Transplantation to replace such diseased or defective tissue as corneas and hearts necessarily requires a dead donor; paired organs such as kidneys, or large or regenerating organs or tissues such as skin, bowel, lung, liver, or blood, can be donated by live donors (see blood transfusion). Skin autografts, employing skin from the patient's own body, are used to replace lost skin; autograft transplants are also done with bowel, bone, cartilage and other connective tissue, and ovarian tissue. Replacement skin for autografts is now also grown in laboratories, and autograft bladders have been laboratory grown and implanted. In 2008 Spanish surgeons implanted a trachea in which autograft tracheal and adult stem cells had grown over the connective tissue scaffold from a donated trachea. Bone marrow transplants can come either from a donor or from stored host bone marrow. Controversial fetal tissue implants have been used for some neurodegenerative diseases and experimentally for fetus-to-fetus transplants in certain genetic disorders. In addition to transplanted human tissues and organs, artificial parts ranging from heart valves to hip sockets are routinely implanted. See also heart, artificial.
In transplanting complex organs (but not small tissue grafts), the larger blood vessels of the organ are surgically connected to those of the recipient. Connective tissue cells gradually link together the graft and host tissue. The main obstacle to successful transplantation is the rejection of foreign tissue by the host (see immunity). Transplanted tissue from another individual (i.e., homograft, or allograft, tissue) contains antigens that stimulate an immune response from the host's lymphocytes. Homograft tissue is normally destroyed within a few weeks; the rejection mechanism is similar to that by which the body resists infection. The greater the number of foreign antigens on the donor organ, the more rapid and severe the rejection reactions.
Organs donated from one identical twin to another are usually viable because such organs are antigenically identical, but even organs transplanted between individuals who are fairly closely matched antigenically, such as siblings, have a good chance of being rejected. An antigenic typing system based on human lymphocyte antigens (HLA typing), pioneered by Jean Dausset in Paris and Rose Payne at Stanford Univ., has made it possible to identify histocompatibility and minimize rejection.
Today, most recipients of transplants are maintained on immunosuppressive drugs. The side-effects of such antirejection drugs, which can themselves be life threatening, include increased risk of infection, cancer, diabetes, and other conditions. In time, however, many patients develop a tolerance to the implanted organs, and some can eventually be weaned off the drugs.
Researchers continue to study various ways to fool the immune system into accepting foreign tissues or to take advantage of the immune response. A new technique for nerve transplant begins with the patient taking immunosuppressive drugs, but after the patient's damaged nerves begin to grow and connect along the transplant, the drugs are discontinued and the immune system is allowed to destroy the transplanted nerve.
Noncellular tissues or tissues where the donor cells are not important to the graft (e.g., bone and cartilage) can usually be successfully transplanted without rejection. In these transplants the grafts provide nonliving structural support within which the recipient's living cells gradually become established. Corneal transplants have a high success rate largely because there are so few blood vessels in the cornea that corneal antigens may never enter the host's system to stimulate an immune reaction. Bone-marrow transplants effectively bring their own immune system with them, often rejecting the new host, instead of the other way around, in a reaction known as graft-versus-host disease.
Implantation of artificial organs, such as artificial bone, is successful because such organs (prostheses) do not produce antigenic substances. Artificial joints made of stainless steel have been developed; newer implants have used nonrusting titanium joints with the midsection of bone substitute composed of lightweight polyethylene.
Organ transplants from animals to humans are subject to hyperacute rejection, and transplantation of tissues from animals has been attempted for almost a century without much success. Some progress has been made, however, in circumventing the immune reaction. In one experimental approach, the tissues and organs of transgenic pigs, genetically engineered animals that have had human genes inserted, are combined with newly developed immunosuppressive drugs. In a potential step toward a different approach to developing swine that could be used as a source of organs, researchers have cloned pigs in which a gene that causes rejection by the human immune system has been genetically disrupted. The endangered species status of chimpanzees, genetically closest animals to humans, has eliminated their use as donors. Although transplants from animals to humans, called xenotransplants, might benefit the thousands of patients waiting for human organs, the possibility that they could spread some unknown animal virus into the human population has caused concern and delayed research experimentation.
Human tissue grafting was first performed in 1870 by a Swiss surgeon, Jacques Reverdin. In 1912 the French surgeon Alexis Carrel developed methods of joining blood vessels that made the transplantation of organs feasible. He advanced this technique further and stimulated the use of transplantation in experimental biology. He also developed fluids and the means of circulating them so that transplanted tissues could be kept alive outside a living body in artificial media. Theoretical work by Jean Dausset, George Davis Snell and Baruj Benacerraf on the genetic basis of histocompatibility paved the way for practical applications. In the 1940s, Sir Peter Brian Medawar and Sir Macfarlane Burnet described foreign tissue rejection and acquired immunological tolerance, opening the way for transplant operations. The first successful identical twin transplant of a human kidney was made by Joseph E. Murray in 1954. The first human heart transplant was performed by the South African surgeon Christiaan Barnard in 1967; in 1968, Edward D. Thomas performed the first successful bone-marrow transplant between people who were not twins. In the following decades liver, kidney, heart, pancreas, bone-marrow, small intestines, and multiple organ transplants became more and more routine.
As transplantation has become more common and more successful, the demand for organs has risen dramatically. The development of heart transplantation has produced an ongoing reexamination of the traditional biological and legal definitions of death, because obtaining a healthy organ for transplantation depends in large part on the earliest possible establishment of the donor's death. More than 2,000 heart transplants per year were being performed in the United States by the late 1990s, with thousands of patients waiting for available hearts. In all, more than 64,000 people were waiting to receive new organs, including hearts, kidneys, livers, lungs, and pancreases. Many people carry organ donor cards, which indicate their wish to donate if they are killed in an accident, and many states require hospitals to request donation from the families of eligible donors. A side effect of the demand for donated organs has been the increasing use of lung and liver tissue, as well as kidneys, from live donors.
In the late 1990s surprising successes were achieved in transplanting body parts other than organs. Surgeons in France and the United States were able to transplant hands that became partly functional without rejection crises. In 2005 a French surgical team achieved a partial face transplant, replacing damage areas (nose, lips, and chin) of a woman's face with skin and underlying tissues from a dead donor. A nearly total face transplant was performed in the United States three years later, and a total face transplant was performed in France the year after that. Although receiving less attention, successful transplants of knees, the trachea (windpipe), and the larynx (voice box) have also been achieved. Such operations, called nonvital transplants, have become possible owing to improved surgical techniques, monitoring of rejection, and drug therapy. Still largely experimental, they must be approved by ethics committees before being undertaken, especially as the risk of taking immunosuppressive drugs may outweigh the benefits of the operation.
See studies by R. Simmons et al. (1987) and M. Dowie (1988). See also L. Gutkind, Many Sleepless Nights: The World of Organ Transplantation (1988) and publications of the United Network for Organ Sharing.
The U.S. Microgravity Laboratory 1 was a spacelab mission, with experiments in material science, fluid physics and biotechnology. It was the first flight of a Space Shuttle with the Extended Duration Orbiter (EDO) hardware, allowing longer flight durations.
Primary payload, U.S. Microgravity Laboratory-1 (USML- 1), made its first flight; featured pressurized Spacelab module. USML-1 first in planned series of flights to advance U.S. microgravity research effort in several disciplines. Experiments conducted were: Crystal Growth Furnace (CGF); Drop Physics Module (DPM); Surface Tension Driven Convection Experiments (STDCE); Zeolite Crystal Growth (ZCG); Protein Crystal Growth (PCG); Glovebox Facility (GBX); Space Acceleration Measurement System (SAMS); Generic Bioprocessing Apparatus (GBA); Astroculture-1 (ASC); Extended Duration Orbiter Medical Project (EDOMP); Solid Surface Combustion Experiment (SSCE).
Secondary experiments were: Investigations into Polymer Membrane Processing (IPMP); Shuttle Amateur Radio Experiment II (SAREX II); and Ultraviolet Plume Instrument (UVPI).
The Space Shuttle Columbia rocketed to orbit for the longest Shuttle flight in history. Columbia touched down almost 14 days later returning with data and specimens amassed from an important suite of microgravity experiments. Shuttle mission STS-50 carried the first United States Microgravity Laboratory (USML-1) to space, conducting long-duration microgravity experiments. Microgravity is a term that refers to a gravitational acceleration that is small when compared to the gravitational attraction at Earth's surface. Through the action of free fall (e.g., Space Shuttle orbiting Earth), the local effects of gravity are greatly reduced, thus creating a microgravity environment.
During Columbia’s extended mission, scientist crew members, working inside the Spacelab long module carried in Columbia’s payload bay, conducted more than 30 microgravity investigations and tests. To maximize the scientific return from the mission, experiments took place around-the-clock. The investigations fell under five basic areas of microgravity science research: fluid dynamics (the study of how liquids and gases respond to the application or absence of differing forces), materials science (the study of materials solidification and crystal growth), combustion science (the study of the processes and phenomena of burning), biotechnology (the study of phenomena related to products derived from living organisms), and technology demonstrations that sought to prove experimental concepts for use in future Shuttle missions and on Space Station Freedom.
Three new major experiment facilities were flown on USML-1. They were the Crystal Growth Furnace, Surface Tension Driven Convection Experiment apparatus, and Drop Physics Module. An additional piece of new hardware on this flight was the versatile Glovebox, which permitted "hands-on" manipulation of small experiments while isolating the crew from the liquids, gases, or solids involved. Some of the USML-1 experiments are described below.
The Crystal Growth Furnace (CGF) is a reusable facility for investigating crystal growth in microgravity. It is capable of automatically processing up to six large samples at temperatures up to 1,600 degrees Celsius. Additional samples can be processed upon performing manual sample exchange. Two methods of crystal growth, directional solidification and vapor transport, were used on USML-1. By analyzing the composition and the atomic structure of crystals grown without the dominating influence of gravity, scientists will gain insight into correlations between fluid flows during solidification and the defects in a crystal. CGF operated for 286 hours and processed seven samples, three more than scheduled, including two gallium arsenide semiconductor crystals. Gallium arsenide crystals are used in high-speed digital integrated circuits, optoelectronic integrated circuits, and solid state lasers. Crew members were able to exchange samples, using a specially designed flexible Glovebox, to provide the additional experiment operations.
The Surface Tension Driven Convection Experiment (STDCE) was the first space experiment to use state- of-the-art instruments to obtain quantitative data on surface tension-driven flows on the surface of liquids over a wide range of variables in a microgravity environment. Very slight surface temperature differences are sufficient to generate subtle fluid flows on the surface of liquids. Such flows, referred to as "thermocapillary," exist on fluid surfaces on Earth. However, thermocapillary flows on Earth are very difficult to study because they are often masked by much stronger buoyancy-driven flows. In microgravity, buoyancy-driven flows are greatly reduced permitting the study of this phenomenon. STDCE provided the first observations of thermocapillary flow in a curved-surface fluid and demonstrated that surface tension is a powerful driving force for fluid motion.
The Drop Physics Module (DPM) permitted the study of liquids without the interference of a container. Liquids on Earth take the shape of the container that holds them. Furthermore, the materials that make up the container may chemically contaminate the liquids under study. The DPM uses acoustical (sound) waves to position a drop in the center of a chamber. By studying drops in this manner, scientists have the opportunity to test basic fluid physics theories in the areas of nonlinear dynamics, capillary waves, and surface rheology (changes in the form and flow of matter). Crew-members, through manipulation of the sound waves, were able to rotate, oscillate, merge, and even split drops. In another test, the crew members were able to create the first compound drop, a drop within a drop, to investigate a process that could eventually be employed to encapsulate living cells within a semi-permeable membrane for use in medical transplantation treatments.
The Glovebox facility perhaps proved to be the most versatile new space laboratory equipment introduced in the last few years. The Glovebox offers crew members the opportunity to manipulate many different kinds of test activities and demonstrations and materials (even toxic, irritating, or potentially infectious ones) without making direct contact with them. The Glovebox has a viewport (window) into a clean workspace, built-in gloves for manipulation of samples and equipment, a negative air pressure system, a filter system, and an entry door for passing materials and experiments into and out of the work area. The primary use of the Glovebox was to selectively mix protein crystals and monitor their growth. The Glovebox allowed crew members to periodically change compositions to optimize the growth, a first for space. Other tests conducted inside the Glovebox included studies on candle flames, fiber pulling, particle dispersion, surface convection in liquids, and liquid/container interfaces. Sixteen tests and demonstrations in all were conducted inside the Glovebox. The Glovebox also provided crew members the opportunity to perform backup operations on the Generic Bioprocessing Apparatus which were not planned.
Another of the Spacelab experiments was the Generic Bioprocessing Apparatus (GBA), a device for processing biological materials. The GBA processed 132 individual experiments with volumes of several milliliters. The apparatus studied living cells, microorganisms used in ecological waste treatment, and the development of brine shrimp and wasp eggs, and other biomedical test models which are used in cancer research. One sample studied, Liposomes, consist of spherical structures that could be used to encapsulate pharmaceuticals. If this biological product can be formed properly, it could be used to deliver a drug to a specific tissue in the body, such as a tumor.
The Space Acceleration Measurement System (SAMS) instrument measured the low-level acceleration (aka microgravity) conditions experienced by the microgravity experiments during the mission. These data are invaluable for the scientists to ascertain whether effects seen in their experimental data are due to external disturbances or not. The SAMS instruments flew on more than twenty Shuttle missions, 3.5 years on Mir, and a new version is presently (2006) on the International Space Station.
While most STS-50 experiments were conducted in the U.S. Microgravity Laboratory, others were operating in Columbia’s mid-deck. Included in the mid-deck experiments were studies of Protein Crystal Growth, Astroculture, and Zeolite Crystal Growth.
The Protein Crystal Growth experiment made its fourteenth shuttle flight, but USML-1 represented the first time crew members were able to optimize growth conditions using the Glovebox facility. About 300 samples were seeded from 34 protein types including HIV Reverse Transcriptase Complex (an enzyme that is a chemical key to the replication of AIDS) and Factor D (an important enzyme in human immune systems). About 40 percent of the proteins flown will be used for X-ray diffraction studies. The increased size and yield can be attributed to the extended crystal growth time provided by this mission. Scientists on the ground will use X-ray crystallography to study each protein's three-dimensional structure which, when determined, may aid in controlling each protein's activity through rational drug design.
The Astroculture experiment evaluated a water delivery system to be used for supporting the growth of plants in microgravity. Plant growth in space is looked at as a possible method of providing food, oxygen, purified water, and carbon dioxide removal for long-term human habitation in space. Since fluids behave differently in microgravity than they do on Earth, plant watering systems used on Earth do not adapt well to microgravity use.
The Zeolite Crystal Growth experiment processed 38 separate samples which were mixed in the Glovebox. Zeolite crystals are used to purify biological fluids, as additives in laundry detergents, and in waste clean-up applications.
STS-50 not only marked the first U.S. Microgravity Laboratory flight, but also the first Extended Duration Orbiter flight. To prepare for long-term (months) microgravity research aboard Space Station Freedom, scientists and NASA need practical experience in managing progressively longer times for their experiments. The Space Shuttle usually provides a week to ten days of microgravity. Thanks to the Extended Duration Orbiter kit, the Space Shuttle orbiter Columbia remained in orbit for almost 14 days and future missions with Columbia could last as long as a month. The kit consists of extra hydrogen and oxygen tanks for power production, extra nitrogen tanks for the cabin atmosphere, and an improved regeneration system for removing carbon dioxide from the cabin air.
One of the practical aspects of remaining in space longer will be the requirement to maintain crew member health and performance. During STS-50, crew members conducted biological tests as part of the EDO Medical Project. Crew members monitored their blood pressure and heart rate and took samples of the cabin atmosphere during the flight. They also evaluated the Lower Body Negative Pressure (LBNP) device as a countermeasure to the normal reduction of body fluids that takes place in space. If the beneficial effects of the LBNP could last for 24 hours, it would improve crew member performance on reentry and landing.
The STS-50 crew members also operated the Shuttle Amateur Radio Experiment (SAREX). Through the experiment, crew members were able to contact short wave radio operators, a Polynesian sailing vessel replica out in the Pacific Ocean, and selected schools around the world.
The Investigations into Polymer Membrane Processing (IPMP) experiment has flown previously on six Shuttle missions. It is used to study the formation of polymer membranes in microgravity with the aim of improving their quality and use as filters in biomedical and industrial processes.
The mission insignia shows the space shuttle in the typical flying position for microgravity. The USML banner extends from the payload bay, in which the spacelab module with the text μg—the symbol for microgravity. Both the stars and stripes on the USML letters as well as the highlighted United States on the earth below the shuttle depict the fact that it was an all-American science mission.