INVITED LECTURES

SPACE MEDICINE: A MODEL FOR PATIENT-ORIENTED MEDICINE IN THE NEXT CENTURY

R. Gerzer
DLR Institute of Aerospace Medicine, 51147 Cologne, Germany

Two developments are presently revolutionizing medicine: the rapid progress in molecular medicine makes it possible to develop highly specific drugs for the molecular treatment of acquired as well as of inherited diseases. In addition, the revolution in information technologies enables the development of highly sophisticated techniques for minimal-invasive diagnosis and treatment procedures. Thus, modern medicine requires a high degree of specialization and diversification for the optimal use of these new possibilities.
The main challenge of medicine in the next century will neither be molecular medicine nor the development of innovative techniques, but to put all these new possibilities together and to make individualized, patient-centered medicine possible. Medicine will therefore have to change from expertise- and procedure-centered approaches and return to patient-centered, individualized procedures.
To achieve this goal, patient information must be obtained as "user-friendly" as possible. Therefore, many diagnostic parameters will be obtained by telemedical diagnosis or monitoring at home in order to allow the respective patient the maximal possible freedom and to minimize the need to visit doctors or hospitals. Diagnosis will also involve genotyping and phenotyping as well as minimal-invasive anatomical and functional analyses. Treatment will not remain "symptom"- or "disease"-centered, but will be based on the functional state of the individual as a whole, not only representing single symptoms, but a systems approach respecting the whole person. Ultimately, monitoring the success of the treatment will be conducted as flexible as possible to allow even the patient at risk to remain as mobile as possible, but still be protected by teleassistance possibilities.
At the same time, the major challenges for this medicine of the future are tasks that have to be fulfilled in space medicine as early as today: the astronaut's health needs to be monitored as minimal-invasively as possible. The astronaut aboard a space station cannot go to a medical specialist for routine check ups, which means that most diagnoses need to be made by telemedicine in order to allow him to stay "at home" (aboard the space station). Finally, diagnoses always need to be made in a systems approach to allow the maximal scientific return from experiments or the optimal diagnosis of a possible disease state. In the future, geno- and phenotyping of astronauts will also be essential in order to obtain optimal diagnoses.
Since current space medicine already incorporates tasks that are major challenges for the medicine of the future, space medicine should take up the challenge and strive for excellency and leadership in the integrative systems approach, which will be the major challenge for medicine during the next century.


THE PHYSICS OF FOAMS

D. Weaire
Physics Department, Trinity College, Dublin, Ireland

We review recent progress in the basic physics of foams, in terms of elementary models. Using a combination of advanced computer simulations, experiments and theory, the cellular structure of liquid foam together with its evolution in time (coarsening, drainage) and response to stress (rheology) have come to be well understood. This is most true in the limit of a static (or quasistatic) stable, dry foam. Remaining questions therefore concern the behaviour of wet foam and a variety of dynamic effects on all scales - microscopic, mesoscopic, macroscopic. The subject is still a challenge to further interdisciplinary research, and microgravity experiments should be useful in exploring the wet limit. In more practical terms, foam formation in microgravity may provide new possiblities - for example, in making solid metallic foams.
ACKNOWLEGMENT : Research supported by Enterprise Ireland and Shell Research, also benefiting from ESA support for Topical Team Meetings.


BIOREACTORS IN SPACE

I. Walther
Space Biology Group ETH-Technopark, Technoparkstr. 1, 8005 Zurich, Switzerland

Biotechnology has already been used for centuries on Earth for the production of food and beverage. But it is in the last decades, thanks the use not only of micro-organisms, but also of plants and mammalian cells, that it has really flourished in the domains of pharmacology and waste treatment. Lately, also the medical world interest in bioreactors has risen drastically with the possibility of tissue cultivation. New devices and cultivation processes have been developed for the growth of mammalian tissues. Continuous cultivation in the defined and controlled environment of a bioreactor is a prerequisite for the quality and the reproducibility of such cultures. Moreover a very low shear force environment is one of the most important factor for a successful cultivation of mammalian cells. Such an environment is provided by microgravity. Bioreactors in space are not only interesting for the production of mammalian tissue. They are the key element for the treatment of waste products (air, water, etc.) and they provide a controlled environment for cell growth.
We review here the bioreactors hitherto developed for space in the USA and in Europe and present the results obtained with the Swiss miniaturised bioreactor (SBR I) aboard STS-76.
The first instrument developed in the USA was the so-called Woodlawn Wanderer 9 apparatus. It consisted of a fully automated perfusion chamber with devices for light microscopy and a cinecamera. It was installed aboard the US space station Skylab in 1973. Later came the Space Tissue Loss (STL) system, based on the hollow-fiber technology, providing flexible feeding capabilities, thermal regulation and chemical fixation of the cells. It fitted in a middeck locker of the Space Shuttle and was used on three flights. A set of bioreactors, all based on the principle of the rotating wall vessel (RWV), was developed by NASA at the Johnson Space Center. Both the fed-batch and the perfusion systems are available, and oxygenation is achieved by diffusion through a silicone membrane. The first flight of a RWV bioreactor took place with mammalian cells in 1991. Data on later flights are not yet available.
The instruments described above are all of rather large size. Two other bioreactors developed in Switzerland, the dynamic cell culture system (DCCS) and the SBR I are smaller and fit in standard Biorack Type I (81x40x20 mm) and Type II (87x63x63 mm) container, respectively. The DCCS consists of a culture chamber of 200 µl supplied continuously with fresh medium by an osmotic pump. It was used twice in space, the first time with plant protoplasts, the second with hamster kidney cells. In the SBR I, a 3 ml culture chamber is supplied continuously with fresh medium by means of a piezo pump, the flow rate of which can be modified during cultivation. The pH is recorded and regulated electrochemically, a magnetic stirrer is also available. This instrument flew in 1994 and 1996. This instrument was designed for yeast cells that we chose as a model organism. It is fitting in an ESA standard container Type II (87x63x63 mm). The cells were provided with fresh medium at different but fixed dilution rates during the whole experiment (8 days) by means of a piezo-electric pump. A microsensor measured in situ different parameters (pH, temperature), and the pH of the culture was regulated electrochemically, so that no concentrated base had to be used. The technical data were delivered on-line to the ground during the missions. The bioreactor was outfitted with an additional sensor to monitor the flow rate. Technically, the bioreactor functioned according to expectations. Biological data were gathered by means of samples, taken at preset intervals during the 8 days cultivation. The biological analyses were performed post-flight. They included morphological studies (electron microscopy, budding scars analyses), metabolite measurements (glucose, alcohol), physiological analyses (optical density, cell cycle, cell size).
Biological analyses and electron microscopy showed that the general metabolism and morphology of the cells were similar in space as on ground. Interestingly, we observed that the specific bipolar bud scar positioning was altered under microgravity conditions. In fact, a statistically significant higher numbers of flight cells show a random distribution of scars compared to the ground samples where scars are localised at both poles in the majority of the cells.
In conclusion it can be said that the technology used for this bioreactor has been proved adequate for the continuous cultivation of cells in space and can be further used for the development of an instrument adapted to the cultivation of mammalian cells.


INVESTIGATION OF GRAVITY DEPENDENT EFFECTS IN MAGNETIC FLUIDS: RECENT RESULTS AND FUTURE PERSPECTIVES

S. Odenbach
ZARM, University of Bremen, Am Fallturm, 28359 Bremen, Germany

Stable suspensions of small magnetic particles - often called ferrofluids - show a combination of normal liquid behavior with superparamagnetic properties. That means that it is possible to influence and control the flow and the properties of these magnetic fluids by means of weak magnetic fields with field strength in the order of 10 to 50 mT. This unique feature of magnetic fluids results from the fact that the magnetic particles suspended in the liquid have a mean diameter in the order of 10nm. Therefore they can be treated as small permanent magnets having a magnetic moment in the order of 10⁴ µ_B. These small permanent magnets are interacting with an external magnetic field forcing them to align with the field direction. The alignment is counteracted by thermal motion yielding a paramagnetic magnetization behavior of the fluid with an initial susceptibility of about 1 - that is 10⁴ times higher than in usual paramagnetic salt solutions. Since the force exerted by a magnetic field gradient on the fluid is proportional to it's susceptibility even weak magnetic fields can exert reasonable forces to magnetic fluids. These magnetic forces, which can drive flow in the fluid or change it's properties, are well controllable concerning strength and direction. In some experiments the magnetic effects may be suppressed in others overlaid by gravitational ones, leading to a lack of observability of the effects themselves or at least to a modification making comparison with theoretical approaches much more difficult. Thus it is often advantageous to carry out magnetic fluid experiments under conditions of strongly reduced gravitational acceleration.
The possibilities provided by use of microgravity experiments in problems related to magnetic fluid research will be illustrated with two examples. On the one hand a magnetic flow control - driving a thermal flow without the action of gravitational acceleration or surface tension, just induced by thermomagnetic forces will be discussed. This thermomagnetic convection is an excellent example for the differences appearing when it becomes possible to observe the pure magnetic effect without the overlaid action of normal thermal convection forced by the interaction of a density gradient in the fluid with gravitational acceleration. This phenomenon has been investigated using sounding rocket and drop tower experiments and it is planned to be extended in experiments on the International Space Station. The results obtained in former experiments will be presented as well as the perspective and research goals of the planned ISS experiments will be discussed.
The second example concerns the change of properties of magnetic fluids. The most famous influence of magnetic fields on ferrofluids is the change of viscosity provided by the hindrance of free rotation of the particles in a shear flow due to the action of magnetic fields. As an extension of this effect the appearance of viscoelasticity has been discussed for many years. One the prominent effects in viscoelasticity is the appearance of the Weissenberg-effect due to normal stress differences. This rise of a free fluid surface at a rotating axis is to small in magnetic fluids to be observed in normal terrestrial experiments. Thus microgravity can help to amplify the effect of the normal stress differences. Experiments showing Weissenberg-effect in ferrofluids have been carried out during parabolic flight missions. The results and problems occurring here will be reported.