Science Fare

Pat Brown talks about his path to becoming a physician and scientist, the importance of a bench-to-bedside-back-to-bench approach in drug development, and targeted cancer therapy. Using his work in leukemia as an example, Pat talks about how changes at the level of DNA sequence change proteins and can lead to the development of cancer, and how scientists can use this knowledge to develop specific cancer treatments. Works cited in this conversation:The Emperor of All Maladies: A Biography of Cancer by Siddhartha MukherjeeJanet Rowley and her work on cancer genetics FLT3 inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer, in the European Journal of Cancer, March 2004 The biology and targeting of FLT3 in pediatric leukemia, in Frontiers in Oncology, September 2014 Episode highlights:*Susan introduces Pat [1:58];*Pat talks about his journey to becoming a physician and scientist focusing on pediatric leukemia [5:08];*What is leukemia? Pat gives us an overview [8:46];*Why leukemia has been at the forefront of cancer research and treatment [11:58];*Pat’s early research and clinical work in leukemia [13:38];*When, how, and why cancer treatment shifted from a one-size-fits-all approach to something more targeted [15:45];*Some of the specifics of Pat’s work — what is FLT3? Why is it important in leukemia? [21:12];*Pat’s work in developing clinical trials for treatments for children with leukemia — bench to bedside and back again [28:00];*Success with the small molecule lestaurtinib, a first-generation FLT3 inhibitor [30:10];*Pat’s group partnered with another company to produce a monoclonal antibody that could target FLT3 [31:12];*Main challenge with both treatments (and challenge with all cancer therapies) is cancer developing resistance to treatment — people try to prevent resistance with multimodal treatments [32:20];*Leads to the idea of personalized therapy — in each person, what are the genetic characteristics driving the cancer and can those be targeted with a cocktail tailored to that person? [35:40];*Liquid biopsy’s potential in helping us see solid tumor cancers earlier and more comprehensively [36:58];*Pat’s reflections on working in “translational medicine” — as a physician and a scientist — and the importance of bedside to bench as well as bench to bedside [39:21];*How working as a scientist in academia is different from working in industry [43:25];*What Pat is working on now, and his hopes for a decade or two out [50:04];*High school science portion of the episode — Focusing on leukemia as an example, Pat tells us how changes in the DNA sequence of a gene can result in cancer. This connects to one of the Next Generation High School Science Standards in Life Science, which states that students should be able to construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells [55:23];*Pat shares a memory from high school science [1:02:43];*Pat’s advice to high school students today who are interested in science [1:04:05]

Focusing on leukemia as an example, Pat Brown tells us how changes in the DNA sequence of a gene can result in cancer. This connects to one of the Next Generation High School Science Standards in Life Science, which states that students should be able to construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

Naomi Oppenheimer and Matan Yah Ben Zion talk about their path to becoming physicists and their latest work — a look at the diffusion of a substance made of repulsive particles. Most often when high school students learn about diffusion, the assumption is that the particles feel no attractions to each other. When you place a drop of dye into a flask of water, the dye spreads. Microscopically, the particles of dye and water bounce off each other due to thermal motion but we assume they experience no significant attraction or repulsion to each other.But what happens if the particles DO repel each other? It turns out that this often the case, in scenarios ranging from collections of proteins to groups of people. Naomi and Matan studied diffusion in this scenario, and they share their findings here and the implications for larger questions.Papers cited in this conversation:Compact Expansion of a Repulsive Suspension in Physical Review Letters, June 2024 Bustling through the physics of crowds in Knowable, November 2024 Lane nucleation in complex active flows in Science, March 2023 Scientist bios:Naomi is an assistant professor of Exact Sciences in the school for Physics and Astronomy at Tel Aviv University. She is interested in complex fluids, statistical mechanics, soft matter, and biology-inspired physical systems. She uses theoretical analytical tools, numerical simulations, and a dash of experiments. Some of her research achievements include predicting the effect of protein concentration on membrane viscosity and understanding why crumpled paper is shapeable, and her future directions include studying heterogeneous materials in biology and for next-generation functional materials.Matan is an assistant professor of artificial intelligence at the Donders Center for Cognition at Radboud University in Nijmegen in the Netherlands. Matan’s research focuses on natural computation and collective behavior. He uses a combination of applied physics, statistical mechanics, artificial intelligence, and materials science to explain collective behavior in nature and to realize it in robotic swarms. Some of his research achievements include programmable self-assembly on the sub-cellular scale, developing a synthetic swarm or micro-swimmers on the cellular scale, and designing decentralized learning in robotic swarms. Episode highlights:*Susan introduces Naomi and Matan [1:28];*How Naomi and Matan became scientists and ended up working together [3:25];*What is regular thermal diffusion? [10:45];*How Naomi and Matan got the idea to look at diffusion in a repulsive substance [15:52];*What did they think they might see? [18:32];*Repulsive particles are ubiquitous [20:20];*How theory, simulations, and experiments came together in this work [25:15];*How the expansion of a repulsive substance difference from normal diffusion [29:25];*Why are the results significant and what new questions do they raise? [36:53];*Relevance of this work to thinking about crowds of people [40:20];*How this work helps broaden how students think about diffusion [44:30];*Naomi and Matan share memories from high school science [48:00];*Naomi and Matan give advice to high school students interested in studying science [51:18]

Season 2, Episode #4. In this mini episode, Naomi Oppenheimer and Matan Yah Ben Zion talk about their path to becoming physicists and their latest work — a look at the diffusion of a substance made of repulsive particles. Most often when high school students learn about diffusion, the assumption is that the particles feel no attractions to each other. When you place a drop of dye into a flask of water, the dye spreads. Microscopically, the particles of dye and water bounce off each other due to thermal motion but we assume they experience no significant attraction or repulsion to each other.But what happens if the particles DO repel each other? It turns out that this often the case, in scenarios ranging from collections of proteins to groups of people. Naomi and Matan studied diffusion in this scenario, and they share their findings here and the implications for larger questions.If you like this episode, stay turned for the full length interview in a few days! Scientist bios:Naomi is an assistant professor of Exact Sciences in the school for Physics and Astronomy at Tel Aviv University. She is interested in complex fluids, statistical mechanics, soft matter, and biology-inspired physical systems. She uses theoretical analytical tools, numerical simulations, and a dash of experiments. Some of her research achievements include predicting the effect of protein concentration on membrane viscosity and understanding why crumpled paper is shapeable, and her future directions include studying heterogeneous materials in biology and for next-generation functional materials.Matan is an assistant professor of artificial intelligence at the Donders Center for Cognition at Radboud University in Nijmegen in the Netherlands. Matan’s research focuses on natural computation and collective behavior. He uses a combination of applied physics, statistical mechanics, artificial intelligence, and materials science to explain collective behavior in nature and to realize it in robotic swarms. Some of his research achievements include programmable self-assembly on the sub-cellular scale, developing a synthetic swarm or micro-swimmers on the cellular scale, and designing decentralized learning in robotic swarms. 

Our guest today is Dr. Leo Otterbein, a professor of surgery at Beth Israel Deaconess Medical Center and Harvard Medical School. Leo’s research group focuses on the role of carbon monoxide as a therapeutic agent in medical applications ranging from organ transplant to infection to cancer. Inhaled carbon monoxide is currently in numerous FDA trials based in large part due the research in Leo's lab over the past decade. Leo is also chair of the Beth Israel Deaconess Medical Center (BIDMC) Institutional Animal Care and Use Committee. As the site miner for the BIDMC Center for the Integration of Medicine and Innovative Technology and member of the Boston Biomedical Innovations Center Technology Assessment and Development Group, Leo mentors and provides specialized expertise in entrepreneurial start-up ventures for innovative technologies. Leo trains graduate students, post-doctoral fellows, surgical residents, and junior faculty in basic research, grant proposals and career guidance. On the episode, we talk about the myriad possibilities of carbon monoxide (yes, carbon monoxide!) in medicine, ranging from its use in organ transplantation, cancer, wound care, and sickle cell anemia.

Season 2, Episode #2. Dr. Dan Hatfield is a senior public health researcher at FHI360 with 15 years of experience developing, evaluating, and replicating community and behavioral interventions promoting healthy eating and physical activity, particularly in children, adolescents, and families. Previously, as a Research Assistant Professor at Tufts University, he served as principal or co-investigator on 13 federal and foundation-funded research grants, and he taught graduate courses in behavioral theory, health communications, and public health. His subject-matter expertise spans diverse domains, including nutrition, physical activity, obesity prevention, health communications, and theory-based intervention design.Dan talks with us about the opportunities for and barriers to programs that aim to get communities more physically active.Highlights of the episode:*Susan introduces Dan [0:56];*Dan’s background and path to becoming a scientist [2:08];*Dan talks about the more and less well known benefits of physical activity [7:27];*Some of the impediments to getting individuals and communities active [12:37];*Dan’s work in helping to establish physical activity programs in a community in East Boston [18:11];*Dan’s current NIH study in partnership with New York Road Runners [29:13];*Dan’s hopes for the next 5 - 10 years for getting more people moving more [30:39];*Was there a time when people in the US were moving a lot more? [34:46];*High school science section — Dan talks about how when solving a problem, you determine the “necessary qualitative and quantitative criteria and constraints for solutions,including any requirements set by society,” (From the Technology and Engineering Massachusetts standard HS-ETS1-1. Analyze a major global challenge to specific a design problem that can be improved.) [37:12];*Dan shares a memory from high school science [44:20];*Dan gives advice to high school students interested in studying science [46:04]

Season 2, Episode #1. Mike Shelley is an applied mathematician who uses modeling and simulation to better understand the physics and biology of complex systems. He is the director of the Center for Computational Biology, which is part of the Flatiron Institute — the scientific research arm of the Simons Foundation located in NYC. He also co-founded and co-directs the Courant Institute’s Applied Mathematics Laboratory at New York University.Today, Mike is going to talk about elucidating how things in the cell find their proper place. Most listeners likely know that the cell is the basic unit of life, and within the cell are important structures like, for example, the nucleus which holds the DNA, and the ribosomes, where proteins are made. There are other structures that are actually transient, like the spindle, for example, and yet are crucially important for cell division — the process of making new cells. Mike and his colleagues have done extensive work to understand how the spindle and related structures form, get in the right place, and stay in the right place for successful cell division. His work is a beautiful example of how physics and biology together help solve problems and push forward our understanding of the complexities of life. Papers mentioned in this conversation:“Forces positioning the mitotic spindle: Theories, and now experiments,” 2016, Bioessays“Stoichiometric interactions explain spindle dynamics and scaling across 100 million years of nematode evolution,” 2020, eLife“Laser ablation and fluid flows reveal the mechanism behind spindle and centrosome positioning,” 2023, Nature Physics Highlights of the episode:*Susan introduces Mike and today’s topic [0:56];*Mike’s background and path to becoming a scientist [2:50];*The art of biophysical modeling and how it’s different from mathematical modeling [6:52];*The technological and computational advances that have strengthened modeling [9:20]; *What is the spindle and why is it so important? [15:36];*Different sets of forces have been proposed as key drivers in positioning the spindle — how was Mike’s group able to combine experiments and biophysical modeling to determine that pulling forces were predominant? [18:00]; *An earlier review paper from 2016 suggested that pushing forces were predominant — how changes like this are part of the scientific process [27:08];*Other scientific problems Mike is excited about [28:45]; *High school science section — Mike talks about how understanding forces in the cellular world is quite different from what we see in the typical macroscopic world of the physics classroom with its ramps, balls, pendulums, etc. [32:18];*Mike shares a memory from high school science [40:02];*Mike gives advice to high school students interested in studying science [42:15]

In this episode, I give a quick summary of the interview with Christie del-Castillo Hegyi and Jody Segrave Daly that aired on Science Fare on Monday, June 17, 2024. Christie and Jody are the founders of the Fed is Best Foundation and authors, along with Lynnette Hafken, of the forthcoming book, Fed is Best. In today’s episode, we talk about:*The Next Generation High School Science Standard entitled, “Engaging in Argument from Evidence.” In this standard, high school students are asked to evaluate the claims, evidence, and reasoning behind currently accepted explanations or solutions to determine the merits of arguments. I ask Christie and Jody how their work demonstrates this standard. [3:33];*The advice Jody and Christie would give to high school students interested in science [14:50]