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Discovery & Development Drug Discovery, Advanced Medicine, Profession

Afraid of Banality, Driven by Beauty

Did you always want to be a scientist? 

I was born and brought up in India and most of my early science lessons came from my father – a veterinarian turned scientist. He introduced me to a laboratory where he performed cell culture for vaccine research. It became as much a part of my upbringing as dinner table conversations. Personally, I am terrified of banality – day-to-day repetition. I like change and, for me, science and the arts are two extremely dynamic areas that naturally complement each other.

How do you combine art and science?

Art was also a very big part of my upbringing. Art and science are, for me, the two most beautiful things – although I will include sports as a close third! There is a pattern – you need to recognize the beauty in the pattern and strive for perfection. A “good enough” mentality is not going to solve the big problems. I'm fortunate to have extraordinary team members who subscribe to the same philosophy of seeing beauty in science. Science is an art in its own sense.

I'm a big fan of impressionism. If you get too close to an impressionist canvas, you'll see blobs. In pointillism, you'll see points and dots. You need to step back. That's the beautiful connection between the detail and the big picture. If you get closer, you will realize the criticality of every dot, but you really don't know what you're looking at unless you zoom out. This is exactly how science has to be practiced. You cannot be irreverent towards the detail and you cannot be oblivious to the big picture. 

How does the artist in you manifest today?

I painted for many years when growing up, but now photography is my primary inspiration. I think photography is a powerful combination of both science and art; you need to understand the science of light, as well as the mechanics of your equipment. For me, science is the same as photography – visual intonations influence the way I do science. I don't like ugly science. There’s a lot of it – and some of it even works – but I’m not going to work in an environment where that becomes the norm. 

What big scientific moments have excited you recently? 

At the risk of sounding a little obvious, the CAR-T field is a great success story, but I also think its early success is a bit of an issue for cell and gene therapy because it has reached the point of “good enough.” It sometimes feels like people don't want to change a lot in that field now, and there is a reluctance to understand the fundamentals of what drives both safety and efficacy for these living drugs. This highlights one of the internal struggles in a profession where we encourage the industry to try and push the boundaries. 

An area I’m excited about is gene engineering. I was very fortunate to be part of the team that led hematopoietic stem cell transplants based on gene engineering all the way from discovery to the clinic. Hematopoietic stem cell engineering is one of the most difficult things in science. To genome engineer cells and cure sickle cell or beta thalassemia patients – which has been done at a previous company I worked for, CRISPR Therapeutics – is science fiction that became science fact. 

In what areas could we see breakthroughs in the future? 

Whenever we talk about cell and gene therapy, the three most important things are delivery, delivery, and delivery. Ex vivo gene therapy is getting pretty crowded – again thanks to everyone rushing to make another CAR-T product. Intellia had an extraordinary breakthrough in liver-directed gene editing, but the delivery problems of being able to use it exactly where it is needed in vivo are not yet solved. The whole CRISPR field exploded because of the excitement around precision genome engineering. If the potential in this area can be realized, it will be a game changer, but I think the key is devising the right delivery technology for each application.

Most of our cells in the body never divide. Because of that, the genome repairing mechanism allows for only imprecise genetic changes. That is what first-generation genome editing technology focused on. Technologically and scientifically speaking, the biggest frontier we need to tackle is where we can make precise genomic changes in non-dividing cells of the body. That will open an entire new universe of therapeutics. With base and prime editing, I think we can get there, but it is not going to be easy. Alternatively, if we want to make precise genetic changes, we need cells that can divide to allow alternate repairing mechanisms to kick in. 

What is Vor Bio’s current area of focus?

We are focused on the treatment of hematopoietic diseases, starting with hematopoietic malignancies such as acute myeloid leukemia, and are making next-generation hematopoietic transplants that are shielded from targeted therapy. We hope these products could become the standard of care in the near future. For this application, we are genome engineering hematopoietic stem and progenitor cells. Creating a stem cell transplant that provides universal protection from targeted therapy may open all kinds of treatment opportunities, and radically change outcomes for patients.

What should be the priorities of the advanced medicine space?

Education across the board. Advanced medicines like cell and gene therapies are still in their infancy, and it is vital to appreciate how radically different these drugs and the different requirements during drug development are in comparison to decades of the existing paradigm. Drug development in advanced medicines has no template. We are the ones creating the template. The quality of science and the quality of scientists who need to drive these priorities are very different now from what they were 20 years ago, so the industry needs to focus on hiring the best brains in the world rather than letting the best brains go into only academia! This has been the case for decades. Yes, the best scientists must be trained in academia, but we have to attract them into our industry. 

We also need to have a pioneering spirit for other aspects of drug development such as process development and manufacturing, matched with creative and rigorous preclinical and clinical development to rapidly bring these medicines to patients.

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