QUANTITATIVE ANALYSIS FOR PREMEDICAL STUDENTS OLAF BERGEIM University of Illinois College of Medicine, Chicago, Illinois
QumTmATIvE analysis is a part of the premedical course as now required by most medical schools. Certainly we have been able to do a much better job of teaching clinical and biological chemistry since this requirement has been in force. A considerable amount of quantitative work is carried out in the medical school in the courses in biological and clinical chemistry. Quantitative methods are used not only as training in the technique of such methods but because quantitative experiments in biological chemistry are frequently the most instructive. In studying an enzyme action or carrying out a functional test on a human subject, a knowledge of the quantitative relations is quite essential. The time allotted for the teaching of biological chemistry in medical schools is small compared with the large territory that must be covered. We feel it important that we should not have to spend too murh time in teaching methods. We are, therefore, concerned that our students should have had good premedical courses in quantitative analysis and are interested in any attempts that may be made to improve such courses. Fortunately, I believe that teachers in medical schools are as well satisfied with the teaching of quantitative analysis in the premedical courses as they are with the teaching of any premedical subject and t,hat this is due to the generally high level of teaching in this field. That the teachers of quantitative analysis are awake to the possibilities of such improvements, as are always possible in any course, seems clear from the very fact of the existence of this symposium. Only the actual teachers of quantitative analysis fully realize what it is possible to do and what it is not possible to do in the way of change without losing more than is gained. As I have indicated, I do not'think there is any d e mand from teachers in medical schools for any radical changes in the coumes as given. We all remember the discipline we ourselves obtained in our first courses of quantitative analysis and with much thankfulness in retrospect. We got a new viewpoint and not in chemistry alone. We doubt that less rigorous treatment would have given it to us. Nor do we feel that the needs of the premedical student are too much different from those of the prospective chemist, chemical engineer, or graduate in home economirs. All need, first of all, a firm grounding in the
theoretical bases of quantitative analysis, resting as they do on a thorough grasp of general chemistry. All need the experience of developing technical facility. All need to learn the meaning of accuracy. All need to be able $0 estimate the limits of accuracy of the procedures they employ. All need a thorough training in chemical calculations. In achieving these results the capability of the teacher will be more important than any particular program. It is, of course, true that the prospective chemist, or chemical engineer, will need work beyond a first course to develop his proficiency in various types of analytical work. It is also true that in some cases it may be desirable to give different courses to the two groups, because the chemists have had more introductory work in general chemistry and qualitative analysis. But it does not seem to me that the courses in general should be very different or that they need necessarily be dierent a t all. In such analytical training we all recognize the essential role of gravimetric analysis. Nothing can take the place of the grounding in the techniques involved and in the use of the balance that gravimetric analysis gives. Nothing can give the same sense of what accuracy means. The student must, therefore, achieve ability with gravimetric procedures. This is true in spite of the fact that the premedical student after completing his course may very well never again run a gravimetric determination. Such determinations are quite commonly omitted even from biological chemistry courses in medical schools, and are not a t all likely to be run in hospital training or medical practice. Whether on this account something less than half of the course time should he devoted to gravimetric analysis, I do not know. Gravimetsic analysis is naturally time-consuming and the time alloted to the average course is veiy short. If teachers of quantitative analysis feel that the general values of gravimetric analysis to the student can be achieved a little sooner, this would be desirable in leaving time for obtaining familiarity with procedures that are more likely to be used in the medical school. From this standpoint, volumetric analysis must hold the primary place because of the simplicity of the apparatus and the rapidity with which determinations can be carried out. The usual work on acidimetry and alkalimetry, with preparation of standard solutions and studies of the choice of indicators, is obviously in order, even though the student later on be able to avoid the necessity for preparing his own standard solutions.
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Volumetric methods are, of course, widely used in biological and clinical chemistry and the essentials of proper manipulation must be well instilled. The development of colorimetric methods of analysis has been a special feature of biological and medical chemistry. This has been largely because of the need for determining biological substances in very small amounts beyond the range of the usual titration methods, or which could not readily be isolated from interfering substances to the extent necessary for such titration methods. As a result, biological chemistry, as well as clinical chemistry, has largely become colorimetric chemistry. At times some of the colorimetric methods developed have not been soundly based and have somewhat tended to discredit this type of procedure. In general, the colorimetric methods have not been of the highest accuracy. This danger has been somewhat counterbalanced by the fact that estimates on biological materials usually have inherent errors due to biological variations rather than errors in analysis. I t has therefore not been so much a question of whether a method was extremely accurate as whether it has given comparative results. Serious errors may, however, readily creep into colorimetric analyses and a familiarity with the possible difficulties is an essential part of training in these methods. So it is not quite safe to say that if a student can run a good titration be will have no trouble with a colorirneter. It seems to me that some brief familiarity with the colorirneter should be a part of any course in quantitative analysis. A single good colorimetric determination with proper consideration of underlying theory and technical sources of error might be sufficient. The popularizat~iou of the spectrophotometer in analysis has greatly extended the usefulness of the principle involved. Determinations can be made in the presence of extraneous coloring matters that would interfere with visual comparisons. Accuracy has been improved and subjective errors of reading removed. Time has been saved. Comparisons in the ultraviolet or of colors too faint to be measured with the eye are possible. A constant expansion of the application of the spectrophotometer to reactions in biological materials is proceeding with no sign of a let up. It has become one of our primary tools. I t seems to me that the student of quantitative analysis should be familiar with the principles involved and the possibilities present and have enough familiarity with the apparatus used not to be afraid of the name spectrophotometer. Spectrophotometers are coming more and more into use in rontine analyses in hospital laboratories. With improvement of instruments for the measurement of fluorescence, it is probable such measurements, because of their delicacy, will find a greatly increased use in biology where we are always concerned about developing procedures of greater and greater refinement. I t seems to me also that some use might be made of electrometric methods in volumetric analysis, including oxidation-reduction titrations. Oxidation-reduction po-
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tentials form, of course, the basis of most of the metabolic changes occurring in the body. The student should also have some familiarity with methods of determining hydrogen ion concentration. Hydrogen ion concentration and its regulation, involving in particular the action of buffers, are of fnudamental importance in biology. Ability to use a glass-electrode pH meter would be desirable. Much of this may well be within the province of the course in physical chemistry which is also now largely required of premedical students. Some of these courses, as given to premedical students, are abbreviated often a t the expense of the work on ionic solutions, which is of such importance in understanding life processes. Some correlation between courses in analytical chemistry and physical chemistry on these points would be desirable. Manometric and volumetric gas analysis methods are also of great importance in biological chemistry. The Warburg apparatus is one of our foremost research tools. The Van Slyke manometric apparatus is widely used in blood and tissue analyses of clinical importance. Determinations of the carbon dioxide combining power of the blood are a routine clinical procedure of great value. These methods are either carried out by our medical students or demonstrated to them. It would be helpful to us if our students had even a little previous understanding of the principles of a gas analysis apparatus of the general type of the Van Slyke instrument In biological chemistry the widest range of analytical procedures is employed. The lazy biochemist is likely to prefer quantitative methods that are not chemical a t all, as in the microbiological estimations of amino acids and certain vitamins. In fact, our students of medicine run such a test. In some cases, of course, bio-assays, using mice or larger animals, are the only methods yet available. It is obvious that a first course in analysis cannot cover the wide variety of methods that the biochemist finds it necessary to employ. The student should, however, realize what a wide variety of physical and chemical principles are utilizable in analytical work. The emphasis in biological work on microanalysis of blood, etc., suggests also that it would be helpful if the student understands to begin with something of the special techniques and precautions involved in the reduction of the scale of an analysis. Such reductions in scale are, of course, coming into wider use because of the saving in space and expense, even where the sample for analysis is not limited. Thus, me commonly use micromethods for urine analysis, although macromethods give a t least as good results. The students should be taught something of the use of isotopes as tracers in chemical investigations, but I am not sure that the course in quantitative analysis is the place for them to get it. It has been asked whether emphasis in the course should be on laboratory practice or the basic principles of analytical chemistry. We are, of course, interested in the laboratory practice since there is no other course
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that will give this training t o the same degree. The basic principles are also of importance not only because they underlie the analytical procedures hut because they furnish a review and amplification of the principles of that general chemistry which is so important for an understanding of bodily processes. As to whether more organic analyses should he included in the course, I do not, see that the techniques involved are sufficiently different to make this a matter of importance. We do determine more organic than inorganic substances, but after all, each organic substance presents a special problem. I t does not seem wise in a first course in analytical chemistry to run through methods which are as inexact as many organic analyses are. After they graduat,e from medical school a few of these students will go int,o research work in which they will personally carry out analyses. These few deserve
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some consideration in course planning. The great number of medical men, even as internes, will not personally do any quantitative work. It is, nevertheless, important that they should he able t o appreciate what accuracy they have a right t o expect in such analyses as their practice requires. They should have some basis for a cyitical view toward the information that is supplied them and also not expect impossibilities of the analyst. They must realize how much time and effort certain analyses involve, so that there will be fewer requests for determinations which do not warrant the expense. Rut it is still as a part of the general education of the medical man, rather t,han in the development of any knowledge of particular methods, that the value of qnantitative analysis lies. Something of the quantitative idea he has gained should persist throughout his later work.
