Aerospace Technology Development

The Future of Medical Research:
The ISS and Biotechnology

IMAGINE BEING A SCIENTIST, BUT ONLY BEING able to get into your best laboratory for 10 days every year or so. The Space Shuttle is an excellent platform for biotechnology research, but it has to return to Earth after two weeks in space, along with the spaceborne laboratory and its outstanding and unique features for performing research. Even if we could fly six Space Shuttle flights per year, each successfully producing crystals to reveal the structure of 1,000 different proteins per flight, it would still take 35 years to learn the structure of all human proteins.

Based on the experience aboard the Russian space station Mir, access to the International Space Station (ISS) promises to increase the rate of advancement in this field by a factor of ten. The Shuttle-Mir program provided the United States with the opportunity to conduct experiments in microgravity for periods of time far exceeding the two-week maximum of Space Shuttle flights. The flight of seven American astronauts and more than 140 experiments on Mir were an important step in preparing for ISS assembly and research.

Microgravity science used cutting-edge technology to increase dramatically the number of protein crystals grown, to allow significant expansion of in-flight tissue culture experiments from weeks to months and to benefit medical research on Earth with knowledge gained. With the ISS, a permanent laboratory will be established in a realm in which gravity, temperature and pressure can be manipulated to achieve a variety of scientific and engineering pursuits that are impossible in ground-based laboratories.

On the ISS, NASA will examine in depth the fundamental effects of microgravity on human health during long-duration space flights, not only for space travelers, but to use the knowledge of the human body at its most basic level to further research here on Earth. A greater understanding of gravity's effects has the potential to bring about a boom in commercial medical products on Earth.

What Is Biotechnology?

Biotechnology is an applied biological science that involves the research, manipulation and manufacturing of biological molecules, tissues and living organisms. It is expected to dominate the 21st century's economy and have a significant impact on our lives.

NASA's dynamic microgravity research in three principal areas—protein crystal growth, mammalian cell and tissue culture, and fundamental biotechnology—will continue aboard the ISS. New opportunities, some just now being explored, will open up in biotechnology on the ISS. Investigators will look into the use of biologically inspired materials and the role that gravity plays in genetic expression.

Marshall Space Flight Center in Huntsville, Alabama, is NASA's Microgravity Center of Excellence for biotechnology. It is supported by the biotechnology program office at Johnson Space Center in Houston, Texas.

Why Conduct Biotechnology Research in Microgravity?

Research on the Space Shuttle and the Russian space station Mir has indicated that protein crystals grown in microgravity can yield substantially better structural information, and disease-treating drugs are designed from protein structure data. Determining protein structure is the key to the design and development of effective drugs for the more than 100,000 different proteins important to the human body's everyday functions and the fighting of disease.

By understanding how a protein's structure affects its function, a drug can be created to "fit" into a protein's active site—similar to inserting a key into a lock—to disable the protein's function. This approach promises to help produce superior drugs for a wide range of conditions, and the ISS could become one of the world's premier sources for critical data on the protein structures needed for this new method of drug development.

ISS facilities will enable investigators to analyze crystals on orbit, decreasing the cost and increasing the quality of research. In addition, the station will be used to study and understand the physics involved in protein crystal growth, helping overcome the difficulties that currently limit much of this research on Earth.

Biotechnology Research Tools and Areas

Pure, precisely ordered insulin crystals of sufficient size and uniformity are in high demand by drug developers. Insulin crystals grown on the ground do not grow as large or as ordered as researchers desire.

Protein Crystal Growth

Microgravity experimentation has shown scientists that low-gravity conditions allow for better and larger crystal production in which cells cluster together in three dimensions, often closely resembling the shape such tissue takes in the human body. Earth's gravity interferes with protein crystal growth on the ground, resulting in cell cultures that are more two-dimensional, which prevents precise definition of the molecules and fine structure and limits the sample's usefulness as a research tool.

In gravity conditions, sedimentation (the separation of materials of different densities) causes the crystals to sink to the bottom of their growth container, but in microgravity, convective flows (flows caused by temperature-driven density differences in a fluid) are greatly reduced, and crystals grow in a much more stable environment. This may be responsible for the improved structural order of space-grown crystals, allowing for precise definition of the molecules and fine structure. Knowledge gained from studying the process of protein crystal growth in microgravity conditions will have implications for protein crystal growth experiments on Earth.

The Bioreactor

By using space-based experiments as a model, researchers have developed a "bioreactor," a mechanism for terrestrial applications that uses horizontal rotation to mimic the microgravity environment. It is successfully being used to culture tissue samples as diverse as liver, muscle, cartilage and bone.

The low-turbulence culture environment provided by the NASA Bioreactor promotes the formation of large, three-dimensional cell clusters and has been instrumental in helping scientists better understand normal and cancerous tissue development.

Traditional and conventional static tissue culture methods form flat sheets of growing cells that differ in appearance and function from their three-dimensional counterparts growing in a living body. However, the rotating wall bioreactor, developed to further enhance three-dimensional tissue formation, cultures cells in a horizontal cylinder, which continuously and slowly rotates, allowing for a suspension of tissue samples in growth fluid (to escape much of gravity's influence) and a reduction of damaging shear forces.

Perhaps most significantly, tissue cultures grown in this type of bioreactor, from just a few cancer cells, possess structures and functions similar to those found in the human body. This allows for tests and the study of new treatments on patient cell cultures rather than on patients themselves, and it avoids the risk of harmful side effects to a patient.

Scientists at NASA's Johnson Space Center are modifying the bioreactor to monitor and control nutrients in the tissue's solution. In the future, this technology will enable quicker, more thorough testing of larger numbers of drugs and treatments. Ultimately, the bioreactor is expected to produce even better results in the microgravity environment achieved in orbit.

Mammalian Cell and Tissue Culture

The study of normal and cancerous mammalian cell and tissue growth holds enormous promise for applications in medicine. Culture tissues have already been grown in the bioreactor aboard the Space Shuttle and on the Russian space station Mir, where even greater reduction in stresses on growing tissue samples have allowed larger tissue masses to develop.

Bioreactors are being designed and modified for the ISS so that the bioreactor's continued and expanded use can improve our knowledge of normal and cancerous tissue development. In cooperation with the medical community, the rotating bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. In the bioreactor, these tumors grow into specimens that resemble the original tumor.

Similar results have been observed with normal human tissues as well. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver cells and kidney cells are examples of the normal tissues currently being grown in rotating bioreactors by investigators. In addition, laboratory models of heart and kidney diseases and viral infections (including those from the Norwalk virus, a major cause of epidemic gastroenteritis, and the human immunodeficiency virus, or HIV) are in development for further study using this technology.

Because space research sheds light on the fundamental effects of gravity on tissue formation and development, continued cell culture research aboard the ISS will allow scientists to refine Earth-based biomedical techniques. Ultimately, tissues cultured outside the body may be used to replace damaged tissues, treat diseases or eventually replace entire organs.

Telemedicine

Telemedicine, the practice of medicine from a distance through the use of advanced information and communications systems, will ensure that our crews receive the best medical care we can deliver. As our astronauts spend longer periods in space at greater distances from Earth, it will not always be practical to return a sick or injured crew member to our planet's surface for care. Neither will it be possible to fly a full complement of trained medical personnel with each mission. General paramedic-level knowledge among the crew will be the norm. With this in mind, NASA and its partners are working to integrate the latest in telecommunications, computers and medical technologies in health care to provide our astronauts the best medical care possible.

The ISS will serve as a testbed for new remote medical and life-support technologies to provide high-quality health care and environmental conditions to next-generation space travelers. NASA is currently conducting ground research on an automated portable intensive care unit. Emerging technologies, such as virtual reality and wireless medical monitoring, are being incorporated into advanced remote health care systems. Work in cybersurgery, surgery using digital models and virtual reality is also ongoing. As our knowledge in these areas matures, we will incorporate these technologies into the ISS medical support systems.

At the same time, we can use these technologies to improve our system of health care delivery on Earth. NASA-developed telemedicine systems have been used to provide high-quality medical advice, instruction and education to parts of our nation and the world where advanced medical care or access to health care is not always available—and where it can mean the difference between life and death in acute medical cases. The highly successfully Spacebridge to Russia program, a joint effort between NASA and the Russian Space Agency, is an Internet-based telemedicine testbed that links academic and clinical sites in the United States and Russia for clinical consultations and medical education. A predecessor project, Spacebridge to Armenia, was used to provide medical consultation services during the recovery from the Armenian earthquake in 1988.

Advanced technologies such as telemedicine will enable specialized medical knowledge to serve more people than ever before. Only a permanently crewed ISS with substantial laboratory capabilities will allow research in these directions to proceed productively.

As we work to advance the state of medical care technology, space clinical practices will incorporate the knowledge gained from ISS research on the effects of microgravity on the human body. The classical medical triad of prevention, diagnosis and treatment will be refined to reflect the effects of space travel. Therefore, facilities for basic biomedical research will be used in conjunction with the ISS crew health care system to advance our state of knowledge and care for our astronauts.

For more information about telemedicine, call the NASA Telemedicine Gateway.
Call: 800/678-6882, E-mail: http://www.nttc.edu/telemed.html For more information on biotechnology, call the Technology Commercialization Office at Marshall Space Flight Center. Call: 205/544-4266, E-mail: http://microgravity.msfc.nasa.gov/ MICROGRAVITY/Biot.html Please mention you read about it in Innovation.