nuclear transfer’, or cloning, as a way to obtain stem cells…
“On the day West met with the Avian Farms delegation.. several [ACT] scientists dropped in to give brief seminars on their work. One of them was Jose Cibelli… He had done graduate studies at the University of Massachusetts in the laboratory of James Robl, one of ACT’s founders and eventually joined the company. As Cibelli spoke, West’s jaw dropped because the Argentine scientist described experiments he had done in Robl’s lab in which he had created a hybrid embryo, albeit short-lived, through the union of a cow egg and an adult human cell.
“When Cibelli showed a slide of the cow-human embryo, West couldn’t believe his eyes… ‘I mean, he showed me human embryos that had made by cloning. And I had no idea– no one in the world had any idea that it’d been done… and I thought, ‘..this is exactly what I want to be doing..’ …What West probably didn’t know is that the 1994 embryo panel specifically mentioned interspecies cloning as one of those Rubicons of experimentation that should not be crossed.” [p167]
“James Robl had stepped in to stop Cibelli’s original line of research at U Mass, but West has always given his scientific colleagues very free rein. West joined ACT as president in the fall of 1998 and immediately instructed Cibelli to get the cow-human work going again. West decided.. that he needed to disclose the company’s intention to pursue this line of experimentation, given the burgeoning controversy surrounding cloning and embryo research (he did not feel similarly compelled to mention Cibelli’s efforts in Israel just a few months earlier). And as he has often done, he went shopping for a friendly media outlet to retail his story. [p168] ‘I was intrigued,’ admitted Alta Charo, who was at the time a member of the Clinton bioethics panel. ‘If it were the case that you could take an enucleated cow egg ad a human cell, and create an entity that functioned like a human embryo..so that you could get the stem cells, and then it decompensated later on, you would have evaded the problems of human embryo research because you would not have destroyed a viable human embryo.’ ” [p171]
“Advanced Cell never set out, of course, to create cow-human embryos… The company first set out to clone barnyard animals, especially cows. Robl wanted.. bovine embryonic stem cells for a simple biological reason: ..[to] pluck these cells out of an embryo, genetically modify them (insert, for example, the gene for a pharmacologically desirable human protein like albumin) and reinsert them into another cow embryo to create..a pharmaceutical factory on hoofs… All of a sudden, Robl’s group had stumbled upon the very techniques.. mentioned as a theoretical route to the creation of human embryos: ‘somatic cell nuclear transfer’, or cloning… Here was a way..to get fetal animal cells for clinical use; the initial interest was the creation and harvest of dopaminergic neurons, the kind of brain cells that steadily disappear in Parkinson’s disease. [p215] Around that time, a..veterinarian from Argentina..arrived in Robl’s lab to pursue a master’s degree. Jose Cibelli..[came] to Amherst in January 1994. [p216]
‘We were talking about cells and organ transplants.. and saying ‘Wouldn’t it be great if there were a source of human tissue for transplants? That’s sort of where it started.’ The three scientists –Cibelli, Stice, and Golueke– knew they couldn’t obtain human [ES] cells because of the federal ban on funds for research… But they bandied about the idea of an audacious..experiment: Why not fuse the contents of an adult human cell with a cow egg? …It’s not clear whether anyone..was aware that the precedent had already been set by Philippe Collas’s similar experiments with rabbit eggs in 1990, although Collas [said] ‘Jose knew perfectly well what had gone on…[p217] His first attempt at human cloning began with..some large cells from the inside of his cheeks. Known as epithelial mucosal cells, these provided the adult cells he would use for nuclear transfer. Using the same techniques honed by years of cattle cloning, he vacuumed out the DNA from the cow eggs and then, using a tiny needle, inserted his own cheek cells, one per egg. ‘And after that, if you don’t do anything, the egg’s going to sit there and it’s just going to ..die after a few days,’ Cibelli explained. ‘It’s waiting for the sperm. So what you do is, you fool the egg..that it is fertilized.’ This bit of biochemical chicanery is achieved by dousing the cow egg with a chemical that makes it behave as though it has been impregnated by sperm… ‘He did a bunch of them,’ Robl remembered, ‘..but [it’s] very difficult to get a blastocyst.’ [p218]. When all was said and done, Cibelli had managed to create several short-term cow-human embryos… The biologists never characterized the cells in their hybrid embryo, and never even bothered to submit a scientific paper reportng it… no one can say with any biological certainty what exactly Jose Cibelli had created in the union of his cheek cell and a cow egg…” [p219] But it was also clear, even then, that cow-human embryos were less than ideal as a source of human stem cells. The best source, obviously, would be an intact human embryo…[T]he world would learn in good time, human oocytes were indeed under consideration at ACT. [p224]
“Ali Hemmati Brivanlou..on the seventh floor of a building at Rockefeller University..the morning of November 10, 2000..[p174]..had already made arrangements with Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York Weill Cornell, to collaborate. ‘He has already given me eight embryos’…[p176] In the summer of 2000, he had reached a tentative..arrangement with Zev Rosenwaks, an Israeli-born expert in reproductive medicine, who had agreed to supply Brivanlou’s lab with surplus human embryos left over from in vitro fertilization..at Weill Cornell’s IVF center..[p177] In purely pragmatic terms, the earliest moments of human development held the key to tissue regeneration and cellular repair… ‘As you know,’ Brivanlou said that day, ‘nobody can stop scientists from doing the experiments they want to do. Nobody.’ [p178]
“[Michael] West was pilloried for announcing that ACT was conducting the experiments, but in fact a number of leaders in he field..end[ed] up pursuing variations on the same general theme: create a ‘thing’ that couldn’t techncally be called a human embryo but could be used to harvest immunologically compatible stem cells… Other researchers, in England and Israel and Singapore, where the political constraints on research were not driven by the same religious concerns, were trying to create embryos in IVF clinics… [p172]
“They never saw it as a way to create copies of animals, or humans for that matter. Rather, they saw it as an immensely powerful biological tool… Following his studies in England, [Douglas] Melton returned to Harvard..[and] began to catalogue the proteins that control the development of organs, especially in the nervous system. They learned that certain of these growth factors, or ‘morphogens’, could basically generate nearly any cellular fate depending on their concentration… [Brivanlou] was astonished to find that when you blocked activin, virtuallyall the cells in [an]..embryo became brain cells…[pp181-182]
“[I]n the late 1990s, work at the Salk Institute, in the laboratory of Fred Gage,..another of StemCell’s cofounders,..electrified the field of neuroscience when they reported the existence of adult neural progenitor cells in the mammalian brain. Gage deliberately shies away from the term stem cell to describe these adult cells, because he’s still not sure what they are. But they can be recovered from the brain tissue of rats, for example, and possess the capacity to differentiate into either of the two main neural cells, neurons and glial cells… [p238] Gage’s group has shown that neural progenitor cells, when transplanted into an adult nervous system, migrate to the zone in the brain where new neurological cells are formed, and will also migrate to areas of injury…’Not only are new cells born, but they undergo synaptogenesis,’ Gage said..meaning they form the connections, or synapses, that link nerve cells.” [p239]
…and finally, a last composition of excerpts from Merchants of Immortality:
“Bone marrow transplants, first attempted in the early 1960s, achieved a routine success by the 1970s..because patients received..hematopoietic (or blood-forming) stem cells. These are progenitor cells of the blood system and possess the ability to differentiate..into all the cells of a healthy and whole blood system… [T]his spongy matrix of tissue, encased in a sanctuary of bone, is..recognized as the body’s safe-deposit box..for some of the body’s most precious regenerative jewels –namely, cells that can differentiate into many other tissues. In fact, adult stem cells from the marrow have actually been a proven..respectable feature of medicine for about four decades. It’s just that..no one referred to them as stem cells.[p229]. The existence of that marvelously prolific [‘mother’] cell was first proposed in the early 1960s and grew out of medical experiments related to nuclear warfare and radiation exposure. Two Canadian researchers, J.E. Till and E.A. McCulloch, ..subjected mice to lethal doses of radiation that destroyed the rodents’ entire blood-making apparatus in the marrow; then they infused small amounts of blood..sufficient to rebuild the animals’ entire blood and immunological systems. [p230] According to [Bob] Deans, these mesenchymal [marrow] stem cells are conspicuously denuded of typical immunological markings…meaning that they can evade a basic form of scrutiny by immune sentinels known as T cells; they also lack a marker known as B-7 which..revs up an immune response. Deans added that these stem cells may even secrete a factor that actively inhibits a normal immune response…’The cells seem to be totally immunoprivileged and we are currently doing a study where we are injecting cells from one animal into another with no immunosuppression, and we are seeing no rejection.’ The cells, in other words, seem to deploy a biological stealth technology to remain immunologically invisible. This…could open the door to the use of universal donor cells…’It changes the whole ball game in terms of commercialization,’ said Brad Martin. When this immunological invisibility was first observed, Osiris scientists were stunned. ‘In the last year, this all came to light, and we are all just amazed,’ said Martin in May 2001.” [p234].
Info on Dr. Atala
“Biotechnology now allows us to genetically engineer animals so that they produce proteins that are human pharmaceuticals. For certain drugs that are difficult to produce using existing methods or are needed in large quantities, production in GE animals offers the most efficient and practical solution… Other applications include making animal organs compatible with humans, a technology known as xenotransplantation. Research is being conducted to produce transplant organs in pigs that may be a source of organs for humans.” http://www.bio.org/foodag/animals/GE_An_Pharm_0908.pdf