Biophysics and Physicobiology
Online ISSN : 2189-4779
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Commentary and Perspective (Invited)
Half a century of biophysics: A comparison of presentation statistics from the 6th and 21st IUPAB Congresses
Mikio KataokaKuniaki Nagayama
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2024 Volume 21 Issue Supplemental2 Article ID: e212013

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Abstract

This is a report on the participation in the IUPAB Congress held in Kyoto in 1978 and 2024 by two senior members of the Biophysical Society of Japan who had the fortunate opportunity to attend the two Congresses. The authors comprehensively compared research presentations (poster presentations and oral presentations) at the two Congresses, which were half a century apart, and considered the academic changes in biophysics. It has been reported that biophysics has changed significantly over the past half century in line with technological advances of the times, and the next stage of biophysics is foreseen as an extension of the trend.

 Introduction

Two senior members of the Biophysical Society of Japan (BSJ) who were fortunate enough to attend both the 1978 IUPAB Congress and the 2024 IUPAB Congress in Kyoto, which were held with the full support of the BSJ and the Science Council of Japan, look back on half a century of biophysics. As we have already reported on the analysis and discussion of the participant statistics of the two Congresses [1], this paper focuses on the changes in the academic aspects, as seen in the two IUPAB Congresses held half a century apart, and thus it will mainly discuss research presentations.

 Consideration of the Presentation Statistics

Table 1 shows the number of symposium speakers, including chairs, as well as the participating countries and the number of participants by region. At IUPAB1978, the speakers of a symposium did not, without exception, chair the symposium. However, there were cases where speakers from one symposium chaired another symposium. At IUPAB2024, on the other hand, the chair of almost all symposia was chosen from among the speakers of the symposia, but there were also a considerable number of chairs who were not speakers. The number of speakers listed here is the total number of speakers and chairs excluding duplications. The number in brackets in Table 1 is also the number of speakers excluding chairs. The number of speakers at IUPAB2024 includes the number of speakers for the Keynote Lecture and the Plenary Lecture, but does not include the number of speakers for the Award Lectures. The number of speakers at IUPAB1978 was 189 (136 excluding chairs), and that at IUPAB2024 was 218 (194 excluding chairs).

Table 1 Comparison of Number of Countries, Participants and Speakers by region between IUPAB1978 and IUPAB2024

Region 1978 2024 Fluctuation
Japan Participants 1081 1225 144
Speakers* 52(30) 84(70) 32(40)
Asia except for Middle East Countries 4 13 9
Participants 44 242 198
Speakers 1(0) 29(29) 28(29)
Middle East Countries 3 3 0
Participants 16 7 –9
Speakers 2(2) 4(4) 2(2)
Western Europe Countries 141 152 1
Participants 253 140 –113
Speakers 52(43) 48(45) –4(2)
Eastern Europe Countries 83 84 0
Participants 93 32 –61
Speakers 6(3) 1(1) –5(–2)
North America Countries 2 2 0
Participants 330 62 –268
Speakers 66(58) 37(36) –29(–22)
South and Central America Countries 4 5 1
Participants 13 13 0
Speakers 0(0) 1(1) 1(1)
Africa Countries 2 2+15 (1)
Participants 4 4 0
Speakers 0(0) 1(1) 1(1)
Oceania Countries 1 2 1
Participants 7 25 18
Speakers 1(1) 8(7) 7(6)
Total Countries 396 526 13
Participants 1841 17507 –91
Speakers 189(136) 218(194) 29(58)

1West Germany, 2Germany, 3East Germany, USSR, 4Russia, 5Unknown, 6Including Japan, 7Except for Sponsors

*Speakers include symposium speakers and chairs for 1978, while plenary and keynote speakers, symposium speakers and chairs for 2024. The number of speakers except for chairs is shown in brackets. If a person is both a chair and a speaker, they are counted as one person.

This table is modified from Table 1 in Ref. [1].

There were 27 symposia at IUPAB1978 (Figure 1). Of these, there were 7 symposia with no Japanese speakers, while there were 8 symposia with two or three Japanese speakers, bringing the total number of Japanese speakers to 30. Although the principle was that each symposium should be chaired by two people, one Japanese and one foreigner, there was one symposium chaired by a Japanese chair only. Speakers were selected from all regions except for Latin America and Africa, but the ratio of speakers from North America and Western Europe, which have a large number of participants, was high. The ratio of speakers to participants was about 20% in North America and Western Europe, compared to 5%, 6%, and 2% respectively in Japan, Eastern Europe, and Asia, where there were relatively many participants. The Middle East and Oceania each accounted for more than 10%, but as the number of participants from these regions was small, this ratio is not statistically significant. The ratio of participants to speakers suggests that biophysics research in 1978 was mainly active in North America and Europe.

Figure 1  Changes in biophysics over the last half century as seen in symposia (classified by session titles): (a) in 1978 where the characters in brackets indicate the size of the hall used (S: small, M: medium, L: large) for a rough estimate of popularity. The symposia that were held twice are designated as “x 2”. (b) in 2024 where the numbers in brackets indicate the number of attendees for a rough estimate of popularity.

The topics of the symposia with more than 2 Japanese speakers were presumably central to biophysics in Japan at the time: Primary process in muscle contraction; Movement in sperm cilia and bacterial flagella; Photophysical process b (vision and bacteriorhodopsin); Structure and function of multi-macromolecular systems; Quantum biophysics and enzyme mechanism; Analysis of visual information by the nervous system; Applications of gel-entrapped organelles and cells in enzyme engineering; and Biorheology. On the other hand, the topics of the symposia without Japanese speakers were Molecular motion and structure of membranes, Bioenergetics a (oxidative phosphorylation), Biophysics of hemoproteins b, Folding of proteins and nucleic acids, Structure of chromatin, Physical methods, and Biophysical problems in a high saline environment, but this does not necessarily mean that these topics were not popular in Japan.

Two or three oral presentations were selected from the poster presentations, including at least one Japanese speaker, some of which are not included in Table 1, for which no materials remain. In fact, the materials that remain show that some young Japanese speakers in their 30s were selected. The proportion of Japanese speakers, including chairs, was 27.5%.

There were 33 symposia at IUPAB2024 (Figure 1). In principle, each symposium was chaired by a Japanese and a foreigner, and in many cases the same person was both chair and speaker. In addition, 23 symposia included a few Japanese speakers, and the ratio of Japanese speakers was 38.5%, an increase of more than 10 points compared to IUPAB1978. It seems that many symposia were planned on the initiative of Japan. Another feature of IUPAB2024 is that speakers were selected from all regions of the world. Compared to IUPAB1978, the number of speakers, including chairs, increased in the following regions: Japan, Asia, the Middle East, Central and South America, Africa, and Oceania. The number of speakers decreased in the following regions: Western Europe, Eastern Europe, and North America. The decrease in the number of speakers in Western Europe, Eastern Europe and North America corresponds to the large decrease in the number of participants, but while the decrease in Western Europe was only 4, the decrease in North America was as much as 29. It is also interesting to note that the number of speakers in the Middle East increased despite the decrease in the number of participants. In Asia, excluding the Middle East, the number of speakers increased significantly to 28, in line with the increase in the number of participants, and it is symbolic, if not coincidental, that this was almost the same as the decrease in North America. The ratio of speakers to participants was as follows: 7% for Japan, 12% for Asia, 57% for the Middle East, 34% for Western Europe, 3% for Eastern Europe, 60% for North America, 8% for Central and South America, 25% for Africa, and 32% for Oceania. The fact that the proportion of speakers from many regions has increased significantly since IUPAB1978 may indicate that the number of participants from outside Asia was limited to speakers and their associates, and that the participation of young researchers such as postdoctoral fellows has declined significantly. The changes in the percentage of speakers from each region out of all speakers are as follows: Japan 27.5% → 38.5%, Asia 0.5% → 13.3%, Middle East 1% → 1.8%, Western Europe 27.5% → 22%, Eastern Europe 3% → 0.5%, North America 35% → 17%, Central and South America 0% → 0.5%, Africa 0% → 0.5%, and Oceania 0.5% → 3.7%. Asia’s progress is conspicuous in response to the increase in the number of participating countries and participants, while North America has seen a sharp decline in the number of participants. We believe that these increases and decreases symbolize the fact that biophysical research has become more active worldwide over the past half century.

It is worth noting that David Baker, the speaker of the Ramachandran Lecture at IUPAB2024, was awarded the Nobel Prize in Chemistry in 2024. It is expected to have been an inspiration to the graduate students and young postdocs who attended. It is also worth noting that Albert Szent-Görgyi, who was a Nobel laureate at that time, was included as a speaker at the IUPAB1978 symposium, and that symposium speakers, Kurt Wütrich and Richard Henderson, later received the Nobel Prizes (both in chemistry). Japanese graduate students including one of the authors, Kataoka, were greatly stimulated by their interactions, which had a positive impact on their subsequent research careers [2].

Next, we will summarize the poster presentations. The number of poster presentations was almost the same, 1132 (IUPAB1978) and 1135 (IUPAB2024). The number of presentations from Japan increased from 454 (IUPAB1978, 40%) to 797 (IUPAB2024, 70%), while the number of presentations from abroad decreased from 678 to 339. It is noteworthy that the number of poster presentations from overseas was greater than the number from Japan at IUPAB1978. This is in proportion to the ratio of the number of participants, and it may indicate that IUPAB1978 was expected by biophysicists from all over the world, especially from North America and Western Europe. In addition, one of the authors, Nagayama, was studying in Switzerland at the time of IUPAB1978, and was counted as a participant and poster presenter from Western Europe. In addition to Nagayama, it is also worth noting that there were a number of Japanese young postdoctoral fellows who participated from their study abroad destinations, and later became active biophysicists. At IUPAB2024, there were also some Japanese studying abroad. We anticipated that they would play active roles as leading researchers in the field of biophysics.

 Changes in Academic Trends as Seen in Posters and Oral Presentations

Let us now take a look at the changes in scientific trends. Table 2 and Figure 1 compare the research keywords in the titles of posters (Table 2) and symposium oral presentations (Figure 1, here 7 oral presentations corresponding to plenary and keynote lectures were excluded), which are supposed to show the changes in academic trends in biophysics.

Table 2 Changes in biophysics over the last half century as seen in posters (classified by research keywords)

Year

Topics

IUPAB1978Kyoto IUPAB2024Kyoto

Protein

(structure, function, methods, physical property, design & engineering, intrinsic disorder, hydration, electrolyte,)

265

Hemoprotein: 42

Actin: 39

Myosin: 38

ATPase: 17

Fluorescent protein: 0

216

Hemoprotein: 7

Actin: 24

Myosin: 13

ATPase: 14

Fluorescent protein: 5

Membrane

(structure, dynamics, channels, signal transduction, receptor, liquid phase separation, membrane proteins, autophagy)

239

Channel: 13

Membrane proteins: 4

Phase separation: 2

Receptor: 27

141

Channel: 34

Membrane proteins: 32

Phase separation: 21

Receptor: 25

Nucleic acids

(DNA/RNA-DNA/RNA proteins, DNA/RNA nanotech, chromatin, chromosomes, nucleosomes)

58

Chromatin & Chromosomes & Nucleosomes: 14

75

Chromatin: 34

Number of posters including word Muscle 78 5

Cell biology

(motility, mol. motor, adhesion, cytoskeleton, signal transduction)

71

Flagella: 15

Mol. Motor: 0

88

Flagella: 20

Mol. Motor: 33

Nerve

(neural, neuro, nerve, circuit, sensory)

38 33

Photobiology

(photosynthesis, vision, optogenetics, purple membrane)

105

Purple membrane: 4

Rhodopsin: 23

Optogenetics; 0

55

Purple membrane: 0

Rhodopsin: 25

Optogenetics; 5

Radiobiology (radia-, radio-) 18 5

Virus

(virus, bacteriophage, SARS-CoV-2)

14

SARS-CoV2: 0

30

SARS-CoV2: 18

Mathematical biology 19 26
Computational biology 112
Single molecule biophysics 27
Mechanosensing & Mechanobiology 13
Bioengineering 20
Synthetic biol & Artificial cell 22
Biophysics of disease 10
Genome biology 8
Origin of Life 15

The underlined number indicates the total number of a given keyword.

 Changes as Seen in Research Keywords in Posters (see Table 2)

1) Proteins: Although there is not much difference in the number of posters, the content varies greatly when looking at individual protein species. The number of posters on heme proteins, actin, and myosin has decreased, while the number of posters on ATPase has remained the same, and the number of posters on fluorescent proteins has increased. This change corresponds to the sharp decrease in the keyword ‘muscle’ that we will see later. Even if we restrict the focus to structural analysis, in 1978 the main focus was on structural research on a small number of proteins using various spectroscopic methods, including NMR, but in 2024 it seems that the main focus was on the structural analysis of a very large number of proteins using cryo-electron microscopy. This change is due to two major progresses in protein research. In 1978, protein samples were prepared from cells and tissues, so the types of proteins available for biophysical research were quite limited. On the other hand, if we can clone the DNA of a protein, we will be able to prepare the proteins in large quantities using recombinant technology. Structural analyses were rather special techniques of the limited number of specialists in 1978, but now anyone can do it if they want to. In addition, in 1978 the ATPases were divided into three categories: myosin ATPase, sarcoplasmic reticulum ATPase and Na+/K+ ATPase, but in 2024, most of the ATPases were F1 ATPase and rotary ATPase. In 1978, the molecular mechanism of muscle contraction and chemiosmotic theory were two of the major topics in biophysics, and in 2024, F1ATPase is one of the main targets of single-molecule observation.

2) Membrane: The total number of posters has halved. However, there was an increase in the number of posters on specific topics such as membrane proteins, channels and phase separation. In 1978, following the establishment of the fluid-mosaic model, many sophisticated spectroscopic methods were developed to detect the diffusions of membrane protein.

3) Nucleic acids: The number of posters has increased. The majority of these are likely to be related to the cell nucleus. In 2024, particular attention has been paid to the coarse-grained dynamics simulations of large systems with a large number of atoms, such as chromatin and chromosomes (e.g. S. Takada, S21-5, B. A. Cohen et al., S24-3, J. Huertas et al., S24-5, T. Terakawa, S27-1, A. Fujishiro, S29-3).

4) Muscle: As mentioned in (1), the number of muscle terms (keywords) has decreased sharply by one-fifth since the 1978 congress. The number of actin and myosin terms has also decreased accordingly.

5) Cell biology: Slight increase. Most of this increase is due to motor proteins.

6) Nerve: There has been little change. The absolute number of posters is small to begin with, so it is not possible to say anything about a trend, but as a field of biophysics it is continuing steadily. It should be remembered that one of the roots of biophysics is the Hodgkin-Huxley theory of nerve excitation.

7) Photobiology: Halved. We have seen a transition between the old and the new in the fields of purple membrane and optogenetics. The number of rhodopsins is about the same, but the content is very different. In 1978, the number of visual rhodopsins (especially bovine) and bacteriorhodopsin was about half and half, but in 2024, the diversity appeared to include various microbial rhodopsins and visual rhodopsins from animals other than bovine. One of the reasons for the halving of photobiology presentations was the spin-off of the field of photosynthesis. Compared to 1978, when top researchers such as M. Nishimura, R. Clayton, L. Duysens, and C. Sybesma were gathered, in 2024, there were only poster presentations from Japan, and there were none from overseas.

8) Radiobiology: There was a significant decline. On the other hand, the development of radiotherapy methods has been remarkable, so perhaps this field has moved into the domain of medical societies.

9) Viruses: There has been a significant increase. Most of this is due to the SARS-CoV-2 virus, so it is probably due to the coronavirus pandemic.

10) Mathematical biology: There is an upward trend, but it seems to be focused on the use of computers, and there has been no change in pure theoretical biology.

11) Computational biology: The rise of computational biology, including bioinformatics, is phenomenal, even among the many new faces. This parallels to the rise of the digital world over the last half century. For example, the molecular dynamics (MD) simulation of the nuclear pore complex (NPC), consisting of about 1000 proteins by G. Hummer (KL-2) was a masterpiece. The mechanical response of the NPC to nuclear membrane tension was studied on the basis of the static structure obtained by cryo-electron tomography. However, the history of the combination of computers and biophysics is surprisingly old, and as early as the IUPAB1972 in Moscow, there was already a symposium on ‘the application of computers to medicine and biological systems [3]. The development of computational biology can be seen as a reflection of the incredible development of computing power. The use of new AI is also becoming routine in various fields.

12) Single-molecule biophysics: This is a field that did not exist in 1978 and has developed rapidly, especially in Japan. Many of the presentations were from Japan.

13) Although we did not mention it explicitly, there was a clear shift between old and new biophysical methods. Various super-resolution optical microscopes, atomic force microscopes, cryo-EM protein structure analysis methods, multi-dimensional NMR protein structure analysis methods, etc., which did not exist in 1978, were born in the last half century and have swept through biophysics (see Biophysics in the Future).

 Changes as Seen in Research Keywords in Symposia (see Figure 1)

The figures in brackets in Figure 1(a) indicate the size of the capacity of the hall used, and the figures in brackets in Figure 1(b) indicate the number of people attending the symposium, and both of which were used as a rough estimate of popularity. The following features emerge from Figure 1.

1) Changes in popular fields: In 1978, the most popular field was membrane-related, the second most popular was muscle-related, and the third most popular was also membrane-related. In 2024, the most popular field was protein structure and function, the second most popular was membrane-related, and the third most popular was single-molecule biophysics and protein design. This clearly shows the changing times.

2) The emergence of new fields in 2024: Looking at the fourth most popular term and below, the first nine terms are all topics that did not exist in 1978. This may reflect not only the content, but also the change in buzzwords due to the changing times. For example, computational molecular biophysics is probably a term that was added to quantum biophysics and enzyme mechanism to reflect the later arrival of computers.

3) Fields that have continued: There are, of course, many fields that have continued. A typical example is protein folding. In other words, the problem of protein folding, of predicting the tertiary structure from the primary structure, is a central issue in biophysics and has always been one of the driving forces of biophysics. AlphaFold2, which has led the world in its predictive capabilities, was the subject of this year’s Nobel Prize in Chemistry. Of course, the news of the award came sometime after the IUPAB2024 Congress, but the field of protein folding, including AlphaFold (26P-224), was also a lively one at the Congress. One of the authors, Kataoka, included the predicted structures of chimeric mutants of a designed protein by AlphaFold2 in his poster (26P-035). It should be noted that the winners, D. Hassabis and J. Jumper, are AI experts and not necessarily biophysicists. In contrast, David Baker, one of the plenary speakers at IUPAB 2024, was also honored for his contributions to computational protein design. Considering that AlphaFold2 was developed after a long journey of more than half a century, starting from Anfinsen’s dogma (Nobel Prize in Chemistry 1972), we understand that this year’s Nobel Prize in Chemistry was awarded to the field of biophysics.

4) Disappearing fields: The terms ‘Biorheology’ and ‘Environment’ have disappeared from the list of keywords in 2024.

The term ‘Environment’ was used in the past to refer to the group of microorganisms that are classified as archaea in extreme environments, but it seems that the term is no longer used as a keyword because it has become clear that a certain level of understanding has been achieved regarding the molecular mechanisms of environmental adaptation, based on analyses of molecular phylogenetic trees, etc. Biorheology was a trend in the early days of biophysics in Japan, but now it seems to have shifted towards medicine and physics.

In addition, there are several academic societies that have developed since the 1970s that have moved away from the Biophysical Society of Japan. These include the Molecular Biology Society of Japan, the Japan Neuroscience Society, Protein Science Society of Japan, Japan Society of Mathematical Biology, and Japanese Society of Photosynthesis Research.

At IUPAB2024, the Hands-on Training was evaluated as a unique attempt that well represented the characteristics of Japan, but it was not held at IUPAB1978, along with the plenary and keynote lectures. Therefore, it will not be discussed further as it is outside the scope of the purpose of this article, ‘The transition over half a century’.

 Biophysics in the Future

Could we have predicted the new fields that exist today half a century ago? One of the authors, Nagayama, chose NMR for study in graduate school, anticipating its future importance. He also foresaw the use of NMR for protein structure analysis. As a result, he arrived at 2D NMR and was able to contribute to the establishment of the protein structure analysis in the solution state, which was one of the main topics of IUPAB2024. Another author, Kataoka, carried out structural analysis of light absorbing proteins in solution in order to determine the structure of transition states. Structural analysis of photoreaction intermediates has made great progress since our low-resolution results, and has developed to the stage of time-resolved continuous femtosecond structural analysis (E. Nango, S23-3).

When we look at the field we have been involved in, we feel that the innovative progress there is inevitable, but the technological innovation in fields that are not our specialty, and the creation of new fields that accompany it, are beyond our imagination. So, although it is impossible to make predictions for most fields, we will make a bold attempt. As in any field of science, research has its ups and downs. A seed can sprout from an unexpected place, grow rapidly and then disappear. We will extrapolate the future of biophysics from the rise and fall of the last half century.

Protein field: From the era of X-ray crystallography alone, the means of structural analysis have expanded to include NMR and electron microscopy, and in particular, structural analysis using cryo-electron microscopy has come to dominate. In addition, femtosecond time-resolved analysis using the XFEL has become a reality, and structural analysis with high spatial and temporal resolution is now routinely performed. In the future, in cell and in situ structural analysis will be desirable to understand physiological functions. Although in cell NMR and in cell neutron scattering have already been attempted, innovative developments using various spectroscopic methods and microscopy techniques are expected in the future.

Cell biology: The development of fluorescence microscopy has been rapid and has made great strides in terms of sensitivity, resolution and selective information processing. The development of new fluorescent proteins and caged compounds is also essential for progress in this field. In particular, optogenetics, the fusion of genetics and photobiology, is expected to make great progress in various fields. In addition, research into the process of information expression at the site of gene expression (in the nucleus) is a vast unexplored field, also linked to developmental biology, and has made great progress since IUPAB1978, leading to the elucidation of chromosome and chromatin structure at IUPAB2024. This is likely to continue to grow as a thriving area of biophysics, and dynamic observation at the resolution of an electron microscope will be key.

The field of information biology: A new field that did not exist in IUPAB1978, and the convergence of genomics and medicine, as represented by the Katchalsky Lecture (F. Zhang, PL-1). He introduced the discovery of the CRISPR-Cas13 family of RNA targeting systems and the development of a toolbox for them. The system can be used for the purpose of searching for new microbial proteins other than genome and transcriptome regulation, which would be a new direction for biophysics.

Imaging and molecular measurements: In the field of single-molecule measurements, a new field not included in IUPAB1978, the Engstrom Lecture by T. Ando (PL-2) showed the current state of the field. Numerous molecular movies were presented as results of high-speed AFM, and the molecular movie of myosin V walking on actin filaments was especially a gold standard. The movie visualized the molecular mechanism of muscle contraction, which is still Japan’s forte since earlier than 1978, in a video that everyone could understand. From now on, it will be necessary to move towards in vivo single-molecule measurements.

It is difficult to predict the future of molecular measurements, but we can predict that innovative methods will be developed in the field of bio-electron microscopy. Electron microscopes themselves handle electrons, but the way they handle them is still classical. If we could create a quantum microscope that treats electrons as quanta, like a quantum computer, it would dramatically increase intracellular resolution, and make it possible to visualize protein dynamics in cells and tissues at atomic resolution.

Computational biology: This field has benefited from the explosion in computing power over the last half century. The Ramachandran Lecture (D. Baker (PL-3)) is a prime example: the design of new generation of artificial proteins, which goes beyond the context of biological evolution and is relevant to human society, using deep learning methods to predict the sequence, then synthesizing the corresponding synthetic gene and experimentally assessing the properties of the expressed protein. This is a bold demonstration of the true path of biophysics, and we can expect further developments.

Biotechnology and industry: In the Hands-on Training session, ‘Millions of Single Live Cell Analysis with the Automated Trans-scale-scope’, the speaker talked about the huge potential of using bioluminescence to illuminate street trees and home lighting by expression of high-efficient, artificial fluorescent proteins in leaves. The application of gene editing technology is involved in the project. The gene editing is tried to apply in medicine, engineering and agriculture, and we can expect rapid progress in the future.

Biomaterials science: Although it is a rather low-key field, biomaterials science is one of the important branches of biophysics. This field involves the study of the physical and chemical properties of proteins, nucleic acids and lipids. But it is overshadowed by the field of information biology. We hope that this field will continue to exist so that biological constants comparable to physical constants can become the basis of human society.

Theoretical biology: Theoretical biology, which is intertwined with evolutionary biology, was presented in the keynote lecture by K. Kaneko (KL-1). He derived an evolutionary fluctuation-response relationship through experiments on the adaptation of bacteria under stress. There is a proportional relationship between phenotypic changes due to environmental adaptation and genetic evolution. He also extended the theory of evolutionary dimension reduction to multicellular systems, showing that evolution and multicellular development by homeostasis are consistent. This line of research, which began with Kubo’s fluctuation-dissipation theorem, can be seen as a paradigm for the future of theoretical biology.

Biophysics of disease: The biophysics of disease was launched at this conference albeit on a small scale. There were 21 posters on cancer, 19 on Alzheimer’s/amyloid, and 27 symposia/posters on drug discovery. We felt a sense of enthusiasm to contribute to human society.

Integration with external fields: An unexpected new field created by technological innovation is optogenetics. This new field is rapidly advancing brain science research. It also attempts to use light stimulation to treat the brain by expressing light-emitting proteins in specific parts of the brain. Contribution of Japanese biophysics to this field is extremely significant, including the discovery and production of new rhodopsins and light-emitting proteins, the development of technology for delivering light deep into the brain, and the development of observation technology. We hope to see contributions to the development of biophysical approaches to the unified theory of the brain and the development of new diagnostic and therapeutic methods for brain diseases. At IUPAB2024, there was a symposium entitled ‘Optogenetics’ (symposium 23) and various poster presentations, but the applications were limited to three presentations (25P-179, 27P-161, 28P-139), including reports on anti-cancer effects and the control of amyloid formation, and it was disappointing that there were no reports on brain research.

The future of optical technology: The development of observation and stimulation techniques using light is essential for the creation of optogenetics, and biophysics is making a significant contribution to this technological innovation. In fact, Japanese biophysics seems to be leading the world in the innovation of optical techniques such as single-molecule observation. On the other hand, the application of optogenetics to various fields has become a fierce competition worldwide. For Japan to survive in this competition, close collaboration between biophysics and other fields is necessary. The invention of next-generation genome sequencers using optical technology has led to revolutionary advances in biology. Although most of the basic technologies for next-generation sequencer were developed in Japan, the actual sequencers themselves were not developed in Japan. Perhaps Japan’s weakness lies in its inability to integrate various seemingly unrelated basic technologies to create something new. We feel a similar sense of loss in semiconductors. There is no doubt that optical technology will be one of the defining technologies of the next half century. Innovative technologies such as AMATERAS have already been realized. In the future, we hope that Japanese biophysics will take a leading role in the development of various element technologies, such as the discovery, development, modification of light-sensitive and luminescent proteins and new lasers, which are the forte of Japanese biophysics, as well as the development of light-emitting technologies and light-observing technologies, and that these key technologies will be integrated to create new fields and industries. We have a strong desire to see Japanese biophysics take a leading role in this, and we believe that this should be the case. When IUPAB1978 was over, Professor Akiyoshi Wada stated that the fields of application based on biophysics were vast. He argued that biophysical techniques and methods should be the basis for all biological industries. Half a century ago, the pioneers of biophysics had the same aspirations and dreams as we do today.

Relationship with AI: Using the genome as a starting point, it is possible to create any protein or protein complex in the laboratory, without having to use real organisms. In line with this trend, the structure and function of a huge number of proteins were discussed at IUPAB2024, but the use of this database is no more than a form of encyclopedic natural history. The hope is that it will lead to the emergence of a theory with a good physical perspective, but the sheer volume of structure and function data, which has never been seen before, may exceed the human ability to digest it. This is where AI comes in. AI is influencing all academic fields. In fact, the Nobel Prizes of this year in both Physics and Chemistry were awarded to AI-related research. Both protein design and protein structure prediction are two of the major fields of biophysics. Biophysics, which is a vast interdisciplinary field that encompasses the self-contradictory concepts of physis and biology, is probably the academic field most susceptible to the influence of AI. AI clearly depends on the skill of the user. We hope that AI will be used by skilled users to generate theories from encyclopedic biophysical data.

 Conclusion

From natural history to physics: As ‘Rocking out biophysics’, the theme of IUPAB2024, the authors enjoyed biophysics to the fullest and were deeply moved by the progress made in biophysics in Japan, Asia and the world over the past half century. Comparing the 1978 conference with the 2024 conference, the advances in technology are remarkable, and various observations and operations that were impossible in 1978 are now possible. As mentioned in the previous section, IUPAB 2024 saw an increase in the number of presentations at the molecular and cellular level of various objects, and an emphasis on the natural historical aspects of biophysics. Advances in prediction technology, such as AlphaFold2, seem to have encouraged this trend. Natural history is the basis of biology, so it is inevitable that biophysics should have a natural history-like character at the molecular/cellular level. But while we recognize biological diversity at the molecular level, those of us who have physics as our backbone feel that this is not enough. In other words, it is interesting from a natural history perspective, but we cannot see physics. ‘Biophysics should be interesting both biologically and physically’, as Professor Fumio Osawa put it.

Ascending the hierarchical structure: Where will the interest in the physical aspects lie in the future? The keynote lectures by K. Kaneko (KL-1) (‘Searching for Universal Laws in Evolved and Evolvable Complex Biological Systems’), D. Baker (PL-3) (‘Design of New Protein Functions Using Deep Learning’) and H. Ruohola-Baker (KL-4) (‘Decoding Regeneration Using Computer Designed Proteins’) may provide some clues. Both of them showed the way to prediction and design, either by unravelling complex systems by treating them as they are. Thanks to advances in computational science and prediction, we are boldly approaching the physical and chemical aspects that give rise to the complexity and hierarchical nature of life, which was not previously understood. Advanced measurement technology, targeting everything from single molecules to small systems, is working with high-capacity, ultra-high-speed computers, and there were many presentations at this conference that are steadily climbing the stairs of hierarchical structure.

The original intention of the BSJ: Professor Masao Kotani, the founder of biophysics in Japan, said at the time of the founding of the BSJ: ‘The ultimate goal of biophysics is to enable us to understand living organisms from a physical science perspective. Biophysics should not be a closed and self-contained discipline, but should be flexible and cooperate with researchers in many fields such as molecular biology, physiology, and biochemistry, and should also enter into these fields. A group of researchers who recognized the effectiveness of physical research attitudes and methods formed a Society’. In the early days of the BSJ, researchers from a wide range of fields were members. As the number of papers at the annual meeting was limited, papers from all fields were given in one or two venues without any order, but by the time of the IUPAB1978, they began to be grouped by topic as they are now. While the presenters and members who felt comfortable with the Society remained and the fixation of fields progressed, researchers in fields such as molecular genetics naturally left the Society and a tendency to form new societies emerged. Perhaps there is an aspect to the fact that the technology brought about by biophysics has become the basis for measurement in all fields, and that the discussions of science developed on this basis are not sufficient within the BSJ.

The number of members leaving the Society as spin-off fields is about the same as the number of researchers joining, which is probably the reason why the number of members of the BSJ has remained almost constant. Some new members are attracted by the new science that biophysics is creating, such as single-molecule measurements, and the others are researchers in new fields, such as synthetic biology. When considering the future of the BSJ, it is necessary to broaden the opportunities for biophysics by incorporating different fields, as well as reaching out to different scientific societies and making people aware of the contributing role of biophysics.

Energize physics: It is generally understood that there is no such thing as a life equation, which biophysics has pursued from the beginning, and now information has become the main topic instead of matter. Biophysics is now more of a field of information biology. Nevertheless, life is supported by matter, and we think that the physical interest of biophysics in understanding the material aspects of life is still alive. At IUPAB2024, we learned that there are researchers who are taking up the challenge of a new biophysics based on a solid foundation of physics. The physical aspects of biophysics are being rediscovered, and it is our dream that within the next half century, biophysics laboratories will exist as a matter of course within physics departments in Japan, which are currently in a state of extinction, and that they will in turn become a source of encouragement for physics.

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