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THE EMERGING SCIENCE OF BIOPHYSICS

By Otto H. Schmitt

University of Minnesota

Minneapolis, Minnesota

Most of us who have survived a college education have been subjected at one time or another to science courses. These may have been in the so-called exact sciences like physics and chemistry where major emphasis is placed upon the manipulation of numbers and formulas, or in the more descriptive sciences like biology where there is more attention to classification of empirically observed phenomena, and theory takes the form of verbal generalization.

In either case, I am sure we received the clear impression that the instructor, at least, knew exactly what Physics, Chemistry, or Zoology was about and that any uncertainty was on the part of the student. We realized that professors differed in their ability to teach and their apparent understanding of their subject, and that they had pet ideas which they introduced as brand new in every second lecture, but we dismissed these as prerogatives of the academic mind. We never doubted the sacred notion that each science has a fixed content which overlaps only a little with other sciences and changes only by slow growth and improvement with advancing research.

This notion is almost totally an illusion brought on by the fact that each of us during his school years sees a science in a relatively stationary state. Like a photograph of a moving scene taken with a 1/20 second exposure, only fast moving objects are noticeably blurred.

Actually most of the sciences move in a series of fads each having a duration of about l5-20 years and each leaving a residue which lasts as “firmly established theory” for perhaps half a century. At any one time there are perhaps half a dozen fads in various states of inception, exploitation, and obsolescence so that there is always room for the innovators, the band wagon boys, and the last decimal brigade.

Even those of us professionally in a field seldom notice these evolutionary changes, for we as biological creatures adapt to our environment, good or bad, and seldom take notice on an absolute basis of our scientific status quo and even less often deliberately take action to change it. There is some validity in the old remark, “Raised on crow, like crow”.

We find it almost incredible that whole fields of science move bodily from one nominal academic division to another during a century and we are startled when we find an author in l750 calmly speculating upon something we thought discovered only this year or last. Recently I chanced to examine one of the American text books of Chemistry for colleges published in 1846 by a certain John William Draper. It purports to cover a course of 89 lectures. Of these I would currently expect 32 to be classified as inorganic chemistry, 30 as physics, 4 as organic chemistry, 4 as biochemistry, 4 as physical chemistry, and 4 as physiology or biophysics. Ohm's law, refraction of light, and specific heat, to cite just a few examples, are presented much as we teach them today in sophomore physics courses. At that time they were taught as a part of chemistry.

Included also are lectures on digestion, function of the nervous system, and the nature of the electric organ found in some fishes and rays. There is also remarkably pertinent curiosity regarding the special role of phospholipids in nervous function. We find a chapter on Tithonic

rays totally foreign until we discover that this refers to ultraviolet light as manifested by photographic image blackening. Today we would call this chapter “Actinic Light and the Photographic Image”.

So now let us see what makes us call a particular section of knowledge or folklore a science with a special name, and to give it some initials like Phys. or Zool. on a registration blank and a building on the campus. There are four main motivations; respectability, administrative convenience, community of interest, and money.

A scientist does not feel that he is fully respectable and really “belongs” unless he is central to a group and has a technical society and a wing of a building carrying the name of his specialty. He hates to be assessed as a biophysicist by his performance as a physiologist or to find that only ten percent of the papers presented at a meeting are of interest to him. Administratively two physicists can bargain effectively with a department head who is also still more or less competent as a physicist for he can understand their problems basically even though the two specialize respectively in magnetic resonance and in cosmic rays. There would be considerable difficulty if a botanist tried to make his needs known to a department head trained in electrical engineering in competition with other electrical engineers. It is also embarrassing as soon as one department member is totally unable to comprehend, much less ask intelligent questions of, another within his department.

Historically, then, as subject matter and theory have grown in the sciences, we have seen the creation of one after another specialty, each of which becomes a new subject for subdivision. Natural Philosophy, covering all the natural sciences, separated into chemistry + physics + biology; chemistry into organic and inorganic, analytic and electro chemistry, etc. Areas of specialization like physical chemistry, chemical physics (which is different), astro physics, geophysics, etc. have only recently begun to assume prominence. So far there has been relatively little recondensation of major areas because within our lifetime science as a whole has been expanding almost exponentially. There has been mainly splintering, subdivision, and specialization. Knowing the habits of exponentials with fifteen year tine constants, you must realize that this process cannot continue very long. Some sciences must die and some must recombine. To date biochemistry is the biggest single area of recombination unless we admit that applied and theoretical physics are once again exchanging subject matter.

Now it is time to ask when we come to biophysics and what it is. Biophysics is not so much subject matter as it is a point of view. It is an approach to problems of biological science utilizing the theory and technology of the physical science. Conversely, biophysics is also a biologist's approach to problems of physical science and engineering although this aspect has largely been neglected.

Biochemistry, the sister science to biophysics, was the first major example of a reconvergence of science after a few decade sojourn apart. As the science that uses chemical thinking in biological science and possibly a little of the inverse process, it began to grow to prominence in Liebig's time around the middle of last century and is now well established. It has departments in every major school, it has its societies, its financial supports, and its record of achievement.

Biophysics is just starting to blossom even though its growth started some years ago. We must expect it to expand much as biochemistry did, but I suspect it has even a larger destiny.

Three centuries ago there were biophysicists at work but they didn't know that their field of experimentation would later be dignified by a special name. Stephen Hales, who lived from 1679 to 1761, performed the experiment of tying down a horse, attaching a long manometer of brass and glass tube to its blood vessels using a goose windpipe as flexible tubing, and then measuring the height of the blood column as he drained one pint of blood after another out of the horse. This sound, if rather grisly, biophysical experiment is presented with beautiful clarity and scientific accuracy in his Statical Essays of 1732 on Haemostatics.

It is hard to think of one of the great physicists of the eras that gave us Newton, Galvani, Volta, Faraday, Heimholtz, and Maxwell who did not in part function as a biophysicist. Did you realize that Michael Faraday undertook quantitative measurement of the electric charge delivered by one of the South American electric eels in shocking its prey?

Helmholtz not only wrote his doctoral thesis on the ganglionic neurons arid their nervous ramifications but also measured nerve impulse velocity, explained the process of eye accommodation and invented the ophthalmoscope, founded a still persistent theory of color vision, explained the mechanics of the ear in audition and recognized the key function of the organ of Corti in hearing. He even pioneered in devising a general theory of biophysical perception. Even our home grown Ben Franklin loved to dabble in biophysics, especially of the applied variety.

For long years, however, such bold combinations of physical thinking applied to biology became submerged in non-popularity. Biologists by tradition did not study mathematics or physics; engineers and physicists studied biology only as a cultural subject or as a means of keeping healthy (or entertained).

Suddenly we are now having an upsurge of new ideas springing from combinations of biological and physical science. In part this is happening because biological and medical scientists are no longer keeping aloof from applied and theoretical physics. In part it is because biophysically applicable theoretical ideas are arising in engineering and physics.

Let us separate the possible sorts of biophysical work vertically into theoretical and applied, and then horizontally into the physical and the biological. We find each group contributing to biophysics mostly unaware of the other three. From the theoretical - physical science quadrant we find, for example, physicists intent on solving the mystery of virus structure by bombarding viruses with radiation and thou calculating collision cross section just as they do routinely in theoretical physics. These people tend to start biophysics departments attached to physics. This is what has happened at Yale where Professor Pollard has a very active group.

The applied physicists — or engineers, to use their common name —find that they need to adapt their aircraft so that humans can live in them or else so that humans can guide them without being in them. This they call human engineering, which is a brand of biophysics. They interest themselves in communication theory and are surprised when they find their discoveries anticipated in biology as in the case of the bats' sound-operated radar, the nerves' pulse code modulation, or the rattlesnakes' conical scan with lobing.

In the theoretical biology quadrant we find biologists timidly approaching the problems of protein specificity and synthesis. They worry about the thermodynamics of open systems and they make beautiful impressionistic models of macromolecular structure and texture. They have calmly and wholeheartedly adopted the electron microscope as their own, brazenly and successfully using their familiar techniques of staining, sectioning, and embedding for electronic light as though it were really interchangeable with ordinary light.

Applied biologists - many of them medical scientists - are rapidly getting into the act. Indeed one group of these scientists, the physiologists, who have for some years been rather close to biophysical thinking, feel quite proprietary toward biophysics and practically begrudge it an independent scientific status. They even go so far as to say that biophysics is nothing more than good physiology.

Where does this leave biophysicists scientifically, economically, and administratively at the present moment? Scientifically, biophysicists are in heavy demand and there are millions of dollars in support for biophysical science, pure and applied, but there are almost no biophysicists.

Because every biophysicist worth his salt can qualify as an engineer, a physicist, or a doctor, all well paid and respectable occupations, there is heavy pressure to divert young scientists from discovering biophysics.

A graduate student faced with the option of taking an engineering job now at $6000 or spending four more years of graduate work with a $l500 assistantship in order to qualify for a $5000 biophysics position has to want very badly to work in this field. Some of this is slowly being rectified but there is a tradition of poor pay and poor facilities in biological science which has first to be destroyed.

Then too there is the administrative problem to which I know no ideal answer. Biophysics, in order to preserve its birthright of symmetry between physics and biology, medicine and engineering, must not come under the domination of one discipline to the exclusion of another. Traditionally these four scientific areas lie in at least three different and highly competitive university administrative domains, yet any educational or research activity must normally be housed and financed by one or the other. Only extraordinary wisdom on the part of academic administrators can save biophysics from becoming lopsided or else falling between three stools.

To illustrate the present explosive growth of biophysics let me give an example. Last year a few of us decided that we should explore the possibility of creating a national biophysical society. We corralled a little government money and invited those interested to come to Columbus last March to talk over whether they wanted a society, and to present regular scientific papers as at a regular physics, biology, or engineering meeting. We found ourselves with over two hundred papers, more than 500 participants, and a 98% vote for the creation of a society on the spot.

Now with the Biophysical Society a going thing, we have to try to predict where the science wants to go, how fast, in affiliation with what organizations, if any, and under what auspices. Should there be a new journal? Who shall be qualified to call himself a biophysicist? What subject matter is to be included in biophysics? Should textbooks be written and if so, on what basis? We need a textbook on the care and feeding of young and precocious sciences but find none in the library.

Now to be completely serious for a moment, what is the future of this new science and how can we give it a healthy environment and draw into it the engineering, medical, biological, and physics talent that should serve it?

First we must make an environment in which the four elements of biophysics are simultaneously welcome and functional.

At the present tine biologists are timid about talking back to physicists and mathematicians. Frankly they have been bluffed into thinking that their qualitative science is worthless in this new field. Actually it is the stockpile from which quantitative theoretitians must draw ideas.

For some reason physicists, by and large, look down upon engineering as mere practical work except when they indulge in it themselves. Surprisingly many physicists are pretty good engineers and surprisingly much theory is arising from engineering work, as witness the remarkable success of communication theory ideas.

Medical scientists stand aloof scientifically from engineers and physicists except when it comes to building gadgets and keeping them running. Then they are very willing to have help. Unfortunately this has led to a tendency on the part of medical science to down rate engineers and even physicists as mere technicians. Perhaps this is because only technician grade physicists and engineers will work for medical scientists. First rate biophysicists will gladly work with medical scientists but not for them. There is a redeeming tendency, however, for medical scientists are beginning to put more and more fundamental science in their formal training so that soon they will be able to appreciate the real beauty and fundamental importance of theoretical and technical advances based on physics and engineering. I wonder if they have even begun to realize the importance to their art of a coming era of theoretical biology.

Our most severe problem at the moment is to create a body of widely competent senior biophysicists who can efficiently lead thinking and training of young scientists in this field. At the moment almost all of our senior biophysicists are specialized near one corner or another of biophysics and often can hardly converse with men from opposite parts of the field. Try as they may, they cannot easily train young men to see biophysics from a symmetrical viewpoint. We must have team efforts from our leading biophysicists with full realization of the limited perspective open to each with his own specialized training.

There are no adequate textbooks and very few non—specialized research and training centers. Government sponsoring agencies are so anxious to support training in this field that they are partially setting aside the old restrictions against subsidy of education and we all hope that there will soon be facilities to make biophysicists otherwise than by training them separately to be physicists, engineers, and biologists or medical scientists. Even a superior student has a finite capacity for learning and a limited lifetime. We must somehow get him into productive science before he is middle aged.

All of this preparation is superfluous, however, if we do not have a full catalog of important projects to work on. What do biophysicists work on scientifically and technically? I have found it convenient in my own thinking to separate their work into three categories of interests; biophysical structure, biophysical function, and biophysical organization.

In the first category we find such challenging topics as ultrastructure of cells and macromolecules where we hope to learn the atomic and molecular makeup of cells arid tissues with the aid of electron microscopy, X-ray diffraction, interference microscopy, and allied techniques. Also included are such contrasting items as the aerodynamic and hydrodynamic design of fishes and birds and the mechanisms of antigen antibody reactions.

Under the biodynamics or function category we find much of what is now of concern to physical science oriented physiologists. How does a muscle utilize oxidative energy efficiently at low temperature to produce mechanical movement? Is the mechanism of color vision an antenna design problem rather than a biochemical one? How do crabs keep track of tidal cycles when isolated in a uniformly lighted room away from the sea? What is the oscillatory pulse code modulating mechanism common to vision, hearing, chemical senses and proprioception? Can we design control mechanisms with dual non-linear functions like those of the animal? How can we measure bodily functions accurately with the aid of biophysical instrumentation? Can we utilize artificial limbs in temporarily disabled biological systems? How can we find simple theoretical principles common to contraction, secretion, electrical generation?

In the last and most exciting category cane problems of brain function, conscious behavior, computer functions, and the whole amazingly effective multiple electric and chemical feedback and feed-ahead system which coordinates the animal, or the plant for that matter.

Biophysics promises to give back to physics and engineering, not only to borrow their theory. We are even now offering to electronic computer designers completely different and perhaps much simpler logical calculus for their machines. These promise imaginative and value judgement decisions in place of the present designs by which computers plod very rapidly.

There is more than a little chance that basically new integrative concepts in biological theory will arise which will make analysis of complex systems much more handleable and symbolically manipulable.

To form a relatively unbiased picture of what biophysicists do actually study, as against what they talk about over coffee or something stronger, let me read you a rough breakdown of the 224 papers read at the recent biophysics meeting.

Biological effects of radiation (ionizing and non—ionizing) 22

Bacteriophage, virus biophysics and specificity 21

Ultrastructure of biological systems 18

Instrumentation 18

Electrophysiology 13

Biophysical chemistry 13

Thermodynamics and molecular interactions 12

Biophysica1 transducers 10

Biophysics of genes and chromosomes 10

Electrocardiography 9

Circulation problems and hemodynamics 9

Biological transport 8

Analog computers 7

Biophysical feedback and control systems 7

Medical physics 6

Teaching of biophysics 5

Ultrasonic biophysics 5

Isotonic tracers 5

Bio-acoustics 4

Bio-ecology 4

Biological effects of electric and magnetic fields 4

Theoretical biophysics 3

Photosynthesis 3

Environmental biophysics 3

Muscle dynamics 2

Electroencephalography 1

History of biophysics 1

Extrasensory perception 1

In conclusion I would like to predict where I think biophysics is going in the coming decades. I believe we will find that biophysics will take a place similar to that of biochemistry midway between the physical and biological parent disciplines. It will be similarly autonomous but much more heavily armed with theoretical concepts and engineering applied science activities.

I believe that its greatest contributions to biology and medicine will be the discovery of sweeping quantitative theoretical generalizations akin to the great laws of physics but of a type most unlikely to arise spontaneously out of physical science and uniquely adapted to deal with biologically organized matter. These will contribute even more than will the vary valuable technological aids to medical science which are sure to appear.

The great contribution to engineering science will be the provision of knowledge and technology whereby the design ideas inherent in living stuff can be imposed upon inert matter for exploitation of our environment for human good and satisfaction of human curiosity. Much of our engineering technology is now really an extension of human faculties to the external world. Biophysics will provide the means to exploit this field effectively.