We need a good chemistry in biology to develop effective treatments against diseases- Vandana
While I was doing my Ph.D. at IIT Bombay, my neighbor Savvy, a biology undergraduate, often asked how my research connected to real-world problems in medicine. She was curious about diseases, why medicines take so long to develop, and what scientists actually do in the lab. One evening, while we were talking, the topic turned to infectious diseases, and I asked her a question.
Van: Do you know any other infectious diseases caused by microbes?
Savvy: Maybe malaria? Dengue? TB?
Van: Right. Let’s take malaria as an example. Even today, millions of people especially in Africa and parts of Asia still badly suffer from it, loosing their lives unfortunately.
Savvy: But don’t we already have medicines for malaria?
Van: We do. Drugs like chloroquine and artemisinin have saved many lives. But over time, one of the parasites that causes the most fatal form of malaria, Plasmodium falciparum, has found ways to survive even with those medicines. That’s called drug resistance.
Savvy: How does that happen, and can we stop it?
Van: Think of medicines as soldiers and parasites as enemies. Over time, the enemies learn to fight or neutralize the soldiers. To stay ahead, we need to understand how the parasite survives and find new ways to block it.
Savvy: How do parasites manage to live inside our bodies? Don’t our cells fight back?
Van: That’s such an interesting and important point. There are several clever ways parasites manage to survive inside us, and scientists are still uncovering how they do it. Let me tell you about one example we’re studying in our lab. These malaria parasites act like microscopic vampire. They invade our red blood cells and feed on hemoglobin, the protein that carries oxygen in our blood, which I call casually as an “infectious hug” between the parasites and our red blood cells.
Once inside, they start breaking hemoglobin into amino acids, which they use as food. To do this, they use a group of enzymes called plasmepsins. There are about ten of them, but four in particular act like molecular scissors to cut the hemoglobin. Without these enzymes, the parasite can’t survive.
Savvy: So, is it possible to stop plasmepsins from functioning?
Van: That’s exactly what we’re trying to do. In our lab, we use recombinant DNA technology to produce plasmepsins in bacteria by cloning their genes. This allows us to study them closely.
Then we test synthetic molecules called kynostatins which act as inhibitors of plasmepsins. These molecules are designed to block the activity of plasmepsins by binding to their active sites. They’re are derived from peptides that mimic the specific sequence in hemoglobin the enzyme normally recognizes and cuts, so when plasmepsins bind to them, the reaction is blocked. The idea is to give the parasite something that looks like its usual target to trick them. That way, the parasite can’t digest hemoglobin, and without that food source, it can’t grow or survive.
Savvy: That’s interesting, so the molecule fits in and blocks the enzyme. But can you actually see that happening like to be sure of that the kynostatin is binding to the right spot on the plasmepsin and stopping its activity?
Van: That’s a great question, and yes, that’s exactly what we try to find out using a technique called X-ray crystallography. It allows us to visualize the interaction between the protein and the inhibitor at the atomic level. First, we grow crystals of the protein in the lab that takes science, patience, and a bit of art. You need the right conditions such as pH, temperature, salts, and sometimes even the tiniest changes in surroundings like vibration can affect the crystal formation.
When you finally see those crystals under the microscope, it feels like a big victory, and some do look like diamonds. While they may not sparkle, they hold something more valuable, the kind scientists look for: the arrangement of atoms inside the molecule that helps us understand how proteins work.
Savvy: Wow, microscopic crystals! I didn’t know proteins could form crystals. wish I could see them! What’s actually inside the crystals?
Van (I smiled, seeing her excitement): You should come to the lab sometime, I’ll show them. They’re beautiful under the microscope. These protein crystals are made up of millions of identical protein molecules, all arranged in a repeating, ordered pattern. When we pass electromagnetic rays particularly X-rays through them, the rays interact with the electrons around each atom in the protein, creating a pattern of tiny spots on a detector screen.
The position and intensity of these spots carry information about how the atoms are arranged in 3D space inside the crystal. We can’t see the protein directly but use computer algorithms to convert that pattern into a 3D structure. That’s how we can figure out the exact shape of the protein, and if our molecule is bound to it, we can even see where it fits and how strong that interaction is.
Savvy: That sounds like solving a 3D puzzle of atoms. You start with scattered dots and end up with the shape of the molecule.
Van: You’re right. It feels like solving a puzzle, one that can take weeks or months. But when we finally see how an inhibitor binds, it gives us a starting point for designing better treatments.
Savvy: So once you have the structure, can you immediately make a medicine?
Van: I wish it were that simple. The structure is only one step in a much longer process. Once we know how an inhibitor fits into the protein, scientists still need to refine it by adjusting the shape, charge, or flexibility so it binds more tightly, works at lower doses, and doesn’t interfere with other proteins in the body.
After that, potential inhibitors must be tested in cells, and eventually in humans. Only after passing those hurdles can the most promising candidates move into human clinical trials. Each of these stages can take years, involve hundreds of scientists and clinicians, and cost millions of dollars. But every step is important to make sure that what started as an idea in the lab becomes a safe, effective treatment in real life.
And the conversation ended over a cup of tea
Conversations like these remind me why science communication matters, not just to share what we discover, but to help people understand how those discoveries are made. And maybe, as scientists, it’s also part of our role to make that process a little more visible. Most people only see the final headline: “New treatment found” or “Promising results in clinical trials.” But behind that headline is often a decade or more of work by scientists, researchers, and collaborators around the world. Because the more people understand the process, the more connected they feel to the science that’s ultimately meant to serve them.
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