Misconduct Case Stresses Importance Of Good Notekeeping

"It should be painfully clear to every scientist now that if they have good record-keeping habits, they're not going to get themselves into that kind of bind in the future," says Howard M. Kanare, manager of chemical services for Construction Technology Laboratories in Skokie, Ill., and author of Writing the Laboratory Notebook (American Chemical Society, Washington, D.C., 1985). Keeping a good notebook is a skill that goes with the territories of science and cuts across all boundaries. "Students need to keep good lab notes because they are going to use their notes in the future to pass classes and may use them as references for their dissertation," says Kanare. "For the industrial scientist, meticulous notes are essential for documentation with regard to patent protection. And, for other industrial or academic researchers, carefully kept notebooks not only provide documentation of work, but also improve productivity, effectiveness, and efficiency." Says Mountcastle, "It's just impossible for me to see how a scientist can order his or her work without extremely careful protocol-keeping. The primary reason for keeping good notes is scientific, and being able to prove what you've done, actually, should be secondary." Nevertheless, in this era, when science is virtually exploding with new information and competition is stiff, being able to prove what you've done in a notebook that is neat, ordered, and appears credible to an outsider is becoming more and more important, if only from the standpoint of maintaining public trust. Yet scientists are "notorious for not being good record keepers from the standpoint of legally enforceable and acceptable documents," says attorney and former research chemist Walter Buting, chief patent and licensing counsel for Genentech Inc., a biotechnology firm based in South San Francisco, Calif. Every busy scientist knows the difficulty of finding the time to be diligent in record-keeping. Kanare suggests to young researchers that the sooner they begin to make it a habit, the better off they are. "If you're not used to taking the time to think about what you're doing and write it down clearly for other people to read, it will only become more difficult as you progress in your career," he says. Two-time Nobel laureate Linus Pauling recalls that he began taking "meticulous" notes while in graduate school. "Dr. Roscoe G. Dickinson [a professor of chemistry at the California Institute of Technology, now deceased], who was teaching me X-ray crystallography, gave me a large, bound laboratory notebook and showed me how to introduce data," Pauling says. "He suggested that the thing to do was to introduce the data at the time they were taken--not write them down on some other piece of paper and later transfer it." Pauling later recognized that it was "a good idea" to date every page of the notebook, to write down the city in which the work was done, and to sign every page. For years, Pauling says, he's instructed his students and associates to follow suit. The basics of keeping a good notebook are relatively simple, Pauling and others say: write in a permanent ink; be thorough and objective as you enter data directly into a bound notebook; time and date the entry; identify the place or lab in which the work was done; sign every page; and, for new findings or critical experiments, have a witness sign and date the log. The particular methods and requirements used to document scientific research do, however, vary from field to field and from institution to institution. At the Cancer Research Institute at the University of California Medical Center, San Francisco, all researchers and technicians in the lab headed by AIDS researcher Jay Levy, a professor of medicine, are required to keep standardized laboratory notebooks. "In those, they write down the experiment number, the date, the title of the experiment, the protocol. Then you give a number to the culture or experimental material you're using, and follow them over time," he says. Researchers make notes on any changes they see in the culture as well as write periodic reports when they change the media of the culture. Levy instructs those working under him to make their observations and entries as clear as possible. "One thing I mention is that we don't know what's going to happen if you disappear, and we need to be able to read your notebook and know what you did so we can continue on." Researchers leaving his lab are required to turn in complete, up-to-date notebooks on what they've done, a common practice in the research community. "While the original notebook stays with us," Levy says, "the scientist can photocopy his or her notes and take them" to his or her new job. While it is the responsibility of individual scientists to maintain their own notebooks, supervisors and heads of labs are responsible for making sure the notebooks of those under their direction are in order. For Levy it hasn't been too arduous a task: "I might have to tell a technician once in a while to be neater in writing down notes, but otherwise I haven't had any problems." Pauling doesn't check the notebooks of all the researchers at the Palo Alto, Calif.-based Linus Pauling Institute--that, he says, is the job of the director of research. Nevertheless, he does keep "an eagle eye" on those with whom he collaborates. "Recently, I decided I should check the notebooks that one of our experimentalists kept to make sure that statements we're making in an upcoming paper on heart disease were compatible with the experimental record as recorded in the notebook," he says. "That's what Baltimore should have done--that, I think, was his duty." Although neatness--at least in terms of legibility--counts, it is not always the most important concern. "If a mistake is made when you're doing an experiment, you should simply cross it out and put in the correct calculation, and not worry about making it aesthetically pleasing," advises Pauling. In fact, when it comes to Food and Drug Administration (FDA) regulations for conducting toxicology studies--Title 21 of the Code of Federal Regulations, Part 58, known as "Good Laboratory Practices, Nonclinical Laboratory Studies"--any changes that are made cannot obscure the original data entry and must be accompanied by a reason for the correction or change. These rules apply to any person or company working on an FDA-regulated product; anyone seeking market approval for his or her product must follow these regulations, and documentation must pass inspection. "In other words, these guidelines are not just guidelines, they are regulations promulgated by law," says Paul Lepore, coordinator of the FDA's bioresearch program. "Quality and integrity are the two things that I would apply across the board," says Lepore. "The two concepts associated with integrity are that the data is the same no matter where it appears and that data sources retain the same identification no matter where they are"--various organs from a laboratory animal, for example, should retain the same ID number as that animal. "Quality is a matter of accuracy and consistency, but it's also a matter of permanent record, something written down that won't fade." At Genentech, for example, the guidelines are "pretty standard," says Buting. "Basically, it's a matter of asking the researchers to record on a daily basis what they're doing, in ink, in some kind of permanent form, preferably a bound notebook. If it's something that comes off a machine, then preferably they affix it to a page in the notebook, and have it dated and witnessed." The Genentech guidelines differ from those of some other companies in that, Buting says, "we require that it be witnessed by someone who is not part of the same project." Buting stresses the importance of immediately recording notes in their proper place. "There's a tendency to record things on the handiest piece of paper available--looseleaf pages, for example, and even on towels," he says. "All researchers and scientists should develop the habit of recording data as they're being done and on a permanent basis." The collection method changes, however, from field to field. Theoretical physicist Alan Guth of the Massachusetts Institute of Technology, for example, writes his calculations on looseleaf paper daily. "While I sometimes collect them in a notebook, it's more likely that I keep them in an order that's determined more by logic, as opposed to chronology, so I can locate them easily," he says. "If, for example, I go back and extend a calculation I did two months ago, I would probably put those pages with the earlier pages, and they usually end up in folders in my filing cabinets." In other fields, computer technology is changing the entire concept of the laboratory notebook. "You can't possibly keep notes by hand now in the work that I do, because it goes too fast," says Mountcastle. In his neurophysiology lab at Johns Hopkins, a continuous protocol is run during experiments on a second or third computer, a duty that is assigned to a specific person. "In that, we insert descriptions of everything that's done, as well as the titles of all computer runs, and we print it out at the end," he says. Since the team is dealing with numbers, any error in writing them down can be devastating. "So, at the end of each day we cross-check the numbers of the computer files with the protocol and what we actually stored." Additionally, Mountcastle says, "we keep detailed notebooks on the training of animals, which are a separate set of notebooks called a training protocol." Like many scientists, Mountcastle keeps as many of his old notebooks as possible--not just for posterity's sake, but for their research value. "I keep the notebooks of every experiment I've done for nearly 20 years," he says. "You don't often consult the old ones, but sometimes they're absolutely critical. For example, one of my younger colleagues is now taking up work on the parietal lobe, which I stopped about five years ago, and some of the old notes are of great value to him." In the field of particle physics, notekeeping is rarely as simple as one or two scientists, or even a small group, keeping one notebook. Usually, there are dozens--sometimes hundreds--of scientists working on any given experiment and contributing to the documentation. "I was in the lab the other day and looking at the standard books we keep, and was wondering what they [outside investigators] would think of them if anything ever came to an issue," says Leon Lederman, a professor of physics at the University of Chicago. In experiments such as those Lederman is working on currently, involving the properties of quarks, the actual data are recorded not in lab books, but on magnetic tapes. "In particle physics, we have electronic data-acquisition systems, which receive information from the bombardments that are taking place in the apparatus when the accelerator is on," Lederman explains. "That data is usually digitized, encoded--and appears on the magnetic tapes as a whole bunch of ones and zeros. It's very abstract data, and the ledgers are large and thick, and we go through at least a dozen of them for any given experiment. It's voluminous stuff." While these ledgers list the tests conducted and are full of information about the experiment, very little of the actual data that the experiment delivers is in that book. "The data can be called up, but I would defy the guy who doesn't have a Ph.D. in physics to make anything of it without spending enormous amounts of time," Lederman says. What becomes critical in this situation is that all the researchers realize the importance of the notes they take, since their work reflects on everyone s. "These experiments are really an orchestration of people from many, many different institutions, and because the experiments are so complicated you need this critical mass of people to operate the experiments. Therefore, they must be team players, and leaving proper, detailed notes is a part of that," Lederman says. While handwritten notebooks remain the standard, particularly when patentable matters are at issue, electronic notekeeping is quickly becoming a reality. Says Kanare: "The principles that apply to handwritten records in previous years still, and will, apply to computerized records: They should be timely, contemporaneous with the actual event, clear and complete, [and] copies should be printed out and signed by a witness--even though it may not be bound into a notebook." The problem is how to protect the work. While systems have been developed that will time, date, and allow scientists to sign their notes, there's always the chance somebody could access a particular re-searcher's digital signature file. "That comes down to human nature: No matter what system you develop, there are always going to be people who won't use it or who will get around it one way or another," says Kanare. Howard Kanare, author of Writing the Laboratory Notebook (American Chemical Society, Washington, D.C., 1985), suggests the following tips for ensuring accurate records of lab work: 1. Describe the work objectively and completely so that it can be understood without additional explanation. 2. Make sure each section has a clear, grammatical heading that describes the work reported. 3. Write all entries in the first person, and be specific about who did the work. 4. Write entries in ball-point pen or a permanent ink. 5. Make sure handwriting is clearly legible and that numbers and symbols are unambiguous. 6. Make sure the notebook's table of contents is up to date. 7. Sign and date each entry. 8. Think in your notebook--enter ideas and observations immediately and directly into the book, not on scraps of paper to be transcribed later. 9. Make sure the entries are witnessed. 10. Store the notebook safely when it is not in use. --A.J.S.R. Kanare suggests that a government agency, similar to, say, the Library of Congress, be established for documenting, filing, and protecting the work of scientists. "You would [send] your document over a modem, then run it through an algorithm, which [the agency would] spit back to you with a check sum, or code, that is dated and stamped and could only have come from them," he says. Levy is one scientist who is resisting the idea of the electronic notebook. "When you have all your data stored in a computer, what happens when it breaks down and you lose it?" he asks. "Some of my people do use computers, but I have been pretty strong in saying that there's nothing like written-out notes and comments." Computers are impacting note-keeping in other ways, as well. "At a time when we'd like to be reiterating how important it is to keep complete records, the movement in many schools is to work computers into the curriculum, so the student may no longer be performing a titration with a burette and colored indicator and writing down the weight of the sample, et cetera," says Kanare. "Instead you have an automated instrument that prints out a finished report, so while it's as important as ever to have these complete records, there isn't the attraction for the modern student to sit down and write." Whether it is done electronically or manually, keeping a good notebook is the responsibility of all scientists, those working alone and those functioning as part of a team. Inevitably, there will be glitches. "Anyone who deals with more than one scientist is going to have problems, and it depends on theindividual as to how severe the problem might be," says Buting. "If you're lucky, the problem is not going to arise in a case where you're in litigation on an important subject matter"; rather, he says, difficulties generally lie in situations in which "the conformance to good record-keeping of scientists is not very high." "There have been millions of dollars won and lost because of poor record-keeping, but companies will not talk about it," says Kanare. "One of the things that judges have looked for in the past is proof of a chronological record--if there's a bound notebook, a consistent way of keeping the notes, and the experiments clearly follow one another. That paints a picture as a whole that is credible," he says. Another point to consider when maintaining a notebook is the historical value. Kanare, who is an admitted chemistry history buff, says, "There is nothing more fascinating than sitting down and looking at someone's handwritten notes, notes they took at the instant they actually discovered something." As scientists move through their career, they need to approach their notekeeping with thoroughness as well as flexibility. The kind of work a scientist does will inevitably change; consequently, says Kanare, one needs to be able to shift gears. "It is critical to record everything that happens, especially when you're working on something new and original, because you never know when something will happen that will give you a clue that you'll come back to a few weeks, months, or even years later and discover it was a significant observation," he points out. However, it isn't always necessary to keep intricately detailed notes of such things as routine experiments. "For routine tests that someone can pick up and still follow by referring to a reference, it's not necessary to write out every detail," Kanare says. "For example, a scientist might write, `I performed ASTM [American Society for Testing and Materials] test number C-1084...' The person reading the notes can then pick up the ASTM volume and follow that test." Normally, for work that could potentially involve litigation, a scientist probably doesn't want to speculate in the notebook or write conclusions about the research being conducted--unless all of the work is done. "On the other hand, if you're pursuing a new type of material for a patent or manufacturing process, it's appropriate to speculate wildly [in writing] for what it might be used for," says Kanare. The importance of keeping thorough documentation simply cannot be stressed enough. "No one can hide in science," says Mountcastle. "No one can deceive anyone permanently, because people are always doing new experiments. What is false or what might have even been a case of fraud is always finally exposed. Sooner or later the truth always pops out." A.J.S. Rayl is a freelance writer based in Malibu, Calif.

Misconduct Case Stresses Importance Of Good Notekeeping

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