Bulwark Takes - Nothing Could Put a Dent in Pancreatic Cancer. Until Now. (w/ Zeke Emanuel)

Episode Date: June 3, 2026

Jonathan Cohn talks with oncologist and UPenn vice provost Zeke Emanuel about the breakthrough new pancreatic cancer treatment—what the science actually means, why it took so long, and what Trump's cuts to federal research funding put at risk.

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Wealth isn't a fixed point. It's a journey guided by a steady hand through uncharted waters. At Canoe Financial, we are active fund managers and independent thinkers focused on building and protecting your wealth. Chart your course. Ask your advisor about Canoe Financial. Hey, everybody, welcome back to Bullwork Takes. I am Jonathan Cohn here. we've had some really big news from the world of medicine, a major breakthrough in the treatment

of pancreatic cancer. I've been covering medicine and healthcare for a long time, really the reaction to this discovery and this trial results we're about to hear about. One of the more pronounced and celebratory reactions I've seen to a research development in recent year. So what does all this fuss about? What does this breakthrough really mean? What doesn't it mean? And what does it say about the system we have, the ecosystem for promoting this kind of research and what's happening to it under the Trump administration. Our guest today is uniquely positioned to talk about these things. It's Zeke Emanuel. You may know him. He's written for the bulwark before. He's also a vice provost at the University of Pennsylvania, author of a new book called Eat Your Ice Cream. Most relevant for this

discussion, he's also an oncologist. So he knows all about cancer and cancer research. He's been at the National Institutes of Health. Zeek, welcome. Thanks for making time for us to talk about this. Great. Thank you for having me. So real quick, pancreatic cancer 101. I mean, it kills, I think, more than 50,000 Americans a year. Yeah, it's a third largest killer. So roughly the way to think about it, about 70,000 people get, Americans get pancreatic cancer each year. More than 50,000, 52, 53,000 die of pancreatic cancer. That tells you it's pretty deadly. And the main reason, is that by the time we find that a person has pancreatic cancer, it's already spread. And patients in whom it's spread, there's no cure for it, and it's pretty rapid.

It's pretty widespread by that time. And the chemotherapies, frankly, we have, aren't that effective. Occasionally, and I actually have a very dear friend, a guy well-known to the healthcare community, Leonard Schaefer, who had pancreatic cancer, and actually looks like he's been cured of, it, but it was found incidentally. They weren't looking for the pancreatic cancer. It was found incidentally. And let me just tell you, the treatment to cure him was horrendous. So I have heard for as long as I mean, I can remember that pancreatic cancer was this sort of this impossible, not impossible, but just the most difficult. Research was going nowhere. It was so hard. Why was it so hard?

Why has it been so hard to attack? It has been deadly. And, you know, we used to just sort of shake your head, another patient with pancreatic cancer. Less than 15% of people live for five years. And the chemos just don't work against it. It has this, and this is key to the breakthrough, it has this what's called the RAS mutation. RAS is a family. RAS, right, RAS, R. Big A, A, B, A, B, A, big A, big S, right. And this is a family of genes that are critical for telling cells when to divide and when to differentiate to become more mature kind of cells. And the big problem in pancreatic cancer is that the rash mutation is turned on. So it just says divide, divide, divide, divide, divide, and you can't turn it off.

And for a long time, this sends molecular signal into the cell. And for a long time, people refer to this mutation as undrugable. They couldn't find a drug to get in there. And what has happened is that they've found some ways around that problem by targeting it independently. And also they've actually combined multiple approaches to deactivating the RAS gene and the mutated gene. So it's not always on. And it's sort of three different approaches that combine into one pretty amazing response by turning the rass down and really stopping the cells from proliferating. And it also accumulates in the cell.

And that's another very important finding. So one of the, sorry, John, I'm going on to. No, no, no. This is interesting. Keep going. One of the big problems of chemotherapy, as everyone knows, is you get all these side effects, nausea, vomiting, hair loss, diarrhea. your blood counts go down. That is a response of chemotherapy, not targeting the cancer, but targeting all these other

normal cells and causing them to die as well. That's the cost we take for the chemotherapy affecting the cancer. One of the interesting things about this new drug is that it actually accumulates in the cancer. and so the effect on other cells is way, way less, and it doesn't affect them and kill normal cells and kill them. And so that's a big additional advantage. So one of the surprising things, certainly to an oncologist, regular oncologist, is how few serious side effects that were.

It's not like there were no side effects, but they were what we call grade one or two. not grade three or four much less life threatening. So that's, that means it's way, it's very tolerable. So you've got this bad disease with a very tolerable and really much more effective therapy. That's a kind of winning combination you'd love to get in any oncology setting. And what are the side of? Because I mean, I think this is the drug, right, that Ben Sass is also taking, I think. Is that right? I don't know if you know the answer to that. Yeah. Yeah. Yeah. So I know he had a rash. from it. Is that one of the know? You've got, you've got rashes, you've got some diarrhea. You know, his rashes has been pretty, you know, I don't know on the scale and I don't know

what his skin was like before. And I don't watch TV, so I haven't seen a lot of them, but I have seen a picture of him. And it looked pretty, pretty severe. Nonetheless, let's be honest. Yes, the skin looks pretty bad and it probably hurts because, but he's been doing TV. He's been going around. It's not like he's bedridden because of the chemotherapy. Right, right, which is what you get sometimes. Now, also, and just to be kind of realistic,

when we say the headlines out of, we haven't said the name of the drug. What is the name of the drug? pronounce it for me. Direction, RASIP. So, okay, I'm going to have to learn this. And, you know, look at the end, RASIB, right? That's RAS inhibitor.

Right. Rass inhibitor. And the company that it comes from is called Revolution. Yeah. Revolution. Okay. The headlines out of this all were the double-douled survival. What does that mean in practice? What does that look like?

When we say it's doubled survival. First of all, we need to make something really clear. The reports that we're seeing are of patients who had previously been treated with standard chemotherapy for pancreatic cancer. That's four drugs combined. And that's been, so those people are what we call pre-treated. They've already been treated. Their cancer has already seen chemotherapy and it's recurred or it's grown through the chemotherapy. It didn't shrink it grew through.

So that is typically not a good situation. So anyone who's had a relative of cancer knows that if the cancer goes through the chemotherapy or comes back after you got the chemotherapy, you're kind of behind the eighth ball. That's the patients we're seeing. And typically in those situations, patients have lived an average of six months. So gives you a sense, again, a feel for how deadly pancreatic cancer is. This drug doubled that over 13 and a half months. And the latest reports suggest that patients are going out even longer, maybe as long as,

14, 15, 16 months. That doubling, that's pretty remarkable for, again, pre-treated patients who've already gotten the chemotherapy and have grown through or had a recurrence with the chemotherapy. And that's prompted two things, the FDA to say, all right, you know, you can, this is a breakthrough kind of drug, and you can begin sending it out to patients, but also to say you can give them a revolution authorization to move up instead of trying a chemotherapy and then giving the drug move the drug into patients who are newly diagnosed and let's see what it can do in that context in addition to routine chemotherapy that's you know that that's where if this really

has the possibility of either totally suppressing or you know god willing even curing this or maybe doing it so you can cure patients, that's a big, that would be a huge, huge breakthrough. The deadliest cancer now has a drug that could, you know, double lifespan. And maybe, you know, who knows if you got a newly treated cancer patient. I noticed you've been very careful appropriately and sort of saying could be, might be. I mean, because we're still learning about this. Yeah, they've treated like 500 patients or something. and all together.

And, you know, hype. It's easy to hype. These are very responsible researchers. And I don't, you know, I think everyone wants to be very, very careful not to over promise. Now, the drug was developed by a private company. And I think I'm still checking on this. I think mostly it was with their own capital they raised. But obviously it didn't come out of nowhere.

Can you talk a little bit about, the science that led to this, and in particular, the role that federally funded research played in getting us to this point. So, I mean, it's a great question. And, you know, the whole understanding of genes that get turned on that cause cancer, the rash mutations, it's signaling pathway, what it does inside the cell, the pathways that it excites. all of that is federally funded or funded by not by foundations in conjunction with federal research to delineate the three different rash genes, the mutations on the genes that led to the pancreatic that are seen highly in pancreatic cancer. The whole way the gene turns on DNA and the proliferation of cells, the way it gets turned off So that cell cycle, they don't just, aren't just proliferating and going,

reproducing and creating cancers. All of that is the stuff that's been, you know, elucidated for the last, you know, 30, 40 years by both get the human genome project, but then also really delving into which genes are turned on and which cancers. that's why this gene set was known for a while, you know, and thought to be undruggable because we knew this was the key, the rash gene, the key mutation that sort of drove pancreatic cancer. So last question, we've been in the last 16 months, I want to say, in an environment where there's been a lot of instability, there's been cuts, talks about changes in policy to federal funding for medical research, changes in NIH.

There's talk about now a proposal to put an extra layer of political approval on grants over the top of peer review. Now, I know we've talked about this before. I know you're one of those people that says actually NIH needed some reform, but overall... This isn't the reform it needed. Politization of research and science is not the reform it needed. Right, right. So are you worried? Oh, it's dreadful.

First of all, Jonathan, You have made an important point about trying to politicize the granting mechanism. But there's also a problem. So there's a problem of cutting the research grants. There's a problem of trying to cut what they're called indirects. That's like the funding to keep the lights on, the funding for the centrifuges, the funding for other incidental things that you don't buy new for every grant. There's also a lack of leadership.

You know, most of the institutes now do not have a price. permanent leader, and that's hard to create a strategic plan. We're going to go in this direction, and that's a super serious problem. So my criticism to the extent that I think important reform was needed at the NIH, I think that there were two important reforms that would really help the NIH. One is to move a lot more money to younger people. Now, we've had a bunch of research that has shown. The most creative science is done by people early in the their career, the late 30s, early 40s. We know this from Nobel Prize winning data. It's too late to basically start doing medical research is what you're saying.

Well, the older you get, the more, I don't want to say rigid, but you're doing the, you know, you're following the same path. And your framework, the sort of mental picture you have is sort of set. So we know that younger people are just, you know, let's be honest, more creative. And so I think shifting a lot more money to earlier, really, really important. and the NIH should be sending a whole lot of money earlier. The second thing I want, the big reform I think would be important is stop investing in projects, three-year projects. You know, venture capital invests in people.

Businesses invest in people. They have good ideas. And they recognize, oh, yeah, they've got this idea, but they're going to pivot three or four times before they settle on the right way to go forward. And so you invest in people. And by the way, the Howard Hughes Medical Institute, HHMI, big institute with billions of dollars that it gives away, they invest in people, not projects typically. And they give people long-term grants and say, you know, do your best work. And that's, so those are the two big reforms, I think, the NIH should have.

The idea that we're going to politicize these grants is ridiculous. You know, that doesn't get you the best science by a politician who knows nothing about medicine, deciding. what is better for the country. You don't think Stephen Miller making research decisions is a terrible idea. And we've seen this, you know, when they screened all those grants for the word diversity because they didn't like diversity, equity, and inclusion, they got a lot of diversity. You know, I have a project which is diversity of age span. All right.

It has nothing to do with racial or sexual diversity. But, you know, that gets beaten because it's diversity. I mean, that's just a moronic approach to this. But I would also say, you know, you may remember and your readers may remember way back, like, you know, six months ago, the government, the Department of Education released this compact it wanted to make with 11 elite universities, selective universities, and say, you know, if you play ball with us, if you're loyal to us, we'll prioritize your grants. That is non-meritocratic. Now, this is an administration which says it's one people admitted to university on the basis of merit, not on the basis of race, sexual, or anything, whatever, right? And then they're about to say, oh, but we're not going to evaluate grants on the basis of merit. We're going to look at all these other things.

You know, are you loyal to us? You know, where are you located that have nothing to do with scientific quality? That is a hypocrisy from start to finish, as far as I can tell. We should fund science. and public wants to fund science, and it wants to fund science based upon the merit of the ideas and the creativity of the people doing the research, not their political orientation, their loyalty. There is no evidence, and as a matter of fact, there's pretty good evidence from the Soviet Union that research based upon political loyalty does not win the day.

Yeah, yeah. Well, on that note, Zika Manuel, thanks so much for making time today. listeners, followers, stay tuned to the bulwark to read about medical advances like these and the role of federal government in hopefully bringing you more of them. Thanks a lot. Take care. Thank you, Jonathan, for having me.