The following is an edited transcript of the audio story. Interviews have been edited for length and clarity.

Chris Conner: Hello, my name is Chris Conner. I had the privilege of interviewing several participants at the Welch Conference on Chemical Research held in Houston, Texas in October of 2022. We’ll dive into the science in a bit, but first, let’s hear from Doug Foshee, Chairman of The Welch Foundation.

Doug Foshee: We’re trying to raise awareness of the importance of basic research in chemistry for everyone’s lives. And I can’t think of a more important time than right now to emphasize to the average person that actually science is really important.

Chris Conner: The Welch Foundation has funded basic research in chemistry at institutions across Texas for 68 years. Their mission is advancing chemistry and improving life. With this conference, you might add defending science to that list.

Doug Foshee: We want to make sure that people know about these things, especially because we’re in this moment where there seems to be an anti-science movement, which, if I could speak personally, is I think, really dangerous. It’s really dangerous. It hurts people, and I don’t think people know that it hurts people. So the more that we can do to say, “Hey, you can’t make it through your day without the benefit of 50 years ago basic research and chemistry, then the more people might say, Oh yeah, well, the polio vaccine is actually a good thing” as an example.

Chris Conner: For the first time, a keynote speaker has been added to the program. Peter Hotez is professor of pediatrics and molecular virology at the Baylor College of Medicine, where he is also the Dean of the National School of Tropical Medicine and co-director of the Texas Children’s Hospital for Vaccine Development. Peter’s keynote described work that he and others are doing to make vaccines available in underserved areas of the world. He also talked about the growing anti-science movement in the United States and around the world, and its evolution from early anti-vaccine campaigns to what happens when scientists themselves are targeted.

Peter Hotez: They’re not only targeting the science, they’re targeting the scientists and increasingly portraying us as enemies of the state. And that’s where I get really worried because you don’t want to let that code too far because it will have disastrous and chilling consequences. And as I mentioned at the end of my talk, the kind of threats I get is saying the army of Patriots is coming to hunt me down. And to which I say, well, first of all, you don’t need an army. It’s just now me and Anne and Rachel and the cat at home. One or two Patriots will do it. But the other is I say, look …

Chris Conner: Each year the Welch Conference is organized around a theme, bringing together the best scientists from around the world to share their work and exchange ideas. This year’s theme was molecules and sculpted light. The organizer was W.E. Moerner, Mosher professor of chemistry at Stanford University and a recipient of the 2014 Nobel Prize in chemistry. Here is how explains he concept of molecules and sculpted light:

W.E. Moerner: Let me tell you what I, what is meant by this molecules and sculpted light business. You all know that molecules have ground states in excited states, and it’s very nice that there are different ways to interact with molecules. You can break bonds, you can do all kinds of chemistry, but here we’re interested in using light, to promote transitions in the molecules, for example, from a ground, single state to an excited state, and there might be other processes later, such as emission and so on.

Now, the idea, of course, is we want to sculpt the light. So one thing you can do is to sculpt the incoming light. That is, you can sculpt the light that is pumping the molecule in various ways in order to change the light-molecule interaction. That means you might change the phase of the light, or you might change the behavior of the light that’s coming in by using tiny sub-wavelength, tiny metallic objects, that are very small or carefully designed dielectric structures to sculpt the incoming light.

You can also sculpt the outgoing light or the emitted light to extract more information from the molecule. This can be done by modulating, for example, the phase of this emitted light far away before detection. Or you can change that emitted light use again, tiny sub-wavelength, metallic structures or dialectic structures that are designed to enhance particular properties of interest.

So that’s the sort of regime in which we’re going to, hear about sculpted light, in the conference today and tomorrow.”

Chris Conner: You’re bringing together spectroscopy, plasmonics, metamaterials, which is my impression that those groups while doing related things, maybe have not made all the connections that you think are possible?

W.E. Moerner: The idea here in the Welch Conference that’s particularly nice about it is to bring those different groups of people together and then they actually hear and see, oh, it’s amazing that you can do that, or it’s amazing that you can change this or that or use that technique to get a bigger signal and so on, talking amongst these different groups. Some of them come from physical chemistry, some of them come from, if you like, biosensing. Some of them come from other sorts of application areas of chemistry, catalysis, and so all those themes together are in the same room, which is very nice.

Chris Conner: By sculpting light, scientists can learn more about the structure or locations of molecules themselves, drive reactions more efficiently, detect pathogens or predict harmful algal blooms. To give you a sense of the kinds of topics discussed at the meeting, we spoke to a handful of speakers and session organizers. One of those is Matthew Lew, he’s an associate professor of electrical on systems engineering at Washington University in St. Louis. Let’s just talk about your session, kind of the things that are going on there.

Matthew Lew: I was the lead of the first session, single molecules and phase. And to kick off this conference, it really linked nicely to the overall title. Every single photon time we get either probing a molecule or it scattering light back at us has this thing called phase that we have to manipulate or think about in order to do the science and develop the technology that we want to develop. So my session was really about all of the cutting-edge technology and science that can be accomplished if we really think hard about phase and manipulate light in very, very special ways to push the envelope of what's possible for measurements and for technology.

Chris Conner: I understand phase in the sense of audio waves.

Matthew Lew: Yeah.

Chris Conner: But how do you shift the phase of light?

Matthew Lew: Yep. The way that we think about phase is that actually any time you shape light, you are changing the shape of the wavefront of light. So a lens actually changes that wavefront just because the refractive index of that lens is different from air and there's a shape associated with a lens, this sort of spherical shape. So you change the wavefront, you change the way light evolves in an imaging system or in a microscope or even inside a cell. So if we think about how to do that, whether it's this fancy phase mask that Yoav Schectman showed, or whether it's these nanoparticles, you change that phase, you change the way light behaves, and you get to see something new in your system.

Chris Conner: Which allows you to reveal, for example, what?

Matthew Lew: Because phase is a part of how a photon behaves, then what that means is that as that photon travels through a cell or travels through an electrochemical reactor or whatever situation you happen to be probing, that phase has imprinted on the information that we'd like to collect. What Yoav Schectman showed was that if we do these fancy things to the light after it's left the sample, we can actually retrieve properties of the sample that we never would've been able to measure otherwise. Things like all the 3D positions of molecules inside a cell, even if they're really close together, you reshape the light correctly, you can see that. Or even without using a color sensor, if you use the right type of phase manipulation, you can see color with a grayscale sensor.

Chris Conner: We've just heard that by manipulating the phase of light, we can reveal properties unseen before. Another way to manipulate light is to increase signal-to-noise with nanoantennas. You're probably familiar with how an antenna can pull a weak radio signal out of the air, but you probably haven't thought about how an antenna can work on visible light at a much smaller wavelength. Julie Biteen, professor of chemistry and of biophysics at the University of Michigan explains a few concepts from her session on nanoantennas.

Julie Biteen: Two of the main themes that were coming out in this session were to really focus the light and change what things look like on the nanometer scale. And then on the other side, focusing the light to catalyze chemical reactions.

Chris Conner: So what's so magical about gold nanoparticles?

Julie Biteen: People are using small gold nanoparticles as antennas, that couple light to the molecular scale, bringing down the micron scale of light down to the nanometer scale of molecules. So a gold nanoparticle works much in the same way as a rooftop antenna. So if you think about a rooftop antenna as interacting with radio waves or TV waves, very long wavelength in the same way a gold nanoparticle can interact with light waves. So the light comes in and sets off electron oscillations. But the end of the story there is that the light field is now focused down to a much, much smaller scale. And then bridging to what Naomi Halas was talking about with the photocatalysis, the point that she was making that was really cool is that the thermal budget, just the amount of heating that's needed to make chemicals in industry is really high. And so if you could bring the light in and focus it really well, you can actually catalyze those reactions and make them go at much lower energies.

Chris Conner: Naomi Halas is the Stanley C. Moore professor of electrical and computer engineering at Rice University. Here she describes the coupling of nanoantennas to catalytic metals.

Naomi Halas: If you look in general at all the catalytic metals, they tend to have very poor interactions with light. So by themselves, you don't really excite them optically very efficiently. But instead, if you put them right next to an antenna particle, then that antenna as it's being driven by light, it also has a field around it. So the electrons now can get driven just like the electrons in the antenna particle. So they do different things that they wouldn't do normally. Now you have, you converted palladium, or nickel, or iron, or ruthenium, you convert all of those types of metals that are not known for optical properties to a photo catalyst.

Chris Conner: This has big implications, for example, for the hydrogen economy in terms of energy requirements.

Naomi Halas: So 90% of all hydrogen is made by these processes where you remove the hydrogen from the methane, and this is a high temperature process. Instead, if you drive this reaction with light, using a plasmonic photo catalyst, you actually could drive this reaction without any external heat source. So you don't need to be dumping all that extra energy in. It's just that we never had a good way to do it before. Then you have solid state lighting, which was its own revolution. You make very, very cheap photons, and these photons have the kind of energy you need to actually perform chemical reactions. And so you can think about an LED based chemical reactor.

Chris Conner: Jennifer Dionne is an associate professor of material science and engineering at Stanford University. In the session on metamaterials, she described some very practical applications of sculpting light.

Jennifer Dionne: We're using sculpted light for analysis of both clinical and environmental samples. And one area that we're really excited about is multi-omic detection in ocean samples. So for example, how can we monitor phytoplankton distributions and how they're metabolizing, and use the signals from both whole phytoplankton as well as their metabolites to be able to better predict harmful algae blooms.

Chris Conner: Describe what kinds of analyses you're doing.

Jennifer Dionne: We've been using vibrational scattering signatures both to detect and identify pathogens and also to detect and identify various proteins and peptides. And Raman scattering is a really specific fingerprint of what you're looking for, but generally you are challenged by sensitivities because only one in a million or one in ten million photons will inelastically scatter. So the efficiency of Raman is not particularly high. And how we use sculpted light is first of all to enhance the sensitivity of Raman scattering so we can make the efficiency much, much higher and closer in many cases, to the efficiency of fluorescence. And then we can also use light to focus the light to the molecule or to the cell. So we not only increase the likelihood that Raman scattering will occur, but we essentially tune the impedance between the incident light and the molecule. So we're basically getting the light to go exactly where the cell or the molecule is.

Chris Conner: The other thing that stood out to me was doing analyses on a chip, that would be the equivalent of a basketball court full of 96-well plates.

Jennifer Dionne: That's right. So the amazing thing about using sculpted light for molecules is you can tap into the existing IT industry and telecommunications industry and use a lot of the processes from CMOS fabrication to scale the nanostructured sensors that we have. So we've created devices that have cross-sectional dimensions of about 1 micron by 10 microns, all on a silicon-compatible platform. And we can pack them very close together on chip for multiplexed biosensing. And as you mentioned, we can fit now about 3 million sensors on a silicon chip. That would be equivalent to over 31,000 96-well super-resolution plates, as you mentioned about the size of a basketball court that we're packing into a 1 centimeter square chip.

Chris Conner: The Welch Conference is also where the foundation presents the Welch Award in Chemistry. Its purpose is to foster and encourage basic chemical research and to recognize in a substantial manner the value of chemical research contributions for the benefit of humankind. Doug Foshee, Chairman of the Welch Foundation talks about this year’s recipient.

Doug Foshee: We're so proud that our awardee this year is Carolyn Bertozzi, and she's such a fantastic scientist, but you don't have to be with her for longer than about 30 seconds to realize what a great teacher she is and a mentor. And there are hundreds of Carolyn Bertozzis being born from her work. And then I would say to people that are going to listen to this podcast who aren't scientists, she has this amazing ability to translate very complex science concepts into language that the rest of us can understand. And people should watch her TED Talk. You can take 19 minutes out of your life to watch that and walk away and say, "Oh, I halfway understand what she's devoted her life to and how important it is to the world."

Chris Conner: Carolyn Bertozzi has become well known for her work on glycans and glycobiology. Shortly after being announced as the Welch Award recipient, she also received a share of this year's Nobel Prize in chemistry. I asked her, "Is there anything that sparks something for your research around glycans or analyzing single molecules?"

Carolyn Bertozzi: Oh, definitely. I love that you use the word spark because light and sculpting light and applications of light for molecular imaging is one of the themes of this conference. And it also happens to be one of the earliest and most impactful applications of my particular brand of chemistry, which we call bio-orthogonal chemistry in biological research. So I pay special attention when scientists talk about new types of imaging probes. And here we heard about photonic crystals and inorganic nanomaterials, which have really unusual ways of interacting with light. Also, you might not know that one of the organizers of this conference, W.E. Moerner, who you've had at the microphone, he and I have collaborated on a project in which we use bio-orthogonal chemistry for super-resolution imaging of cell surface glycans related to cancer. And in fact, we're both very proud of a paper we co-authored in the journal, Developmental Cell, in which we got the cover photo for that issue. And it's an image, it's a super-resolution image of cell surface glycans. So I feel very inspired by this conference.

Chris Conner: Those Super-resolution images provide scientists a glimpse of important details of the chemistry of life that haven’t been seen before.

Carolyn Bertozzi: It started with both of us becoming interested in the molecular features of synapses between immune cells and cancer cells. And those junctions are very important because they allow immune cells to recognize cancer cells as diseased and then to kill them. So he already had a project focused on imaging the proteins at these junctions. And my lab had a long-standing interest in the glycans at those junctions, and we realized that his super-resolution imaging technologies might teach us a lot about how the glycans are organized at those synapses. So a postdoc from his lab and a student from my lab started talking. He came up with an experimental plan, and that just evolved.

Chris Conner: It turns out that some immune cell checkpoint receptors bind glycans on cancer cells. This is a new discovery that both W.E. Moerner and Carolyn Bertozzi’s labs are investigating together.

Carolyn Bertozzi: I think it's fascinating the fact that you can actually study really complex biological samples like cells, tissue slices from a human cancer, all the way down to what individual molecules are doing. It's incredible, so powerful.

Chris Conner: All the work presented at the Welch conference that you just heard is about advancing chemistry and improving life. That is what these scientists are doing every day. Peter Hotez believes scientists need to do a better job of communicating their work and their value to society. I'll give him the last word.

Peter Hotez: Look, we're the patriots. I mean, this is a nation built on its research universities and institutions. Science helped the US defeat fascism in World War II and win the Cold War and slowly winning the war on HIV AIDS. We're the patriots, not those guys. And somehow we've got to bring that back and make people realize that.