Medical Science

The role of biotechnology in organ transplantation in the past 70 years has been very crucial. Some of the older technologies such as making bread and wine, brewing beer, etc are considered to be accidental discoveries, whereas the new biotechnology is all about living things in the past 75 years and how they work (Schacter 2006). The cells use genetic material in the making of proteins and provide the engines to produce enzymes needed to keep them alive. This led to the study of genetic engineering. Genetic engineers enable transfer of genes from one living organism to another and change the proteins made by the new organism, whether it is a bacterium, plant, mouse or even a human. Biotechnologists first engineered bacterial cells, producing new proteins useful for medicine and industry (Schacter 2006: xxiv).
Basically biotechnology is a mix of sciences using biology, chemistry, physics, engineering, computers, and information technology to develop tools and products that hold great promise. Biotechnology is also described as ‘use of living organisms by humans.’ Today biotechnology has developed to a great extent that molecular changes are carried out besides visual physical changes. In molecular biotechnology, the desired characteristics are selected at the molecular level and added to the organism's genetic makeup (Schacter 2006).
Biotechnologists are the ones who are academically trained in biology or chemistry. Some of them are laboratory scientists trained in the tools of genetic engineering. The laboratory methods allow a gene for a particular protein to be isolated from one living creature's DNA and are inserted into another's DNA in such a way to allow the new cell to manufacture the required protein (Schacter 2006).
Organ transplant is nothing but replacing the diseased organ with a healthy one from a donor. For example, transplantation of kidney, heart, lungs and pancreas has been carried out since over 50 years. The role of biotechnology in transplantation today is to provide immunological tolerance and long-term acceptance of the allograft (Schacter 2006).
The first organ transplantation was carried out in 1951. It was kidney transplantation. Today kidney transplantation has become a commonplace occurrence with more than 100000 defective kidneys getting replaced every year. Researches in biotechnology are focused on the immune system and its resistance offered to the new organs. There were about 325000 transplants carried out in the United States between 1988 and 2004. The average number of transplantation done in a year is about 25000. Successful transplantation of organs is a breakthrough with new developments laying the groundwork for biotechnology (Grace 2006: 57).
Human system has the potential to recognise self from non-self. Each lymphocyte carries a unique tag of self-identity (Yadav 2003: 252). The human immune system recognises a variety of antigens. The B cell is able to respond directly to a single antigen, but the T cell is activated only if that antigen is displayed on the surface of a lymphocyte. The T cell has to distinguish itself from its foreign counterpart to cope up with immune function. If the T cells cannot distinguish between an antigen and self, these cells may begin to attack the body tissue (Yadav 2003). A class of proteins is coded by a relatively large gene cluster called major histocompatibility complex (MHC). Unless the donor and the recipient MCH are genetically identical, the graft is generally rejected. Graft rejection implies that unrelated individuals have different sets of MHC genes (Yadav 2003: 252).
The above mentioned problems remained as a major hurdle in transplantation in the past decades. This has been overcome gradually with research in biotechnology meeting the challenge. In spite of the huge success achieved in transplantation, many allografts, regardless of the HLA compatibility between donor and recipient and immunosuppressive therapy are lost over a period of time. The criteria for rejection diagnosis differ within the various transplant teams. Some emphasize clinical and biochemical features while others use histological criteria. However, immunologic processes such as antigen recognition and proliferation of alloreactive lymphocytes are key elements in the clinical onset of rejection episodes (Mishra 2009).
Improved immuno biological processes and graft function are going to be the potential therapeutic strategies for a successful transplantation. Immune parameters such as sensitization status of the recipient, donor specific anti HLA antibodies and cytokines and its genetic polymorphism involved in immune response are major predictors of graft outcome (Mishra 2009: 273). Infection remains as the major cause of death after organ transplantation. In transplantation, genetics remains as a major influences in allowing infection to intrude. Patients with genetic susceptibility to infection may benefit from less potent immunosuppressive therapy and more intense preventive measures.
Researches in biotechnology aim at bringing perfect immunological tolerance. Attempts to induce tolerance to immunological reactivity in the case of graft rejection are the major challenges (Mishra 2009: 276).
Immunosuppressive drugs become a necessity after organ transplantation. Some of the immunosuppressive drugs like cyclosporine, FK506 etc are known to mediate their therapeutic action by inhibiting the calcineurin pathway of T cells activation. However, they suffer from the limitation of non-specificity, suppressing T cell function indiscriminately. This deactivates the function of T cells involved in controlling the infections and immune surveillance. Extensive researches are in progress to specifically inhibit the T cells responsible for alloreactivity (Mishra 2009: 276).
Sirolimus, also known as rapamycin has been discovered as a product of Streptomyces hygroscopicus bacterium obtained from the soil (Biotech Articles 2011). Biotechnology research will increase the longevity of transplant in the future.
Currently, the drugs given to transplant recipients suppress the immune system and prevent rejection. This may lead to serious health complications and side effects. As an alternative to these drugs, scientists at King's College London are looking at other ways which involve using a type of white blood cell - regulatory T cells found in healthy individuals - as a treatment to prevent an individual's immune system from becoming over active and rejecting the organ. The scientists are hopeful that this method will clear clinical trials in the near future (Science Daily 2011).
Yet another milestone in biotechnology in the recent years is the transplantation of animal organs into humans. It is known as xenotransplantation. Among many animals such as chimpanzees, baboons and pigs, it was found that the organs of pigs – especially heart valves – and cow suit human patients. So pigs have been proved to be a valuable donor for humans due to their fast growth. Also the infection risks are minimised. Earlier organ transplants from animals suffered a setback due to the rejection issues and the risk of transmission of animal diseases to humans. Many biotech companies have undertaken serious research to resolve any issues relating to non-suitability of organs (Kayser & Müller 2004: 266).
Once the initial hurdles are overcome in transplantation, the physiological limitation to the survival of a xenograft posed a major challenge. A xenograft might engender medical complications for the xenogenic host. Also the xenograft might transfer infectious agents from the donor to the host. From the host, such agents might spread to other members of the society. All these difficulties are to be overcome in the development of xenotransplantation and it is a real test for genetic engineering to tackle these issues (Kayser & Müller 2004: 266). Xenotransplantation from transgenic animals is getting more attention in the pharmaceutical industry.
Organ transplantation is an efficient and cost-effective treatment for severe and life-threatening diseases of organs especially heart, liver and kidney. In Europe, there are about 35000 patients and in the United States about 60000 patients are on organ recipient lists. Organ transplantation costs vary from 60 Euros to 120000 Euros and demands lifelong drug therapy with immunosuppressive drugs to avoid transplant rejection. Genetically modified organs and cells from other organisms like pigs proved to be effective in overcoming shortage of human organs. But the imminent danger of infectious pathogens and oncogenes are to be taken care of (Raju & Sreenivasulu 2008).
The generosity of people in donating organs saves many lives. However, it is sad that there are about 6000 patients who die every year waiting for organs. The shortage of organ donors limits the number of transplantation (Schacter 2006: 123). On the other side it opened up avenues for research turning the focus on artificial organs, engineered tissues, stem cell transplants and xenotransplants. Xenotransplants of the heart, lung, kidney, and pancreatic islets function well enough to sustain life. Ongoing discoveries indicate the possibility that animal tissues and organs might be less susceptible to disease recurrence compared to allotransplants. Developments in cellular and molecular biology and genetics create the use of cells, tissues, and organs to address the complications of disease, not only by replacement of abnormal cells and tissues but also by the use of transplanted tissues to impart novel physiological functions. Here xenografts proved to be useful in introducing a new biochemical process to assist the transplant recipient (Raju & Sreenivasulu 2008).
In order to make organ transplant successful, the tissue produced through stem cell research is being used. As stem cells can develop into any organ of human body, tissue that suits and matches both the transplanted organ and the body could be produced through stem cell research. Stem cell research also helps treating heart ailments. It produces healthy heart muscle cells that can replace the damaged ones (Raju & Sreenivasulu 2008).
Tissue engineering is yet another developing field in pharmaceutical biotechnology. It combines cell biology and biomaterial science. Tissues consist of scaffolding material such as collagen, biodegradable polymers, etc which eventually degrades after forming organs or cell implants (Kayser & Müller 2004: 5).
Advanced research provides ways to treat human diseases by changing genetic information in the cells and tissues in a patient's body. Changing the genetic material may prevent humans from disease but there are other profound ethical issues found in these types of gene technologies. It becomes inevitable for human beings to understand the positive and negative sides of biotechnology in order to draw the limit of biotechnology in healthcare (Schacter 2006: xxiv).
The human body has a remarkable capacity to repair and maintain itself. For example, the liver can regenerate up to 50% of itself. An astonishing fact in modern transplantation is that part of a liver which can regenerate itself (Schacter 2006: 123). The body's toolbox for self-repair and maintenance contains many different proteins such as growth factors and various types of stem cells that have the capacity to cure diseases, repair injuries and reverse age-related wear and tear (Kreuzer & Massey 2008: 43).
Transplantable hearts are produced with the help of stem cells taken from the recipients themselves. According to a report, one such transplantable heart has passed an important laboratory tests recently in Minnesota. This technique is called organ decellularisation which starts the functioning of heart tissue. After cleaning the old heart cells from a rat, the stem cells were injected into the scaffold of tubes that once were the organ's blood vessels. Now nutrients were supplied that would allow them to grow and create a new organ. Within eight days, the heart was pumping. This method is being used to create many of the heart valves that are implanted in current operations (Biotechnology Learning Hub 2011).
Attempting the same process to develop human heart is not far away. Presently, it is theoretically possible to use stem cells from a recipient's body to regenerate a heart that is immunologically similar to the recipient. To make it practical, several tests are to be conducted until the results are achieved (Snapshot Science 2011).
Stem cells respond to what is around them. They provide a lot of favorable signals from stem cells to become heart cells. They take stem cells that want to become heart cells and make them act appropriately. Every year, 50000 heart patients on waiting list die without donor heart. The stem cell research may bring a new lease of life to such patients. In the near future, stem cells may be an alternative to xenotransplantation. Stem cell is capable of becoming any type of body cell. Stem cells are found in brain, liver, bone marrow, embryonic tissue and cord blood. New organs or tissues could be grown from an individual’s own stem cells (Biotechnology Learning Hub 2011).
In another experiment, scientists used the scaffold from a rat liver and developed a new liver with the help of new liver cells. The new liver worked only for a few hours. With enhanced research in the near future, livers for human transplantation can be produced in the laboratory. Thousands of discarded livers with damages can be used for scaffolds and new livers can be produced. Stem cells from the patient could be used to grow the new liver cells. Scientists have to be extra cautious while doing research because the new tissue in the lab has not lived up to the hype in the past (Edelson 2011).
Scientists have also tried using plastic antibodies to recover mice stung with bee venom. In this experiment, antibodies are produced through a process called molecular imprinting. They used monomers and a catalyst to stimulate polymers to form around the molecules of bee venom. This would form cross-links and then solidify. They then dissolved away the venom, leaving plastic nanoparticles 1/50,000th the width of a human hair. If this technique works out well in humans then it will be a giant leap in transplantation using biotechnology (Snapshot Science 2011).
For patients with leukaemia or severe disorders of the blood, bone marrow stem cell transplantation is carried out. After chemotherapy, the patient receives a transplant either of their own bone marrow, or bone marrow from a person with a similar genetic makeup (Biotechnology Learning Hub 2011).
Bone marrow transplants are now carried out in many parts of the world and are a fine example of a successful stem cell therapy. Matching donor and recipient tissue type is vital for the success of a bone marrow transplant. The donor and recipient tissue must have the same type of HLAs. If the HLAs differ, the donated bone marrow stem cells may attack the recipient’s tissue. This is known as graft-versus-host disease (GVHD). In the case of GVHD, the transplanted tissue attacks the patient (Biotechnology Learning Hub 2011).
Stem cell research plays a major role in treating patients suffering from cell-based diseases such as diabetes, Parkinson's diseases, Alzheimer's disease and spinal cord injury.
Currently, organs cannot survive outside the body for more than around 24 hours. A new method known as protein therapeutics prevents donor organs. Owing to the lack of blood flow and poor oxygen supply, the organs lose the 'complement system' that prevents them from any infection. Once the complement system is lost, the organ gradually loses its quality of functioning thereby leading to rejection in transplantation. Once transplantation is complete the ‘complement system’ supports the recipient's own blood cells in its attack on the organ resulting in organ rejection. Working with the biotechnology industry, scientists at the MRC Centre for Transplantation have discovered a method for coating the inner surface of donor organs with a protective layer made from a substance which is a natural regulator of proteins in humans. The results of this valuable research will help many patients who are on the wait list for quality organs for a transplant (Science Daily 2011).
Genetic engineering has advanced to develop a protein that controls blood clotting in hemophilliacs, a hormone that stimulates red blood cell production to fight anemia and antibodies that discourage organ rejection by transplant patients (Institute for Research 2000: 4).
Biotechnology has created options to save lives. Though biotechnology is aiming to achieve a long-term acceptance of the allograft, one has to wait and see the outcomes in the long run (Mishra 2009: 276).
People have fear and hopes about the way biotechnology conducts research in the field of organ transplantation. It is absolutely correct to say that the medical industry is today's biggest customer for biotechnology. The industry includes everyone including physicians, manufacturers of every kind of equipment, diagnostic techniques, drugs, hormones, vaccines, and other biochemicals utilised in transplantation as well as in the post care treatment (Grace 2006: 57).
When biotechnology is making headway in transplantation methods, there are concerns raised and the National Organ Transplant Act, USA put a check on the rapidly growing transplantation methodologies. It prohibits the sale of human tissue and organs for transplantation. However, the prohibition does not apply when it comes to research.
The federal government banned federally funded human embryology research for 15 years between 1979 and 1994. However, some research continued with private funding (Polkinghorne 2001). The practice of organ transplants from animals to humans is increasing rapidly and so the National Academy of Science's Institute of Medicine has created a committee to examine the practice. The concern is about "How to protect the rights of the first 'pioneer' patients and about how to prevent the introduction of dangerous animal pathogens into the human population" (Polkinghorne 2001). The FDA has also expressed concerns about dangerous pathogens as a result of animal-to-human transplants. The FDA wants to safeguard patients from pathogens, create protocols to quarantine patients, and create colonies of "clean" animals.
Amidst rapid developments in biotechnology, there are ethical issues questioning whether all the outcomes of research are to be implemented. The reason being, some of the developments in biotechnology are the result of manipulations in the genomes of plants and animals (Polkinghorne 2001).
Should biotechnology tamper with our lives or not? The growth of genetics-based biotechnology is very rapid and there is a possibility of technological compulsion pushing humans to forgo ethical considerations. Heart transplants are as radically unnatural as gene transplants, but most people consider them to be ethically acceptable (Koehler 1996: 8).
Advanced technology is handled by experts and professionals. These experts can easily be bound to work in the interests of companies to develop business rather than following any ethical terms. These ethical issues are to be fairly evaluated with the participation of general public, beneficiaries and experts. The respect for life and a balanced approach has to be followed. The memories of unfortunate incidents, such as the bovine spongiform encephalopathy (BSE) crisis in the UK still lingers in the minds of many and stay as a lesson (Koehler 1996).
The transnational corporations are keen on making profit out of their products and so the issues relating to ethics are only next to business motives. The moral necessity to utilise technology for acceptable means plays a decisive role. Although the repair of damaged tissues in the ill is seen as being highly desirable, the creation of a 'replacement person' is not so acceptable. Respect for the human forbids this. Debates on the ethical issues raised by biotechnology will certainly continue into the 21st century. Science, by gaining knowledge, gives power. We need to use our wisdom to transform this knowledge into effective ways. For people to better understand biotechnology, a considerable educational programme will be useful. Let us hope that the debates of the 21st century will be both scientifically better informed, and also ethically acceptable (Brodwin 2000). The advantage of biotechnology over other technologies is that it is based on biology. It can work with organisms in predictable ways. Of all the technologies developed so far, biotechnology has the potential to be most compatible with sustainable life on this planet (Kreuzer & Massey 2008: 43).