Ground Truths

Dr. Susan Monarez was the first CDC Director to be confirmed by the Senate and served from July 31, 2025 – August 27, 2025. Because she refused to give approval to new vaccine recommendations without ever seeing them or their evidence and firing scientists without cause, she was fired. In my view, she’s a hero for standing up for science and speaking truth to power.In her first live interview since leaving the CDC, we review her background. That includes growing up in rural Wisconsin and getting her college and PhD education at UW-Madison, the latter in microbiology and immunology. She then went on to 18 years of government service with an extensive portfolio of jobs and management at BARDA, the White House, ARPA-H, and others, before becoming Acting Director of the CDC in early 2025.We discussed the horrific CDC shooting on August 8th, days after she started. Then we reviewed a conversation that we had on August 19th in which she laid out her exciting vision for the future of CDC, emphasizing the goal of prevention (BTW, CDC stands for Centers for Disease Control and Prevention) and asked me to help as an advisor. At the time, she was well aware, with growing tension, that her tenure at CDC might be limited. I asked about her perspective for the jobs of 4,300 people at CDC who have been terminated, which account for more than 1/3rd of the workforce, no less the gutting of the budget.Then we got into what she learned from this ordeal and her plans for the future, which includes a very ambitious initiative: 90/90/2035. As you’ll see from our conversation, Dr. Monarez is exceptionally resilient and an optimist. She’s got lots to do in the years ahead to carry out her mission of promoting human health!Dr. Monarez just started a Substack The Road Best Traveled so you can follow her there. It was a real privilege for me to do this interview with her. In deep admiration of her willingness to not only take on the job of CDC Director in tough circumstances, her professionalism during testimony at the Senate committee hearing, her impressive yet unrealized vision for transforming the CDC, and refusing to cave to immense pressure from the HHS Secretary to move ahead with his agenda. Thank you Julie, Stephen B. Thomas, PhD, David Dansereau, MSPT, Dr. Sara Wolfson, Vau Geha, and >500 others for tuning into my live video with The Road Best Traveled! Thanks for being a Ground Truths subscriber! Please spread the word. Get full access to Ground Truths at erictopol.substack.com/subscribe

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Thank you Bruce Lanphear, Clyde Wilson, Tracy Dennis-Tiwary, Diego Pereyra, Dr Mike Hunter, and many others for tuning into my live video with Charlotte Blease! Join me for my next live video in the app.Whether A.I. will transform the practice of medicine in a positive way remains controversial. Health researcher Prof Charlotte Blease, on faculty at Uppsala University in Sweden and researcher at Harvard University, has written a new book —Dr. Bot—that critically assesses the unmet needs in healthcare and whether A.I. can fulfill them. She provides an optimistic viewpoint (see the subtitle), and our conversation probes whether that is justified. She has a substack, too, hereThanks for listening to Ground Truths. Through analytic essays and podcasts, I try to cover the important issues and discoveries in life science and medicine. If you have suggestions for topics I should get into, please pass them along. Get full access to Ground Truths at erictopol.substack.com/subscribe

Thank you Jose Bolanos MD, Dr. Zeest Khan, Lawrence Toole, Julie, Stephen B. Thomas, PhD, and many others for tuning into my live video with Dr. Sanjay Gupta. Join me for my next live video in the app.A Brief Summary of Our ConservationWe discussed the new understanding and approach to chronic pain, which affects nearly 1 in 4 adults. Dr. Gupta gets personal telling the story of his wife, Rebecca, who has an autoimmune disease and at one point he had to carry her up stairs. He also tells the story of his mother who had a back injury and didn’t want to live because of the pain. How his family members got relief is illuminating.Our whole understanding and approach to pain has changed, with the acronym change from RICE to MEAT.A newly approved drug Suzetrigine (Journavx) exploits the sodium channel gene mutation initially discovered via a family of fire walkers. It’s the first new pain medicine approved for more than 2 decades. Many other new non-opioid treatments are reviewed, no less lifestyle changes (anti-inflammatory diet and sleep), and acupuncture.Sanjay’s research over the past few years has led to a video special on CNN with the same title as the book, set to air 9 PM EST Sunday. If you know someone suffering chronic pain, please share the post. Get full access to Ground Truths at erictopol.substack.com/subscribe

This is a hybrid heart disease risk factor post of a podcast with Prof Bruce Lanphear on lead and a piece I was asked to write for the Washington Post on risk factors for heart disease.First, the podcast. You may have thought the problem with lead exposure was circumscribed to children, but it’s a much bigger issue than that. I’ll concentrate on the exposure risk to adults in this interview, including the lead-estrogen hypothesis. Bruce has been working on the subject of lead exposure for more than 30 years. Let me emphasize that the problem is not going away, as highlighted in a recent New England Journal of Medicine piece on lead contamination in Milwaukee schools, “The Latest Episode in an Ongoing Toxic Pandemic.”Transcript with links to the audio and citationsEric Topol (00:05):Well, hello. This is Eric Topol with Ground Truths, and I'm very delighted to welcome Professor Bruce Lanphear from Simon Fraser University in British Columbia for a very interesting topic, and that's about lead exposure. We tend to think about lead poisoning with the Flint, Michigan, but there's a lot more to this story. So welcome, Bruce.Bruce Lanphear (00:32):Thank you, Eric. It's great to be here.Eric Topol (00:33):Yeah. So you had a New England Journal of Medicine (NEJM) Review in October last year, which was probably a wake up to me, and I'm sure to many others. We'll link to that, where you reviewed the whole topic, the title is called Lead Poisoning. But of course it's not just about a big dose, but rather chronic exposure. So maybe you could give us a bit of an overview of that review that you wrote for NEJM.Bruce Lanphear (01:05):Yeah, so we really focused on the things where we feel like there's a definitive link. Things like lead and diminished IQ in children, lead and coronary heart disease, lead and chronic renal disease. As you mentioned, we've typically thought of lead as sort of the overt lead poisoning where somebody becomes acutely ill. But over the past century what we've learned is that lead is one of those toxic chemicals where it's the chronic wear and tear on our bodies that catches up and it's at the root of many of these chronic diseases that are causing problems today.Eric Topol (01:43):Yeah, it's pretty striking. The one that grabbed me and kind of almost fell out of my chair was that in 2019 when I guess the most recent data there is 5.5 million cardiovascular deaths ascribed to relatively low levels, or I guess there is no safe level of lead exposure, that's really striking. That's a lot of people dying from something that cardiology and medical community is not really aware of. And there's a figure 3 [BELOW] that we will also show in the transcript, where you show the level where you start to see a takeoff. It starts very low and by 50 μg/liter, you're seeing a twofold risk and there's no threshold, it keeps going up. How many of us do you think are exposed to that type of level as adults, Bruce?Bruce Lanphear (02:39):Well, as adults, if we go back in time, all of us. If you go back to the 1970s when lead was still in gasoline, the median blood lead level of Americans was about 13 to 15 µg/dL. So we've all been exposed historically to those levels, and part of the reason we've begun to see a striking decline in coronary heart disease, which peaked in 1968. And by 1978, there was a 20% decline, 190,000 more people were alive than expected. So even in that first decade, there was this striking decline in coronary heart disease. And so, in addition to the prospective studies that have found this link between an increase in lead exposure and death from cardiovascular disease and more specifically coronary heart disease. We can look back in time and see how the decline in leaded gasoline led to a decline in heart disease and hypertension.Eric Topol (03:41):Yeah, but it looks like it's still a problem. And you have a phenomenal graph that's encouraging, where you see this 95% reduction in the lead exposure from the 1970s. And as you said, the factors that can be ascribed to like getting rid of lead from gasoline and others. But what is troubling is that we still have a lot of people that this could be a problem. Now, one of the things that was fascinating is that you get into that herbal supplements could be a risk factor. That we don't do screening, of course, should we do screening? And there's certain people that particularly that you consider at high risk that should get screened. So I wasn't aware, I mean the one type of supplements that you zoomed in on, how do you say it? Ayurvedic?Supplements With LeadBruce Lanphear (04:39):Oh yeah. So this is Ayurvedic medicine and in fact, I just was on a Zoom call three weeks ago with a husband and wife who live in India. The young woman had taken Ayurvedic medicine and because of that, her blood lead levels increased to 70 µg/dL, and several months later she was pregnant, and she was trying to figure out what to do with this. Ayurvedic medicine is not well regulated. And so, that's one of the most important sources when we think about India, for example. And I think you pointed out a really important thing is number one, we don't know that there's any safe level even though blood lead levels in the United States and Europe, for example, have come down by over 95%. The levels that we're exposed to and especially the levels in our bones are 10 to 100 times higher than our pre-industrial ancestors.Bruce Lanphear (05:36):So we haven't yet reached those levels that our ancestors were exposed to. Are there effects at even lower and lower levels? Everything would suggest, we should assume that there is, but we don't know down below, let's say one microgram per deciliter or that's the equivalent of 10 parts per billion of lead and blood. What we also know though is when leaded gasoline was restricted in the United States and Canada and elsewhere, the companies turned to the industrializing countries and started to market it there. And so, we saw first the epidemic of coronary heart disease in the United States, Canada, Europe. Then that's come down over the past 50 years. At the same time, it was rising in low to middle income countries. So today over 95% of the burden of disease from lead including heart disease is found in industrializing countries.Eric Topol (06:34):Right. Now, it's pretty striking, of course. Is it true that airlines fuel is still with lead today?Bruce Lanphear (06:45):Well, not commercial airlines. It's going to be a small single piston aircraft. So for example, when we did a study down around the Santa Clara County Airport, Reid-Hillview, and we can see that the children who live within a half mile of the airport had blood lead levels about 10% higher than children that live further away. And the children who live downwind, 25% higher still. Now, nobody's mapped out the health effects, but one of the things that's particularly troubling about emissions from small aircraft is that the particle size of lead is extraordinarily small, and we know how nanoparticles because they have larger surface area can be more problematic. They also can probably go straight up into the brain or across the pulmonary tissues, and so those small particles we should be particularly worried about. But it's been such a long journey to try to figure out how to get that out of aircraft. It's a problem. The EPA recognized it. They said it's an endangerment, but the industry is still pushing back.Eric Topol (07:55):Yeah, I mean, it's interesting that we still have these problems, and I am going to in a minute ask you what we can do to just eradicate lead as much as possible, but we're not there yet. But one study that seemed to be hard to believe that you cited in the review. A year after a ban leaded fuel in NASCAR races, mortality from coronary heart disease declined significantly in communities near racetracks. Can you talk about that one because it's a little bit like the one you just mentioned with the airports?Bruce Lanphear (08:30):Yeah. Now that study particularly, this was by Alex Hollingsworth, was particularly looking at people over 65. And we're working on a follow-up study that will look at people below 65, but it was quite striking. When NASCAR took lead out of their fuel, he compared the rates of coronary heart disease of people that live nearby compared to a control group populations that live further away. And he did see a pretty striking reduction. One of the things we also want to look at in our follow-up is how quickly does that risk begin to taper off? That's going to be really important in terms of trying to develop a strategy around preventing lead poisoning. How quickly do we expect to see it fall? I think it's probably going to be within 12 to 24 months that we'll see benefits.Eric Topol (09:20):That's interesting because as you show in a really nice graphic in adults, which are the people who would be listening to this podcast. Of course, they ought to be concerned too about children and all and reproductive health. But the point about the skeleton, 95% of the lead is there and the main organs, which we haven't mentioned the kidney and the kidney injury that occurs no less the cardiovascular, the blood pressure elevation. So these are really, and you mentioned not necessarily highlighted in that graphic, but potential cognitive hit as well. You also wrote about how people who have symptoms of abdominal pain, memory impairment, and high blood pressure that's unexplained, maybe they should get a blood level screening. I assume those are easy to get, right?Bruce Lanphear (10:17):Oh yeah, absolutely. You can get those in any hospital, any clinic across the country. We're still struggling with having those available where it's most needed in the industrializing countries, but certainly available here. Now, we don't expect that for most people who have those symptoms, lead poisoning is going to be the cause, right. It'd still be unusual unless you work in an industry, for example, smelting batteries to recycle them. We don't expect it to be real common, and we're not even sure, Eric, whether we should be doing widespread screening. If I looked at this as a population scientist, the real focus should be on identifying the sources. We mostly know where those are here and radically moving it down. Getting rid of the lead service lines, which was such a big part of what President Biden was doing, and it was perfect. For every dollar invested to reduce lead exposure from those lead service lines. Ronnie Levin at Harvard said there'd be a 35-fold return in cost, benefits really, and this has always been true, that reducing lead exposure throughout the past 40 years has always been shown to be amazingly cost beneficial. The problem is operating within a free market health system, even though there's tremendous social benefits, that benefit isn't going to be monetized or privatized. And so, who's going to make those decisions? We hope our government is, but that doesn't always play out.Eric Topol (11:52):Well. What's interesting is, as opposed to the problems we have today that are prominent such as the microplastic, nanoplastics, the air pollution, the forever chemicals, that just keep getting worse, I mean, they are just cumulative. This one, there was tremendous improvement, but it’s still not enough. And I guess you're zooming in on the lead lines. That'd be the most important thing to work on today. Another thing that has come up, there's been trials, as you may I'm sure, because all over this field of chelation, there's a trial that was run by the NIH, supported by NH that looked at chelation to prevent coronary disease. Is there any evidence that people who have a problem with lead would benefit from chelation therapy?Bruce Lanphear (12:44):Well, there's two major studies that have been done, and Tony Lamas was in charge of both of them. The first one Trial to Assess Chelation Therapy (TACT) study, it was a randomized controlled trial, not intended specifically to focus on lead, but rather it was to look at sort of this alternative therapy. They found significant benefits about an 18% reduction in subsequent cardiac events. That led to a second study that was just published last year, and it was focused on people who had diabetes. They saw some benefit, but it wasn't significant. So whether that's because there wasn't enough variability and exposure, it's not entirely clear, but we've seen this with lead in IQ deficits in kids where we can show that we can reduce blood lead levels. But ultimately what tends to happen is once you've taken lead out of the blood, some of it's released again from the bone, but you still have all that lead in the bone that's there. You get some of it out, but you're not going to get the bulk of it out.The Lead-Estrogen HypothesisEric Topol (13:47):Right. It's a reservoir that's hard to reckon with. Yeah. Now another thing, you have a Substack that is called Plagues, Pollution & Poverty, and you wrote a really provocative piece in that earlier and April called How Estrogen Keeps Lead - and Heart Attacks - in Check, and basically you got into the lead estrogen hypothesis.Eric Topol (14:10):Can you enlighten us about that?Bruce Lanphear (14:12):Yeah. A lot of the seminal work in this area was done by Ellen Silbergeld, who's a brilliant and somewhat peculiar toxicologist and Ellen for years, I focused on childhood lead exposure, and for years Ellen would tell me, almost demolish me for not studying adults. And because she had found back in 1988 that as women go into menopause, their blood lead levels spike increased by about 30%, and that's where most of our lead is stored is in our bone. And so, as I was thinking about this, it all became clear because blood lead levels in boys and girls is about the same. It's comparable up until menarche, and then girls young women's blood leads fall by about 20%. And they stay 20% lower throughout the reproductive years until menopause. And especially during those first few years around menopause, perimenopause, you see fairly striking increases in the weakening of the bone and blood lead levels.Bruce Lanphear (15:19):So that might very well help to explain why estrogen is protected, because what happens is throughout the reproductive life, women are losing a little bit of lead every month. And estrogen is at its lowest during that time, and that's going to be when blood lead is at its highest because estrogen pushes lead into the bone. Not only that, women lose lead into the developing fetus when they're pregnant. So what Ellen found is that there was less of a spike around menopause for the women that had three or four pregnancies because they had offloaded that into their babies. So all of this, if you put it together, and this is of course in a very short note of it, you can see that lead increases dyslipidemia, it leads to tears in the endothelium of the arterial wall, it's going to increase thrombosis. All of these things that we think of as the classic atherosclerosis. Well, what estrogen does is the opposite of those. It decreases dyslipidemia, it repairs the arterial endothelial wall. So how much of it is that estrogen is protective, and how much is it that it's moving lead out of the system, making it less biologically available?Eric Topol (16:46):Yeah, I know. It's really interesting. Quite provocative. Should be followed up on, for sure. Just getting to you, you're a physician and epidemiologist, MD MPH, and you have spent your career on this sort of thing, right? I mean, is your middle name lead or what do you work on all the time?Bruce Lanphear (17:09):Yeah, I've been doing this for about 30 years, and one of my mentors, Herb Needleman spent 40 years of his career on it. And in some ways, Eric, it seems to me particularly in these very difficult entrenched problems like lead, we don't have any pharmaceutical company reaching out to us to promote what we do. We've got industry trying to squash what we do.Bruce Lanphear (17:35):It really does take a career to really make a dent in this stuff. And in a way, you can look at my trajectory and it is really following up on what Herb Needleman did and what Clare Patterson did, and that was finding the effects at lower and lower levels. Because what we do with lead and most other toxic chemicals, the ones that don't cause cancer, is we assume that there's a safe level or threshold until we prove otherwise. And yet when you look at the evidence, whether it's about asbestos and mesothelioma, air pollution and cardiovascular mortality, lead and cardiovascular mortality, benzene and leukemia, none of those exhibit a threshold. In some cases, the risks are steepest proportionately at the lowest measurable levels, and that really raises some tremendous challenges, right? Because how are we going to bring air pollution or lead down to zero? But at the same time, it also provides these tremendous opportunities because we know that they're causing disease. We know what the sources are. If we could only bring about the political will to address them, we could prevent a lot of death, disease, and disability. I mean, about 20% of deaths around the world every year are from air pollution, lead, and other toxic chemicals, and yet the amount of money we invest in them is just paltry compared to what we invest in other things. Which is not to pit one against the other, but it's to say we haven't invested enough in these.Eric Topol (19:14):No, absolutely. I think your point, just to make sure that it's clear, is that even at low levels, this is of course where most of the population exposure would be, and that's why that's so incriminating. Now, one of the things I just want to end up with is that we know that these are tiny, tiny particles of lead, and then the question is how they can synergize and find particulate matter of air pollution in the nanoplastic, microplastic story and binding to forever chemicals, PFAS. How do you process all that? Because it's not just a single hit here, it's also the fact that there's ability to have binding to the other environmental toxins that are not going away.Bruce Lanphear (20:10):That's right. And in a way, when we talk about lead playing this tremendous role in the rise and decline of coronary heart disease, we can't entirely separate it out, for example, from air pollution or cigarette smoke for that matter, nor plastic. So for example, with air pollution, if we look at air pollution over the past century, up until the 1980s, even into the 1990s, it was leaded, right? So you couldn't separate them. If you look at cigarette smoke, cigarette tobacco in the 1940s and 1950s was grown in fields where they used lead arsenic as an insecticide. So smokers even today have blood lead levels that are 20% higher than non-smokers, and people who are not smokers but exposed to secondhand smoke have blood lead levels 20% higher than non-smokers who aren't exposed to secondhand smoke. So in a way, we should try to tease apart these differences, but it's going to be really challenging. In a way we can almost think about them as a spectrum of exposures. Now with plastics, you can really think of plastics as a form of pollution because it's not just one thing. There's all these additives, whether it's the PFAS chemicals or lead, which is used as a stabilizer. And so, all of them really are kind of integrated into each other, which again, maybe there's some opportunity there if we really were ready to tackle.Eric Topol (21:40):And interestingly, just yesterday, it was announced by the current administration that they're stopping all the prior efforts on the forever chemicals that were initiated in the water supply. And I mean, if there's one takeaway from our discussion, it's that we have to get all over this and we're not paying enough attention to our environmental exposures. You've really highlighted spotlighted the lead story. And obviously there are others that are, instead of getting somewhat better, they're actually going in the opposite direction. And they're all tied together that’s what is so striking here, and they all do many bad things to our bodies. So I don't know how, I'm obviously really interested in promoting healthy aging, and unless we get on this, we're chasing our tails, right?Bruce Lanphear (22:31):Well, I think that's right, Eric. And I was reading the tips that you'd written about in preparation for your book release, and you focused understandably on what each of us can do, how we can modify our own lifestyles. We almost need six tips about what our government should do in order to make it harder for us to become sick, or to encourage those healthy behaviors that you talked about. That's a big part of it as well. One of the things we're celebrating the hundredth anniversary. This is not really something to celebrate, but we are. The hundredth anniversary of the addition of tetraethyl lead to gasoline. And one of the key things about that addition, there was this debate because when it was being manufactured, 80% of the workers at a plant in New Jersey suffered from severe lead poisoning, and five died, and it was enough that New York City, Philadelphia and New Jersey banned tetraethyl lead.Bruce Lanphear (23:31):Then there was this convening by the US Surgeon General to determine whether it was safe to add tetraethyl lead to gasoline. One scientist, Yandell Henderson said, absolutely not. You're going to create a scourge worse than tuberculosis with slow lead poisoning and hardening of your arteries. Robert Kehoe, who represented the industry said, we know lead is toxic, but until you've shown that it's toxic when added to gasoline, you have no right to prohibit us from using it. So that is now known as the Kehoe rule, and it's relevant not only for lead, but for PFAS, for air pollution, for all these other things, because what it set as a precedent, until you've shown that these chemicals or pollution is toxic when used in commerce, you have no right to prohibit industry from using it. And that's the fix we're in.Eric Topol (24:27):Well, it sounds too much like the tobacco story and so many other things that were missed opportunities to promote public health. Now, is Canada doing any better than us on this stuff?Bruce Lanphear (24:40):In some ways, but not in others. And one of the interesting thing is we don't have standards, we have guidelines. And amazingly, the cities generally try to conform to those guidance levels. With water lead, we're down to five parts per billion. The US is sticking around with ten parts per billion, but it's not even really very, it's not enforced very well. So we are doing better in some ways, not so good in other ways. The European Union, generally speaking, is doing much better than North America.Eric Topol (25:15):Yeah, well, it doesn't look very encouraging at the moment, but hopefully someday we'll get there. Bruce, this has been a really fascinating discussion. I think we all should be thankful to you for dedicating your career to a topic that a lot of us are not up on, and you hopefully are getting us all into a state of awareness. And congratulations on that review, which was masterful and keep up the great work. Thank you.Bruce Lanphear (25:42):Thank you, Eric. I appreciate it.________________________________________________My Recommendations for Preventing Heart Disease (Markedly Truncated from Text and Graphics Provided in SUPER AGERS)Recently the Washington Post asked me for a listicle of 10 ways to prevent heart disease. I generally avoid making such lists but many people have de-subscribed to this newspaper, never subscribed, or missed the post, so here it is with links to citations:Guest column by Eric Topol, MDThe buildup of cholesterol and other substances in the wall of our arteries, known as atherosclerosis, is common. It can lead to severe plaques that narrow the artery and limit blood flow, or to a crack in the artery wall that can trigger blood clot formation, resulting in a heart attack.While we’ve seen some major advances in treating heart disease, it remains the leading killer in the United States, even though about 80 percent of cases are considered preventable. There are evidence-based steps you can take to stave it off. As a cardiologist, here’s what I recommend to my patients.1. Do both aerobic and resistance exerciseThis is considered the single most effective medical intervention to protect against atherosclerosis and promote healthy aging. Physical activity lowers inflammation in the body. Evidence has shown that both aerobic and strength training forms of exercise are important. But only 1 in 4 Americans meet the two activity guidelines from the American Heart Association: aerobic exercise of 150 minutes per week of at least moderate physical activity, such as walking, bicycling on level ground, dancing or gardening, and strength training for at least two sessions per week, which typically translates to 60 minutes weekly.The protective benefit of exercise is seen with even relatively low levels of activity, such as around 2,500 steps per day (via sustained physical activity, not starting and stopping), and generally increases proportionately with more activity. It used to be thought that people who exercise only on the weekend — known as “weekend warriors” — put themselves in danger, but recent data shows the benefits of exercise can be derived from weekend-only workouts, too.2. Follow an anti-inflammatory dietA predominantly plant-based diet — high in fiber and rich in vegetables, fruits and whole grains, as seen with the Mediterranean diet — has considerable evidence from large-scale observational and randomized trials for reducing body-wide inflammation and improving cardiovascular outcomes.Foods rich in omega-3 fatty acids, such as salmon, also form part of a diet that suppresses inflammation. On the other hand, red meat and ultra-processed foods are pro-inflammatory, and you should limit your consumption. High protein intake of more than 1.4 grams per kilogram of body weight per day — around 95 grams for someone who is 150 pounds — has also been linked to promoting inflammation and to atherosclerosis in experimental models. That is particularly related to animal-based proteins and the role of leucine, an essential amino acid that is obtained only by diet.3. Maintain a healthy weightBeing overweight or obese indicates an excess of white adipose tissue. This kind of tissue can increase the risk of heart disease because it stores fat cells, known as adipocytes, which release substances that contribute to inflammation.In studies, we’ve seen that glucagon-like peptide (GLP-1) drugs can reduce inflammation with weight loss, and a significant reduction of heart attacks and strokes among high-risk patients treated for obesity. Lean body weight also helps protect against atrial fibrillation, the most common heart rhythm abnormality.4. Know and avoid metabolic syndrome and prediabetesTied into obesity, in part, is the problem of insulin resistance and metabolic syndrome. Two out of three people with obesity have this syndrome, which is defined as having three out of five features: high fasting blood glucose, high fasting triglycerides, high blood pressure, low high-density lipoprotein (HDL) and central adiposity (waist circumference of more than 40 inches in men, 35 inches in women).Metabolic syndrome is also present in a high proportion of people without obesity, about 50 million Americans. Prediabetes often overlaps with it. Prediabetes is defined as a hemoglobin A1c (a measure of how much glucose is stuck to your red blood cells) between 5.7 and 6.4 percent, or a fasting glucose between 100 and 125 milligrams per deciliter.Both metabolic syndrome and prediabetes carry an increased risk of heart disease and can be prevented — and countered — by weight loss, exercise and an optimal diet.As the glucagon-like peptide drug family moves to pills and less expense in the future, these medications may prove helpful for reducing risk in people with metabolic syndrome and prediabetes. For those with Type 2 diabetes, the goal is optimizing glucose management and maximal attention to lifestyle factors.5. Keep your blood pressure in a healthy rangeHypertension is an important risk factor for heart disease and is exceptionally common as we age. The optimal blood pressure is 120/80 mm Hg or lower. But with aging, there is often an elevation of systolic blood pressure to about 130 mm Hg, related to stiffening of arteries. While common, it is still considered elevated.Ideally, everyone should monitor their blood pressure with a home device to make sure they haven’t developed hypertension. A mild abnormality of blood pressure will typically improve with lifestyle changes, but more substantial elevations will probably require medications.6. Find out your genetic riskWe now have the means of determining your genetic risk of coronary artery disease with what is known as a polygenic risk score, derived from a gene chip. The term polygenic refers to hundreds of DNA variants in the genome that are linked to risk of heart disease. This is very different from a family history, because we’re a product of both our mother’s and father’s genomes, and the way the DNA variants come together in each of us can vary considerably for combinations of variants.That means you could have high or low risk for heart disease that is different from your familial pattern. People with a high polygenic risk score benefit the most from medications to lower cholesterol, such as statins. A polygenic risk score can be obtained from a number of commercial companies, though it isn’t typically covered by insurance.I don’t recommend getting a calcium score of your coronary arteries via a computed tomography (CT) scan. This test is overused and often induces overwhelming anxiety in patients with a high calcium score but without symptoms or bona fide risk. If you have symptoms suggestive of coronary artery disease, such as chest discomfort with exercise, then a CT angiogram may be helpful to map the coronary arteries. It is much more informative than a calcium score.7. Check your blood lipidsThe main lipid abnormality that requires attention is low-density cholesterol (LDL), which is often high and for people with increased risk of heart disease should certainly be addressed. While lifestyle improvements can help, significant elevation typically requires medications such as a statin; ezetimibe; bempedoic acid; or injectables such as evolocumab (Repatha), alirocumab (Praluent) or inclisiran (Leqvio). The higher the risk, the more aggressive LDL lowering may be considered.It should be noted that the use of potent statins, such as rosuvastatin or atorvastatin, especially at high doses, is linked to inducing glucose intolerance and risk of Type 2 diabetes. While this is not a common side effect, it requires attention since it is often missed from lack of awareness.A low high-density lipoprotein (HDL) cholesterol often responds to weight loss and exercise. We used to think that high HDL was indicative of “good cholesterol,” but more recent evidence suggests that is not the case and it may reflect increased risk when very high.To get a comprehensive assessment of risk via your blood lipids, it’s important to get the apolipoprotein B (apoB) test at least once because about 20 percent of people have normal LDL and a high apoB.Like low HDL, high fasting triglycerides may indicate insulin resistance as part of the metabolic syndrome and will often respond to lifestyle factors.The lipoprotein known as Lp(a) should also be assessed at least once because it indicates risk when elevated. The good news is scientists are on the cusp of finally having medications to lower it, with five different drugs in late-stage clinical trials.8. Reduce exposure to environmental pollutantsIn recent years, we’ve learned a lot about the substantial pro-inflammatory effects of air pollution, microplastics and forever chemicals, all of which have been linked to a higher risk of heart disease. In one study, microplastics or nanoplastics in the artery wall were found in about 60 percent of more than 300 people. Researchers found a vicious inflammatory response around the plastics, and a four- to fivefold risk of heart attacks or strokes during three years of follow-up.While we need policy changes to address these toxic substances in the environment, risk can be reduced by paying attention to air and water quality using filtration or purification devices, less use of plastic water bottles and plastic storage, and, in general, being much more aware and wary of our pervasive use of plastics.9. Don’t smoke This point, it should be well known that cigarette smoking is a potent risk factor for coronary artery disease and should be completely avoided.10. Get Good SleepAlthough we tend to connect sleep health with brain and cognitive function, there’s evidence that sleep regularity and quality are associated with less risk of heart disease. Regularity means adhering to a routine schedule as much as possible, and its benefit may be due to our body’s preference for maintaining its circadian rhythm. Sleep quality — meaning with fewer interruptions — and maximal deep sleep can be tracked with smartwatches, fitness bands, rings or mattress sensors.Sleep apnea, when breathing stops and starts during sleep, is fairly common and often unsuspected. So if you’re having trouble sleeping or you snore loudly, talk to your doctor about ruling out the condition. Testing for sleep apnea can involve checking for good oxygen saturation throughout one’s sleep. That can be done through a sleep study or at home using rings or smartwatches that include oxygen saturation in their sensors and body movement algorithms that pick up disturbed breathing.Eric Topol, MD, is a cardiologist, professor and executive vice president of Scripps Research in San Diego. He is the author of “Super Agers: An Evidence-Based Approach to Longevity” and the author of Ground Truths on Substack.*********************°°°°°°°°°°°°°°°°°°°°Thanks to many of you Ground Truths subscribers who helped put SUPER AGERS on the NYT bestseller list for 4 weeks.Here are 2 recent, informative, and fun conversations I had on the topicMichael Shermer, The SkepticRuss Roberts, EconTalk I’m also very appreciative for your reading and subscribing to Ground Truths.If you found this interesting PLEASE share it!That makes the work involved in putting these together especially worthwhile.All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don't hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past three years. Just a week ago we just had nearly 50 interns (high school, college and medical students) present posters of the work they did over the summer and it was exhilarating! Some photos below Get full access to Ground Truths at erictopol.substack.com/subscribe

Eric Topol (00:05):Hello, it's Eric Topol from Ground Truths, and I've got some really exciting stuff to talk to you about today. And it's about the announcement for a new Center for pediatric CRISPR Cures. And I'm delight to introduce doctors Jennifer Doudna and Priscilla Chan. And so, first let me say this is amazing to see this thing going forward. It's an outgrowth of a New England Journal paper and monumental report on CRISPR in May. [See the below post for more context]Let me introduce first, Dr. Doudna. Jennifer is the Li Ka Shing Chancellor's Chair and a Professor in the departments of chemistry and of molecular and cell biology at the University of California Berkeley. She's also the subject of this book, one of my favorite books of all time, the Code Breaker. And as you know, the 2020 Nobel Prize laureate for her work in CRISPR-Cas9 genome editing, and she founded the Innovative Genomics Institute (IGI) back 10 years ago. So Jennifer, welcome.Jennifer Doudna (01:08):Thank you, Eric. Great to be here.Eric Topol (01:10):And now Dr. Priscilla Chan, who is the co-founder of the Chan Zuckerberg Initiative (CZI) that also was started back in 2015. So here we are, a decade later, these two leaders. She is a pediatrician having trained at UCSF and is committed to the initiative which has as its mission statement, “to make it possible to cure, prevent, and manage all diseases in this century.” So today we're going to talk about a step closer to that. Welcome, Priscilla.Priscilla Chan (01:44):Thank you. Thanks for having me.Eric Topol (01:46):Alright, so I thought we'd start off by, how did you two get together? Have you known each other for over this past decade since you both got all your things going?Jennifer Doudna (01:56):Yes, we have. We've known each other for a while. And of course, I've admired the progress at the CZI on fundamental science. I was an advisor very early on and I think actually that's how we got to know each other. Right, Priscilla?Priscilla Chan (02:11):Yeah, that's right. We got to know each other then. And we've been crisscrossing paths. And I personally remember the day you won the Nobel Prize. It was in the heart of the pandemic and a lot of celebrations were happening over Zoom. And I grabbed my then 5-year-old and got onto the UCSF celebration and I was like, look, this is happening. And it was really cool for me and for my daughter.Eric Topol (02:46):Well, it's pretty remarkable convergence leading up to today's announcement, but I know Priscilla, that you've been active in this rare disease space, you've had at CZI a Rare As One Project. Maybe you could tell us a bit about that.Priscilla Chan (03:01):Yeah, so at CZI, we work on basic science research, and I think that often surprises people because they know that I'm a pediatrician. And so, they often think, oh, you must work in healthcare or healthcare delivery. And we've actually chosen very intentionally to work in basic science research. In part because my training as a pediatrician at UCSF. As you both know, UCSF is a tertiary coronary care center where we see very unusual and rare cases of pediatric presentations. And it was there where I learned how little we knew about rare diseases and diseases in general and how powerful patients were. And that research was the pipeline for hope and for new discoveries for these families that often otherwise don't have very much access to treatments or cures. They have a PDF that maybe describes what their child has. And so, I decided to invest in basic science through CZI, but always saw the power of bringing rare disease patient cohorts. One, because if you've ever met a parent of a child with rare disease, they are a force to be reckoned with. Two, they can make research so much better due to their insights as patients and patient advocates. And I think they close the distance between basic science and impact in patients. And so, we've been working on that since 2019 and has been a passion of ours.Eric Topol (04:40):Wow, that's great. Now Jennifer, this IGI that you founded a decade ago, it's doing all kinds of things that are even well beyond rare diseases. We recently spoke, I know on Ground Truths about things as diverse as editing the gut microbiome in asthma and potentially someday Alzheimer’s. But here you were very much involved at IGI with the baby KJ Muldoon. Maybe you could take us through this because this is such an extraordinary advance in the whole CRISPR Cures story.Jennifer Doudna (05:18):Yes, Eric. It's a very exciting story and we're very, very proud of the teamwork that went into making it possible to cure baby KJ of his very rare disease. And in brief, the story began back in August of last year when he was born with a metabolic disorder that prevented him from digesting protein, it's called a urea cycle disorder and rare, but extremely severe. And to the point where he was in the ICU and facing a very, very difficult prognosis. And so, fortunately his clinical team at Children's Hospital of Philadelphia (CHOP) reached out to Fyodor Urnov, who is the Director of Translational Medicine at the IGI here in the Bay Area. They teamed up and realized that they could quickly diagnose that child because we had an IRB approved here at the IGI that allowed us to collect patient samples and do diagnosis. So that was done.Jennifer Doudna (06:26):We created an off-the-shelf CRISPR therapy that would be targeted to the exact mutation that caused that young boy's disease. And then we worked with the FDA in Washington to make sure that we could very safely proceed with testing of that therapy initially in the lab and then ultimately in two different animal models. And then we opened a clinical trial that allowed that boy to be enrolled with, of course his parents' approval and for him to be dosed and the result was spectacular. And in fact, he was released from the hospital recently as a happy, healthy child, gaining lots of weight and looking very chunky. So it's really exciting.Eric Topol (07:16):It's so amazing. I don't think people necessarily grasp this. This timeline [see above] that we'll post with this is just mind boggling how you could, as you said Jennifer, in about six months to go from the birth and sequencing through cell specific cultures with the genome mutations through multiple experimental models with non-human primates even, looking at off-target effects, through the multiple FDA reviews and then dosing, cumulatively three dosing to save this baby's life. It really just amazing. Now that is a template. And before we go to this new Center, I just wanted to also mention not just the timeline of compression, which is unimaginable and the partnership that you've had at IGI with I guess Danaher to help manufacture, which is just another part of the story. But also the fact that you're not just even with CRISPR 1.0 as being used in approvals previously for sickle cell and β-thalassemia, but now we're talking about base editing in vivo in the body using mRNA delivery. So maybe you could comment on that, Jennifer.Jennifer Doudna (08:38):Yeah, very good point. So yeah, we used a version of CRISPR that was created by David Liu at the Broad Institute and published and available. And so, it was possible to create that, again, targeted to the exact mutation that caused baby KJ’s disease. And fortunately, there was also an off-the-shelf way to deliver it because we had access to lipid nanoparticles that were developed for other purposes including vaccinations. And the type of disease that KJ suffered from is one that is treatable by editing cells in the liver, which is where the lipid nanoparticle naturally goes. So there were definitely some serendipity here, but it was amazing how all of these pieces were available. We just had to pull them together to create this therapy.Eric Topol (09:30):Yeah, no, it is amazing. So that I think is a great substrate for starting a new Center. And so, maybe back to you Priscilla, as to what your vision was when working with Jennifer and IGI to go through with this.Priscilla Chan (09:45):I think the thing that's incredibly exciting, you mentioned that at CZI our mission is to cure, prevent, and manage all disease. And when we talked about this 10 years ago, it felt like this far off idea, but every day it seems closer and closer. And I think the part that's super exciting about this is the direct connection between the basic science that's happening in CRISPR and the molecular and down to the nucleotide understanding of these mutations and the ability to correct them. And I think many of us, our imaginations have included this possibility, but it's very exciting that it has happened with baby KJ and CHOP. And we need to be able to do the work to understand how we can treat more patients this way, how to understand the obstacles, unblock them, streamline the process, bring down the cost, so that we better understand this pathway for treatment, as well as to increasingly democratize access to this type of platform. And so, our hope is to be able to do that. Take the work and inspiration that IGI and the team at CHOP have done and continue to push forward and to look at more cases, look at more organ systems. We're going to be looking in addition to the liver, at the bone marrow and the immune system.Priscilla Chan (11:17):And to be able to really work through more of the steps so that we can bring this to more families and patients.Eric Topol (11:30):Yeah, well it's pretty remarkable because here you have incurable ultra-rare diseases. If you can help these babies, just think of what this could do in a much broader context. I mean there a lot of common diseases have their roots with some of these very rare ones. So how do you see going forward, Jennifer, as to where you UC Berkeley, Gladstone, UCSF. I'm envious of you all up there in Northern California I have to say, will pull this off. How will you get the first similar case to KJ Muldoon going forward?Jennifer Doudna (12:13):Right. Well, IGI is a joint institute, as you probably know, Eric. So we were founded 10 years ago as a joint institute between UC Berkeley and UCSF. And now we have a third campus partner, UC Davis and we have the Gladstone Institute. So we've got an extraordinary group of clinicians and researchers that are coming together for this project and the Center to make it a success. We are building a clinical team at UCSF. We have several extraordinary leaders including Jennifer Puck and Chris Dvorak, and they are both going to be involved in identifying patients that could be enrolled in this program based on their diagnosis. And we will have a clinical advisory group that will help with that as well. So we'll be vetting patients probably right after we announce this, we're going to be looking to start enrolling people who might need this type of help.Eric Topol (13:18):Do you think it's possible to go any faster right now than the six months that it took for KJ?Jennifer Doudna (13:26):I think it could be. And here's the reason. There's a very interesting possibility that because of the type of technology that we're talking about with CRISPR, which fundamentally, and you and I have talked about this previously on your other podcast. But we've talked about the fact that it's a programmable technology and that means that we can change one aspect of it, one piece of it, which is a piece of a molecule called RNA that's able to direct CRISPR to the right sequence where we want to do editing and not change anything else about it. The protein, the CRISPR protein stays the same, the delivery vehicle stays the same, everything else stays the same. And so, we're working right now with FDA to get a platform designation for CRISPR that might allow streamlining of the testing process in some cases. So it'll obviously come down to the details of the disease, but we're hopeful that in the end it will be possible. And Priscilla and I have talked about this too, that as AI continues to advance and we get more and more information about rare diseases, we'll be able to predict accurately the effects of editing. And so, in some cases in the future it may be possible to streamline the testing process even further safely.Eric Topol (14:51):And I also would note, as you both know, well this administration is really keen on genome editing and they've had a joint announcement regarding their support. And in my discussions with the FDA commissioner, this is something they are very excited about. So the timing of the new Center for pediatric CRISPR Cures is aligned with the current administration, which is good to see. It's not always the case. Now going back, Priscilla, to your point that not just for the liver because delivery has been an issue of course, and we're going to try to get after a lot of these really rare diseases, it's going to go beyond there. So this is also an exciting new dimension of the Center, as you said, to go after the bone marrow for hematopoietic cells, perhaps other organs as well.Priscilla Chan (15:42):I mean what the expertise and feasibility, the immune system is going to be the next target. Jennifer Puck has been a pioneer in this work. She's the one who designed the newborn screen that will be the tool that picks up these patients as they are born. And I think the thing that's tremendous is the immune system, first of all is active in many, many diseases, not just these cases of children born with partial or absence of immune systems. And the course right now that these babies are left with is complete isolation and then a very long and arduous course of a bone marrow transplant with high morbidity and mortality. And even if after the transplant you have complications like graft versus host and immunosuppression. And so, the idea of being able to very specifically and with less the conditioning and morbidity and mortality of the treatment, being able to address this is incredible. And the implications for other diseases like blood cancers or other hematopoietic diseases, that's incredible. And that actually has an incredibly broad base of patients that can benefit from the learnings from these babies with severe combined immunodeficiencies.Eric Topol (17:10):Yeah, I think that goes back to a point earlier maybe to amplify in that previous CRISPR generation, it required outside the body work and it was extremely laborious and time consuming and obviously added much more to the expense because of hospitalization time. This is different. This is basically doing this inside the affected patient's body. And that is one of the biggest reasons why this is a big step forward and why we're so fortunate that your Center is moving forward. Maybe before we wrap up, you might want to comment, Jennifer on how you were able to bring in to build this platform, the manufacturing arm of it, because that seems to be yet another dimension that's helpful.Jennifer Doudna (18:01):Indeed, yes. And we were again fortunate with timing because you mentioned briefly that the IGI had set up a program with the Danaher Corporation back in January of last year. We call it our Beacon project. And it's focused on rare disease. And it's a really interesting kind of a unique partnership because Danaher is a manufacturing conglomerate. So they have companies that make molecules, they make proteins, they make RNA molecules, they make delivery molecules. And so, they were excited to be involved with us because they want to be a provider of these types of therapies in the future. And they can see the future of CRISPR is very exciting. It's expanding, growing area. And so, that agreement was in place already when the baby KJ case came to our attention. And so, what we're hoping to do with Danaher is again, work with them and their scientists to continue to ask, how can we reduce the cost of these therapies by reducing the cost of the molecules that are necessary, how to make them efficiently. We already, it's very interesting, Fyodor Urnov has toured their plant in North Dakota recently, and he found in talking to their engineers, there are a number of things that we can already see will be possible to do that are going to make the process of manufacturing these molecules faster and cheaper by a lot.Eric Topol (19:28):Wow.Jennifer Doudna (19:28):So it's a win-win for everybody. And so, we're really excited to do that in the context of this new Center.Eric Topol (19:36):Oh, that's phenomenal because some of these disorders you don't have that much time to work with before they could be brain or organ or vital tissue damage. So that's great to hear that. What you built here is the significance of it can't be under emphasized, I'll say because we have this May report of baby KJ, which could have been a one-off and it could have been years before we saw another cure of an ultra-rare disorder. And what you're doing here is insurance against that. You're going to have many more cracks at this. And I think this is the excitement about having a new dedicated Center. So just in closing, maybe some remarks from you Priscilla.Priscilla Chan (20:24):I just want to emphasize one point that's really exciting as we talk about these ultra-rare cases that they're often like one in a million. All these learnings actually help maximize the impact of lots of research across the sector that impacts actually everyone's health. And so, our learnings here from these patients that have very significant presentations that really can stand to benefit from any treatment is hopefully paving the way for many, many more of us to be able to live healthier, higher quality lives through basic science.Eric Topol (21:13):And over to you, Jennifer.Jennifer Doudna (21:15):Couldn't agree more. It's a really interesting moment. I think what we hope we are, is we're at sort of an inflection point where, as I mentioned earlier, all the pieces are in place to do this kind of therapeutic and we just need a team that will focus on doing it and pulling it together. And also learning from that process so that as Priscilla just said, we are ultimately able to use the same strategy for other diseases and potentially for diseases that affect lots of people. So it's exciting.Eric Topol (21:46):For sure. Now, if I could just sum up, this is now a decade past the origination of your work of CRISPR and how already at the first decade culminated in sickle cell disease treatment and β-thalassemia. Now we're into the second decade of CRISPR. And look what we've seen, something that was unimaginable until it actually happened and was reported just a little over a month ago. Now going back to Priscilla's point, we're talking about thousands of different rare Mendelian genomic disorders, thousands of them. And if you add them all up of rare diseases, we're talking about hundreds of millions of people affected around the world. So this is a foray into something much bigger, no less the fact that some of these rare mutations are shared by common diseases and approaches. So this really big stuff, congratulations to both of you and your organizations, the Innovative Genomics Institute and the Chan Zuckerberg Initiative for taking this on. We'll be following it with very deep interest, thank you.****************************************************Thanks for listening, reading and subscribing to Ground Truths.If you found this interesting PLEASE share it!That makes the work involved in putting these together especially worthwhile.Thanks to Scripps Research, and my producer, Jessica Nguyen, and Sinjun Balabanoff for video/audio support.All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don't hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. Get full access to Ground Truths at erictopol.substack.com/subscribe