A brightly lit, sterile-white lab opens the scene. The latest technology shines from all corners of the room. Scientists in white lab coats and glasses concentrate with furrowed brows on microscopes. They talk. They laugh. They cry in frustration. Failure after failure results in tempers lost and emotional strain. They furiously scribble failed attempts and minor successes. The tension builds to a climax of scientific proportions. The scientists become so desperate they consider experimenting on themselves, blowing up the lab or killing their best friend, but finally in one “Eureka!” moment, the researchers discover the secret formula to the complex question that will save the day.
Or so it goes in the movies. Real-world laboratories aren’t quite as easily caricatured. Each research laboratory, whether it is a private lab or a university lab, has its unique climate and purpose. According to David Lim, M.D., executive vice president of research and head of the Gonda Department of Cell and Molecular Biology for House Ear Institute (HEI), “Different investigators have different ideas about what would be the ideal laboratory.” With that caveat, here are some of the essential elements of the research lab – the behind-the-scenes inner ticking that makes innovations in hearing and balance science possible.
The People
“In my opinion, to have a very successful laboratory, you have to have very good people,” says Lim. “My wife always says in order to make the best steak you have to buy the best beef. And if you don’t buy the best beef, you are not going to make the best steak.”
As a recruiter for the Institute, Lim likes to enlist the very brightest post-doctoral fellows for the private sector molecular otology laboratory at HEI. “They come from an M.D. or Ph.D. track,” he says. “Some of them are physicians who want to take time off to do research and then go back to practice. The Ph.D. is a researcher that will spend his lifetime in the laboratory doing research, or teaching. ... There are only select people I keep. They are outstanding. They can be promoted to independent scientist positions. … Most of the other fellows go back to teaching or another fellowship or go to industry. One important thing about a fellow, I always look at intellectual curiosity. If a person doesn’t have intellectual curiosity then he won’t make a good researcher.” According to Lim, who has over 120 people reporting to him, a researcher can expect to spend anywhere from two to seven years or more in a single lab depending on the path he takes.
Yehoash Raphael, Ph.D., professor of otolaryngology and director of the Otopathology Laboratory at Kresge Hearing Research Institute of the University of Michigan in Ann Arbor, agrees and elaborates: “The basics are to have excellent personnel (talented, dedicated, motivated, skilled), adequate and appropriate space, a feasible and interesting line of research topics and funding.”
In the university realm, Raphael, whose lab staff fluctuates from eight to 12 people, has a different staff in mind: “I like to keep my lab relatively small, so I can be involved with all the projects, help design experiments and evaluate data. I participate actively in data collection and writing publications, in parallel to training students. It is important to have people at several levels, from visiting scholars and fellows all the way to undergraduate students.” His ideal lab staff includes some research assistants (career technicians) who Raphael calls "stable elements," transient staff (students of all levels) and additional collaborators (those who come in to use the equipment and work along with lab personnel).
Raphael also emphasizes the importance of the principal investigator’s (PI) personality. “It is important to match the PI personality with the staff. A PI who likes to strictly manage attendance and performance needs people who can handle that. “Some people, like me, are more permissive and so if I were to work with people that are not motivated and are just trying to waste my time, that’s not a good match. The degree of distance versus a close personal friendship between PI and staff/students is also important and needs to match the PI personality. The personality of the PI is constant. The choice of staff is an important variable.”
Does changing out the lab staff upset the balance of the work? Not according to Lim. “Before we select a fellow, we evaluate her background. Sometimes she brings a new background and a new perspective to the lab … It is good to have some rotation. The downside of losing someone’s perspective can be a problem but also there’s a positive side, which is bringing in a new mind, a new brain, a new skill.”
The Interface
Proximity to the clinical world is essential to a well-functioning laboratory according to Raphael. “Because I’m a researcher, I don’t see patients, but I do need to be able to talk to those who see patients, so I don’t work in the void and I stay connected.” This connection also allows the researcher to participate in meetings, seminars, even coffee talks in the corridor with clinical collaborators, fostering brainstorming teamwork.
It’s not just over the water cooler where bright ideas emerge between colleagues. Cyber interactions make collaboration possible all over the world. Raphael elaborates: “If I have some idea but I need to use some other expertise, collaborators don’t necessarily need to be next door to me. They could be in Japan. Collaborative work on multidisciplinary issues is often beneficial and exciting. I like to balance my projects between those that are principally the core of the lab and others in which the lab collaborates.” However, there is a downside to cyber-collaboration: online colleagues cannot look under the same microscope and immediately discuss the results.
The Notebook
The notebook is an essential tool for researchers. Lab techs of all levels scribble fearlessly in their notebooks knowing that the research records they are keeping will guide future tests and contribute to success.
“The first thing I teach post-docs is to keep research records,” Lim says. “It’s very important for two reasons. If you have a failed research or experiment, you record it so that you know later what went wrong. If you discover something new, when you try to patent it, that notebook can back you up. The patent office can look at the notebook and decide who invented it first.”
Lim also states that the notebook provides data for publications in peer-reviewed journals, where research results first “hit the press.” When a lab or its scientists publishes a paper or a graph, it undergoes a critical evaluation by other scientists to ensure accuracy in procedures, calculations and conclusions. Anticipating the day when each of his fellows’ work will be scrutinized by a panel of experts, Lim requires most of his fellows to undergo a vigorous first-year training program in which they learn research methods, design, interpretation of data and all manner of skills needed to develop a research program and execute a project.
Top Secret?
When it comes to keeping research secrets, the university lab and the private sector lab are worlds apart. Raphael says data sharing in the university environment is mostly encouraged. “Promote the field ahead of the needs of your own lab. Share your ideas even if it means someone will jump on them and beat you to the data. We all present our data and our plans in conferences and in meetings. … In every chat that I have with people I say, ‘Yeah, that would be a great experiment to do but I don’t necessarily intend to do them all by myself.’ Ideas are cheap. … I’m very happy to disseminate my ideas. The meaning of ‘university’ is that it’s universal; it’s open to all, so if it were to be a secret, it wouldn’t be a university. There are also labs that keep ideas very close to their chests. I could probably double my salary in the private sector but I would have to be working in secrecy and I don’t like that. It’s just one of the many reasons I prefer to remain in academia.”
The need for secrecy in private labs is tied to the patent process. Patents are important for ideas that will become pharmaceuticals or medical devices. Private laboratories rely on patents to protect their investment in projects. Lim explains: “The organization does not invest in something if its intellectual properties are not protected. If it’s an open technique, why would they invest millions of dollars when some competitor can come in and copy it and do the same? Even the government encourages protecting intellectual properties. Congress passed into law the Bayh-Dole Act (see sidebar on p. 19) to encourage researchers to patent.”
Funding
The final essential component of the working research laboratory is funding from a variety of sources:
•National Institutes of Health grants or other federal funding for program grants and collaborative efforts
•Personal grants for each researcher or a PI with others as collaborators – the main source is the Deafness Research Foundation, which has funded more than 2,100 grants since its founding nearly 50 years ago
•Translational work (work that leads to a product that will benefit the community, such as hearing aids) with the backing of pharmaceutical and other types of companies.
“Fundraising is a challenge, yet it is gratifying in more than one way,” Raphael states. “It’s a challenge because it takes time and effort and because it’s hard to go to somebody and be very nice but, in the end, what you’re saying is come on and give me your dollars. For someone who deals with scientific issues, it’s a pretty different type of job and I find it challenging. It’s gratifying because the people appreciate it and because in some cases the relationship that develops between donors and myself is very close, warm and enriching in many ways. People who come to donate usually have some kind of personal experience that makes them motivated to donate to that cause. Either they themselves, their family or friends are affected, so they are very appreciative of what scientists do to advance the field. It’s nice to see.”
The Approach
Tenacity is the final essential element to a successful lab. It’s not uncommon for experiments to yield unexpected results, and when that happens, a researcher must be honest and refuse to accept defeat. As cut and dried as conducting experiments may seem, the temptation to fudge results is real and something many researchers must confront and conquer.
“There are plenty of horror stories of someone fabricating data that doesn’t exist,” acknowledges Lim. “If somebody’s experiment doesn’t work out, it’s very tempting to generate false data to make it look good. That is always my fear – in a very busy lab and with a lot of pressure on those guys, it’s very dangerous. I think it’s important to allow them to make a mistake and it’s my job to find out what went wrong in there. If there’s any evidence of dishonesty, it could be fatal to their career as well as mine.”
In addition to keeping it real, Raphael suggests these guidelines: follow original ideas, thoughts and concepts, regardless of initial resistance and rejection; do not let failures of some projects influence the motivation to continue others; be nice, helpful and supportive of others; and review, promote, share and publish your findings.
Lim’s lab, large and private, has a very different “personality” than Raphael’s more tightly-knit academic environment. Neither perpetuates the Hollywood cliché – most labs don’t. Rarely, if ever, do scientists self-experiment or cause unintentional explosions. To be honest, the average day at the lab is not the stuff of which “thrillers” are made. Nonetheless, research is exciting stuff – particularly to the people doing it and those benefiting from the new discoveries. n
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