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Quantum in Biology

The first day of the workshop focused on quantum in biology, which examined the study of quantum concepts that drive biological processes. The day started with a keynote address by Thorsten Ritz, professor of physics at the University of California, Irvine, which reviewed the history of research and theory in quantum biology and discussed emerging work. Following the keynote, three panel discussions covered probing intracellular and intercellular correlations in biology, bioelectromagnetic fields, and quantum photonics in biological systems. Each discussant on the panels was asked to give 7 minutes of opening remarks, which were followed by a moderated audience question and answer session. (See the workshop agenda in Appendix B.)

OLD AND NEW QUANTUM BIOLOGY

Thorsten Ritz

Ritz began his keynote talk by noting that quantum biology is defined by two closely connected questions: Is the machinery of life quantum mechanical, and can quantum mechanics be used to study the machinery of life in new ways? The design of new quantum tools could be bio-informed, meaning that the tools can incorporate an improved understanding of the biological systems and processes that are under study.

Quantum biology has been studied for decades by researchers siloed by disciplines. To make progress, Ritz urged that new collaborative, cross-cutting studies are needed to inform the entire array of interested communities. Using his own field, magnetic sensing via coherent electron spin reactions, as a focal point, Ritz highlighted “old” quantum findings, presented future opportunities in “new” quantum, and suggested open questions in each realm.

“Old” Quantum Biology Findings

Klaus Schulten’s early work on the impact of Earth-strength magnetic fields on chemical reactions at room temperature demonstrated that it was possible to set up molecular pairs to create targeted effects, an approach that has been consistently validated (Hore and Mouritsen, 2016; Schulten et al.,1978). This work has helped move three separate fields forward: physical chemistry, molecular biology and genetics, and animal navigation and orientation.

In physical chemistry, several studies were able to design a radical pair sensitive to Earth-strength magnetic field effects (Hiscock et al., 2016; Maeda et al., 2008; Procopio and Ritz, 2020; Timmel and Hore, 1996). However, Ritz said that there are other measures beyond the radical pair that should be investigated, such as response times and signal-to-noise (SNR) ratios.

In molecular biology and genetics, several studies have suggested that cryptochromes, a class of photoreceptors, are also a potential magnetic receptor. These receptors are unique because they are light receptors that respond to the stimulus of light on a biological timescale, which gives a direct coupling of light to the biological responses (Maeda et al., 2012; Ritz et al., 2000). There are still many unknowns about cryptochromes, but multiple studies have shown that they can affect circadian rhythms in Drosophila (Green et al., 2014; Helfrich-Förster et al., 2001).

Magnetic resonance experiments have shown that birds’ orientation instincts can be disrupted (Emlen and Emlen, 1966; Wiltschko and Wiltschko, 1972; Wiltschko et al., 1994) (see Figure 2-1), but oscillating magnetic fields at varying intensities can also disrupt avian orientation (Ritz et al., 2004; Wiltschko et al., 2005).

“New” Quantum Biology Opportunities

Cross-cutting research ideas, such as enzymatic actions in the protein environment, are pushing quantum biology forward. Dynamic, non-equilibrium collective responses in proteins, such as cryptochromes, may be necessary to produce quantum features, such as tunneling, and it may also be possible to control these responses and activate similar mechanisms.

In addition, looking at cryptochromes structurally with newer, more advanced tools could produce greater knowledge about biological functionality and answer many open questions about photosynthesis. Integrated platforms, such as those described by Kush Paul and co-authors (2017), could be used to investigate other open questions. These open questions include the effects of light conditions on phenotypical responses. One challenge, however, is that the connection between cryptochromes and neuronal response is poorly understood. One possible explanation for the connection is that cryptochromes may directly affect rhodopsin, the most prominent light-responsive protein in the eye (Paul et al., 2017; Stoneham et al., 2012).

Another potential area of study is NV-center diamonds, which could be emulators for cryptochromes because the physics of their spin effects is very similar. Bringing physicists, engineers, and biologists together to look at these systems in a unified, collaborative way would create progress in understanding—and potentially drive research in—biological systems.

Ritz concluded that quantum technology has come a long way due to the original work by Shor (1994), and the time is right to think beyond individual, siloed research and work together to push the field forward.

Discussion

A participant asked if it was possible to have evolved receptors wherein the unpaired electron is encased in a molecular edifice and the stabilized nucleus spins. Ritz answered that he believes it is possible for nature to work in harmony with the quantum state, at least on very short timescales, which is the case in enzymes. Although this is an important question, the available evidence is insufficient to provide a definitive answer at this point.

When asked how to test if the spectral density of an enzyme is an evolved property, Ritz replied that it is important to find the right ladder upon which to construct an answer. He suggested dynamical modes in thermal conduits in the

context of adaptations of amino acid substitutions as a starting place. He also added that very short coherence times are critical to biological functions. The transition from classical to quantum thinking will improve as more is learned about how quantum science matters in biology.

PROBING INTRACELLULAR AND INTERCELLULAR CORRELATIONS IN BIOLOGY

Philip Kurian, founding director of the Quantum Biology Laboratory at Howard University, moderated the workshop’s first session. The panelists were Marco Pettini, professor at Aix-Marseille University; Allyson Sgro, assistant professor of biomedical engineering at Boston University; Martin Plenio, director of the Institute of Theoretical Physics and the Center for Quantum Bio-Sciences, Ulm University; and Gürol Süel, professor of molecular biology, University of California, San Diego.

Long-Range Electrodynamic Interactions Among Biomolecules

Marco Pettini

There are an incredibly large number of biological reactions continuously taking place in living organisms, and thousands of metabolic interactions occur within each molecule. The fundamental question that drives Pettini’s work is, how do these biochemical cognate partners meet so efficiently and successfully?

The current explanation is that they meet randomly via Brownian motion, but a different possibility builds off Fröhlich’s (1968) idea that collective vibrations can be induced. Pettini’s team has observed this possibility in several proteins by exciting cryptochromes with lasers, creating protein quakes observed at the Terahertz level (Nardecchia et al., 2018). Another possibility for exciting long-range reactions is electrodynamic interactions, such as DNA–protein and protein–protein interactions (Preto et al., 2015).

Manipulating and Controlling Molecular-Scale Processes to Engineer Multicellular Biological Behaviors

Allyson Sgro

Manipulating molecular processes could be a means to control multicellular systems and create a paradigm for synthetic biology (see Figure 2-2). First, however, it is necessary to quantify a single cell’s behavior and engineer those behaviors to create protein-based tools and techniques to understand and exploit quantum biology.

Cells take internal action and signal to other cells based on inputs they receive. To understand how these inputs affect group behaviors, such as the collective scaling of vibration modes, Sgro’s team uses microfluidics and optogenetics to control and quantify cell inputs and link them to quantified outputs. For example, Sgro’s team used optogenetics to instruct a cell to initiate tissue repair.

New protein-based tools would illuminate ways that quantum effects are important in cell behavior. Existing imaging and sensing technologies have spatial and temporal limits that make it hard to capture ultrafast dynamic biological processes or relay instructions quickly enough. Other limitations are resolution, sampling frequency, depth, SNR ratio, and toxicity.

Quantum Sensing and Dynamics for Biology

Martin Plenio

Biological processes such as photosynthesis or magnetoreception can be viewed as very small, fast thermodynamic engines that have quantum potential. Some of the interactions that drive these processes happen at nanosecond and smaller timescales, and current open questions are how quantum mechanics might play a role in biological systems, how the interactions can be modeled, and how these interactions could be verified through experimentation (Huelga and Plenio, 2013). Direct quantum effects have not been observed over longer time ranges of days or years, but Plenio noted that there may be indirect effects.

Using color centers in diamonds is a promising way to examine the quantum effects of individual spin dynamics in biological systems at micro- and nanoscales. This makes it theoretically possible to search for magnetoreceptors in birds, detect redox reactions, and execute protocols for high-precision spin sensing (Barton et al., 2020; Cao et al., 2020; Müller et al., 2014; Schmitt et al., 2017; Schwartz et al., 2019; Wu et al., 2016). Collaborative efforts with biologists in these areas could answer important quantum effects questions.

Importance of Ionic Interactions

Gürol Süel

Inorganic ions, which are essential to life, underlie the majority of a cell’s composition and interactions (Milo and Phillips, 2015) (see Figure 2-3). The study of ionic interactions has enormous and exciting potential for the future of quantum biology, but it has been neglected for several reasons.

First, there is a lack of tools to study ionic interactions, which are noncovalent, making these interactions the unmeasurable “dark matter” of biology (Ross, 2016). In addition, the concept of ion homeostasis is misleading; the concentrations and locations of metal ions are frequently in flux. Finally, cells cannot make or destroy ions; they must regulate their ion content through channels and transporters. Although quantum effects have not explicitly been defined or tested, Süel noted that much more needs to be done to determine the role of quantum in cellular systems that regulate ion fluctuations.

Süel posited that the lack of knowledge or tools for studying inorganic ions poses an important challenge for many reasons. At the cellular level, certain ions can influence antibiotic resistance; for example, bacterial cells can protect their ribosomes from antibiotics by controlling the amount of magnesium ions inside the cell (Lee et al., 2019). At the population level, bacteria use ion channels to orchestrate community stress responses (Humphries et al., 2017; Prindle et al., 2015). Süel urged increased attention to this area at both the technical and theoretical levels.

Discussion

Kurian moderated a discussion that covered the need for new tools and theory, quantum effects versus quantum underpinnings, and probing ionic enhancements.

New Tools and Theory

Kurian asked what tools the panelists needed to pursue their work. Süel replied that beyond new tools and techniques, new theoretical frameworks are needed to understand cellular-level actions and predict cell behavior to design and use new tools. Sgro agreed, adding that theorists and experimentalists should work in tandem to build the tools to test these predictions in a closed loop.

Plenio, a theorist, added that the presence of so many unknowns in biological systems makes it difficult to formulate theories. Theorists and experimentalists working closely together could make progress by making, testing, and adjusting models. Pettini agreed that the theory–experiment gap is large, and noted that he is studying basic mechanics, such as cryptochromes and optogenetic molecules, to develop theory and design experiments around those building blocks.

Quantum Effects Versus Quantum Underpinnings

In response to a question, Sgro stated her belief that cell aggregation might be a quantum effect for two reasons. First, cell aggregation relies on a number of molecular-driven processes, which may be quantum-based. Second, the tools used to study cell aggregation are dependent on quantum phenomena but are not yet optimized to understand quantum properties. Kurian added that even phenomena that can be described classically may still have quantum underpinnings.

Sgro also noted that it can be challenging to tell which gene systems are activated during cell interactions. Different genes control internal cell activities than those that govern external interactions, and these external interactions could

have quantum underpinnings. She stressed the importance of improving research tools to better understand external processes.

Probing Ionic Enhancements

Süel stated that because so little is known about the inner workings of cells, nothing can be ruled out. The fact that life has evolved with inorganic ions and cannot live without them, however, points to their being essential. Solving these important questions will require a community-wide effort, he concluded.

BIOELECTROMAGNETIC FIELDS

In Session 2, Clarice Aiello, leader of the Quantum Biology Technology Laboratory at the University of California, Los Angeles, introduced the topic of the exploration of how organisms interact with electromagnetic fields. Such bioelectromagnetics might involve quantum properties, which points to the possibility that organisms may, for a short time, be living quantum sensors.

Aiello went on to explain what she meant by quantum, noting that she delineates the definition into several levels. This includes a base level of “quantum-ness,” which reflects that all matter is made of atoms, and when these particles are isolated they behave based on quantum mechanical principles. A second level is related to quantum coherence, where a single quantum object might be found in a coherent superposition state. A final level, which she described as the quantum-entangled level, involves multiple quantum systems which are entangled among themselves. Aiello noted that the area of bioelectromagnetism mostly touches on the quantum coherence level of quantum-ness, and she explained that the speakers would touch on the topic of spin, relating it to magnetic field sensing and the coherent superposition of spin states.

The speakers were Margaret Ahmad, research director of Centre National de la Recherche Scientifique (CNRS), Sorbonne University; Wendy Beane, associate professor of biological sciences at Western Michigan University; Douglas Wallace, geneticist and evolutionary biologist at the University of Pennsylvania; and Michael Levin, director of the Allen Discovery Center at Tufts University and the Tufts Center for Regenerative and Developmental Biology.

How Are Organisms Regulated by Electromagnetic Fields?

Margaret Ahmad

The class of photoreceptors known as cryptochromes, found throughout biology, are good candidates for magnetoreceptors because they absorb the blue light that migratory birds need to orient (Ritz et al., 2000). Many animals’

cryptochromes can be manipulated by magnetic fields, which indicates that they can perceive magnetic signals (Ozturk, 2017). This is possible because cryptochromes undergo photoreduction to form oxidation reduction (redox) states, a process that requires oxygen, and then generate protein changes, which produce measurable biological signals (Ritz et al., 2010). Reactive oxygen species (ROS), which are highly active cellular messengers, are also produced. Even though much is known about this process, there are still many unanswered questions that need to be addressed to enable predictions of cell behavior. There is also a need for further development of imaging technology, Ahmad said.

Understanding these quantum forces also has potential therapeutic applications. Light and electromagnetic fields stimulate short bursts of ROS, making them anti-inflammatory agents (Sherrard et al., 2018). This raises the possibility that they could be used to defeat cytokine storms, which are highly modulated by ROS. A cytokine storm is an overreaction of the immune system to an invading pathogen and plays an important role in the pulmonary effects seen in the lungs of some COVID-19 patients as well as others affected by infectious organisms. Ahmad suggested that such approaches could also potentially work for other noninfectious diseases that are modulated by ROS, such as cancer and many chronic diseases.

Quantum Control of Stem Cells

Wendy Beane

Beane and colleagues study whether quantum effects can regulate stem cell activity in planarian flatworms. These organisms are notable for their large number of stem cells in adult tissues, and their high capacity to regenerate (Oviedo et al., 2008; Sánchez Alvarado, 2007). Specifically, Beane and colleagues explore how external magnetic fields can be used to manipulate the radical pair spin state to either increase or decrease ROS levels. Using this approach, they found that magnetic field strength regulates stem cell activity through relative threshold levels of ROS. Weak magnetic fields, which lower the level of ROS present, inhibit new tissue growth, gene expression, and downstream gene proliferation, while strong magnetic fields and the resulting high levels of ROS increase growth (Van Huizen et al., 2019) (see Figure 2-4).

The sensing of weak magnetic fields is more influential in biology than previously thought and could hold promise for developing noninvasive therapeutic applications for regenerative medicine and cancer treatment. However, Beane said, more research is needed to advance knowledge about quantum sensing in cells. She added that a shared language and improved, organism-specific imaging tools are needed to facilitate productive interdisciplinary work in this area.

Are Mitochondria the Source of Electromagnetic Radiation That Emanates from the Brain?

Douglas Wallace

Electromagnetic wave measurements that are used to diagnose neurodegenerative diseases have been assumed to come from neuronal cells. However, Wallace raised the possibility that oscillating electromagnetic fields of mitochondria could be generating the electromagnetic radiation seen in electroencephalograms (EEGs) or magnetoelectroencephalography (MEG). This could be because mitochondria have a higher membrane potential than neurons and because there are far more of them than neurons.

The brain emanates oscillatory electromagnetic radiation, and MEG measurements in the brains of patients with autism show a marked difference from those of patients without autism (Port et al., 2015). Wallace’s team created a mouse with features that mimic autism and have an altered electroencephalogram pattern. This model was created by introducing a single point mutation in the mitochondrial DNA. The team then determined that the mitochondria communicate to generate an intense, oscillating electromagnetic field, similar to what is found in patients with autism (Yardeni et al., 2021). In addition, mitochondria align via electrostatic repulsion, creating an oscillating system along the mitochondrial membrane whose fluctuations generate the electromagnetic radiation that may be used in signaling (Brand et al., 2005).

Endogenous Bioelectric Pattern Memories in Embryogenesis, Regeneration, and Cancer

Michael Levin

Cells are incredibly competent at working together to create complex, three-dimensional morphologies. During development, a cell’s genetic code acts not as a hard-wired set of instructions for anatomy, but as a system executing error minimization loops to achieve the correct target morphology in the organism as a whole. Studying this goal-directed process in tadpoles, Levin and colleagues found that the tadpole’s craniofacial tissue will migrate to the appropriate locations during development to form normal frog faces, even when the tissues are artificially moved so that the eyes, nostrils, and mouth start in the wrong positions. This suggests that, rather than each cell following a preprogrammed path to its ultimate location in the face, cells make collective decisions about their arrangement and work together toward the correct formation. However, the mechanisms by which cell groups robustly implement specific anatomical goals are largely not understood.

In subsequent studies, Levin’s team found that bioelectric signals likely form a key communication channel enabling these collective decisions. Tracing cellular conversations by monitoring bioelectric signals in developing frogs, the team was able to observe typical bioelectric patterns as cells cooperate normally, as well as abnormal bioelectric patterns that occur when oncogenic mutations cause cells to defect from the group and lead to abnormal morphology (Levin, 2021). This communication is not local but rather propagates across the whole body and does not depend on innervation (Busse et al., 2018). Levin noted that the nonlocal nature of the signal mirrors the types of event seen in quantum mechanics, but he did not suggest that there was evidence that these events were exhibiting quantum mechanical behavior.

To manipulate these bioelectric patterns, Levin’s team uses molecular-level techniques to manage standing patterns of cellular voltage in tissues that instruct cell activity in multiple ways, including nonlocal activity, and creates computational models to guide the discovery of interventions that would normalize or repair damaged organs (Chernet et al., 2016).

This physiological “software” situated between the genome and anatomy can be read with voltage dyes and written by modulation of ion channels via drugs or light. Levin suggested that cracking the code of these quantum-esque bioelectric patterns represents a massive opportunity for biology and biomedicine, although better voltage imaging technologies will be needed.

Discussion

Aiello moderated a discussion covering other possible biomagnetic molecules, the need for more tools, and short-term electric field effects. Ritz also joined the panelists for the discussion.

Other Biomagnetic Molecules

A participant asked what other molecules, besides cryptochromes and ROS, might be affected by magnetic fields. Beane answered that anything with a magnetic dipole could be affected, and Ahmad added that any redox enzyme could be affected as well in the right environment. Wallace noted that if a mitochondrion’s magnetic field could be modulated, it could regulate ROS.

Ritz added that to set up quantum effects, the radical pair has to be embedded in a meaningful way in order to drive magnetic field effects, which is challenging. He is currently studying metabolic responses to understand this process.

Need for More Tools

Aiello asked what is needed to say unambiguously that something is or is not a quantum effect. Ritz answered that multiple pieces are missing, such as integrated experiments with quantum tools alongside other system tools, and a way to turn off quantum-ness, perhaps via amino acid mutations.

Ahmad agreed that there is a dearth of necessary tools and said that studies conducted to date have not yet produced biological proof of quantum-ness. A good first step would be building the simplest possible biological model to pinpoint that a quantum effect is driving a meaningful response. Beane agreed, noting that while a clean, synthetic cell could help connect the dots, she would like to see inside real, messy, organism-level changes and to manipulate magnetic field spins to determine if they are working in a quantum manner.

Wallace cited several unanswered questions: Can physics modulate biology, and is that physics acting in a quantum way? What is generating and receiving the signal, and what is the signal structure, especially at a distance across an organism? Some questions can be answered with current tools, but confirming quantum effects would require more research and tool development, he said.

Short-Term Electric Field Effects

Aiello asked panelists to speculate about short-term electric field effects in cells. Levin replied that his work usually takes hours or days, but there may be ultrafast dynamics at play that go unnoticed. Beane suggested that local cellular

communication may happen quickly, but the feedback loop takes longer. Wallace added that researcher Peter Burke is studying mitochondrial antennae and frequency signaling, and it may be that, as Beane suggested, a short-term signal gets repeated over a longer time frame.

QUANTUM PHOTONICS IN BIOLOGICAL SYSTEMS

Prineha Narang, assistant professor of computational materials science at Harvard University, moderated Session 3, which covered the roles of coherence, theory, and computation in biological systems. In addition, panelists described new quantum spectroscopy, optical, and photonic techniques to identify and differentiate these various mechanisms.

The panelists were Michelle Digman, associate professor in the Department of Biomedical Engineering at the University of California, Irvine; Scott Cushing, assistant professor of chemistry at the California Institute of Technology; Giuseppe Luca Celardo, professor at the Institute of Physics, Benemérita Universidad Autónoma de Puebla, and the Department of Mathematics and Physics, Università Cattolica del Sacro Cuore; and Tjaart Krüger, associate professor of physics at the University of Pretoria.

Quantum-Enabled Sensing and Imaging for Biology

Michelle Digman

Digman’s laboratory uses imaging technologies, including fluorescence lifetime imaging microscopy (FLIM) and multiphoton excitation, to study biophysical cellular mechanisms and interactions, especially when cells are under stress. These technologies could also be developed to study quantum effects in biological systems. For example, total internal reflection fluorescence measures protein displacement and diffusion (Di Rienzo et al., 2014, 2016; Digman and Gratton, 2009; Digman et al., 2008). In addition, single plane illumination microscopy enables monitoring of molecular dynamics within a cell, not just at the membrane, to create a map of spatial and temporal dynamic molecule behavior (Unruh and Gratton, 2008).

Digman uses these tools to study voltage-gated potassium ion channels (Kv), which could play a crucial role in increasing the understanding of cellular system activity and may be influenced by cryptochromes (Dixit et al., 2020). Her team mapped and measured diffusion and the length of confinement in Kv to produce a quantitative measure of the dynamics of these proteins (Tedeschi et al., 2021).

Entangled Spectroscopy

Scott Cushing

Cushing posited that entangled photon spectroscopy could inspire new tools for detecting quantum effects (Szoke et al., 2020). Such tools could be as simple as a desktop device that analyzes data or a high-powered quantum spectrometry tool to stimulate activity and detect quantum effects.

Entangled photons can be created by taking one photon and splitting it into two photons, resulting in two photons with different spatial, temporal, and polarization domains (see Figure 2-5). Two entangled photons tend to act as one when interacting with matter. For example, two entangled photons leave the same side of the beam splitter or diffract on a grating at the wavelength of the original pump photon. Their entanglement also enables measurements of the quantum correlations of light (Kalashnikov et al., 2017; Ostermeyer et al., 2009). Nonlinear-type spectroscopy of entangled photons has recently demonstrated linear two-photon fluorescence and absorption (Dayan et al., 2005; Lee and Goodson, 2006). While the exact mechanics are still unknown, entangled photon spectroscopy is a promising method to see and measure quantum effects.

To make an easy-to-use quantum spectrometer, very bright sources of entangled photons are needed, and they must work on short timescales to avoid disturbing the fragile entangled state in complex materials. For example, Cushing is studying whether on-chip sources with continuous wave diode lasers connected to a microscope could enable neural-type sensing.

Cooperativity Functionality and Sensing: A Bio-Inspired Sunlight Pumped Laser

Giuseppe Luca Celardo

Biological systems can process extremely weak energy sources and signals, such as the Earth’s magnetic field or sunlight. To accomplish such efficient coherent effects, the systems have to be highly symmetrical and hierarchical. Using these principles, many teams have studied biomimetic quantum devices (Creatore et al., 2013; Dorfman et al., 2013; Higgins et al., 2014; Romero et al., 2017; Scully et al., 2011). More recently, researchers have increasingly focused on cooperative effects for their relevance to robustness and functionality, for example (Celardo et al., 2019; Chávez et al., 2020; Gullì et al., 2019; Mattiotti et al., 2020b).

Celardo’s team is studying bio-inspired sunlight pumped lasers (Mattiotti et al., 2020a). A laser pumped by natural, renewable sunlight could collect, store, and distribute solar energy efficiently. Conventional sunlight-pumped lasers face technical challenges, but Celardo’s biomimetic design works with natural, unconcentrated sunlight (Yabe et al., 2008). The technology’s inspiration comes from bacterial photosynthesis, a process that relies on cooperative effects from the highly symmetrical and hierarchical organization of chlorophyll molecules that collect sunlight and efficiently transfer it.

Photosynthetic Light-Harvesting Complexes

Tjaart Krüger

Krüger posited that photosynthetic light harvesting complexes may be the best proof that biological systems use quantum effects to enhance function. Through subtle protein conformations, photosynthetic light-harvesting complexes use exciton-phonon coupling to dynamically tune the interplay between exciton delocalization and quantum decoherence. The level of tunability varies depending on the type of light-harvesting complexes that are used. Krüger’s team is investigating this tunability via two experimental methods.

First, they use single-molecule spectroscopy with quantum techniques to investigate how single protein complexes perform the sensing and tuning of the light-harvesting efficiency. Second, they use ultrafast transient absorption

spectroscopy to resolve energy transport, illuminating which pigments in the light-harvesting complexes, and which energy levels, participate at which time. By employing coherent control, it is also possible to actively tune the degree of light harvesting.

Two emergent technologies from this work, quantum illumination and ghost imaging, have promising biosensing and imaging advantages. Quantum illumination, in particular, can greatly enhance the signal-to-noise (SNR) ratio, improve accuracy and resolution, provide clarity in diagnostics, reveal protocol effectiveness, detect new pathways for optimizing biochemical processes, increase optical power, and minimize photodamage, all without being limited by combined time and frequency resolution. In practice, however, various sources of noise, such as interactions between excitons with vibrational modes in the immediate environment, severely limit the actual SNR enhancement, and the main benefit of these technologies lies in the use of fewer photons to obtain the same information as in classical measurements. In reply to a question, Krüger noted that his team has not studied quantum illumination for superresolution imaging but focuses instead on spectroscopic applications.

Discussion

Narang moderated a discussion touching on finding coherence signatures, quantum imaging, and entangled photons and spectrometry.

Finding Coherence Signatures

Narang asked the panelists how they could find coherence signatures, both theoretically and experimentally. Celardo answered that, first, these structures need to be fully understood and exploited, but it may be possible to simplify aggregates as dipoles through thermal relaxation and cooperativity. Exploiting hierarchy to understand the role of symmetry can also prove the efficiency of designed biomimetic structures and would be an indirect, theoretical hint at the role of coherence.

Cushing added that the biggest experimental challenge is whether the toll being induced is creating the effects seen. Separating combined quantum effects such as coherence and entanglement is difficult, but studying natural excitation, such as by sunlight, is promising. It is technically possible to excite something and determine if it is a quantum effect, but other tools are needed to study generic systems with varying properties.

Quantum Imaging

Ralph Jimenez, University of Colorado Boulder, asked Digman if quantum imaging could bolster her experiments. She replied that it is possible, for example, when monitoring a signaling event in Kv, an area widely under study. Digman also noted that although her laboratory does not measure quantum coherence, they do excite naturally occurring fluorescent molecules, and it may be possible to disentangle, monitor, and measure them. Cushing added that diffraction techniques for imaging still need improvement.

Entangled Photons and Spectrometry

A participant asked how entangled photons have different diffraction capabilities. Krüger replied that the improvement in the SNR ratio could apply to sensing and imaging, due to the soft Poissonian photon statistics. There is a limit, although the limit is lowered significantly with a very large number of photons.

Bern Kohler, The Ohio State University, asked Cushing if ultraviolet (UV) bandwidth could be increased in entangled light spectroscopy. Cushing replied that his laboratory is working on a prototype using a designed nonlinear element and diode lasers that he hopes can create ultrafast sources in UV. Celardo added that efficient photon sensing is key to learning more about biological processes.

BREAKOUT DISCUSSIONS

Attendees were invited to join several small breakout sessions for more in-depth discussion. For the first part of the breakout session, participants introduced themselves and discussed a range of topics, including the difference between coherence and entanglement, the role of ROS in wound healing, quantum versus classical coherence, different interpretations of coherence, different coherence timescales, and possible coherence measurements. For the second part, participants documented their thoughts on topics surrounding the concepts, technologies, and advancements to improve biological sensing and imaging. In addition, participants were asked to list outstanding questions they would like to see addressed during the remaining workshop sessions.

In these discussions, participants wondered if it were possible to reveal underlying quantum effects either by probing biosystems with quantum light or probing the quantum properties of the emitted light. Workshop participants pointed out several areas of importance for continued advancement of the field, including collaborations with synthetic chemists to create a bottom-up approach for building clean test systems to study entanglement, better readout mechanisms, and reaching n photon measurements. Finally, participants suggested future studies that could investigate using the ubiquity of ROS in metabolic signaling

processes, the use of quantum squeezing to measure biological action potentials, and the uses for quantum illumination and ghost imaging. They listed the following outstanding questions for the workshop and the field in general:

1. What kinds of “quantum 2.0” techniques can enhance biological function?
2. What are the emergent properties of a system that can only come from quantum effects, such as nonlocality and entanglement?
3. Is the spectral density of motions in a biological system somehow tuned to enhance quantum effects?
4. What infrastructure at national laboratories would improve measurements on biosystems, such as flux, precision, and entanglement?
5. Can more be learned about photosynthetic systems with single photon measurements?
6. Is there a role for quantum measurements in looking at ion interactions?
7. How does a system transition from quantum to classical?
8. Does nano imply quantum?
9. Can coherent control techniques be used?
10. How can the lack of shared language be fixed?
11. What is the next improvement in resolution after quantum illumination?
12. What are the advantages of quantum light over increased laser power?