Back to Basics

Did you ever consider why the thing scientists do is called "research"? If what they're seeking is so new, why isn't the work they do just called "search"? Where did the "re" come from? If it derives from "repeat," as some might suggest, then it is no surprise that the answer to that question really defines why science is what it is.

Rarely has there been a scientific discovery that stood in such isolation, with nothing preceding it, that it could be called completely "new." That is not to say that nothing really new comes from scientific study but that all new ideas arise from elements of past observation. In testing those new ideas, scientists follow what is called the "scientific method," which mandates that any study be directed at testing a hypothesis. Hypotheses themselves don't just come to scientists as if someone had turned on a light in a dark room. The light typically first comes as a glimmer that barely allows objects to be discerned in the dark of missing knowledge. As those objects come into slightly better view, the scientist begins to make an educated guess (hypothesis) about what those objects are and what they mean. Of course, there has to be an object in the dim light in the first place. Someone else generally has put that object into the room through their own research, and the scientist begins to look again and again at that object. Thus, there grows the concept of "research." Often in seeking clarity of the obscure object, scientists must confirm that original observations are valid, and they have to redo some of those studies to prove their reproducibility.

The public expects scientists to engage in this rigorous approach to their work, which, at its core, must be pure and organized both to avoid bias and to assure the validity of the outcome. Make no mistake: Scientists really do want their ideas to be correct and to discover new things, but their guide -- the Constitution under which they are bound, if you will -- is the strict scientific method. By applying that method and choosing good questions to answer (hypotheses to be tested), the scientist seeks to assure that every study can contribute to our understanding of our world whether the study proves or disproves the scientist's hypothesis. Each of those little insights, while not alone leading to someone's yelling "eureka," can become the dimly lit object in another scientist's mind, an observation on which the next scientist builds a new hypothesis, and, stepwise with succeeding scientists, those insights may lead to a real "eureka" moment. It is indeed because the rooms of our minds may have so many dimly lit objects that we must engage in basic research to understand the meaning of the objects before those of us who study disease can make the desired large steps toward treatments or a cure. As a result scientists carefully examine their data (the product of their work) to see if their findings fit or don't fit with their hypothesis and with what is "known." The scientist stays alert for those things that vary from what they thought was known and, not quite fitting with the first hypothesis, may lead to new hypotheses that lead to discovery. It is important for us all to realize that the process of science and discovery takes time. Particularly during economic uncertainty, we become impatient for cures, and there are calls for the National Institutes of Health (NIH) to direct more of its allocated taxpayer money to specific diseases. However, unless there is a foundation of basic knowledge of how the system, organ, cell or disease functions, efforts to find a "cure" are not likely to succeed. These efforts, when ungrounded in basic science, are often wasteful and unproductive. Without basic studies investigators may find themselves in a joust with windmills, and poorly lit windmills at that. Not only that, but basic scientific studies often place objects in the dark room of a neighbor's house.

To avoid carrying that metaphor too far, let me explain. Scientific literature is, more than ever, open to the world and to scientists across all disciplines. Therefore, a discovery in one area of science, regardless how remote from the area of a given scientist's study, can lead to important discoveries, even cures, in a seemingly unrelated area. Indeed, it is just as likely, if not more so, that the seminal discovery that might lead to a cure came from work that no one would have dreamed had anything to do with the disease being cured.

What is it that assures the American taxpayer that the product of research, whether basic research or disease-related research, may lead to positive benefits for humankind? That assurance comes not only from a disciplined approach to research but also from a system that brings together expert peers from the field associated with any given application for federal grant support. The applicant's peers, not friends but critical reviewers, carefully examine every element of the application to determine whether it brings together knowledge of the past and innovative hypotheses for the future. They further examine whether the methods are the right ones to test the hypothesis, and whether the applicant has the expertise to perform those methods. It is the reviewers' charge to guide and advise the funding agency to assure its best use of the money that the American taxpayer provides to the agency. The agency then can support scientific study that has the greatest likelihood of advancing new and valuable knowledge. The charge to reviewers is taken very seriously, for they are not only stewards of taxpayer money but also stewards for maintenance of the highest quality science. They know that new and verifiable data will be necessary to advance their own studies. Thus, their failure to execute objective reviews would not only violate the public trust but would also compromise their own future efforts.

If you are not convinced of the value of the scientific process to your own health and the quality of funded research that led to better health, let's look at a little history. In the 1970s, when confronted with a child who had acute lymphocytic leukemia, physicians basically had to await the child's death. There was simply nothing we could do, but basic scientific study that had been progressing for years was leading to an understanding of the steps and mechanisms of cell division. Recognizing those steps allowed clinical investigators to apply that knowledge to new drugs that attacked malignant cells (in this case leukemia cells) when they were most vulnerable. As a result, we have gone from having acute lymphocytic leukemia be a death sentence to our expecting a cure for children confronted with it in the 21st century. Think further about heart attack and stroke, both caused by clots that clog arteries and cut off vital blood flow to the heart and brain respectively. Again in the 1970s we were faced with having to deal with the aftermath of damage to either organ, and people, if they survived, were often left with not only damaged organs but damaged lives, restricted in what they could do or simply unable to do many things that we all take for granted. Imagine being forever unable to move a side of your body or being unable to speak to or understand your loved ones, and you will feel the plight of the stroke patient of the 1970s. But dramatic changes were on the horizon. Because of basic scientific studies into ways blood clots evolve, new therapies arose to attack clots where they formed so that many patients can now be treated before the heart or brain has become irreparably damaged. I have personally taken care of stroke patients who have received these "wonder" drugs that opened blocked vessels and turned a person, who came to the hospital unable to move or speak, into a normally functioning individual.

Not convinced yet? Let's consider, then, the advances that have come in Parkinson's disease. Notice I didn't say "cures" but "advances." We're still working on the cure, but as a result of work that led to a Nobel Prize, scientists began to understand how a vital chemical for normal brain function was manufactured and where it was located in the brain. Their understanding of the enzymes needed to synthesize that chemical and recognition that the chemical, in this case dopamine, was vitally missing in the brain of patients with Parkinson's disease, led to drugs that enhance synthesis of dopamine or replace missing dopamine at the very sites on brain cells where the missing chemical would have been working. Further, an understanding of how different brain regions may communicate with each other and modify function of other regions has led to surgical approaches to Parkinson's disease. Finally, understanding how cells in depleted areas may function has led to our foreseeing the day when stem cell therapy may repopulate areas depleted of cells that make dopamine. Examples of bedside treatments that arose from basic discovery could go on and on.

So what if you're convinced about the process for recognizing what might be discovered and assuring that the best ideas are funded, but you're just not convinced that we as a nation should be placing more valuable resources toward that effort. I could argue that we give far too little thought to the value of expenditures in science. If we keep in mind that anticipated outcomes from scientific discovery hold the promise of extending and enriching the lives not only of our citizens but also of citizens of the world, scientists can be seen as waging battle in a noble war. What is the cost of that war? Annual funding of the entire U.S. research portfolio in 2009 was $140 billion, and over half of that amount was dedicated to military research and development. Contrast that with the $1.2-trillion cost of the Iraq war, and you should wonder if we could not afford to engage in more battles on the scientific battlefield of discovery. If one of the aims of our money spent is to position our country more strongly on the world stage, it would be good if we kept the words of Louis Pasteur (the same scientist who gave us pasteurized milk) in mind. He said, "Science knows no country because knowledge belongs to humanity, and is the torch which illuminates the world. Science is the highest personification of the nation because that nation will remain the first which carries the furthest the works of thought and intelligence." We scientists live Pasteur's thought by sharing our findings with others, both near and far, knowing that the findings of one study will lead to the hypothesis of another and to the research of the future. That is outsourcing in the best sense of the word, because we scientists in the U. S. also constantly "insource" information from studies done outside the U. S. With adequate resources we can put that incoming information to great advantage and ultimately to the benefit of us all.