Author turns Entrepreneur | Pulitzer Prize winner Siddhartha Mukherjee starts BioTech Company
Pulitzer Prize winner, Siddhartha Mukherjee has become one of the most famous cancer researchers in the world. The reason of his popularity is not his research, but his exquisite style of writing.
His book, The Emperor of All Maladies, became a bestseller and won him the Pulitzer. Later on, it was also turned into a documentary series on public television.
Mukherjee is also a doctor and scientist, an assistant professor at Columbia University who studies blood cancers and who has published his work in top journals like Nature and Cell.
And now this author cum academic researcher has announced his spin off as an entrepreneur. His work is being taken into a company, Vor BioPharma, which will for now exist within another biotech, PureTech Health, whose business model is to create and spin out biotech companies.
Vor BioPharma is in the hot field of chimeric antigen receptor T-cells (CAR-Ts), which are genetically modified white blood cells that hunt down cancer, a field epitomized by companies like Juno Therapeutics and Kite Pharma. Vor’s tech has only been tested in test tubes and Petri dishes. The new company’s first task will be
to explore them in mice. Even if that works, nine of ten treatments that help mice don’t help humans.Mukherjee has also been beset by controversy over the past week over an excerpt from his new book, The Gene: An Intimate History, that ran in the New Yorker recently.
Jerry Coyne, a researcher at the University of Chicago, has written several scathing blog posts about the New Yorker piece, which in turn reference opinions from many of the top biologists in the country, all of them negative with regard to Mukherjee’s article.
Mukherjee was asked about that, too. Below are excerpts from the conversation of Matthew Herper and Siddhartha Mukherjee, edited for length and clarity.
Matthew Herper: Sid, what exactly is this? I mean, I see that it’s something involving a novel approach to chimeric antigen receptor therapy. But can you explain a little more about exactly what this novel approach is?
Siddhartha Mukherjee: Some of it is still going through Columbia patent system, so I’ll have to be a little bit cagey about it. We’ve studied literally hundreds of patient samples with pre-leukemia and leukemia, myeloid leukemia. In the process of doing that, we began to find that there were antigens that were specific for these leukemias and that we could create CAR-Ts that would not kill normal cells but would kill uniquely the cancer cells.
As you know, that’s been a huge challenge for CAR-T therapy. We focused on blood cancers, number one because I run the clinic and have many, many patients. We also focused on blood cancers because of the success so far with CAR-Ts on blood cancers.
MH: Is there anything special about the CAR-T cells, or are they kind of like the CAR-Ts that we’ve seen? It sounds like it’s the targets that are the main thing here.
SM: I think that the crucial realization came from understanding the target, and that’s the understanding that you could take even the standard CAR-T technologies and modify them appropriately to recognize unique, novel cancer cells. That was one recognition. That said, actually in the process of doing that, we asked to also activate new kinds of CAR-T cells. It’s really a combination of two kinds of technologies, the cancer cell and the immune cell. We have technologies that are relevant to both.
MH: What kind of validating experiments do you need to do to get this to the next stage?
SM: I can talk to that a little bit. We created a technology that allows these CAR-Ts to be cancer-specific but not normal steam cell-specific. They do so very well in vitro or in test tubes and petri dishes, frighteningly so. I mean, they completely spare the normal cells and kill the cancer cells. The next step would be to do this in a mouse model, and the final, once we’re that phase, we can think about clinical trials or early clinical trials.
I could tell you that high risk myelodysplastic syndromes and acute myeloid leukemia are lethal diseases. People talk about how pancreatic cancer is a terrifying cancer. The risk of death and relapse in acute myeloid leukemia is just as terrifying. People haven’t understood that idea, but it’s just as terrifying. People die of the disease just as much as any of the other lethal cancers. It remains as an extremely lethal disease.
MH: Sid, I also wanted to take a moment just to ask you about the feedback you’ve gotten on your recent piece in The New Yorker on the field of epigenetics. Scientists including Tom Maniatis and Jerry Coyne have been very critical. Are the calls for corrections to the piece correct?
SM: It’s a longer and separate conversation. I’m going to give you some quick thoughts about it. I want to make two points.
Number one is that the piece is an excerpt from a six-hundred-page book, and when an editorial excerpt is created, it’s impossible to cover the rich detail that’s in the book. This piece had a relatively specific focus on histones and methylation and changes in gene expression, and we tried to keep that focus. Otherwise, we didn’t want to give a re-hash of the entire history of regulation. That’s point one.
Point two is that contrary to what everyone is saying, because I’m not sure they’ve read the piece, the idea that transcription factors are denied their role in the piece is wrong. There are four or five references to transcription factor genes being turned on and off in cells that are explicitly in the piece. There’s an incredible sensitivity to that idea. That’s why these things were put in, and if you look at the piece carefully, you’ll see that every time we talk about histone modification, we talk about transcription factors. I’ll give you one example and you can look for the rest.
Number one, one example I tell you is that in discussing one sentence says, “Genes are turned on and off in response to these cues and epigenetic marks are laid subsequently or later, whatever they might be.” That’s just one example of how we make it very clear, because we knew the field, I knew the field very well. Genes are turned on and off and transcription factors turn on and off, and epigenetic match factors are secondary.
The third and the last one that I want to say is that the recent book described in this piece is not weird, peripheral research. This is the work of David Allis [of Rockefeller University]. That was the focus of the piece. And Danny Reinberg [of New York University]. David Allis has won countless prizes in the scientific community including the Breakthrough Prize. Danny Reinberg is a Howard Hughes investigator. These are not sort of peripheral ideas.
I think there’s a lot of internal debate about what epigenetics is because very ambiguous about it and it seemed that the piece got in the crossfire of that debate. It was not intentional. If people want me to say, transcription factors are important in epigenetic regulation or gene regulation, I’d be delighted to say it. I work on transcription factors myself, so if that’s what it takes, I’d be delighted to say that transcription factors.
You can quote me: “Transcription factors are crucially important in epigenetic regulation.” I welcome people to get beyond that point and look at where their downstream effects on histones and methylation can also be important in gene expression.
