For those of us who are not familiar with the ins and outs of the scientific community, Gusella and MacDonald believe that there are many misconceptions about researcher work because then many different activities that are necessary to attack a disease like HD tend to be lumped together. In reality, these activities require quite different skills, levels of funding, and working environments.
Myth #1: All labs are the same.
Reality: There are important distinctions between academic labs (like the MacDonald and Gusella labs), industrial labs, pharmaceutical labs, clinical research labs, and clinical testing labs. All carry out different kinds of activities that are important to HD research. Generally, academic labs are responsible for discovering the biology behind a disease. Well-funded industrial and pharmaceutical labs are responsible for developing drugs that treat the disease and testing them on animals raised for that purpose. Clinical research labs are responsible for conducting clinical trials of treatments and drugs using consenting human subjects. Clinical testing labs do not do research, but instead conduct diagnostic tests for disease, in a government-approved manner, that are ordered by physicians.
Myth #2: Researchers spend all their time researching.
Reality: In fairly large academic labs like MacDonald’s, the principal researcher does little or no actual lab work (often referred to as “bench work” because the lab tables are called benches). Rather, MacDonald hires postdoctoral students and technicians to do the bench work, dividing up the different tasks and projects among them and spending time to direct their efforts. MacDonald herself spends much of her time interpreting results, strategizing for future projects, and doing administrative work, such as writing and reviewing grant proposals and sitting on scientific committees.
Myth #3: Researchers are paid by the hospitals they work for.
Reality: Researchers like MacDonald rent lab space from their institution, such as a hospital, and must do their own fundraising to obtain money for equipment and employees’ salaries. This fundraising is accomplished by applying for grants.
Myth #4: Treatments that work on mice will usually work on humans.
Reality: Most experimental drugs and treatments tested on mouse models of various diseases do not work on humans. Mice are often used to test the toxicity of the chemical compounds involved in various treatments before drugs are developed and approved for human consumption. The process of testing treatments on mice, developing drugs, getting government approval for the drugs, and putting them on the market is quite slow, has many steps, and involves making enough of a particular compound for large groups of people.
Some scientists think that a larger animal model may be a promising alternative to a mouse model of HD in terms of shortening the clinical trial timeframe. A large animal model may be physiologically more similar to a human, which will give scientists a better sense of what kinds of treatments may work on humans. MacDonald mentioned that a researcher named Russell Snell at the University of Auckland in New Zealand is currently developing a sheep model of HD. Because researchers will see much more nerve cell death in sheep than in mice or rats, they might be able to get a more accurate picture of the progression of the disease in people. It will thus be easier to study the pathology of the disease in its final stages. Not only is the physiology of a sheep is closer to that of a human than a rodent’s, but a sheep model can provide other benefits in terms of HD experimentation. For example, living experiments (experiments conducted in the living animal), transplantation of cells and tissues, and protection of the nerve cells against deterioration (a process called neuroprotection) will be easier to perform.
Myth #5: The nerve cell is healthy, and then it changes and gets sick after the onset of HD.
Reality: The nerve cell in a presymptomatic person with HD is never normal. If a genetic mutation is present, then the cell is abnormal from the start. It is a common misconception that if a cell is not presently sick, it is normal. Yet, according to MacDonald, the cell merely gives the appearance of being normal by trying its best to remain healthy for as long as possible.
Myth #6: There is one big, important change that occurs in the body to make a person sick with HD.
Reality: There is certainly more than one big, important change; in fact, there is a whole series of changes! Visualizing HD in terms of a timeline allows us to think about the changes sequentially (i.e. what happens, when, and in what order during the disease cascade). MacDonald says that one of the earliest changes involves the RRS1 gene. RRS, which stands for regulator of ribosome synthesis, directs the production of this small organelle that, in turn, directs the synthesis of nuclear proteins (proteins found in the nucleus of the cell). At the beginning of the disease cascade, more RRS1 is made, perhaps because the cell needs to change its protein synthesis. Other subsequent changes take place, leading to “derangements;” for example, in energy metabolism, which lead to other changes, and so on.
Myth #7: Scientists will find a “magic bullet” to cure HD.
Reality: MacDonald thinks that it is highly unlikely that one chemical
compound will work well in all people with HD. Yet she believes that HD researchers may, as a first step, be able to develop a drug to delay the onset of disease symptoms for about five years, which is the size of the effect in some individuals with a certain version of the GRIK2 (Glu6) gene. The GRIK2 gene is a genetic modifier in HD, meaning that its expression in different people can have an effect on age of onset. For instance, by manipulating this gene in a certain way, scientists can perhaps stall the onset of HD and thus shift the disease cascade in such a way that when onset actually does occur, the symptoms will be less severe.
Last Modified: 05/22/2009
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