What Can We Learn From The Investigation Of Misconduct?

[Editor's note: Discussions of research misconduct are becoming more and more prevalent, in the halls of academic and research institutions as well as on the front pages of newspapers. But few in the scientific community have experienced the issue as personally as the six authors of the now infamous Cell paper, among them MIT's David Baltimore and Tufts' Thereza ImanishiKari. Since May 1986, when Margot O'Toole, a postdoc working in Imanishi-Kari's lab at MIT, first raised doubts about some of the results printed in the paper, three different investigations—conducted by MIT, Tufts, and NIH—and two congressional hearings have been held to probe into the affair. In the most recent hearing, held last month, Rep. John Dingell (DMich.), chairman of the Subcommittee on Oversight and Investigations of the House Energy and Commerce Committee, asked several people to describe how their institutions handled—or mishandled—the allegations brought by O'Toole. What follows are excerpts from the testimonies of key figures in the dispute. The comments are not intended to prove or disprove specific allegations, nor are they meant to provide any kind of overview of this one case. Rather, they are reprinted here to provide a glimpse into how scientists at the center of such a dispute do their jobs, how they see themselves, and how they are viewed by others; as well as to illuminate some personal elements of a bitter and protracted debate.] What It All Means David Baltimore, Director Whitehead Institute for Biomedical Research Mr. Chairman, there are many scientists here today who are concerned about this investigation and this hearing. They argue that it could have a chilling effect on science in America... I do not question the right of this subcommittee to conduct this investigation. I do not question the right of this subcommittee to demand accountability for government funding of scientific research. But I do question, in the most serious way, the manner in which this investigation has been pursued... I must tell you, Mr. Chairman, that I am very troubled about how this situation got so out-of-hand. I have a very real concern that American science can easily become the victim of this kind of government inquiry. So what is the case against us? That there are legitimate disagreements over the results of our work? This I recognize and encourage. That we were not as perfect as, in hindsight, we might have been? This I concede. That scientists keep notes in ways that are sometimes orderly and sometimes not? Of course. That we committed fraud, created data, or misrepresented the facts? This I reject categorically. The subcommittee can point to nothing that supports these allegations. I should like to reflect on what I have learned from this affair. First, having been forced to think through how scientific data is verified, I am committed more than ever to the classic mode of verification by scientific replication and further development. Second, I realize that, with the increased sensitivity about scientific fraud, it is more crucial than ever that scientists keep records that can easily be referred to, so that the scientific basis for published results is easily determined at any time. Third, it is important that the institutions that support science—the universities, the research institutes, and the NIH—respond quickly to any allegations of irregularities in the scientific process, and in a way that safeguards the reputation of those accused as well as those who accuse. Fourth, scientists and politicians must figure out a better way to communicate our concerns than through headlines in newspapers. Conflict Within The Lab Thereza Imanishi-Kari Assistant Professor of Immunology, Tufts University I met Dr. Margot O'Toole in 1985, and found that she was looking for a place to work. I knew that she had experience with biology techniques and especially with bone marrow transfers. Because our research results on immunogenetics could only be explained by cellular interactions, I thought that it would be a good idea to have a person experienced in those techniques. When I hired Dr. O'Toole in the fall, I told her that I was interested in her doing adoptive cell transfer experiments to test a hypothesis that came out of experiments later reported in the Cell paper. She agreed to do these experiments, but asked to do some additional experiments on her own. I agreed that she could do her own experiments as long as she also worked on the adoptive cell transfer experiments.... It wasn't a good start. Soon after her arrival, we began disagreeing about many things, like materials to be used in experiments, procedures, and who did what. Margot didn't want anybody else in the lab doing experiments related to hers. In late April of 1986 I decided to try to perform the adoptive transfer experiments myself, since Dr. O'Toole was having difficulties with the experiment and the quantities of reagents were limited. At this point, my relationship with Dr. O'Toole was bad, and soon we weren't even speaking to each other.... What It's Like To Be A Whistle-Blower Margot O'Toole, Immunologist The reaction of the scientific community to me and to the events surrounding my challenge clearly indicates that most scientists do not understand what happened, or why it happened.... The scientists remain focused on the science, Mr. Chairman, and many do not seem receptive to your criticism of the process. My case should demonstrate to them that the current process of adjudicating disputes of this nature simply does not work, and this is bad for science and for scientists. This case has been extremely painful for all involved. All of us wish it out of our lives.... My battle now is to make sure that those who follow me will get a fair and thorough hearing, that they will be allowed to examine the evidence and see the reports. Most of all, I want to see a process that does not require three years and five investigations before a report can be issued that does not fall apart on the basis of the available evidence.... I discussed at length with Dr. Rowe [of MIT] the professional consequences to me if I did as she recommended and brought formal charges. I had a nontenure track appointment at Tufts, and I had an opportunity to apply for grants as a Tufts researcher. If I pursued the matter further, I felt certain that Dr. Wortis [chairman of Tufts' investigation committee], who was very influential at Tufts, would seek to prevent my return. Dr. Rowe assured me that coming forward was the right thing to do, and that she would speak to the dean and the chairman and enlist them in making sure that a position would be found for me in an MIT lab.... After the meeting, I called Dr. Eisen [the professor in charge of the MIT investigation] and protested his failure to insist that false claims be corrected. I discussed specific scientific issues we had covered, but Dr. Eisen said that he could not remember them. He said that my continuing pursuit of the matter indicated vindictiveness. I called Dr. Rowe, who indicated that Dr. Eisen had made a verbal report to her and indicated that there were no problems with the paper. I reminded Dr. Rowe that she had said she would help me to secure another laboratory position. Dr. Rowe replied that I should have arranged the position before I had handed in my memo and that the time during which she could have helped me had now passed.... If any scientists doubt that I have been damaged as the result of my challenge to this paper, Task them to answer the following questions. When was the last time they hired someone who eminent scientists have described as one who purloins data and lies under oath? Who among them has ever hired anybody who reputable people say selectively copied notes to make trouble, or to support a particular point of view? Who would want someone who cannot accept an alternative interpretation of data, who cannot distinguish important issues from trivial ones, who does not accept the reviews of eminent and qualified reviewers, and who has unfairly besmirched the public's view of research? All these things are being said about me, and all these things are false. Mr. Chairman, anyone who tells you that my career has not been badly damaged, even irrevocably damaged, is insulting your intelligence. What I Want To Accomplish Rep. John Dingell (D-Mich.) Chairman, House Energy and Commerce Committee This subcommittee has examined a number of instances of proven misconduct that have not been handled well. The apparent unwillingness on the part of the scientific community to deal promptly and effectively with allegations of misconduct is unfair to both accuser and accused. Even more important, it impairs the conduct of research, its present and future value to other scientists, and its benefits to the public.... Some critics have questioned whether the Congress is the appropriate forum for examining the issue of misconduct and fraud in science. We are not here to judge whether the research was done correctly, and I hope that we will never be in a position to judge science and scientific research. But Congress authorizes approximately $8 billion annually for NIH alone, and it is the subcommittee's responsibility to make sure that this money is spent properly and that the research institutions, including the NIH, that receive these federal funds behave properly. This committee has far better things to do than to police science. One of my fondest hopes is that the institutions and the NIH will respond to the subcommittee's concerns and develop the incentive and the will to act properly. Other critics have claimed that the Congress is not capable of understanding science, or even raising questions about science. However, no one questions our capability when the Utah scientists demand $25 million for cold fusion experiments, or the Air Force asks for $70 billion for the Stealth bomber program, or when enormous sums are requested for a new accelerator.... I am well aware of the attacks on the subcommittee's activities by prominent scientists around the world who are unfamiliar with the facts of this case. Some have suggested that we do not know the difference between fraud and error. The jailhouses of this country can testify that this committee understands the difference. We know that error is inevitable in the process of scientific research. Congressional legislative efforts to prevent error would do enormous damage to the scientific enterprise. What these critics seem to ignore is that science makes progress by correcting its own errors, and that science is essentially a quest for truth. The refusal to investigate concerns raised by fellow scientists, and to correct known errors, is antithetical to science.... Very few in the scientific community deny that misconduct is a serious problem in science. But there is less agreement on exactly how widespread it is, and what to do about it. Institutions seem to have a real problem agreeing on how to handle allegations of error, misconduct and fraud. They are currently developing guidelines, but they must also develop the will to handle the problem m a responsible an6 timely manner. Three Views From The Minority Rep. Norman Lent (R-N.Y.) Ranking Minority Member, Energy and Commerce Oversight Subcommittee I share the concerns of my colleagues that oversight and criticism embodied in congressional inquiry should not interfere with the way scientific research is evaluated. Scientific disputes ought to be resolved not in the bitter and highly charged atmosphere of congressional hearings but in the halls of our nation's institutions of higher learning. If the scientific profession needs to judge itself better, let it do so. Surely, professional review panels need to follow some basic procedures to avoid subsequent questions of their impartiality and the comprehensive nature of their review, if government needs to demand such vigilance, let it do so. But we must do so with a sensitivity to the public's narrow understanding of complex research work and processes. America is becoming a science-poor nation. If we allow leading-edge scientific work to suffer because of misguided attacks and public efforts to discredit our best and brightest, then instead of encouraging sound research and informed debate by scientists, we will soon find ourselves with no scientists and nothing to debate or criticize. Rep. Thomas Bliley, Jr. (R-Va.) Member of Oversight Subcommittee I think that this entire investigation points up the fact that the scientific community is not immune to outside oversight and criticism, nor should it be. I too support the basic theme of this investigation-to examine how science deals with assuring the soundness and honesty of research. I have long maintained that our limited but massive research dollars are far too precious to waste on low quality, unreliable work.... I am concerned that the facts, as adduced by testimony at earlier hearings, will show only the complexity and uncertainty of pure science, and the difficulty of imposing external judgments on scientific work. What we should be asking is how far scientific research should be investigated for fraud. Misrepresentation may be present when results cannot be obtained repeatedly. But when research is carried out and reported openly, results verified by the same, similar, and different methods, and the conclusions drawn are logical, we must question whether this is not all we-can ask from scientists. Rep. Alex McMiIlan (R-N.C.) Member of Oversight Subcommittee As a congressional oversight panel, we purport to be legislative experts to determine the compliance with, or the need for, legislation. In my limited understanding of the scientific research world, I am concerned that the legalistic approach of the legislative process differs dramatically from the approach of scientific research. It is imperative that we remember this in reviewing, from a legislative point of view, the research and publication process within the scientific community. The Significance of the Paper David Weaver, Lead Author of Cell paper, Assistant Professor of Microbiology, Harvard University If there is one thing to remember about this study, it should be that the Cell paper is a good paper. Scientifically, it generated both some interesting findings and stimulated more hypotheses about the genetic control of the immune system. The work in this paper has been confirmed and extended by other labs, which I think is not only a measure of reliability, but also of interest. The paper also reflects the complexity of a biological system in that there were a number of possible explanations for our observations. This doesn't mean that our methods were wrong or that our logic was faulty. It simply reflects the scientific process in action. How Tufts Handled Its Inquiry Henry Wortis, Professor of Pathology, Tufts University School of Medicine We did not prepare any written report of our review until the time of the first NIH inquiry [almost one year later]. At that time, I prepared a draft, circulated it to Drs. [Brigitte] Huber and [Robert] Woodland for review and comment, and finalized the report. It is important to realize that we did not consider ourselves a formal review committee conducting an official review. We were acting as scientists, to review a dispute among scientists as to the conclusions of a paper. There were no allegations of fraud or misconduct.... The next time the matter was raised to me was when I received a telephone call from Mr. Walter Stewart in late 1986 or early 1987. He claimed to be interested in two questions: (1) whether the published findings in the Cell paper were supported by the original data; and (2) whether it was worthwhile that this question be answered. After questioning Mr. Stewart about his intended methods and procedures for conducting his review, I declined his requests as I did not believe his method for review was scientific nor that he was qualified to undertake such a review. On the Low Incidence of Fraud Louis Lasagna, Dean, Sackler School of Graduate Biomedical Sciences, Tufts University Tufts has always recognized that scrupulous honesty in the conduct and publication of scientific research is essential not only to the legitimacy of the results, but also to the integrity and reputation of the researcher, his or her collaborators, and the university. The advancement of learning, the protection of the public, and the prudent and effective use of research funds and other scarce resources devoted to scientific inquiry are all dependent upon the integrity of the men and women who produce and publish scientific data and analyses.... The intentional falsification of scientific research is indefensible and intolerable. Happily, it is also quite rare. In my five years as dean, no allegation of such impropriety other than the one which Dr. O'Toole has raised has come to my attention. On the Importance of Trust John Deutsch Provost, MIT We recognize the importance of being, and of being perceived to be, responsible custodians of public funds and to carry out our research and education programs in a manner which is both understood and supported by the public, elected officials in congress and the federal sponsoring agencies. At the most fundamental level, realizing the benefits of the scientific enterprise for society is only possible if there is broad public understanding and support for how science functions.... The history of this case impresses upon me, once again, the importance for academic science to explain how research is conducted in the university environment. The academic community and other legitimate participants in the scientific enterprise must be able to discuss serious issues without a sense of confrontation. Unquestionably, the issue of how science deals with allegations of misconduct will continue to be a matter of public interest. MIT intends to continue to work toward improving public understanding of how basic research functions and to be responsive to legitimate concerns about these activities. How it Looks to NIH James Wyngaarden Director, NIH We have learned a lot about the problems that must be faced in investigating cases as complex and technically advanced as this one. It clearly is important to distinguish between scientific error and misconduct, but such distinctions frequently are very difficult to make in practice. We must recognize that allegations of error may lead us to findings of falsification or misrepresentation, and we must also ensure that the procedures in place at both awardee institutions and the NIH do not require too high a threshold before a formal investigation is begun. On the other hand, we must not view every disagreement among scientists as a charge of misconduct which must be investigated. Scientific experiments often yield results with multiple interpretations.

What Can We Learn From The Investigation Of Misconduct?

The Scientist Staff

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