From: Brett Paatsch (paatschb@ocean.com.au)
Date: Tue Feb 11 2003 - 02:03:27 MST
RE: the extropic aspirations to life extension and life
enhancement.
The following excerpt is from a 2001 physiology text
- "Human Physiology: From Cells to Systems" 4th Edn
- Lauralee Sherwood.
I thought this might serve as bit of a primer for some extropes
*interested in* the Xenotrans and tissue engineering stuff but
perhaps not yet specifically up to speed. I *like* useful
primers myself and any crappy emailed ones (which some
may see this as) can be easily ignored or dealt with by the
delete button.
There would be a few aspects in which the following is out of
date (eg. in stem cells the term pluripotent rather than totipotent
is more often used now). I'd be interested in what out-of-date
observations any others might see as well.
Regards,
Brett
---- XENOTRANSPLANTATION and TISSUE ENGINEERING: A Quest for Replacement Parts. Kidney failure, extensive burns, surgical removal of a cancerous breast, an arm mangled in an accident - though our bodies are remarkable and serve us well, sometimes a body part is defective, injured beyond repair, or lost in situations such as these. In addition to the loss of the quality of life for the affected individuals, billions of dollars are spent to treat patients with lost, permanently damaged, or failing organs, accounting for about half of the total health-care costs in the United States. Ideally, when the body suffers an irreparable loss, new, permanent replacement parts could be substituted to restore normal function and appearance. Fortunately, this possibility is moving rapidly from the realm of science fiction to reality of scientific progress. One solution for replacing damaged or lost parts is implantation of synthetic devices, such as artificial joints or artificial heart valves. More advanced synthetic devices even interface with the brain. An example is a surgically implanted electronic device that enables a deaf person to "hear" by converting sound waves into electrical signals in the nerve pathways that carry information to the brain for sound perception. Even though remarkable advances have been made in this field, no synthetic device manufactured thus far can perform the functions of a body part as effectively as the normal, healthy original part... Another solution to organ failure is transplantation of organs such as kidneys, hearts, and livers from donors (recently deceased in the case of most donated organs) to patients whose survival depends on a healthy replacement. Over the last two decades organ transplantation has become almost commonplace. The major obstacle limiting the number of transplantations is not a lack of technical capability but a shortage of donor organs. Waiting lists for replacement organs outstrip the number of organs available as much as tenfold. Because of the limitations of implanting synthetic devices and transplanting donor organs, some researchers are exploring two alternative methods for replacing body parts that are no longer serviceable: xenotransplantation and tissue engineering. Interest in XENOTRANSPLANTATION, (transplanting organs from one species to another), is growing not only because of the shortage of human donors but because our technical capabilities have improved to the point that this technique is now becoming feasible. One of the major hurdles to xenotransplantation has been the swift rejection of the animal organ by the human recipient's body. The patient's immune system, recognizing the donated animal organ as 'foreign,' immediately launches a destructive attack on the transplanted organ. Pioneering efforts on several fronts are breaking down this barrier to xenotransplantation. First, researchers now have a more thorough understanding of the underlying immune mechanisms that cause rejection of transplanted tissue. This knowledge has led to better immunosuppressive drugs (drugs that suppress the immune system's attack on the transplanted organ). Even recipients of human donor organs must be treated with immunosuppressive drugs because of the differences in 'self-identity markers' found on the surfaces of the donor's and the recipient's cells. Because the differences in these cells surface markers are much greater between humans and animals, more powerful drugs must be used to prevent the rejection of xenotransplants. An unfortunate side effect of immunosuppressive drugs is the reduced ability of the patient's immune system to defend against potential disease-causing microorganisms, or pathogens, such as bacteria and viruses. To avoid depleting the transplant recipient's defence capabilities, a second advance toward xenotranplantation has been the development of transgenic animals through genetic engineering. A transgenic animal possesses not only its own genes but also some specific genes of another species that have been artificially introduced. Scientists have bred transgenic pigs that carry human genes for use as organ donors for xenotransplantation. Pigs were chosen because they are easy to breed and raise and because their organs are comparable in size as well as anatomically and physiologically similar to human organs. The goal is to trick the human xenotransplant recipient's immune system into viewing the pig organ as human, thus reducing the extent of the immunological attack and minimizing the need for immunosuppressive drugs. Even as the technical barriers to xenotransplantion are crumbling, however, several obstacles to continued progress in this area are emerging. Scientists are vigorously debating the likelihood that xenotransplantation will introduce new infectious agents from an animal source into the human population. Opponents of xenotransplantation fear that an undetected pathogen lurking in a donor animal could cause infection in a human recipient and spread from there into the general population. The risk of cross-species infections is magnified by the fact that the immunosuppressive drugs used to minimize rejection of the xenotransplant reduce the ability of the recipient to fend off any potential pathogens that might be present in the donated organ. To reduce the potential for spread of disease from pigs to human recipients, donor animals are now raised under conditions to maintain them free of specific diseases to which humans are known to be susceptible. Yet, there is still concern that pigs may harbor viral stowaways that are harmless to the animals but could cause as-yet-unknown diseases when abnormally introduced into a xenotranplanted patient. One new encouraging study demonstrated, however, that patients who had received living pig tissue, as in skin grafts, over the past 12 years showed no evidence of infection by one such recently idnetified viral stowaway. Even thought individuals might be willing to take this risk for the benefit of a life-saving transplant, an important ethical dliemma is whether society as a whole should be placed at risk of the potential spread of a xenotranplant-derived disease throughout the population. Another ethical concern raised by some is the exploitation of animals as sources of spare parts for humans. Other counter that humans already routinely kill pigs for another self-serving purpose- for food. Against a backdrop of lively public debate about such scientific challenges, public health risks, and ethical issues, federal guidelines have been developed that permit limited pig-to-human transplantation to proceed, although the use of nonhuman primate tissue has been temporarily halted. Under these guidelines, the number of individuals and the types of disorders for which xenotransplantation is being utilized as a treatment are continuing to grow. Early samples include treatment for specific degenerative brain disorders, diabetes, acute liver failure, damaged heart valves, and extensive burns. Besides xenotransplantation, the second frontier in replacement parts is TISSUE ENGINEERING - growing new tissues in the laboratory that can be implanted to serve as permanent replacements for body parts that cannot be repaired. The era of tissue engineering is being ushered in by advances in cell biology, plastic manufacturing, and computer graphics. Most human cells can already be cultured; that is, when removed from the body, they will continue to thrive and reproduce in laboratory dishes when supplied with appropriate nutrients and other supportive materials. Now researchers are working towards growing specific tissues and even whole organs in the laboratory for use as replacement parts. Using computer-aided designs, highly pure, dissolvable plastics are shaped into three- dimensional molds or scaffoldings that mimic the structure of a particular tissue or organ. The plastic mold is then 'seeded' with the desired cell types, which are coaxed, through the application of appropriate nourishing and stimulatory chemicals, into multiplying and assembling into the desired tissue. After the biodegradable plastic scaffolding dissolves, only the newly generated tissue remains, ready to be implanted into a patient as a permanent, living replacement part. To prevent rejection by the immune system, without the necessity of lifelong immunosuppressive drugs, the plastic mold could be seeded, if possible, with appropriate cells harvested from the recipient. Often, however, because of the very need for a replacement part, the patient does not have any of the appropriate cells to seed the synthetic scaffold. This is what makes the recent isolation of embryonic STEM CELLS so exciting. Embryonic stem cells are the "mother cells" resulting from the early divisions of a fertilized egg. Embryonic stem cells are totipotent (meaning "having total potential"), because they have the potential of becoming every cell type in the body. During development, these undifferentiated cells give rise to the many different highly differentiated, specialized cells of the body. As the stem cells divide over the course of development, they branch off into the various specialty tracks under the guidance of particular genetically controlled chemical signals. Some stem cells are forced along a career path of specialising as muscle cells, while others are irreversibly cast in lifelong roles as various other specialized cells. Now, for the first time, researchers have succeeded in isolating embryonic stem cells and maintaining them indefinitely in an undifferentiated state in culture. Furthermore, early experiments suggest that these cells have the ability to differentiate into particular cells when exposed to the appropriate chemical signals. Further stem cell research has far-reaching implications that could revolutionise the practice of medicine in the twenty-first century. As scientists gradually learn to prepare the right cocktail of chemical signals to direct the undifferentiated cells into the desired cell types, they will have to grow customized tissues and eventually whole, made-to-order replacement organs, such as livers, hearts, and kidneys. Through genetic engineering, these stem cells could be converted into 'univeral' seed cells that would be immunologically acceptable to any recipient. Thus, the vision of tissue engineers is to create universal replacement parts that could be put into any patient who needs them without fear of transplant rejection or use of troublesome immunosuppressive drugs. Following are some of the tissue engineers' early accomplishments and future predictions: ENGINEERED SKIN PATCHES have already been used to treat victims of severe burns. LABORATORY-GROWN CARTILAGE has already been successfully implanted in experimental animals. Examples include artificial heart valves, ears, and noses. Considerable progress has been made on building ARTIFICIAL BONE. ARTIFICIAL ARTERIES composed entirely of human cells have already been produced but not yet tested for function and durability in humans. TISSUE-ENGINEERED SCAFFOLDING to promote nerve regeneration is currently undergoing testing in animals. Progress has been made on growing two complicated organs, the LIVER and the PANCREAS. Another tissue-engineering challenge under development is the growth of completely NATURAL REPLACEMENT BREASTS for implantation following surgical removal of cancerous breasts. ENGINEERED JOINTS will be used as a living, more satisfactory alternative to the plastic and metal devices used as replacements today. Ultimately, complex body parts such as arms and hands will be produced in the laboratory for attachment as needed. Thus, tissue engineering holds the promise that damaged body parts can be replaced with the best alternative, a laboratory-grown version of "the real thing". Despite this potential, stem cell research is fraught with ethical controversy because of the source of the cells. These embryonic stem cells were isolated from embryos from an abortion clinic and from unused embryos from an in-vitro fertility clinic. Because federal policy #3# currently prohibits use of public funding to support research involving human embryos, the scientists who isolated these embryonic stem cells relied on private money. Public policy makers, scientists, and bioethicists are now faced with balancing a host of ethical issues against the tremendous potential clinical application of stem cell research. Such research will proceed at a much faster pace if federal money is available to support it. In a controversial decision, federal policy makers recently issued guidelines permitting the use of government funds to support studies using established lines of human embryonic stem cells but not research aimed at deriving new cell lines. This decision was based on the premise that investigators using already established embryonic stem cell lines would not entail destroying embryos for scientific purposes. As a possible alternative to using the controversial totipotent embryonic stem cells for tissue engineering, other researchers are exploring the possibility of exploiting tissue-specific stem cells harvested from various adult tissues. These specialised stem cells do not have the complete developmental potential of embryonic stem cells, but partially differentiated stem cells from adults have been coaxed into producing a wider variety of cells than originally thought possible. For example, provided the right supportive environment, neural (nerve-cell producing) stem cells have given rise to blood cells. Thus, researchers may be able to tap into the more limited but still versatile developmental potential of specialised stem cells in the adult human body. ----
This archive was generated by hypermail 2.1.5 : Tue Feb 11 2003 - 01:40:17 MST