September 16, 1957
Dr. Robert Von Engen, Editor
Journal of the National Academy of Sciences,
Constitution Avenue, N. W.,
Washington, D. C.
I am taking the liberty of writing you this letter since I read your published volume, “Logical Control: The Computer vs. Brain” (Silliman Memorial Lecture Series, 1957), with the hope that you can perhaps offer me some advice and also publish this letter in the editorial section. Your mathematical viewpoint on the analysis between computing machines and the living human brain, especially the conclusion that the brain operates in part digitally and in part analogically, using its own statistical language involving selection, conditional transfer orders, branching, and control sequence points, et cetera, makes me feel that only you can offer me some information with logical arithmetic depth.
The questions raised in this letter are designed principally to reach the embryonic and juvenile scientists ... the scientists-elect, so to speak. (I think the “mature scientists” are irretrievably lost.) For many reasons, some of which will be explained in the following paragraphs, I think that it is of the greatest importance that some stimulatable audience be reached. As yet, the beginners have no rigid scientific biases and thus may have sufficient curiosity and flexibility about the world in which they live to approach experimentation with a mind devoid of “the hierarchy of memory registers which have programmed in erroneous data.”
What I have to say will not surprise nor shock you, or those who are at present engaged in scientific investigation. In fact, I have read many science-fiction stories that deal with the same problem. Perhaps that is the only way that it can be approached, through the medium of a story? Yet why not present it for what it may be? Let me tell it my own way, and then, please, let me have your coldly logical opinion.
As to my background, I am a graduate student in the Zoology Department of a midwestern university working toward a Master’s degree, or actually a doctorate--we can bypass the M.S. if we choose--in the field of Cellular Physiology. My sponsor is an internationally known man in the field. The area of research that I have selected is concerned with the effects of physical and chemical agents on the synthesis of nucleic acids of the cell. Obviously, this is a big field, and I hope to select from among the different agents, one or two that will give “positive results.” I have been doing active research for about half a year testing the different agents. As for the fundamental questions raised, I am positive that it would make no difference in what field of science I were to work.
By now I have had enough course work to realize that when performing any assigned laboratory exercise--they should not be called experiments--even of a cook-book type, little or even major discrepancies arise, and always on the initial trials, no matter how carefully one works! As you are probably aware, the teaching assistant in charge of the lab or the instructor, generally runs through the exercise before the class does in order to get the “bugs” out of it--I am deliberately generalizing, since the above holds for all of the laboratory sciences--so when the student gets confusing or rather contradictory results, the instructor can deftly point out the error in the setup or calculations, or what have you. He may even indicate what results may be expected. The last is critical. Similarly other students in the laboratory usually have friends who have had the course before and know what results are expected--this technique is frowned upon. Or one may consult textbooks and published papers. (This, by the way, is known as library research, and is generally conceded to be indicative of the superior student, especially if he points out the fact that he is so interested that he just had to delve into the literature.) By any technique, the expected results are always obtained. Always. And by everyone. The initial confusions--that some honest students perpetuate--are easily brushed aside as errors due to inexperience, sloppiness, lack of initiative, stupidity of congenital sort, et cetera, et cetera.
Since being a teaching fellow, even simple cook-book experiments don’t seem as cook-bookish. Some pretty weird things have happened when I tried out an exercise prior to the class. Fortunately, I was taught to keep data--in duplicate: indelible purple Hexostick original and carbon copy. These, vide infra, are a few of such happenings.
Elementary General Physiology Laboratory:
1. Initial maximal vagal stimulation:
Expected results: inhibition of heart beat.
Obtained results: one series of increased heart beats.
(Possible explanation: I missed the vagus nerve)????
2. Frog nerve-muscle preparation:
Expected results: a single muscle twitch.
Obtained results: a beautiful nerve twitch.
(Explanation: Eyesight? How can nerves twitch?)??
3. Hypotonic hemolysis:
Expected results: red blood cell destruction.
Obtained results: crenation.
(Explanation: switched salt solutions unconsciously)?????
4. Curarized muscle preparation:
Expected results: a synaptic block with no response of nerve when stimulated.
Observed results: a typical strychnine response, violent
tetanus, et cetera.
(Explanation: again, I switched bottles)????
5. I shall avoid the obvious mention of mishaps with mechanical or electrical pieces of equipment. I assure you there were similar deviations in initial attempts.
Since I realize that you are preparing a paper on Memory Registers: Stimulation Criteria, for the VIth Annual International Meeting of the Society of Theoretical Biomathematicians in London, and are short of time, I shall avoid going into the same kind of detail as the above for other Biology Labs, and get into the real heart of the thing ... the research problem. (After all that is what both of us are interested in.) By the way, please send me a reprint of the paper when it comes out.
I guess I am really hepped up on this, because I’ve just got to point out for emphasis other incidences usually of a type that involved missing a whole organ in dissections or a tissue structure in histology only on the first study, and then re-reading the assignment--after knowing what to look for--and subsequently finding it exactly where it is said to be. (Ever hunt for an unknown quality--or quantity?) So it was there all the time, sloppy technique? Or is this branching at a control point? cf. LC: C. vs. B. p. 251.
To get back to my thesis research, the pieces of equipment that I have been using in the research are fairly standard in physiological research: a Beckman spectrophotometer, a Coleman photometer, a van Slyke amino nitrogen apparatus, a Warburg respirometer, pH meters, Kjeldahls, Thunbergs, et cetera. Mostly, I’m in the process of getting used to them. Also there is a high voltage X-ray generator, U. V. source and other equipment for irradiation purposes. We also have an A. E. C. license so that we can get at least microcurie amounts of the usual isotopes for radioautographic work.
Now the literature in my area is pretty controversial. (You can appreciate that, especially since Bergbottom at the Kaiser Wilhelm Institute bombarded you with criticisms of your theories.) Different and actually contradictory results have been obtained for the same substance in the same organism, e. g. alkaline phosphatase in the frog liver cell (Monnenblick, ‘55, Tripp, ‘56, and Stone, ‘57). To give an example, when I start a run for respiration effects using a Warburg I don’t know what results to expect. Whenever this has been the case, my results have been confusing ... to say the least.
On nitrogen-mustard treated cells, in some instances the controls respired significantly more--even with a statistical analysis of variance--in some instances the experimentals respired significantly more; and in other cases the respiration for both was exactly the same--even closer than the expected deviations that should be found in any random population. One run, the blank run, containing no cells ... and grease-free ... consumed the greatest amount of oxygen. To cut this letter short, the same inconstancies apply to other trials that I have made. Whenever I didn’t know what to expect, and particularly where the literature was controversial, my results have been completely haywire.
Needless to say, I was not happy with this so I discussed it with other graduate students. They have all encountered the same thing! But most professors won’t admit this to be true and merely tell me that my technique is lousy. If anything, I am an overly careful worker. Why is it when I know what results are expected, I get comparable results even on the first trial?
Remember, I obtained the expected results when the literature wasn’t confused or when my sponsor--a most important man in my life--gave me a clue as to what kind of results to expect. Only then.
Now this is the heart of the matter ... The obvious explanation is the lack of experience. But, and this is what haunts me... what if those so-called contradictory results are meaningful? What if they were executed with care--and they were--and are not the results of sloppiness or inexperience? What if a nerve can twitch?
Very respectfully yours,
May 3, 1958
Dr. Robert Von Engen, Editor, Journal of the National Academy of Sciences, Constitution Avenue, Washington, D. C.
Dear Dr. Von Engen:
I would like to thank you for your encouraging letter and advice. I agree completely with your statement that science has a long way to go before we can explain the various inconsistencies that crop up in research. But I certainly can’t see how the letter is far too “unsophisticated” for inclusion in the Letters to the Editor portion of your journal. While your letter should have calmed me, I feel even more strongly now after a year of research about the matter than I did before. I have deliberately postponed answering your letter until I had more facts.