#485 — The New Science of Cancer

**Sam Harris** (0:21)
I'm here with Siddhartha Mukherjee. Sid, it's great to see you again.

**Siddhartha Mukherjee** (0:24)
Pleasure, Mike.

**Sam Harris** (0:25)
So we have a lot to talk about. You have an updated version of your Pulitzer Prize-winning book, The Emperor of All Maladies, A Biography of Cancer, which came out 15 years ago, but you've updated it and there are four new chapters in the new paperback. So I want to focus on that. I want to spend some time on how our thinking about cancer has changed in the interim. And I think we'll break this into three chapters, prevention, detection, and treatment slash cures. But also you have an AI startup, which I want to talk about, because the utility of AI here in any one of these stages is obviously something that people are hoping for. And I'm glad to see you're trying to push that forward. But let's start with just kind of the basic conceptual framework and maybe how that's changed in the intervening years. How should we think about cancer as a disease? I mean, is it 100 different forms of disease? Is it one? I mean, when we get a cure for this thing, is it going to be one cure or there are going to be hundreds, do you think?

**Siddhartha Mukherjee** (1:31)
Well, I'm almost certain that there'll be hundreds, but there will be common themes running through it. So one question that I try to answer very often is exactly the question you asked, which is, is it 100 different things? Is it one disease? Is it many diseases? If it's many diseases, why do we call them cancer in the first place? Why shouldn't we just separate all of them out? Then the answer is somewhere in the middle, it's every form of cancer. In fact, every individual form of cancer, every individual specimen of cancer is its own disease in the genetic sense. So in the sense that a one woman who walks into your clinic with, let's say breast cancer, has a particular spectrum of mutations. Mutations are changes in DNA that drive the cancer cells growth. The second woman might come into your clinic with breast cancer, looks the same under a microscope. It's called breast cancer, but her spectrum of mutations, maybe she has 100, maybe she has 20 Her spectrum of mutations is slightly different. So why do you call them all of them cancer? Well, first of all, there are some broad physiological commonalities. So the broad physiological commonality is that in all cases, the first woman, the second woman, the third woman, all with breast cancer. In all three cases, the problem is that the cells don't know how to stop dividing.
In a few cases, they don't know how to stop living, or essentially, they don't know how to die. But let's say that most of the most part, they don't know how to stop dividing. And in that, driven by that malignant growth, these cells, these cancer cells have started co-opting, hijacking, you might call it, normal pathways that normal cells use to survive. So just like normal cells use nutrients to survive, cancer cells also need nutrients to survive. You could say they need kind of a special kind of nutrient to survive, special kinds of nutrients to survive, special pathways that they've hijacked from normal cells. Just like normal cells in the body move around and go to other places, cancer cells also acquire the property to move around.
So there are deep commonalities that run between all these diseases called cancer. And yet, it's also true that each individual specimen of cancer is its own cancer.

**Sam Harris** (3:40)
Is there one conceptual bottleneck here that most troubles you in our making progress? I mean, is there one question that if we had the answer to it, you think it would unlock the greatest promise here for treatment or prevention or detection or all of it?

**Siddhartha Mukherjee** (3:55)
Well, I think we should really speak about prevention, detection and treatment differently. Let's start with treatment. I mean, the big unlock for treatment is always going to be, can we find something in the cancer cell that's different from the normal cell? That's always been the problem. Cancer cells are very close cousins, if you will, to normal cells and that's obvious because they're derived from normal cells.
So the big conceptual unlock here is, can we find one pathway, two pathways, five pathways, 10 pathways that are different enough between a cancer cell and a normal cell? By pathway, I mean, a series of it, you can think of it as a kind of baton race between one signal and another signal. Ultimately, all the signals are going to the same place. They're telling the cell, grow, grow, grow. But these pathways are unique to cancer cells and the job, one of the big jobs in treatment is to find the difference, the unlock, as it was it were, is to find the difference between what the cancer cell is able to do or is doing and what the normal cell is able to do and is doing. If you can find that unlock across not one but multiple specimens of cancer, we'll have different treatments. There may be some common ones, there may be some different ones, but that's the big unlock there.