The Scientific Method: The Importance of Basic Science in Spinal Cord Injury Research

The ultimate dream for many people with a spinal cord injury (SCI) – or for those who care about someone with SCI – is that a cure will be found as quickly as possible. Every few months a newspaper, magazine, or television show seems to re-port a new “breakthrough” for people with SCI, yet those optimistic reports never seem to be followed by stories of people “cured” of SCI. If these scientific “breakthroughs” are occurring, then why is SCI still incurable? Why don’t these “breakthroughs” lead to actual improvements in the conditions of those whom we know have a SCI?

The purpose of this information sheet is to analyze why scientific findings often called “breakthroughs” are of importance to people with SCI and to understand how the term “breakthrough” can be misused. Although an important finding at the basic science level will not lead to an immediate remedy for SCI, progress in basic science is essential to the ultimate goal of finding a cure for SCI.

Spinal Cord Injury – The Problem
When spinal cord damage occurs, its most obvious effect is a loss of sensation or movement below the level of injury. Useful function is eliminated below the site of neural damage. For some rae-son, the body is unable to restore this path of communication, so the consequences are permanent. In contrast, a broken leg will cause some temporary Disability, but eventually the bone will mend. Even with other serious injuries, such as burns, new skin may re-grow, although it often is badly scarred.

The Peripheral nervous system (PNS) includes all of the nerves in the body except for the brain, spinal cord, eye, and optic nerve and is able to heal itself after an injury. For example, if you have a bad cut on your finger you may temporarily lose some sensation if a nerve has been damaged. However, nerve endings in your finger eventually will grow back and re-establish their appropriate connections, as is the case with nerves in the PNS.

With a SCI though, or damage to other Central Nervous System (CNS) cells, the loss of function is usually permanent. This has two fundamental causes. When there is a traumatic injury leading to the death of nerve cells, the CNS is unable to grow new cells to replace the damaged ones. Even more important, however, many of the nerve cells that are injured, but not killed, are effectively unable to grow new sprouts that reconnect with other injured (or uninjured) nerve cells on the other side of the damaged zone. Without such a precise form of reconnection, as can occur following PNS injuries, the loss of function becomes permanent.

Clearly, the long term clinical goal of research in SCI is to develop a means of assisting the nerves in the spinal cord to heal, or regenerate. Before this objective can be accomplished, however, there are some fundamental problems to overcome. The most import-ant dilemma is our ignorance of biological processes normally in control of the growth and Regeneration of the nervous system. In fact, biologists still know rather little about the crucial regulatory systems that allow a single fertilized egg cell to grow into an elaborate animal.

To attempt to find a “cure” for SCI before understanding these basic facts is like trying to bake a cake without knowing the ingredients, the correct amounts of those ingredients, or the temperature at which they would need to be baked in order to come out with a successful finished product. It is, of course, possible to conduct trial and error experiments with cake ingredients and eventually develop a reasonable facsimile of a cake. However, the spinal cord is many times more complex that this proverbial cake! Moreover, it is not yet known for sure the “ingredients” required, much less the relationship of those ingredients to each other and the cellular Environment in which they operate, making trial and error approaches to a cure for SCI unreasonable.

The only way an appropriate “recipe” for spinal cord regeneration can be developed, therefore, is to find the answers to the basic questions about cell formation, interactions between cells and cell death. Once scientists have a fairly good idea about the answers to those questions, it will be possible to begin in earnest the task of finding a way to change the CNS’s response to injury to allow for regrowth – or regeneration – of the spinal cord.

Basic Science – Important Questions for Spinal Cord Regeneration
The CNS is composed of the brain, spinal cord, eye and optic nerve. While it was once thought that CNS cells cannot regenerate, it has recently been shown that they can, but do not do so effectively in mammals. In order to understand why nerves do not grow properly under some conditions, it is first important to determine what actually happens when they grow. One important way to look at regeneration, therefore, is to carefully examine the processes of nerve growth and regeneration wherever they are most accessible to our current techniques. Consequently, many scientists study nerve cells in animals that one would not expect to have particular relevance to the human spinal cord – such as goldfish, frogs, or even the sea snail, Aplysia.

Despite the obvious differences between species within the animal world, experiments conducted in “simple” animals compared to the more complex animals can provide important answers to basic biological questions that will be helpful to answering human centered issues as well as questions about those specific species. These simple animal models provide relatively neat and uncluttered environments in which to study specific questions. The less complicated a theory is, and the fewer complicating variables there are when studying it, the more likely one is to be able to come up with a definitive result.

The human spinal cord is an incredibly complex organ. Proper spinal cord function is dependent upon an intricate interaction among individual cells, each of which has a specific function and a unique role in the CNS. The best way to study the unique roles of cells and their interactions with other cells is to develop simple animal models that enable one to isolate a particular cellular relationship rather than to try to sort out a multitude of relationships at the same time. Once those basic relationships are clearly understood, it will be possible to examine with some degree of understanding the complex Environment of several different processes occurring at the same time.

At the present time, scientists still do not understand clearly how a human spinal cord functions under normal conditions. Thus, one of the most pressing concerns today is to develop definitive answers to questions concerning basic CNS function. A second import-ant area to examine is that of cellular response to injury. How does the CNS respond to injury? Again, a good way to address this questions is to look at animal systems that do regenerate CNS cells. If scientists can determine how other animals accomplish what we would like to see in humans, then they can begin applying that knowledge to finding a cure for SCI.

It is important to realize that the goal of basic science research is to answer basic questions about biology. Once the answers to the most basic biological questions are found, then it will be necessary to determine how the various systems work together in animals and in humans. Much further down that road of course is the development of experimental treatment approaches to reverse the effects of SCI.

Evaluating “Breakthroughs”
Every once in awhile, a newspaper or magazine article will announce that a particular scientist recently reported findings at a meeting or in a scientific journal that represents a potential “breakthrough” for people with SCI. The implication of the article often is that the results announced by this scientist will make paralysis due to SCI a thing of the past, or at the very least, will speed up the process of finding a cure. How is one to interpret these kinds of reports?

One important factor to keep under consideration is that the process of scientific investigations is a long and complicated one, with many basic questions still unanswered. A “breakthrough” re-gar-ding even one of the most basic biological questions discussed earlier certainly may represent an important step forward in one particular area of understanding, but many equally important fundamental questions about cell function still remain unanswered. The “breakthrough” in and of itself, therefore, is unlikely to lead to any significant advance in our understanding of the mechanisms that occur as a result of SCI, and certainly will not lead directly to a “cure.”

A second factor to keep in mind is that science is not as definitive a discipline as most lay people would like to think. Even though one scientist may propose a particular theory about how the CNS works, and may indeed provide evidence to support that theory, it is extremely difficult to prove without a doubt that one’s theory is completely correct. In fact, unproven theories may be presented, other scientists may agree with the interpretation of the data, yet eventually the theory will be proven to be completely incorrect.

In the medical field, for example, the practice of “bleeding” a patient was once used widely by physicians. Because the common belief was that “bleeding” was beneficial, doctors continued with the practice and interpreted the “data” to support the theory that “bleeding” was a good treatment. In other words, the eventual survival of some patients was attributed to good care, including “bleeding,” while death was attributed to other factors.

In science, the same kind of thing can happen, but because of the lack of knowledge most of us have about basic science principles, and because of our intense desire to have answers that will lead to clinical advances, we are less aware and less willing to accept the lack of “hard data” to support various theories. Consequently, it is important to realize that a reported “breakthrough” may or may not represent an important step forward, and that time will be the best judge of its value.

A cure for SCI is clearly needed, and for those who have an injury or know someone with SCI, the amount of time it is taking to develop a cure seems unacceptable. It is easy to see why we want to accept claims of “breakthroughs,” and why we are willing to believe promises by scientists or others that a “cure” will be found in five years, or ten years, or some other specified time period. With the amount of knowledge currently available about spinal cord function and dysfunction, however, it is impossible to predict when or even if a cure will be found.

As much as we would like to see an immediate cure for SCI, “shortcut solutions” are unlikely to produce one. The key to finding an eventual cure is in supporting basic research efforts slowly developing the answers to the most fundamental questions in biology. Only when those questions are answered will it be possible to develop approaches toward curing SCI and other unacceptable medical conditions.

The National Spinal Cord Injury Association would like to thank Lynn Phillips-Bryant for contributing her time and expertise in the preparation of this Factsheet. This Factsheet is offered as an information service and is not intended be a comprehensive overview of work in the field. Any information you may have to offer to further update this Factsheet would be greatly appreciated. The National Spinal Cord Injury Association Resource Center (NSCIRC) provides information and referral on any subject related to spinal cord injury. Contact the resource center at 1-800-962-9629.

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