¿Cómo afecta el congelamiento de fondos de los NIH a las investigaciones sobre el cáncer de mama (seno)? Un científico lo explica

Welcome to The Breastcancer.org Podcast. The podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor, Jamie DePolo.

Jamie DePolo: Hello, as always, thanks for listening.

The National Institutes of Health are the largest funder of cancer research in the world. An executive order from the current administration has frozen NIH funding and cut indirect cost payments. Another executive order has halted all public communications by a number of federal agencies. Challenges to the orders are winding through the courts. 

My guest is Dr. Donald McDonnell, professor of medicine, pharmacology, and cancer biology and cell biology at the Duke University School of Medicine. His research aims to develop new medicines for breast cancer and prostate cancer. He’s going to help us understand how many of the current political actions are affecting cancer research and what that means for people with breast cancer. 

Dr. McDonnell, welcome to the podcast.

Donald McDonnell: Jamie, always a pleasure to talk to you.

Jamie DePolo: Thank you so much for doing this. I guess I’ll start by asking just a general question. So, how does this freeze on NIH funding affect cancer researchers like you? Like, do you have grants that are now stopped? Do you have projects that you had to end?

Donald McDonnell: First of all, let me just state, if you don’t mind, just to be clear. Although I'm a professor at the university, these are my own opinions and not necessarily the opinions of the university. My own personal opinions. 

So, your question is very important, as how does it affect?

I don’t think that people actually understand the multiple ways that this affects us. And if you don’t mind, I'm just going to go down through it in layers because ultimately what it has done, it has introduced a chaos into research right now that has really put a pall of doom or a black cloud over research.

I was quoted in a newspaper article the other day, and I’ll stand by this quote, is that it’s just difficult to think in this chaos. Actually, I and my colleagues should be thinking about what is the best way, the next step, that we can, you know, the next problem that we can tackle in breast cancer research. Not really worrying about, you know, what the next mandate that’s going to come upon us that’s going to limit our research. So, that’s the overarching thing. 

So personally, we have grants that are in holding tanks. We don’t know where they are. We submitted them for review and they’re basically in holding tanks. They’re not selected for an institute yet. They’re not selected for review. There are no council meetings. So, even if the best-case scenario occurred, if tomorrow morning they hit the start button, it is unlikely that if we were successful in the first round we would see this money until the end of the year. That would be ambitious.

Most of us in cancer research, we live from year to year, okay. Our budgets go from year to year. That we’re going to get one or two grants a year and that’s going to keep us, you know, at an even keel. We’re looking at the situation that notwithstanding the contributions of various foundations, there may be no federal money coming into our programs this year. 

Yesterday evening I was at a dinner, and I heard that now in the current congressional budget, they’re talking about a 57% reduction in the CDMRP program. This is the program that funded prostate cancer research and breast cancer research through DOD. This has been an incredibly, incredibly successful program for over 30 years, and basically it already funds at a level of about 4% or 5%. If you cut that in half, you're talking about 2%. I mean, they talk about efficiency, we were already probably one of the most efficient disciplines and now they’re asking us to go basically from being very efficient to going broke. 

Jamie DePolo: Right. And I do want to ask you…I mean, my understanding is that most of the drugs that are used today to treat breast cancer, tamoxifen, all the aromatase inhibitors, they all came out of NIH-funded research. That’s why we have those medicines today. 

Donald McDonnell: Yeah. It’s interesting you said that because I was asked in a lecture the other day, could I think of, in the breast cancer arena, could I think of drugs who didn’t really start their life in academic research. So, tamoxifen is a little bit different, actually. Just for your reader’s interest, tamoxifen was actually a repurposed oral contraceptive. It was not really developed as a breast cancer drug. And it was Craig Jordan, the late Craig Jordan, who actually repurposed that drug. 

But if you look at the aromatase inhibitors, that came out of purely NIH-funded, NCI-funded research from Angela Brodie’s lab at the University of Maryland. You look at all the SERDs. I mean, to be honest with you, but with some humility I’ll say, we started the oral SERD field that came out of NIH-funded research. And in fact, elacestrant, which is the drug that was just approved, that my lab discovered its utility for, was just approved last year. That drug came out of research that was done on my NIH grants. And so, now what I'm looking at is, where is the money going to come from? You know, I get people saying, oh, breast cancer is well-supported by the ACS or well-supported Komen. We appreciate that funding, but there is nothing, nothing is going to substitute for the stability and the magnitude of NCI/NIH funding. 

Jamie DePolo: Right. And I know, or least my understanding, the other part of the problem is because this public communication has been halted…so, you were talking about the study group meetings, the groups that need…

Donald McDonnell: Study sessions. Yeah. 

Jamie DePolo: …study sessions to approve the grants or even decide, you know, which grants go where, there has to be public notices of those meetings in the Federal Register. And so, that’s been quashed. So, even if the courts said, no, you have to restore the funding, they can’t allocate the funding because they can’t put the notices in the Federal Register. Am I understanding that correctly as well?

Donald McDonnell: That’s right. And that’s the first step, Jamie. The first step is what’s called peer review. So, I’ll just give you the timeline.

A grant that would’ve been submitted in February of this year should have been reviewed in June. Then that grant would go…if it was positively received…it would go to council in September or October for funding in December. That’s the timeline. Those grants that all of us submitted in February, we have no idea when they’re going to be reviewed. So, now that basically kicks things off. And to my knowledge, and I could be wrong on this, but to my knowledge there have been no council meetings since these mandates. And so, that basically means that no new money is being given out. 

Jamie DePolo: Right. And I know most federal grants are dispersed quarterly or I shouldn’t say that. 

Donald McDonnell: Annually. DOD is actually interesting. DOD is better. For us it turned out, it’s great. Your DOD grants when you get awarded it for three years, you get the check for the three years. 

Jamie DePolo: Oh, you get it all at once. Okay.

Donald McDonnell: I'm delighted that I got my DOD money now. 

Jamie DePolo: Right. Because otherwise no new money is coming in so, you know, I assume there’s a point where, like everything has to stop if no new money comes in. Is that right?

Donald McDonnell: Absolutely. Jamie, I have two screens open right now just because I was working on something before you came on, and it’s the spreadsheet. It’s a spreadsheet looking at where the cliff is and I'm looking at it right now. I'm not going to tell you the numbers because you’d fall off your chair, but I'm going to hit a cliff in about October of this year. And that’s the point where I'm going to have to make decisions about contracts for the next year. 

Jamie DePolo: Right. And it’s also, you know, to sort of extrapolate off that, so if you have to make those decisions, I'm assuming that also affects graduate students. So, we’re completely sort of crushing, downsizing, the pool of new scientists coming up to do new research. 

Donald McDonnell: There are two things. So, you're absolutely right. So, I'm actually meeting right now with young graduate students because this is the time of year when students come in. Students who matriculated last July and August, will now pick their labs to do their doctorate research. They spent their formative year doing classwork, something like that. And they are stressed out of their minds because the professors can't commit because we don’t know what’s going to happen. And so, what happens with a graduate student is that when we accept them into our lab, we accept financial responsibility, obviously, for that student for the duration of their training. 

And so, even though they may be the last in, they’re not the first out. So, we would have to let go research technicians, post-doctoral fellows, and things like that because students have got to be continually funded for the duration of their studies.

So, what that means is the professors are a little bit hesitant of taking a risk. Now I'm personally going to take a risk. I'm going to take on some students because I feel that I have to keep my operation going, but I'm running a risk. And the risk is that, you know, come next year I'm going to be in a bad situation. So, that’s one thing, if you don’t mind. 

The second thing though is that the students, they don’t have as many avenues to apply for grants anymore. So, again there are three, if you want, typical ways that a graduate student can get funded. Notwithstanding foundations and things like that, which are very rare to get funded.

The first one is what’s called the F31. The F31 is basically a pre-doctoral fellowship that’s for three to four years. It’s funded by either NIGMS or NCI, okay. My students are applying for those right now because the announcement of those is still on the website. So, in other words, you still can apply, but unfortunately, they’re still going to go into a holding pen right now, but at least you're in. Okay. 

The other one…I disagree with this one, and that is they have stopped diversity supplements, and this is probably something that I'm willing to be outspoken on. We need to have people from different backgrounds, different parts of the world, everything working together. When you come together with different backgrounds like that, we think differently, and we address problems differently. And it is absolutely, positively established that there’s a diversity bonus in research. And so, that’s why it pains me now that there’s no things like diversity supplements. So, I can't apply for grant supplements to actually encourage people from diverse backgrounds to come and work in my lab. 

I'm losing now. I'm not losing just financially, I'm losing the potential to have that input in my research. You know, we’re talking about breast cancer research, triple-negative breast cancer is one of the things that I work on an awful lot. I work on prostate cancer. Triple-negative breast cancer disproportionately affects Black women over Caucasians. That’s not political, that’s biology. And so, we have to address these problems differently, okay? And it’s not just cancer, there are lots of other diseases that are different according to our genetic background. Sickle cell anemia, there’s another one. So, I mean, it just boggles the mind that you can just take a sweep and take away all of that which we have developed, which I believe, is incredibly positive. So, I hope that this is one of those things where we overcorrect and then come back. I really do. 

Jamie DePolo: Well, and following up on your comments about diversity, I know that there was an executive order that all these diversity, equity, and inclusion programs, and accessibility; diversity, equity, inclusion, and accessibility, were ended and I know a lot of people feel, besides sort of limiting your pool of researchers, it’s also going to make clinical trials less diverse because, you know, how can you recruit if you don’t have these special programs? I mean, we already have a problem with a lack of diversity in clinical trials. 

Donald McDonnell: Yeah. This is not something I'm directly involved in, but I am peripherally in my role as assistant director of translational research at the cancer institute, I see this an awful lot. And we strive to actually enroll clinical trials in a manner that allows proportional patients enrolled to reflect the catchment area, if you want. And you know, we’re in Durham and we have large minority populations in Durham, okay? And it’s very difficult to actually attract people of Hispanic and African-American [heritage] into clinical trials. There’s a little bit of distrust for obvious reasons. 

And now, this is a further burden right on top of it. So, now the outreach that we do, the funded outreach that we do, that would be considered no-go. An area not to go in anymore. Now you're starting to actually say, oh, I am potentially disadvantaging people now because I'm not allowing them to go onto these tailored trials or allowed to be into this avant-garde or contemporary trials. That point has not really come across very well.

Jamie DePolo: Right. And just one more point on that. I know that some of the outlets I've been reading, some of the stories are saying that papers with keywords that the Trump administration doesn’t like, including gender, transgender, they’ve been removed from PubMed. And PubMed is sort of a big repository of research papers that anyone that can access, I use it all the time. You can go in, you can search, you can find these papers. What I've read is that the papers that have been removed you can still find them in the original journal, but as a scientist, I'm asking you, I mean, I think that would be also a huge disadvantage for research because you’d have to go to like five, 10 different places to find the appropriate papers.

Donald McDonnell: There are other ways of doing it. I mean we can go through Google Scholar or other ways to get to the original journals, but that’s not the point.

The point is that the arbitrary removal of scientific information is counterintuitive to what we’ve always done and to what we are, you know? We are a nation that basically has always really taken the facts, built on the facts, and formed our own opinions. I actually have no problem with people having different opinions than me. But you know, on that note, I'm not going to get into the politics. They can waste their time up in Washington doing that.

I'm more interested really in advocating for the fact that money spent in research is money well spent. That’s the other way of looking at this. 

I could sit here and whine and complain that my research has been cut. As people have said to me when I've been on podcasts like this and pro shows like this, stop whining. You’ve got a great job. You're a university professor. That’s not the point. The point is, is that we are doing phenomenal, I believe, and I use we globally, are doing phenomenal things. Look at the advances that we’ve made in breast cancer for instance. Look at estrogen receptor-positive breast cancer. I got into this field in 1978, or I started in this field when I was a teenager when my mother-in-law got breast cancer. She was basically told to go home and settle her affairs. 

Now 97% of women who present with early-stage, ER-positive breast cancer never hear of that disease again. I'm saying this only because it’s kind of humorous. You know, one of the comments I got by email after my comment was, you're a research failure because you only discovered one drug in 30 years. That’s incredible. That’s just incredible. People just don’t understand that this is a very complicated disease and day by day we’re knocking it off, we’re knocking away the edges of it. And it’s not just breast cancer, it’s prostate cancer. It’s even the tough cancers we’re making progress. It’s money well spent. We can't be any more efficient, Mr. Musk, than we are. We really can't. 

Jamie DePolo: Right. And I don’t have the numbers, and I wouldn’t even know how to start to calculate this, but it would be very interesting to know for the research money spent and the drugs developed, how many lives have been saved. I'm sure somebody could do that math. Somebody who’s better than me with all those…

Donald McDonnell: I’ll tell you an interesting number. This is a long time ago. I remember Craig Jordan was giving a lecture, the late Craig Jordan, on tamoxifen. He was giving a lecture at San Antonio, and he was introduced…and I can't remember who introduced him, and again, I stress it was a long time ago because the number was mindboggling then. When he introduced him he said, this is Dr. Jordan whose repurposing of tamoxifen has been responsible for saving 800 million years of women’s lives. 

Jamie DePolo: Right. And that’s just one drug. 

Donald McDonnell: That was one drug, one person’s activities. And of course, all the people who helped at the clinical trials and things like that, and that speech has got to be 15 years ago. 

Jamie DePolo: So, it’s only exponentially larger.

Donald McDonnell: Exactly. That number has stuck with me. I use it with my students and it’s exactly for the point that you're trying to make, Jamie, is that these drugs are incredibly effective…look at Herceptin. Herceptin started off as a basic research observation in Denny Slamon’s lab and if it wasn’t for Dennis Slamon this drug would never, in my opinion, would never have seen the light of day. Now Genentech is the ones who went and did the clinical trials, but they were not that excited about it until Dennis Slamon, and then worked on by the late Bill McGuire, who basically identified which patients should get it. Look at the success of it and the second generation and the third generation. 

Pembromizulab, the ADCs, Enhertu. You know, these are all building off the same things. Most of it being academic research or at least the foundation was fundamental academic research. I know it’s a bit melodramatic to say that science is going to stop, but what’s going to happen is we’re going to get a pause and it’s going to take a while for us to get back in on it again. We’re going to flush out a lot of young investigators who decide, time out, I don’t want to do this. This is just too difficult. We’re going to have reduced numbers of people that’s going to graduate school. The trickle down of the knock-on effect I believe is going to be substantial, even greater than the immediate effect it’s having on us now. 

Jamie DePolo: Right. There is one more thing I wanted to ask you about funding, because I'm not sure anybody who hasn’t worked in academia understands it, and that’s the overhead costs or the indirect costs. And that was a big thing that got reported on and you know, I used to work in academia so I know what that is, but if you could kind of explain. I know one of the executive orders capped NIH indirect funding costs at 15%. So, could you explain what they are and then why that’s an issue?

Donald McDonnell: Okay. So, you know, the best way to describe it is that somebody asks me to do a project, okay? They ask me to develop a drug that can inhibit the estrogen receptor, okay? And I sit down at my computer, and I figure out, that’s going to take five years, three graduate students, two post-docs, and a portion of my salary. I calculate it and it’s going to cost about 70% salaries and 30% supplies. That’s the cost of doing the project, okay?

Okay. But I need somewhere to sit. I need benches. I need equipment. I need lights. I need someone to manage my budgets. I need someone to overview my protocols to make sure that I'm in compliance with local and federal laws. I need someone to oversee my animal studies. I need someone to actually help me to get IRB approval to get patient data and patient samples. All of that huge infrastructure costs money. 

So, the next thing I've heard though, Jamie, is that yeah, but it doesn’t have to be 60%, which is 61% here at Duke. What people don’t know is that this is not just a number we pulled out of the air. This is a number that is negotiated with the government over years where they go through line item by line item. How much, you know, they’re going to allow for rent for the building. How much they’re going to allow for electricity. You know, right down to the nth detail and then they can put in a number. And then we’re stuck with that number.

And what most people also don’t realize is that even with that 60% overhead, Duke still has to support my research to the tune of 40 cents on the dollar over that. Even with the cost of the project with the indirect costs, it still costs another 40 cents more, which Duke basically pulls out of its coffers. I can tell you right now if indirect costs end up at 15%, which I think in the end they won’t and I don’t want to be over dramatic, but this mission is over. 

Jamie DePolo: Yeah.

Donald McDonnell: We cannot survive in an environment of 15% indirect costs. It’s just not possible. 

Jamie DePolo: Right. And that’s what I don’t think people understand, you know, if you get, say a $2 million grant to do the research, you know, the indirect costs are paying for is what you said, you know, keeping the lights on, the refrigerators that run the things, you know, the benches, the desks, the paper, the copy machines, the computers, all that kind of stuff. It’s like asking somebody to live but not giving them a house or any food or anything like that.

Donald McDonnell: I mean, it’s like when you do a factory and asking someone how much is it going to cost to make that widget. And the guy says, well, it’s going to cost me five cents worth of plastic. It’s going to cost me 20 minutes of a technician’s time to run the machine. So, maybe $4. Okay, so it’s $4. Well, no. Because we actually have to have a building. We have to be able to ship the widget to your place. People are forgetting, they’re not thinking about…they’re thinking about these research grants as funding the project and everything associated with it. They don’t. They fund the very specific project. Now, we could change the model. It wouldn’t help anybody. We could change the model where we actually build indirect costs into the cost of the grant. Right? So, in other words, I'm just making this up. You know, it’s X dollars per square foot for rent and things like that. We could calculate that, but it’s going to come out of the exact same number. 

Jamie DePolo: Right.

Donald McDonnell: And what it would do is…it’s better that the government comes in and negotiates this every N years because then I don’t have to do it every single time I put a grant in. Because you can imagine the other way, I’d have to negotiate this every single time and again I want to emphasize I'm a much better scientist than I am a bookkeeper. 

Jamie DePolo: Right. I feel like that’s what a lot of these executive orders are doing, you know, when you said, you can't think right now. They’re not allowing you to do science, they’re making you worry and think about other things. 

Donald McDonnell: It’s chaos. I mean, the long-term consequences of these need to be thought through. You know, biomedical research in America is an incredibly strong enterprise. We are among the best biomedical researchers and I'm going to be boastful enough to say that I would say 90% of the new medicines come from research that’s done in the United States. I probably have to go and do some research to get the exact number, but a lot of it comes from research. And it’s because America has always been willing to support big projects, big initiatives, okay? Big bold moves. The moon shot. They were great. They were like big bold moves. Although he didn’t do it, even Nixon supported, you know, the war on cancer. We were never afraid of big things. The problem is that research costs money and people just don’t understand it. Unfortunately, even with the cuts the amount of money that they are going to save is really relatively small.

Jamie DePolo: Right. Right. And how many lives will be lost while research is paused. And I guess that’s probably a good way to sort of conclude. So, ultimately, what does this mean for people, like say, somebody who has been diagnosed with breast cancer this morning?

Are we going to have delays in developing new treatments? I'm talking to somebody next week, a researcher who has developed…you talked about ADCs, antibody-drug conjugates. He is working on developing an antibody-toxin conjugate to treat breast cancer a little bit differently. But that’s like in phase II, you know, that’s not going to be available in the clinic for a while. And now I'm thinking that instead of say 10 years before we saw it now it could be 20 or 30, and how many people are going to have to die?

Donald McDonnell: I think we’re going to have to rely, we always have…so most of the registration, well, nearly all registration trials are done in collaboration with large pharmaceutical companies. But they have got priorities, too, and the laws have changed for the way that they do business as well, and so they’re much more selective.

I think a clinician is probably better qualified to tell you how Mrs. Jones walking in this morning is going to be affected. But as the translational researcher who develops drugs, I mean, it’s just intuitive. Basically, you slow down the funding on new, contemporary avant-garde medicines, Mrs. Jones or Mrs. Jones’ daughter is not going to do as well as she would the day before you cut the funding out. I mean, that just makes common sense. 

I really am, you have known me long enough, Jamie, to know I'm a very positive person. I think we’ll get through this, but I'm not really – well, I am worried about myself, actually morning, noon, and night I'm worried about it. But it’s really the young investigators that are coming into the field right now. I’ll just give you one example, if you don’t mind. I have a phenomenal young lady, Bonita, and she’s a post-doctoral fellow who has been looking at how estrogens regulate tumor immunity. And I want to tell you just two little anecdotes about this.

One is, she just put a grant in that’s going to be reviewed whenever. But she was terrified that there’s a new requirement that you test your hypothesis in both males and females. Well, she has to put estrogens into males, right? And we’re terrified that will get caught by some DOGE person up in Washington because that’s perfectly scientifically justified, it’s got nothing to do with transgender, nothing. Males have estrogen. Right. So, that’s the first thing. 

But the second thing, which is interesting, is that she’s now in the job market. She’s published some amazing papers. She’s one of the best candidates I've had in years. And all we’re getting letters back is, sorry, hiring is paused. So, I bet you that is happening in thousands of places and with thousands of people, young investigators across the world. And so, people like that say, well, gosh, do I really want to go forward with my career in academics. Maybe, I’ll find an easier path, and that’s what I'm afraid of, Jamie. 

Jamie DePolo: Right. Or they’ll go to a different country. 

Donald McDonnell: That’s also the case. You know, it’s interesting because what we’re seeing now and I was actually looking at this the other day, the number of applicants that I get for training positions from Europe, from China, from Asia, has gone down to a trickle. I mean, a trickle. And if you come into my lab and walk around it, right now as of now, we have probably about six or seven countries covered here, and that’s power. I mean, having people from different backgrounds is very useful and now we’re kind of not in that position. 

Jamie DePolo: Well, Dr. McDonnell, thank you so much. I appreciate your insights. I'm hoping that funding goes forward, and things will move forward and start to work again. I just keep thinking about the people, just like the average person, the average people who are going to be affected by this and it makes me very sad.

Donald McDonnell: Well, if you just keep getting the message across that we’re doing good, we have done good, and we will do good. And that we need to get back to normalcy. 

Jamie DePolo: Yeah. Thank you very much. 

Donald McDonnell: Thank you, Jamie. 

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