Columns Journey of a YI

Bedside to benchside and back

Charanya Ramachandran

Charanya Ramachandran is a Scientist at the Sudhakar and Sreekanth Ravi Stem Cell Biology Laboratory at LV Prasad Eye Institute, Hyderabad. In this invited article, she writes about her journey from the clinic to the laboratory and back, and some important lessons learned along the way.

Charanya Ramachandran
Charanya Ramachandran 

Conducting research in the laboratory is so much simpler than translating it to the clinic. And I say this because research in the laboratory is defined and dependent on fewer human variables than its translation to the clinic. I chose the path of translational research because of my training both as a clinician and basic researcher. While the former made me realize the gaps in our understanding of human biology (in my case the eye), the latter prepared me to address the gaps.

My journey started with training for four years to become an optometrist. During this time, I learnt about the optics and biology of the eye, as well as the diseases afflicting this small organ. I learnt ways to use both my observational skills and technology to diagnose diseases and treat some of them. It was a fascinating time and it made me realize a couple of things. First, a good clinician can have a huge positive impact on society, and second, very few clinicians practice evidence-based medicine (in fact, most practice eminence-based medicine). And the sad part is that most medical programs fail to give rigorous training to think critically, ask meaningful questions, and answer them in a scientifically sound manner.

This made me switch from the bedside to the bench and I landed at Indiana University (Bloomington, USA) where, for my PhD, I studied molecular mechanisms that could potentially drive a slowly blinding eye condition called glaucoma. My focus instantly went from the macro level (studying/​treating the eye) to the micro level (teasing apart the cellular signalling pathways driving the contraction of a subset of cells in the eye). I used to wonder what was there to learn for 4 years (undergraduate) about the eye, an organ which is mostly filled with jelly, and here I was spending another 6 years studying the mechanism driving the contraction of a subset of cells in the eye. It was a humbling yet liberating experience. 

The freedom of the lab, in terms of the work hours and schedule, was in such contrast to the clinic. The days were what you defined them to be, the atmosphere more relaxed, the timings more forgiving. When I was interning in a lab at the Ohio University, the senior research associate there took me to fly a plane in the time that it took to run a PCR. Now, this was something you could never dream of doing while in the clinic, where your schedule is defined by the patients. 

My PhD was one of the most enjoyable periods of my life, where I learnt not just to think critically but also that there is nothing called the right question. Any question that is driven by curiosity and a fairly good hypothesis is worthy of asking, in my opinion. Knowledge from such curiosity-driven research is what has, and will, enhance our basic understanding of any mechanism. Such knowledge is also a pre-requisite for translation.

This is when my husband and I decided to return to India. Like most people returning to India, we were apprehensive about the job opportunities, funding, environment etc. It was not easy finding the right place” because there are very few institutes in India that focus on the eye and fewer that do research, let alone translational research in this field. Fortunately for us, we found our match in the LV Prasad Eye Institute, Hyderabad. 

Although a private not-for-profit set up, the institute, right from its inception, had incorporated basic research into its core functioning. The most important selling point though was the immediate access to the patients, clinicians, human samples and data. The icing on the cake was the community reach (through its network of clinics and hospitals) that this institute has, thus bringing each of the three critical pillars of translational research viz bedside, benchside and community, within easy reach of the scientist.

Having decided to join the institute, I spent my first 3 years as a post-doc dabbling in tissue engineering. And this is when my tryst with translational research began. I was involved in developing a synthetic material for delivering stem cells to the surface of the eye. The product was developed, tested in the lab, followed by testing in animals, and was ready for the clinic in under 2.5 years. 

This is when I was exposed to the reality of clinical trials — the mounds of paperwork, the many presentations (and representations) and the delayed approvals. To cut a long story short, it took us 2 years to convince the regulators and receive approval to conduct our clinical trial and another year to do so. I will say this again, it is so much easier to perform basic research than to translate it to the clinic.

Following this, I started my journey as an independent researcher all fired up to do some translation. This is still work in progress and here are a few very important lessons that I have learnt along the way

1) Find a good clinical partner: This is of paramount importance. Unless you have a committed clinical partner who is invested in your ideas and product, the quest to translate your research is bound to fail. This is something that I have learnt the hard way. Also, it is important to recognize that the needs and focus of the clinic(ians) can be quite different from the lab. The best option is to engage with a clinical partner right at the beginning of product development so that the translation is smooth.

2) Hire a good regulatory consultant: Procuring approval for conducting a clinical trial requires a lot of paperwork to be submitted. And it is a lot of time-consuming work which an individual PI cannot manage. The best approach would be to get on board an experienced regulatory consultant who can help with navigating the complex web of regulations (which keep changing so often) and make it manageable. It is important to bear in mind that this can be expensive and it is better to allocate some funds towards the same.

3) Intellectual property: This is an important consideration to bear in mind, especially if the product is of commercial value. It again becomes important to hire someone that can help assess the value of the patent, look for available competitive products in the market etc. Many universities have this as a part of their administration and it might be useful to contact them before placing the information in the public domain. And again, filing a patent is a time-consuming and expensive process and therefore, should be given careful consideration.

4) Patience: It is of paramount importance to remember that clinicians in general (exceptions exist, of course) are an impatient lot. Probably the rush of the clinic contributes to this. They always want the product yesterday. I find this the most difficult task to balance but it is certainly something that can be worked out with a few sessions of open conversations.

While the bedside and benchside may seem like they are on parallel paths, connecting the two is not impossible and would greatly benefit society. A lot of patience combined with careful planning will certainly make the whole journey less stressful and more enjoyable.

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