[Introductory remarks by Mary Jo Nye]

Frederic L. Holmes: Does contemporary scientific biography pose problems for the historian that are fundamentally different from scientific biography in general? The answer to that question depends on a number of subsidiary questions: Is contemporary science itself different from earlier science? Do contemporary scientists live their lives and practice their sciences in different ways? Does the scale, complexity, and organization of science in our time modify the way in which we can and want to treat the lives of individual scientists? Do such changes alter our criteria for selecting the scientists who merit the formidable task of producing a full biography? Is biography a less appropriate unit for illuminating the nature of creative scientific activity during our time than it has been to chronicle great deeds of the past?

Besides these questions comparing the intrinsic nature of contemporary scientific activity to that of earlier eras, we encounter questions concerning the records of scientific lives available for their reconstruction. We hear often that modern means of communicating and recording information drastically alter what we can learn about our subjects. Some lament the disappearance of correspondence, opining that the long distance telephone and the ubiquity of travel to conferences has eliminated the permanent traces of incipient scientific thought and exchange that we must recapture if we are to make meaning of the private and semi-private worlds behind the public performances of the scientist. Others hope that fax and E-mail, if the latter is not systematically deleted from our subjects' files, may one day restore the intimate glimpses of informal exchange once preserved for us through the letters of scientists, who could depend one hundred fifty years ago on conventional postal deliveries more rapid than those of our era.

Some historians believe that these differences create special problems for writing contemporary history of science that set it apart from the styles we have devised for writing the history of science and of scientists in the older periods in which our scholarship was once concentrated. Having worked on scientists of the eighteenth, the nineteenth, the early and the mid-twentieth centuries, I am convinced that these differences are not as deep as supposed, that the similarities in the lives and endeavors of creative scientists of all these eras are strong enough to justify common approaches. The complexity of scientific thought and practice, and the intricate networks of interaction between scientists today are, indeed, formidable challenges to historical interpretation. I believe, however, that these complexities have been great enough to saturate the historian's capacity to encompass them since at least the mid-nineteenth century. Moreover, the quantity and quality of source materials surviving to retrace the thoughts and actions of individual scientist have in the far, as the near past, varied so greatly according to the habits of the person and the accidents of preservation, as to overshadow the systematic differences in our access to such information across periods from at least the nineteenth century to the present.

There is, however, one difference so fundamental to the relation between the biographer and his contemporary subject, compared to the biographer and a subject from the past, that I would like to concentrate my attention exclusively on that: it is, of course, the opportunity for the biographer to meet and to talk with the scientist about whom he will write.

The most powerful effect of the living scientist on the biographer's work is his or her very presence. Having written both about scientists whom I have known only through written traces of their thoughts and activities, and those whom I have come to know personally, I can testify that it is a very different matter to construct a personality living only in the past, than to project into the past a personality whom, in a later stage of his life, one has come to know. Perhaps in our discussion we can dwell on both the advantages and the risks entailed in writing about a scientist whom one has come to know well through personal interaction, or with whom, if the interactions are successful and prolonged, one may have become a friend. Here, however, I want to move instead to the questions most often raised about such encounters: what kinds of information can we derive from them, and with what cautions should we use such information to reconstruct the life and work of our subject?

Some historians take the position that we should treat the recollections we can elicit from scientists with radical mistrust. Not only are memories unreliable, they say, but the scientist has a vested interest in projecting a preferred image, in concealing what would be unflattering to a biographical portrait. The task of the biographer, according to this view, is in part to penetrate the facade, to reveal the darker sides of the subject's character and past actions that the subject tries to hide from scrutiny. I have, so far, not found it necessary or productive to adopt such a strategy. If the biographer realizes, during the course of her interviews, that her subject is deliberately misleading or maneuvering her, she will, of course, have to find means to counteract such efforts, or give up the project. But I believe that it is best to begin with the expectation that a relation of mutual trust will evolve, and that from that trust will flow the information most meaningful for the reconstruction of a scientific life.

What kind of information? The simplest answer is that the goal of the historian is to find out things that are not already contained in written records pertinent to the subject. That requires knowing everything that has already been written down, whether in publications, diaries, laboratory records, correspondence, or scraps of paper. It is no easy task. In my experience, scientists tend, in answering questions, to repeat what they have previously written somewhere. Only if the historian immediately recognizes when this is happening can she nudge the interview past what she can find out elsewhere, to obtain those precious nuggets of information lurking nowhere else but in the recesses of the scientist's memory.

What kinds of information do we have the best chance to elicit this way, and what kinds are most pertinent to our efforts to reconstruct personal scientific activity? Naturally the answer varies greatly, not only because the qualities of individual memory vary, but the purposes of individual historians differ. I would like to concentrate, for the rest of my talk, on one type of memory that is very likely to be absent from the records the scientist leaves behind, and to be of considerable interest for scientific biography: that is, the details of time, place, and circumstance surrounding "moments of discovery." We want to know not only the reasoning behind the steps leading to the discovery, but the arrival of the unexpected insight or observation associated with it, the feelings attending it, the imagery of the place in which it occurred, the spontaneous response that followed it, and other details which only the person who experienced it can tell us. The appeal of such events is witnessed by the frequency with which we retell such famous episodes as Kekule's dream about the snake swallowing its tail, Darwin's recollection about having the idea of the principle of divergence while riding in a carriage, and similar dramatic instants.

Such stories, related in isolation, provide more drama than understanding. On their own they can mislead us into compressing creative scientific activity into moments of high insight unconnected with the daily investigative forays that constitute the texture of scientific life. Memory tends to reduce past actions to such peak episodes and to retain only generic accounts of the more ordinary events preceding and following them. Were we to rely on such recalled stories alone, we could not grasp their fuller meaning within the investigative pathway in which they were once integrated in time. Consequently, the historian must seek to incorporate these recalled moments into narratives constructed around other forms of surviving evidence. When she does so, however, she is apt to find that the fit is not perfect, that contradictions, inconsistencies, or ambiguities arise. The standard wisdom among historians in such cases is that one should treat the contemporary documents as more reliable than the distant memory, and to modify or discard the latter where it conflicts with the former. From my experience reconstructing narratives of such events, I have learned to question such assumptions. Contemporary documents are not transparent witnesses to historical truth, and memories, even when incorrect in details, still provide irreplaceable clues about the subjective experience of the original event.

In the remaining time I will illustrate my contention with two examples, one drawn from my completed study of the early career of Hans Krebs, the other from my ongoing study of the origins of the Meselson-Stahl experiment.

The discovery which established Hans Krebs as a promising young investigator of intermediary metabolism, and which remains one of his two most visible achievements, was that of the ornithine cycle of urea synthesis. Published in 1932, the cycle as he formulated it then remains today the outline around which that fundamental biochemical process is understood. In 1973 Krebs wrote a retrospective account of the discovery, which included the following brief description of what he called "the first crucial finding":

"So we measured the rate of urea synthesis under many different conditions, and these included the presence of mixtures of ammonium ions and amino acids. It was in the course of these experiments that we discovered the exceptionally high rates of urea synthesis when both ornithine and ammonium ions were present. The interpretation of this finding was not at once obvious."

In 1978, two years after I had begun extended interview conversations with Krebs, he recovered, from the widow of the research assistant who had carried out many of the experiments on urea synthesis in 1931 and 1932, the laboratory notebook which contained the full record of these experiments. It was not difficult to identify in this notebook the experiment which gave rise to this "crucial finding" about the effect of ornithine. Preceding it were a number of experiments in which the substances tested were intermediates in carbohydrate metabolism. We examined these pages of the notebook together in August, 1978. As we looked at these earlier experiments, Krebs commented, "I just looked systematically, whether any other substances had an influence on the rate. In the course of this, the ornithine effect came to light." A little further on he said, "It was just without any too specific ideas that we tested the effect of all sorts of substances. That was part of the general philosophy -- just to investigate systematically which substances influence the rate either as inhibitors or as activators."

When we arrived at the first experiment including ornithine, and I asked whether "this first one is already decisive?" he said, "Yes, that was striking." I noted that ornithine appeared suddenly in the midst of a series of experiments that seemed to be moving away from the amino acids he had tested earlier, and I started to ask whether anything might have happened to turn his attention in the direction of ornithine. He replied, "It may be that some amino acids we had in stock, others had to be ordered, and that the sequence of experiments was ... dictated sometimes merely by the availability."

When I began to reconstruct a narrative of these experiments, shortly afterward, it seemed to me that the pattern I found in the notebook record did not quite fit Krebs' memory that ornithine was merely one of the many substances that he tested systematically. Instead of testing a wide variety of substances, he had concentrated on a few, particularly the most common amino acids, under varied conditions. Even the criterion of availability seemed to make it unlikely that he would include ornithine by mere chance. The notebook recorded that it had been procured from Hoffmann-LaRoche. I was able to obtain from that company a catalogue for the year 1932, which revealed that ornithine was one of the most expensive amino acids in their stock. Because Krebs had a very tight budget, it seemed to me improbable that he would order it for no particular reason, in preference to a large number of cheaper amino acids that he had not yet tested. For almost all of the earlier experiments I had reconstructed, it had been possible to infer some motivating idea underlying it. I persuaded myself that an idea that he had already told me he had briefly entertained -- that one of the two nitrogen atoms in urea might derive from ammonia, the other directly from an amino acid -- might have led him to consider especially an amino acid, such as ornithine, which contains an amide nitrogen in addition to the standard amino group. I gave this as a "conjectural" interpretation, acknowledging that Krebs did not agree with it, and commented that "if my reconstruction is valid, it would be an elegant example of the way in which ephemeral hypotheses stimulate experiments whose surprising outcome overshadows the original motivation for performing them."

When Krebs read my paper, which appeared in Federation Proceedings, he wrote me, in June 1980,

"The paper stimulated me to think again and again on my mental processes in 1932, in particular on the background situation, which somewhat molded one's ways of thinking. What limited biochemical experimentation at that time was the availability of reagent chemicals, and to some extent experiments therefore depended on what one could buy.... You refer to this in detail, and in fairness to me state that my use of ornithine, according to my own recollections, was not inspired by a particular hunch. I still stick to this view but I look forward to discussing with you some novel aspects when we meet in July."

Our meeting in July added nothing significant to the situation. Krebs remained convinced that he had simply come across ornithine, but did not object to me presenting a different interpretation, because I had clearly indicated where we differed.

When I reconstructed these events in fuller detail for my book on Krebs, I decided that the contemporary evidence I had in favor of my interpretation was not decisive enough to conclude that Krebs' memory had been faulty. Any number of contingent circumstances, long since forgotten, could have made a small sample of ornithine conveniently available to him. It was also possible to think of plausible alternative reasons for making an effort to secure ornithine. I treated the episode, therefore, as an example of the historical indeterminism that the biographer must sometimes accept, even when he appears to have exceptionally rich sources of information.

I quoted from Krebs' letter to me, above, also because its tone indicates that he placed strong trust in me as "his biographer." It was a trust that I also placed in him, that he was telling me exactly what he remembered, not using me to convey a selective portrait of his past. Had I not trusted him so fully, I might have been inclined to treat his account of the ornithine effect as an effort to represent himself as a systematic experimentalist, unprejudiced by presuppositions. I might have presented, especially after his death, my interpretation as the more accurate account of the discovery. I do not believe, however, that my trust, or his trust, was misplaced.

As the foregoing account suggests, Krebs' recollections of moments of discovery in his early career were spare references to the essential circumstances. Though he recognized immediately the notebook record of the first experiment revealing the ornithine effect, that recognition conjured no further images of the time when his assistant, Kurt Henseleit first observed it, where he himself was, how he felt about it, or other associations that would return us to the scene of the drama. In this respect, the austere quality of Krebs' memory contrasted sharply with the vivid memories Matt Meselson conveyed to me concerning comparable moments in the experimental pathway which led to the Meselson-Stahl experiment.

Published in 1958, the result of the experiment that Matt Meselson and Frank Stahl carried out first in October, 1957, provided compelling evidence in favor of the replication of DNA in a manner compatible with the Watson-Crick model. By growing bacteria for a time in a medium in which the sole source of nitrogen was ¹⁵N, then switching abruptly to a ¹⁴N medium, they were able to label parental DNA by the greater density of its molecules, then, by centrifugation of lysed DNA in a solution containing a density gradient, to follow the distribution of parental atoms among progeny molecules. The DNA, they had found in earlier experiments, collected in a sharp band at the place along the density gradient where its buoyant density equalled that of the medium. In the experimental series published in their paper, these bands were located exactly where they should be, if DNA replicated by the separation of two subunits that were conserved through subsequent generations. One notices in ultraviolet absorption photographs that at each time interval after the first, there are two distinct bands (except the last two, which are composites obtained by deliberately mixing solutions representing different generation times).

In a personal memoir about the origin of this experiment Meselson and Stahl wrote in 1965, "The second and third experiments along these lines worked beautifully; so we renumbered them 1 and 2."

During my first conversation with Meselson about these experiments, in 1987, I asked him what had happened in the real experiment number one. He related,

"Frank had warned me not to go both from heavy to light and light to heavy in the same experiment -- [that is, not to grow bacteria initially in both ¹⁵N and normal media and to switch them respectively to the other] -- because I would confuse the tubes.... Well, I thought I could color code it and that everything would work out fine, and I would do it all at once, and I did. And I did it alone. And it was night when I got the results, and the result was that I had mixed up the tubes. I could tell that immediately, because there were three bands."

A little later I asked Meselson if he could remember "a definite moment when you realized that the result was going to be clear-cut and decisive?" He replied,

"When I developed that film, and saw those three sharp bands, I knew there had to be only two bands. I mixed up the samples, but seeing those sharp bands, particularly the one in the middle, I knew that settled it. And I remember I went yelling across the street to the party that was going on in the house."

The direct record of these experiments is less complete than that of Krebs' experiments, because the original laboratory notebook, or its equivalent, has disappeared. In 1992, however, Meselson recovered the centrifuge log and the ultraviolet absorption films associated with them. From these it is possible to reconstruct a reasonable approximation of the original investigative sequence. By comparing the films with the published series, I can identify with reasonable confidence experiment number one with a series of runs completed between October 23 and 30, 1957. The log shows that there was one previous experiment of the same type, carried out between October 15 and 20. If we assume that the log contains a complete record of the centrifuge runs Meselson conducted in this period then these must represent the flawed experiment whose result he described in the conversation with me. The notations for coding the centrifuge tubes can, in fact, readily be interpreted as indicating that the experiment included transfers from both heavy-to-light medium and from light-to-heavy. When I looked at the corresponding films, however, I could find none with three bands. After reflecting on the experimental design, moreover, I could not understand how mixing up the tubes could produce three bands, unless Meselson had mixed two lysates together.

During a discussion at which both Meselson and Stahl were present, I raised this difficulty. I had not found the three bands, and did not see how three bands on one film was possible, "unless you combined two lysates for the same centrifuge run." Stahl supported my position, commenting, "It's hard to get something with three [bands] ... [according to] our present understanding." We spent some time trying to imagine other ways in which Meselson might have mixed up the experiment that would have produced three bands. At one point Meselson asked, "Did I say there were three bands? I probably did, I don't remember ... maybe I dreamt that."

If the log and films in question are those from the experiment in question, then some part of Meselson's initial memory of the event must be inaccurate, but there is reason not to infer that he dreamt the episode as a whole. The centrifuge log corroborates two basic elements of his recollection: 1) preceding the first "successful" experiment was an attempted experiment of the same kind, sufficiently imperfect so that its results were not included in the published report, and 2) the notation for the lysate tubes fits an experiment run simultaneously from light-to-heavy and the reverse. Furthermore, the log record contains a clue to how we might adjust the story to reconcile it with the record, even while recognizing in the discrepancies evidence that memories are recreations, not mere retrievals of information from a fixed storage.

The experimental run that can be most plausibly identified with the events that Meselson recalled took place on Saturday, October 19. Besides the usual cesium chloride solution, the centrifuge cell included "0.010ml. GIIIB-15, and GI-15," a notation which suggests that Meselson intentionally combined two lysates for one run. If so, they probably represented lysates from the heavy-to-light directed portion of the experiment, one taken during the first generation time of the bacteria after transfer to the light medium, the other taken during the third generation.

On the margin of the log record there is a sketch of three bands, labelled heavy-heavy, heavy-light, and light-light, apparently in Meselson's hand. The developed film shows only two bands, whose separation suggests they are heavy and light, the middle one being missing. To reconcile this immediate record of the experiment with Meselson's memory, therefore, we need only to reverse the relation between his expectation and the outcome. While waiting for the completion of the run, he may have sketched the three bands that ought to have resulted from the mixture he thought he had put in the tube. This result would have been equivalent to the result he did obtain in the second experiment mixing lysates from generation 0 and 2, as shown in the second film from the bottom. It would then have been when he saw only two sharp bands that he inferred that he had mixed up the tubes.

This explanation comes close to rescuing Meselson's memory of this vivid moment of discovery, by showing that its essence fits the record; only a detail has been inverted, a common play of memory. There remains, however, a serious flaw: without the middle band, the result does not really settle the question at issue. We must, therefore, make the additional assumption that in his initial excitement Meselson read more into the result than was actually there.

Is this the most reasonable resolution of the difficulty, or should we conclude, as I was forced to do in the example taken from the ornithine effect, that despite strong documentation and the eyewitness account of the sole participant, the event cannot be unambiguously reconstructed? In that case, it was because Krebs did not accede to my attempted interpretation that I decided that the situation was indeterminate. In this case, Meselson has just read my interpretation, and we will find out during the discussion what his response will be.

Skeptical historians might use these examples as arguments against the use of personal recollections voiced long after the event -- they might assert that the discrepancies between memory and record demonstrate the unreliability of the former. But where else are we to find access to these intimate events in the life of the investigator? In neither case would the record, by itself, have revealed that any such thing had occurred. If we exclude the testimony of our subjects, we lose a dimension of scientific experience that is deeply human. Meselson told me that when he saw that film in the dark room, late at night, "It was a mystical kind of thing, just to see it there." I am persuaded that, whether or not we can reconstruct perfectly the circumstances surrounding it, the mystical experience was real, and that it should find its place in a historical account of the origins of the Meselson-Stahl experiment.

I want to leave the last few minutes of my allotted time for Matt to comment on what I have just said, but I must first make one general remark on the reliability of memories that can be elicited through conversations of the type that I have been describing. It should be clear that I am more optimistic than some others. When there are discrepancies, we need not discard everything. I have been impressed, in my encounters with the memories of scientists who have talked with me, at the large amount of the information they have conveyed that has proven, when checked against available records, remarkably accurate. I have, however, been somewhat shaken in my confidence recently, when I happened to become the subject for such an interview. In connection with the possible republication of some of my papers on the history of chemistry, one of my colleagues, who is preparing an introduction, asked me a series of questions about my early life as a historian. In the first encounter I confidently related episodes I have long harbored that encapsulate in my mind formative stages in my intellectual development. At the second encounter, my colleague had done some homework, which not only uncovered some problems in what I had previously told him, but pressed me to fill in blanks he had found between my little stories. I found myself nearly helpless to go beyond my packaged memories. There was one whole year of my graduate education to which I could not attach a single remembered event. When he suggested a possible reason for my having taken up the subject that became one of my first publications, I could not easily decide whether to accept it because it was plausible, to reject it because I had no such recollection, or disappoint him by saying I had no idea whether it was right or not. Unsettling though that experience has been for me, I will go on attempting to elicit useful information from the memories of the scientists about whom I write. If we are to do contemporary scientific biography, we have no other choice.

Postscript

The discussion planned to follow my paper could not be carried out, because Matt Meselson had to leave the conference prior to the session at which it was to occur. As a substitute, he read the paper the night before, and left his response in a note to be incorporated into John Heilbron's commentary. Just before his departure, Meselson explained to me why he thought my interpretation could not be right, and offered an alternative. I was quickly persuaded that his objections to my reconstruction were correct, but thought that his alternative was also insufficient. Several weeks later we met in Cambridge, with all of the documentary evidence before us, and spent more than three hours attempting to construct an adequate account of the experiment. It proved impossible to infer unambiguously the meaning of the notations on the tubes or to reconcile fully the experimental results with his memory of the event. We did agree, however, that the films contain the first indications that the experiment would be successful. The case seems, therefore, like the corresponding event in Krebs' ornithine investigation, to be an example of historical indeterminacy. There are at least two plausible interpretations, each of which preserves key elements of the situation but not all of the remembered details, and insufficient evidence to choose between them. We intend, nevertheless, to search further for some clue that may unlock a more complete solution.