Women in Science: How can drugs be more efficacious? Poonkuzhali Balasubramanian has answers

Editor's note: Starting National Science Day 2018, The Life of Science and Firstpost bring you a series profiling Indian women in Science. The challenges in Indian scientific life are many — more so for women taking up this path. This series honours those who beat the odds and serve as inspirations for the next generation of Indian science — a generation that is slowly and surely on its way to becoming gender equal.

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By Sindhu S

Poonkuzhali Balasubramanian | Clinical pharmacologist | Christian Medical College, Vellore

My morning train to Vellore from Bangalore was a race against time. Caught in a heavy, untimely downpour, I ran like crazy towards platform number six. With exactly a minute left on the giant railway clock, I had made it! Despite being drenched to the bone, it was only my first win of the day. I was on my way to interview Poonkuzhali Balasubramanian, a clinical pharmacologist whose contributions towards treating blood-related diseases is saving many lives.

At Christian Medical College (CMC), I saw crowds of patients and their families, as well as housekeeping staff dressed in blue and medical professionals in white. It was disheartening to see so many people presumably ill, but at the same time hope filled me at the realisation that a large number of people were receiving health care at this institute, which has been at the apex of medical research in India for many years.

Drugs, dosage and genetics 101

Diseases can be treated in a multitude of ways, such as surgery, radiation and physiotherapy, but treatment with pharmaceutical drugs is almost always the first line. This is called Pharmacotherapy. Whenever I pop a painkiller, I wonder how this small bitter tablet knows which part of my body is aching and how to stop it. As a computer science student, I sometimes imagine my body to be huge data center with hundreds of crisscrossing nerves for cable lines. How does a tablet know which nerve signal to block the pain in my tooth? Can we be sure it won’t block my other bodily abilities, such as the sense of touch or smell?

Thankfully, there are specialised fields and a range of experts under the umbrella of pharmacology who can answer these questions. Poonkuzhali is one of them, and she took me through the different terminologies that exist. The branch of pharmacology that determines the effect of a drug on an organism is Pharmacodynamics. Conversely, the study of the fate of drugs themselves making their way through a living organism is Pharmacokinetics. And then there is Pharmacogenetics, since each of us is genetically unique. The drugs that work on one patient may not be effective for the next.

"This is the case with almost all the medication we take. In fact, not just medication but any chemical we interact with in our daily lives – cosmetics, household items, industrial products – nothing is guaranteed safe. Sure, they are all probably approved by authorities after passing extensive tests, but none of these tests were performed on you, or even anyone like you. Most likely they were performed on animals and perhaps, following that, a small group of humans who shared neither your age group, nor your ethnicity, nor your family history, nor your gender, nor a thousand other things that make you different from everyone else. No wonder then, that we all react differently to many drugs,” says Prajakta, a pharmaceutical biotechnologist.

A PhD is just the beginning

Poonkuzhali joined CMC’s haematology department in 1994 as a junior research fellow (JRF). During her time here, she has set up high-tech labs like the one I was guided through. Among the labs she started in was the Advanced Center for Bone Marrow Transplantation, where she set up molecular testing for arsenic therapy. She quips, "Arsenic is actually a poison which, in low doses helps in curing a particular form of leukemia. My interest in leukemia started when I helped establish molecular testing (for it)."

For her doctoral research, she studied the drugs Busulfan and Cyclophosphamide used in hematopoietic stem cell transplantation — the only successful cure for blood diseases like AML, CML, Thalassemia, and Haemophilia. By the end of her PhD in 1999, she was an expert in the methods to measure Busulfan levels. She says, "The bottom line in cancer treatment and research is that whatever we do on the bench (in the lab) should reach the bedside."

Busulfan and Cyclophosphamide are important drugs used in the “conditioning” stage prior to hematopoietic stem cell transplantation (HSCT), when the patient’s body is readied to accept donor stem cells. A few years ago, little was known about the dose required for an ideal response at this stage, as well as the genes responsible for therapy variation in individuals. “The drugs are the same (to treat AML or CML) but people react differently," Poonkuzhali explains. It was at this point that she began her journey into research.

For her postdoctoral work, Poonkuzhali delved deeper into pharmacogenetics by investigating why some patients react better than others to these drugs. She found that a specific protein family in these patients with Beta Thalassemia Major was affecting the success of stem cells transplantations. More recently, she found that when an enzyme called CytochromeP450 expressed itself along with a specific gene, it led to an increased chance of liver injury upon exposure to the Busulfan drug.

HSCT offered today at CMC to patients suffering from CML incorporates the advances that have been made as a result of her scientific work. “At CMC hospital, the idea is to work hand-in-hand with scientists," she says. Furthermore, Poonkuzhali’s discoveries have led to the development of a better pharmacokinetic model for Busulfan and Cyclophosphamide usage, for clinicians everywhere.

Where is the money?

Upon returning from her postdoctoral stint in the US, Poonkuzahi was slightly confused. She recalls, “I was wondering why I came back. During the first year after I returned, there were all these questions about why I was here when I had the opportunity to stay back." Something unknown had brought her back, and there was work to do. But first, she needed resources.

Deeper investigations required physical space for a lab, specialised hardware, technicians to operate the machines and staff to maintain the operations. More often than not, funds for such projects come from grants from premier government bodies, such as Indian Council of Medical Research (ICMR), Council of Scientific & Industrial Research (CSIR) and University Grants Commission (UGC). Applying for grants is a real test of one’s patience and commitment to research. "Writing for funding grants is a journey in itself," Poonkuzhali says.

When one’s work is highly technical, it takes a certain amount of cognitive effort to condense years of research into high-level summaries. “Five minutes is the time given to present five years of research!” she says, as she explains how she had to go through several rounds of convincing grant officials about how important her work is, in the field of haematology.

Currently, thanks to grants from the Wellcome Trust and the Department of Biotechnology (DBT) India, Poonkuzhali is able to investigate the effectiveness of the above mentioned drugs based on clinical data from the labs at CMC. As proud as she is that she can carry on her research for the next five years with financial support, she wonders about the state of biosciences funding in India. “It is hard to run a lab with paid staff without the timely release of funding," she says. She is still waiting on funds for a project that was approved by the ICMR three years ago.

Pharmacologists, biotechnologists, and doctors — tributaries of the same river

The CMC's haematology department comprises both clinical pharmacologists like Poonkuzhali who have a biochemistry background, as well as clinicians like her former guide Mammen Chandy, who entered into haematology after their formal medical degrees. Working with clinicians is crucial, because without clinical data from real cases of treatment and relapse in blood-related diseases, scientists don't have reliable data.

Research and application are two sides of the same coin, and more so within the premises of a hospital. This setup, unique to CMC, closes the feedback loop with hospital data fueling research. Because this data is so readily accessible, researchers like Poonkuzhali don’t have to worry about procuring data from elsewhere.

Doctors treating patients with Beta Thalassemia Major now have an idea of the most effective dosage range of these drugs, without causing detrimental side effects, such as liver damage. They can also get a better estimate of the quantity of these drugs which lead to failure of the HSCT treatment. Detailed studies such as those being conducted by Poonkuzhali add to better drug dosage management. Every improved prescription for blood disease patients is a win for researchers like her.

I asked her naively, “Are you the person who decides which tests a patient must take?” She smiled and said, “Clinicians decide the test, we just make it available to them.”

On mentoring and the question of gender

Poonkuzhali seemed amused when I asked her about gender representation in her field. “In fact, of the six PhD students, only two are boys, and at one point, I only had girls!” she says. What disappoints her is that many of her postgraduate researchers drop out due to family obligations. She recalled the sad story of one of her students dropping out right before submitting her doctoral thesis.

Apart from mentoring doctoral students, Poonkuzhali coordinates the teaching programme offered by her department. She also shoulders administrative duties such as reviewing the staff performance for recommending them for promotions or training.

As a researcher, one has to navigate through vast amounts of data and literature — a skill she acquired because of her love for reading. She has always been a voracious reader. “I always wanted to know the ‘why’ of things around me, right from the start," she says, beaming.

Read more from the Women in Science series here.

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