More than forty years ago, doctors observed an unusual phenomenon in some patients who were anesthetized with succinylcholine. After waking up, these patients remained in a state of stupor for a period and experienced severe difficulty breathing. Subsequently, physicians discovered that these patients had a genetic anomaly: their ability to metabolize the drug was significantly impaired. Scientists traced this phenomenon and found that the slow metabolism of succinylcholine was related to a specific genetic mutation. It is estimated that about 1 in 3,500 individuals carry two abnormal gene variants, putting them at high risk for adverse reactions to the medication.
Understanding and explaining the side effects of succinylcholine on patients can be considered the first acknowledgment by researchers of the relationship between genetic mutations and an individual’s drug response. Since then, although such observations are not numerous, they have steadily increased, helping scientists explain why some patients are highly sensitive to medications while others are resistant, and some may even view the drugs as toxic.
To date, in addition to the genetic mutations that cause abnormal reactions to drugs, doctors have also noted other similar mutations that play a crucial role in creating hidden risks for individuals regarding specific diseases, such as Alzheimer’s disease and breast cancer. Furthermore, the relationship between genetic mutations and diseases helps explain why many smokers do not develop lung cancer, while some non-smokers who are exposed to secondhand smoke do.
The advancement of science in general and biomedicine in particular allows for the hopeful (and sometimes overly optimistic) belief that we are on the brink of an era known as personalized medicine. Genetic tests will enable doctors to determine whether individuals carry any disease risks and subsequently propose appropriate preventive or therapeutic measures. However, it is essential to note that unearthing the responsibility of DNA—specifically, identifying responsible DNA and transforming this information into genetic tests for physician use—remains a significant challenge.
Many other conditions, such as various cancers, cardiovascular disorders, and depression, appear to result from intense interactions between multiple genes and environmental living conditions, such as nicotine in cigarette smoke or excess fat in diets. It goes without saying that diseases caused by multi-gene interactions present considerable challenges for researchers trying to identify the causes of disease development and propose treatment directions. For instance, last summer (2004), a group of researchers discovered that as many as 124 different genes were linked to resistance against four types of leukemia drugs.
Nevertheless, identifying such gene systems is just the beginning. One of the harshest challenges is reconstructing these studies. The task becomes even more difficult with non-fully genetic diseases like asthma or diseases that focus on a very small group of individuals, such as cancers in certain children. In reality, many clinical tests have not routinely collected DNA samples from patients, making it challenging for scientists to find specific responses between diseases or drugs and genes. Microarray technology, which allows observation of the expression of numerous genes at the same time, sometimes yields ambiguous and contradictory results. Moreover, the cost of gene research poses significant barriers.
Despite these challenges, it must be acknowledged that genetic research on certain diseases like cancer, asthma, and cardiovascular conditions is rapidly advancing. In contrast, the process of researching psychiatric disorders seems to be slower. However, it is noted that some patients with depression or psychotic disorders can be easily diagnosed, allowing for treatment plans (including types and dosages of medications prescribed by doctors) that may help them overcome their illnesses; conversely, in asthma, the varied drug responses among patients make it difficult to determine precise medication dosages.
Since the reading of DNA sequences has become “commonplace” and biomedical techniques continue to develop, health issues related to genetics are no longer as daunting for researchers. Genetic tools are still being developed that could enhance the study of disease-causing genes, such as the haplotype map that researchers hope will be used to differentiate genetic mutations in common diseases.
The next step is to design DNA-based tests to help physicians make the most accurate clinical orders. However, it must be recognized that it will take considerable time to implement these tests widely in clinical settings. Especially in emergency cases, such as heart attacks, acute cancers, or asthma attacks, these tests will only be valuable if they yield accurate results in the shortest time possible.
Finally, a comprehensive approach to personalized medicine will only materialize if pharmaceutical companies genuinely desire it—and they will need to invest enormous resources in research and development. Many companies worry that such genetic tests may shrink the market and reduce their profits.
Nonetheless, researchers continue to nurture and seek new opportunities. In May 2005, a company in Ireland—deCODE Genetics—reported that an asthma medication that had been abandoned by the pharmaceutical giant Bayer turned out to reduce the risk of heart attacks in 170 patients with specific genetic mutations. This drug affected certain proteins produced by the aforementioned mutated genes. This discovery seems to signal many intriguing developments ahead as the veil over DNA, drugs, and diseases slowly lifts.
Trần Hoàng Dũng
