Open access to science eprints
TheSparc provides both scientists and the general public free open access to scientific papers that are important for the survival of people and planet
ISIS New Year Essay
Human Farm Incorporated
"Our company offers you a range of services,
- Reproductive or therapeutic human cloning with virgin quality-guaranteed eggs
- Male or female germ-line stem cells from the celebrity of your choice, matured in germ-free, virus-free surrogates
- Your personal germ-line stem cell preservation programme
- Your personal genetic enhancement programme
- Your personal germ-line enhancement programme."
Behind the debates over embryonic stem cell research, human cloning and germline modification, scientists are quietly delivering human reproduction to corporate control under the guise that all knowledge is necessary if not benign, and only the applications need to be regulated. This is the way the Brave New World dawns. Dr. Mae-Wan Ho argues that unregulated research is the prime culprit, and that is what the debate should address.
Robert Winston, Professor of Fertility Studies at Imperial College, London, was highly critical of the Human Fertilisation and Embryology Authority (HFEA) for allowing the parents of a two-year-old boy with a blood disorder causing severe anaemia to undergo IVF and pre-implantation genetic screening of the embryos . The parents want their next baby to be free from the disease and its tissue type to match that of the older brother, so it can donate umbilical cord cells to save the two-year-olds life.
If the initial treatment fails, however, the baby may later be expected to give bone marrow or other tissues, or even organs. Furthermore, the experiment is likely to fail from the start because tissue typing in embryos is very difficult and currently carries no more than a 2 to 3 per cent chance of success. He warns, "The real concern is that we might in time debase our own humanity".
But is Winston opposed to human cloning? No, he obscures the issues by saying it is just like producing twins. "In itself, it is difficult to argue that there is anything wrong with producing a human clone. There are, after all, some 25,000 human clones in the UK living perfectly normal lives - they are identical twins." His main worry about people like Severino Antinori, who wants to clone humans now, is that through their incompetence, they might "bring valuable DNA science into public disrepute".
And although he objects to manufacturing a human clone "at risk of being a commodity", he is an ardent supporter of therapeutic human cloning and embryonic stem cell research, both turning human embryos directly into commodities and nothing else.
Robert Winston, like John Sulston, former head of the Cambridge Centre for Genomics Research, and other high profile scientists, have been going around saying that science is neutral, and even benign, and only the applications need to be debated. By implication, research is sacrosanct, and it would be a sin if not a sacrilege to regulate research. The bioethicists nod their sage heads in agreement while the public nod off at the anodyne debate staged for their benefit.
Obviously, none of the scientists has yet discovered quantum physics which tells us that the knower (observer) and the known (observed) are inseparable, and that how we know determines what we know. More to the point, none of them has noticed that todays science is predominantly application-driven, with a constant eye on marketability.
So, scientists have been getting away not only with murder. They are delivering us to the brave new world of human farm incorporated. Read on to find out whats on the research horizon.
The first human clone and the empty egg donors
The "first cloned human embryo" was announced on Thanksgiving by Massachusetts company Advanced Cell Technology (ACT). Michael West, the companys founder and president, explained on television that it will bring "a whole new era of medicine", it would "give replacement cells and tissues, like the way we repair a car when its broken" .
The announcement coincided with widespread press coverage, and even a cover article in Scientific American. The work itself is published in a little-known electronic journal. West later admitted to have deliberately by-passed the prestigious peer-review journals in order to find an academic outlet that would agree to publish the study simultaneously with U.S. News.
In fact, the company did not produce anything resembling a human embryo. The furthest any egg developed after nuclear transplant the procedure that produced Dolly the sheep - was to the six-cell stage. Unfertilised eggs chemically stimulated to develop passed well beyond that stage before arresting, so the experiment was a complete failure (see Box 1).
The cloning experiment was a complete failure
According to the scientific report , a total of 71 eggs were obtained from seven volunteers, "women between the ages of 24 and 35 with at least one biologic child".
The source of nuclei for transplant was from adult human fibroblasts cultured from skin biopsies from "consenting adult volunteers", or they were from cumulus cells that surround the eggs isolated from egg-donors. The nuclei were removed from the cells and injected immediately into donor eggs from which the egg nucleus was previously removed.
Of the 71 eggs obtained, 22 eggs were chemically stimulated to develop parthenogenetically, and 19 were used for nuclear transplant cloning. It is unclear what happened to the rest. None of the 11 eggs that received fibroblast nucleus transplant divided. Three out of 8 eggs that received nucleus transplant from cumulus cells reached the 4 to 6 cell stage.
By contrast, all chemically stimulated eggs developed to the cleavage (cell division) stage, and 17 out of 22 to a more advanced blastocoele stage, where, normally, an inner cell mass containing the embryonic stem cells that give rise to all the parts of the embryo would have been present. But in the pathenogenetic embryos, the inner cell mass was missing.
Condemnation was swift from the scientific mainstream, not because they disagree with therapeutic human cloning, far from it, but because the shoddy experiment and the way it was hyped could jeopardise the chances of it gaining public approval. A smoke-screen was further created by the British governments hasty introduction of an emergency bill to outlaw such reproductive human cloning (see Box 2).
ACTs paper ended, "It has therefore been suggested that the medical application of NT [nuclear transplant] may have significant merit and should be actively pursued..; however, we urge that the use of NT in human reproduction is currently unwarranted." The suggestion quoted came from none other than the United States National Academy of Sciences . The scientific establishment on both sides of the Atlantic is saying that therapeutic human cloning research should be done.
The scientific establishment is not mentioning the embryos created, only to be destroyed in the process of extracting embryonic stem cells. They are not mentioning adult stem cells, that are showing much more promising . And certainly, they will not mention the seven women volunteers who donated the empty eggs.
The women underwent a battery of physical and psychological tests and tests for infectious diseases before they were chosen as donors. They were subjected to a regimen of hormone treatments to make them over-ovulate and the eggs collected for an unspecified number of days. If this does not turn women and their eggs into commodities, what does? There will be no shortage of women, especially those living in poverty, who would be forced into selling their eggs on the open global market.
What, no cloning?
British regulations on cloning were thrown into disarray in November by a high court decision that current laws did not prohibit human reproductive cloning. The 1990 legislation was challenged by anti-abortion group Pro-Life Alliance .
The emergency Human Reproductive Cloning Bill would "prohibit the placing in a woman of a human embryo which has been created otherwise than by fertilization," with a maximum penalty for the offence of 10 years in prison.
Britains biotechnology industry - the biggest in Europe - and medical associations welcomed the move to close the loophole. The BioIndustry Association said it was "totally opposed" to human reproductive cloning but wanted to see "an enlightened environment for scientific research". This is exactly what the scientists want as well. They insist that therapeutic cloning using embryonic stem cells could revolutionize medicine by allowing them to grow grafts matched to individual patients.
The slippery slide to GM humans and surrogate males
Two recent reports are bringing us closer to creating GM humans, and more.
First, the United States Food and Drugs Administration suspended an experiment in gene therapy because of concerns that it might alter the germ line . The recombinant DNA Advisory Committee (RAC) of the National Institutes of Health met in December 2001 to consider the implications, and several panel members indicated that the research should be allowed to resume.
Mark Kay, molecular biologist at Stanford University, led the study that came under scrutiny in September, when traces of DNA from the vector - an adeno-associated virus - appeared in the semen of a volunteer, the first of nine enrolled. This was detected for a period of 10 weeks, during which the vector could have inserted into the sperm. But one RAC member, neurobiologist Jon Gordon of Mount Sinai School of Medicine in New York City, said he believed the risks of germ-line modification to be extremely low. The FDA is said to be allowing the experiment to resume, but would ask investigators to run tests of germ line effects.
The possibility of germ-line modification in somatic gene therapy is known from previous studies. We have drawn attention to it in a report first circulated in 1999 .
Given the abysmal record of gene therapy that has helped no one thus far , and that the vectors themselves have been found to cause death by toxic shock as well as cancer , it is unthinkable that such experiments should still be approved. And even germ-line modification is being slipped through as just one of the side-effects.
The ease of germ-line modification is graphically illustrated by a report  in which researchers isolated male germ-line stem cells from the testis of mice, and genetically modified them in vitro. The modified stem cells were then injected into the testes of genetically infertile mice, which the cells successfully colonised, and matured into sperms.
Genetic modification of male germ-line stem cells
Genetic modification of male germ-line stem cells was done with a retroviral vector. A retrovirus is a virus with RNA as its genetic material, which needs to be reverse-transcribed into complementary DNA (cDNA) sequence and inserted into the host cell genome in order to complete its replication cycle.
Male germ-line stem cells are cells that proliferate throughout the life of the animal to make male germ cells or sperms. Until quite recently, genetic modification of animals has concentrated on the unfertilised egg, or the female germ cell. But genetic modification of male germ cells is proving much easier.
Sperms are made in the testis of the mature male mice in a highly organised and productive process. It is estimated that 10 million sperms are generated per gram of testis tissue a day, and similar rates are found in all mammals. This occurs throughout the adult life of the male. At the base of this process are the male germ-line stem cells that can renew themselves and give rise to daughter cells that multiply many times to produce sperms, so genetic modification of stem cells will generate large numbers of germ cells to produce many transgenic offspring. Furthermore, these male germ-line stem cells can be frozen and preserved, and they can also be cultured, which make them ideal for genetic modification.
A research group in the School of Veterinary Medicine, University of Pennsylvania has now demonstrated that a retroviral vector can introduce foreign genes into 2 to 20% of the cultured male germ-line stem cells. The retroviral vector used was derived from the mouse leukemia virus carrying a bacterial b-galactosidase that gives a blue colour product when stained. The transgenic stem cells were transplanted into infertile male mice that have no differentiating cells in their testes. Seven of nine infertile male mice that received the transplanted genetically modified male germ-line stem cells became fertile. Five out of the seven produced transgenic progeny. Overall 26/577 (4.5%) of the offspring carried and expressed the transgene. And at least two of the transgenic offspring passed on the transgene stably to the subsequent generation.
The ease with which the genetic modification has been achieved suggests this may become the method of choice for all GM animals in future, including human beings. One obvious and persistent danger that the researchers have not addressed is the generation of pathogenic virus through recombination between the vector and endogenous viral sequences in the genome. Practically all retroviral vectors are derived from pathogenic viruses.
The other significant result is the ease with which the testis of genetically infertile mice could be colonised by male germ-line stem cells to propagate a male-line indefinitely, thus opening the door to corporate control of male reproduction. This is surely a big step up.
In vitro fertilisation, human nuclear transfer cloning, surrogate motherhood, have all passed on with relatively little comment from the establishment probably because they were all aimed at manipulating reproduction in women.
But surrogate human sperm-carriers and propagators are now on the horizon. Some dictator or industrial tycoon might want his germ-line propagated and multiplied indefinitely as a way of gaining immortality. A horde of sterile males will be recruited, or worse, created so their testis could be colonised. They would join their female providers of empty eggs. Both might have to be locked up in germ-free cells for the short duration of their vegetative existence.
- "With this designer baby we open the door to a scientific nightmare" Robert Winston, December 15, 2001 (Reuters, London) via Human Genetics Alert (www.hgalert.org) [email protected]
- "The Cloning Game" by Jonathan Cohn, Daily Express, 29 November 2001.
- Cibelli JB, Kiessling AA, Cunniff, K, Richards C, Lanza RP and West MD. Rapid Communication: Somatic cell nuclear transfer in humans: pronuclear and early embryonic development. E-biomed: The Journal of Regenerative Medicine 2001, 2, 25-31.
- Stem Cells and the Future of Regenerative Medicine. National Academy of Sciences, National Academy Press, Washington, 2001.
- "Hushing up on adult stem cells" ISIS Report by Mae-Wan Ho and Joe Cummins, to be circulated.
- "Planned Cloning Bill Has Loopholes, Watchdog Says" 27 November 2001, London (Reuters) via [email protected]
- Panel reviews risks of germ line changes, Eliot Marshall, Science 2001, 294, 2269.
- Ho MW, Ryan A, Cummins J and Traavik T. Slipping Through the Regulatory Net, Naked and Free Nucleic Acids, Third World Network Biotechnology Series, Third World Network, Penang, 2001.
- "Gene therapy oversold by scientists who disregard risks" by Angela Ryan, ISIS News 9/10, July, 2001, ISSN: 1474-1547 (print); ISSN: 1474-1814 (online) www.i-sis.org.uk
- "Common gene therapy vector causes cancer" by Mae-Wan Ho and Joe Cummins, ISIS News 11/12, October 2001, , ISSN: 1474-1547 (print); ISSN: 1474-1814 (online) www.i-sis.org.uk
- Na1gano M, Brinster CJ, Orwig KE, Ryu B-Y, Avarbock MR and Brinster RL. Transgenic mice produced by retroviral transduction of male germ-line stem cells. PNAS 2001, 98, 13090-5.