Hey young scientist, why don’t you make the vaccine?

I was on a phone call the other day and my aunt jokingly asked me the question – “why don’t you and your colleagues there in pharmacology find the cure to this COVID-19 pandemic?” Well, I giggled a little, but her question was justified to an extent. The field of pharmacology is involved in the process of developing new drugs.  Pharmacology is a branch of medicine that focuses on studying the uses, effects, and mechanisms of action of drugs. The field focuses on observing the relationship between complex biological systems and chemical compounds that affect them. Often confused with pharmacy, a field that focuses on the preparation and dispensing of medication, pharmacology focusses on studying abnormalities that occur in various diseases and investigating drugs that can potentially overcome such aberrations.

The development of drugs is a costly and time-consuming process. It takes approximately 12-15 years of research and can cost as much as R40 billion Rand for a single drug to reach the point where it is available on the market (shown in the figure below). In pharmacology, there are three broad branches of research involved in the research and development of drugs: basic research, clinical research and regulatory pharmacology.

 Figure 1: Overview of the drug development process.

In basic research, a large number of chemical compounds are tested in the lab to elucidate their potential efficacy in targeting some aspects associated with the disease in question. Such experiments involve testing compounds on cells isolated from humans and grown under sterile conditions (cell culture). In cell culture, it is very important that the experiments are done in a way that provides reliable clues of results to be obtained when human or animal experiments done. My PhD is focused on developing advanced cell culture models that allow for better predictions of such results. Below is a 3-minute video explaining how we exactly intend to do that.

When satisfactory results are obtained from cell cultures, the efficacy of drugs is then investigated on animal models (rats, mice, pigs, horses, fish, and many others). All experiments are conducted in accordance with strict ethical guidelines, and when efficacy and lack of toxicity is inferred from these experiments, clinical studies are then conducted.

Clinical research involves the investigation of the efficacy and safety of drugs in human beings. In these investigations, people voluntarily enrol in clinical trials, which consist of various phases. Although many drugs show remarkable potential in basic research, many drugs are eliminated in clinical trials due to harmful effects and/or lack of efficacy. This difference in the results obtained in basic research and clinical studies can be attributed to the obvious difference between animals and human beings.

When clinical data has been completed, it is compiled and sent to regulatory bodies for thorough review and approval before a drug is available on the market. Various regulatory authorities are responsible for ensuring that all guidelines were followed when developing drugs. Such regulations are carried out by regulatory bodies such as the Food and Drug Administration in America and the South African Health Products Regulatory Authority here in South Africa. After it has been proven that all regulatory requirements are met, the drug is finally approved to be available in the market, and you can finally see it in your local pharmacy or hospital.

You may be wondering…. if it takes so long to develop a single drug, how did we manage to have the COVID-19 vaccine in such a short space of time. Well, in respect to basic pharmacological research, similar viruses to the one that caused the pandemic have been studied for a long time, hence it was relatively easy to figure out a vaccine approach to the new coronavirus. Secondly, in some diseases, it takes a long time to recruit participants into a clinical trial. With COVID-19 clinical studies, it was quick to recruit patients, due to the existence of a pandemic, which mean a large number of people were readily available to participate in the studies. Additionally, funds were made available by governments and various to assist in conducting these trials. Lastly, regulatory approval application for COVID-19 based studies had to be prioritized, and this shortened the usually long times as well. Thankfully, we finally have many vaccines against this devastating pandemic.

So, going back to my aunt’s question, it is a big challenge for myself as a PhD student to create a vaccine that can be readily taken by people, given the rigorous process and costs that go into drug development. However, as different researchers across the world, we individually make our contributions to the field of drug development, and these concerted contributions eventually culminate in real-life health solutions.

How does medication know where exactly the pain in my body is?

When you miss a step and fall, resulting in excruciating pain in your knee… you take a painkiller. When you accidentally cut your finger while making dinner… you take a painkiller. When you have an inexplicable headache… you take a painkiller. How do these pain killers seem to work in all of these areas of the body? How does the medication know where the pain is? Pharmacology, a branch of medicine that focuses on studying the uses, effects and mechanisms of action of drugs, helps in providing answers to such questions.

So, here goes… When you swallow a painkiller, it dissolves in the stomach or sometimes the small intestines before it is absorbed into the whole body. Pills are not smart enough to only travel to the place where their action is required. However, the secret to the function of painkillers depends on the mechanism with which pain is mediated in the human body.

When one is injured, cells release molecules called prostaglandins, and nerve endings are sensitive to these prostaglandins. Following prostaglandin release, nerves then transmit signals to the brain communicate the intensity and site of the pain. It would make sense then to reduce the synthesis of prostaglandins to stop transmission of the pain signals, right? This is exactly how pain relievers like aspirin work. They are distributed throughout the body, and reduce prostaglandin synthesis, reducing the transmission of pain signals.

Therefore, a painkiller does not know where the pain actually is, but it works by reducing prostaglandin synthesis in areas where there high levels of production of these chemical mediators of pain, resulting in relief.

However, since the drug travels throughout the whole body, it could potentially work where it is not supposed to, and this unfortunately results in side effects. Regarding pain reduction, prostaglandins are not only released in injured cells, but specific types of prostaglandins are constantly produced by the body for the maintenance of normal bodily functions. As shown in the figure below.

Reduction of the prostaglandins needed for normal bodily functions leads to various side effects. For example, the use of pain killers may result in the loss of prostaglandins needed for protection of the stomach, leading to stomach ulcers. Fortunately, prior to the use of drugs, clinical trials are typically conducted to investigate that any side effects are not detrimental to life.

The phenomenon of how drugs work is not only limited to painkillers. Although many drugs are distributed throughout the body, their main action is based on correcting the abnormalities that occur in the biology of various diseases. For example, many anti-cancer drugs work by targeting cells that grow at a fast rate. Though the medication will kill the fast-growing cancer cells, it will also result in the loss of healthy cells that grow fast, like hair follicles, leading to side effects like hair loss. Therefore, when taking any type of medication, one should keep in mind that the distribution of drugs in the body could result in undesired side effects, and overuse of over-the-counter medications should thus be avoided.

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