‘Leishmaniasis Is A Poor Man’s Disease So Big Co’s Merck or Pfizer Don’t Touch It’

Kashmir scientist, Dr Hira Lal Nakhasi, currently a Director at US’s FDA, has worked to solve many riddles but his key contribution has been the development of a vaccine for Leishmaniasis. Currently being manufactured in India, Dr Nakhasi said that its development was delayed because pharma companies found no profit in a vaccine meant for a disease that inflicts poor men alone. In this detailed interview with Masood Hussain and Humaira Nabi, Dr Nakhasi offered a detailed narrative of his takeoff from Srinagar to the US via Gujarat in the 1980s

Dr Hira Lal Nakhasi (Scientist) FDA, USA

KASHMIR LIFE (KL): What is the FDA all about?

Dr HIRA LAL NAKHASI (HLN): The FDA is USA’s very important regulatory body. Any drug, biologic or device must undergo a safety monitoring process before they are available for use by the public. You cannot sell anything just by making it in a garage or factory. The FDA’s role is to make sure that the manufactured product is safe and efficacious. If any patient is in a need of blood transfusion or organ donation, they must be thoroughly evaluated for any infectious diseases. Similarly, the effectiveness of various vaccines is studied before the common people have an access to them. The FDA has a major responsibility for regulating all these processes.

KL: How challenging has your early learning process been?

(HLN): I was born and brought up in Rainawari, Srinagar. When I was in High School, I studied in Sogam, Lolab where my father, a physician, was posted. Then I shifted to Srinagar and got admitted to SP College and later to Gandhi Memorial College. My father wanted me to be a doctor. Though I was not interested, I still tried but failed. I always wanted to explore life outside Kashmir because at that time we had just two options – medical school and engineering college. With limited seats, it was very difficult for everybody to get there. Other disciplines like pharmacy, biochemistry, and physics were less known. Fortunately, I had a friend who lived close to our neighbourhood in Rainawari. His brother was pursuing his PhD in Biochemistry in Baroda, Gujrat.

I applied for biochemistry at the Maharaja Sayajirao University of Baroda. I excelled in the subject. I did my master’s and I got first division. Then, my professor, CV Ramakrishnan suggested that I should go for a PhD. I obliged and exerted myself for the course. During the course, I got interested in research. After some time, Prof Ramakrishnan asked me to go to the United States of America for six months at Ohio State University to get some training. I took his advice and the training opened my eyes to how research is done.

I came back, finished my PhD and requested Prof Ramakrishnan that I want to go back to the US because I don’t feel I am complete with my research. I knew that if I have to pursue my research career, I have to explore more. So, I joined the National Institutes of Health (NIH), which is one of the world’s foremost medical research centres. I was there at National Cancer Institute. So, I did some work on cancer biology.

Then within two years, I thought I need to get post-doctoral training, so I went to Columbia University, New York, which is a top-notch Ivy League university in the US. My research was based on liver cancer there. Here I was studying breast cancer. During the process, I learnt about molecular biology, then least known. After finishing my post-doctoral in Columbia, I got a job at NIH again but in 1984 I moved to Food and Drug Administration. Then I was given an independent laboratory to work on the projects which FDA recommended. First, I worked on the rubella virus vaccine which had some problems. Because I knew molecular biology, they asked me if I could find out the problem so we did and published it.

All this was followed by a lot of twists and turns in my life. I shifted from one field to another. I learned virology because I was a cancer biologist. I acknowledge the help my colleagues extended to me. They taught me about how to grow viruses and other things. Then my boss, who was at that time division director of our division, told me about a parasitic disease which causes lesions in the body and also infects people it kills. Though there was medicine it didn’t do much. So, he told me to look into it. Then I read about it and found that the disease was very common in India. This disease called Leishmaniasis is prevalent in Eastern UP, Bangladesh, and West Bengal. The major centre epidemic centre is in Bihar and Nepal. Recently I came across cases from Jammu too.

I had to learn new things because I had not seen anything about parasites. Luckily, NIH is a place where you get the world’s experts on every subject. So, I went and talked to a few people. They were very open and giving. They showed me how to culture the parasites but after that, I took the charge of things. In 1990, I started working and immediately I realised that there is no vaccine for this. I felt that I need to develop a vaccine which will cure the people suffering from the disease.

It wasn’t that individuals weren’t trying; rather, there were many people attempting numerous ways, but none of them was successful. The disease had previously infected many Iranian soldiers during the Iran-Iraq war. Ali Kamashpur, an Iranian scientist with US training who was one of my colleagues, had conducted research on Leishmaniasis. He would place a tiny amount of this parasite behind the ear or on the back after removing it from the skin. Even when it led to lesions, the person would recover. It inspired me to wonder if we employ parasites that are non-virulent, produce only minor lesions, and can fight off this infection.

So, I and my colleagues Abhay Satoskar from Ohio State University, Dr Greg Matlashew Ski from Canada and Dr Shinjiro Hamano from Japan got together. I told them about the concept that if we are able to remove the gene which is causing the disease can it be less virulent? It was a novel idea at that time. We used the technology called CRISPR-Cas, which helps remove genes from a cell and developed a vaccine against the disease. The vaccine has passed the approval process by FDA in both preclinical and clinical phases. Luckily, we got funding from Japan, NIH and Welcome Trust because they saw this in a potential partner. We now have this vaccine candidate being manufactured in Pune, India in a company called Genova.

Leishmaniasis is a poor man’s disease so big companies like Merck or Pfizer don’t touch it. When I talk to them about the vaccine, they said there is no profit when your target consumer is poor. However, Doctor Singh CEO of Genova took the challenge because he belongs to India where it is more prevalent. He is now manufacturing the vaccine under good manufacturing conditions (GMP). Hopefully, we will be able ready to put it into people next year.

KL: What were the takeaways from your PhD?

HLN: My professor Dr CV Ramakrishnan suggested me study malnutrition in India, which was very prevalent at that time. He and his wife had already studied the impact of malnourishment on cognitive thinking. He told me to find out what happens to the brain lipid when a body does not get enough food. During the course of my research, I experimented with rat models. I artificially created malnutrition and found that the Myelin sheath which covers the brain tissue is affected if a child suffers from malnutrition. The affected Myelin sheath leads to their cognitive impairment.

After Prof Ramakrishnan came across my research, he asked me to go for further training at Ohio State University, where they were already doing that kind of research with a much more refined technique. In India, I used to measure lipid and protein levels but at Ohio State University Columbus, I got the opportunity to learn new techniques to go a little bit deeper.

KL: What were the other major researches you were involved with other than the leishmaniasis vaccine?

HRN: Since 1990 Leishmaniasis has been my major focus. The development and production of vaccines take years. We were lucky that the Covid19 vaccine took less time because of the new mRNA and other techniques. Though few of them have emergency use authorization, they still worked. I want to thank those people who worked with me over the years. There were 10-15 people who went through the lab and contributed to the project. I was just directing them.

Besides, I also worked on the rubella vaccine when I joined FDA. Almost every child in the USA gets measles and mumps, Rubella vaccine was developed to fight that. But eventually, they found that the people who got this vaccine started developing joint pains. Though not everybody developed the pain there was a significant number of such cases. Also if by mistake a pregnant woman got vaccinated, it affected the child.

So, I was mandated to figure it out so that the companies can incorporate the required changes.  Since I was a molecular biologist; I knew all the molecular biology tools. I sequenced the whole genome which is around 10000 bases. We found out that there were 10-15 changes in the vaccine which would cause arthritis in recipients. The knowledge was then shared with the manufacturing industry to modify the vaccine.

Besides, I have also worked on breast cancer. I studied the disease in mice. There are certain milk proteins which are important for the development of the breast. I found out that if there is a change in the expression of those milk proteins, the gland can become abnormal and eventually lead to breast cancer.

KL: What’s your current role at FDA?

HLN: My current day job at FDA is an administrative one. I am head of the Division of Emerging Transfusion Transmitted Diseases. The blood which is transfused into people has to be tested against various transmissible diseases like HIV, Hepatitis B, zika virus etc.  This helps us prevent any infection through blood transfusion. Earlier, there were a lot of cases who got HIV infection through blood transfusion classical famous case was the tennis player Arthur Ashe. He was suffering from sickle cell anaemia so he needed a transfusion. At that time, the blood was not tested and Arthur contracted HIV from the transfused blood. There are almost a hundred people in the division who look at all these applications because we have a major responsibility to ensure United State’s blood safety and availability.

I simultaneously oversee research at FDA. While my lab is working on the Leishmaniasis vaccine, we have at least 10 independent investigators who work on other different projects and they also review various applications before being approved. This is my overall major responsibility and 80 per cent of my day goes with that. So, I try to balance my research and administrative work at FDA.

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