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important because of its high resolution and versatility. Electrophoresis is based on the electrical characteristics of materials in solution or

suspension and is mostly used for the separation of complex biological

mixtures.

Space and time do not permit a thorough technical review of the

reasons that electrophoresis was singled out for this detailed study.

Some of these were presented in my prior testimony to the Subcommittee

on Space Science and Applications (1), and others are included in the

reprint submitted in the Appendix.

It will suffice to state that electro

phoresis requires stabilization of fluid against gravity-dependent distur

bances.

This stabilization is achievable on the ground by a variety of

subterfuges, but the weightless condition prevailing in orbiting space

craft offers an entirely new approach to the control of these gravity

dependent phenomena.

The possibility of developing new electrophoretic

techniques based on weightlessness proved to be of considerable attraction

to a number of scientists, who have cumulatively spent a great deal of

time serving as consultants, committee members and contractors to the

NASA project. As a result of this international effort, the potential

advantages of weightlessness for electrophoresis have been confirmed in

pilot exper Inents conducted aboard the Apollo 16 (2), the Skylab (3),

and

the Apollo-Soyuz flight (4,5). One of these experiments (5) was developed

by the German government, as part of the European Space Research

Organization.

The current interlude between these pioneering experiments and the

advent of the Shuttle is permitting a thorough reevaluation of the means

and objectives of this program, in terms of equipment and candidate materials

for space processing:

a.

Optimization of Equipment. It is important to emphasize that

electrophoresis is a term which encompasses a family of interrelated tech

niques and Instrumentation. The reason for this multiplicity of approaches

is to be found in the very versatility of the basic process of electropho

resis which can be adapted in manifold ways to suit particular needs.

The prototype instruments flown in prior space missions were developed

to meet the severe constraints of time, space, and facilities available

aboard the Apollo spacecraft, and should not be adopted for the Shuttle

without thorough multidisciplinary reevaluation.

This has been partly

ccomplished already due to

the mathematical modelling and theoretical

evaluation of the performance of continuous flow instruments in zero

and one-G environments by Ostrach (6), Saville (7) and Giannovario and

Griffin (8). Their conclusions will surely be incorporated into future

flight instruments.

Of more serious concern is that all instruments used in the past

space experiments have been adaptations of ground based equipment. Bier

et al (9) and Strickler (10) have proposed instruments more specifically

designed for the weightless environment, and other such instruments were,

no doubt, incorporated into various proposals submitted to NASA. While

it may be difficult to pursue all alternatives, the development of new

concepts should be encouraged.

Only through innovative approaches taking

full advantage of the weightless environment can true breakthroughs in

space processing be realized.

The above instrumental design considerations are nevertheless relatively

simple to evaluate as they fall into the province of engineering.

More

complex is the selection of condidate materials for space processing, for

this demands value judgments and crystal gazing into future needs to a

rapidly changing state of art.

This requires separate discussion of

electrophoresis of living cells and electrophoresis of proteins and other

soluble biomolecules, for these two groups of candidate materials have

different Instrument requirements.

b. Cell Electrophoresis. At the inception of the NASA program, some six or seven years ago, the main emphasis was on the development of

a space facility for the electrophoretic separation of cells. This appli

cation appeared particularly timely.

Rapid advances in cellular immunology

and the recognition of the manifold functions of lymphocytes have shown

the need to obtain functionally pure cell subpopulations. Electrophoresis

appeared particularly promising as ground-based techniques were lagging and the field was nearly dormant.

The situation has changed significantly in the last few years as

characterization of cell subpopulations has become central to much of

present immunological research. Several powerful non-electrophoretic techniques for cell separation have been developed such as electrostatic

cell sorting, sedimentation techniques, affinity chromatography, phase

partition with polymer systems, etc.

There have also been significant

new developments la both analytical and preparative cell electrophoresis.

To a large degree these advances were the result of the stimulus provided

by the NASA program and can be considered a major benefit of the space

program.

The fact that there are now several new methods for ground-based

separation and characterization of cells does not invalidate the premise

that cell electrophoresis may benefit from the microgravity environment.

To the contrary, the new methods permit clearcut focusing on the most

promising areas of space exploration and a thorough evaluation of candidate

materials.

These will also obviate the need for much of the space experi

mentation and will result in a significant saving of funds in the develop

ment of useful space processes.

For cell electrophoresis, the crucial point is to obtain solid data

on the relationship between cell mobilities and the desired cell functions,

whether these be immunological, physiologic, metabolic or synthetic. It

should be emphasized that the establishment of the relationship between

surface characteristics of living cells, as reflected by their electro

phoretic mobilities, and cell functions is not a trivial matter of only

pragmatic value for the space program. Quite the contrary, it is an

Important scientific problem for cell biology, which merits fundamental

research in its own right, i.e., independently of the space program.

It

18 increasingly evident that cell surfaces play a key role in many cell

functions including immunologic recognition, cell-cell interaction or

organ differentiation.

Summarizing the case for cell electrophoresis in space, we wish to

emphasize that:

(1) Studies of cell subpopulations are an important area

of scientific endeavor and there is great need for simple methods for their

separation.

Electrophoresis can make a significant contribution.

(11)

Current ground based techniques for cell electrophoresis have some inherent

problems, such as poor resolution in the continuous flow method, sed imen

tation and artifacts due to polymeric materials in density stabilization

methods.

More rapid means for cell separation are also needed, as well

as the possibility of using more physiological buffers.

There is no doubt

that these problems can be significantly alleviated or completely avoided

In a weightless environment.

(111) There is urgent need for more ground

based research to develop artificial means for increasing resolution of

cell electrophoresis and to obtain better data on mobility distributions in a variety of cell populations.

c. Protein electrophoresis. The situation is rather different for protein electrophoresis, where there are a variety of well established techniques which are in world-wide use in literally thousands of laboratories. There are no major unresolved scientific problems and the usefulness of electrophoresis is based on the fact that there is an exquisite correlation between the molecular structure of the protein and its electrophoretic characteristics. As a result, electrophoresis is used for various analytical and micropreparative purposes in the most diverse areas of biological research, clinical medicine, and quality control in industry. Despite numerous efforts, ground-based technology has failed in one important respect: scaling up the capacity of the instruments for the separation of meaningful quantities of purified components. There are no theoretical reasons that electrophoresis could not be used on the largest possible industrial scale, only limitations in present instrument designs. Some of these limitations may be gravity-dependent, due to the need for fluid stabilization against gravity driven convection.

We are currently actively engaged in an effort to overcome these limitations, using a new principle of recycling isoelectric focusing. Isoelectric focusing is generally recognized as a variant among electrophoretic methods giving the highest resolution, but it offers small throughputs useful only in research. The recycling principle has already shown promise for far greater throughputs, possibly even of industrial capacity. These studies are only in their initial phase, and it is not yet clear to what degree this new process could benefit from weightlessness.

Should our present ground-based studies confirm the expectation that

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