What is reality?

Stephen Hawking was not only a first-class scientist, but also a remarkable communicator who managed to distill his intellectual journey into a single counterintuitive statement: “I have spent my life traveling across the universe inside my mind”.^[1] It is paradoxical that a person whose physical existence was mostly confined to a wheelchair could claim such ubiquity. What reality is Hawking talking about? What is the difference between the mathematics we use to describe nature and nature itself? In physics, the concept of reality applies to something that explains our observations well. Although we cannot see elementary particles with our own eyes, we affirm their existence because the mathematical structures that describe them accurately predict the behavior of matter. Here, the distinction between nature and the mathematics used describe it begins to blur.

We perceive reality through our five senses

In the process of visual perception, it is imperative to distinguish between seeing and perceiving. While the act of seeing is a physical process of receiving light stimuli, perceiving is the cognitive and subjective interpretation of that information. The light that hits the retina is converted into electrical signals processed by different areas of the brain, each specialized in one attribute: color, orientation, contrast, movement, or spatial frequency. The result, a moving yellow tennis ball, for example, is a mental construct.

In our relationship with the environment, we depend on five main senses: sight, hearing, touch, taste, and smell. In all cases, the same distinction can be made between stimulus and perception. These senses—compared to reality as we know it—are quite limited. Our eyes detect only a small fraction of the electromagnetic spectrum. Infrared, ultraviolet, and countless other wavelengths exist beyond our perception, creating an invisible world around us. Our ears pick up sounds within a narrow frequency range, but there are infrasonic and ultrasonic vibrations that are imperceptible to us. Our sense of touch registers pressure, temperature, and texture, but fails to capture the deeper molecular and energy exchanges that occur at the microscopic level. Evolution has adapted our senses to perceive what is necessary for survival and nothing more.

In this framework, language acts as an extension of our senses. Noam Chomsky defines language as a biological faculty that allows us to access layers of reality invisible to other animals: complex causality, future time, and pure abstraction. As Bertrand Russell said, “Language serves not only to express thought but to make possible thoughts which could not exist without it”.^[2]

The discovery of reality through mathematics

Scientific progress has revealed that what is perceived by the senses is merely the superficial veneer of the universe. We are blind to the trillions of neutrinos that pass through our body every second and our intuition fails when trying to imagine the curvature of spacetime. However, we have developed a “sense” capable of capturing this expanded reality: mathematics.

While Einstein’s field equations describe the very texture of the cosmic fabric, Heisenberg’s uncertainty principle explains vacuum energy fluctuations. We owe everything we know about the infinitesimal and the immeasurable to these logical structures. Thus, sensory perception anchors us to immediate and practical reality, but mathematics represents the objective and immutable truth of natural laws.

What does it mean then that Hawking “traveled the universe”? Hawking’s remark about his mental journeys is therefore not poetic license, but a statement about the power of the human mind as a higher-order sensory organ. Through mathematics, thought becomes a form of exploration.

The mental perception of mathematics

Neuroscience has shown that the brain has not developed new areas for mathematics—a cultural milestone far too recent on the evolutionary scale—but has “recycled” neural circuits originally designed for the perception of physical forms and spaces. According to Stanislas Dehaene, high-level mathematical expertise and basic number sense share common roots in a non-linguistic brain circuit.^[3] This architecture suggests that the brain processes abstract mathematical structures following exactly the same protocol it uses to identify an ordinary object.

From birth, we possess innate mechanisms to identify objects and determine their quantities; for our nervous system, number is a dimension of analysis as fundamental and intrinsic as color or shape. As Dehaene explains, “Just as we cannot avoid seeing objects in color […] and at definite locations in space […], in the same way numerical quantities are imposed on us effortlessly”.^[4]

This functional equivalence explains why, to perceive a jug for example, the brain analyzes symmetries, edges, and volumes, and why it uses that same visuospatial machinery to unravel complex abstractions. The brain does not treat mathematics as an intellectual datum, but as a geometric entity. In fact, the crucial difference between a novice and an expert lies in this point: while the former tries to decode an equation sequentially, as if it were language, the expert manages to “see” it and manipulate it mentally as a tangible geometric structure, endowing abstraction with the same physical and spatial entity that an object in the sensible world possesses.

Hawking’s travels

In this regard, it makes sense to say that Hawking traveled repeatedly throughout the universe for more than 40 years. He crossed the event horizon of invisible black holes and remained there, in the realm of pure abstraction, unraveling the connections between relativity, thermodynamics, and quantum physics. Similarly, years earlier, a very young Einstein drew on a similar experience, when at age 16 he asked himself: What happens if we chase a beam of light at the speed of light? This inward inquiry led him to the formulation of special relativity.

Hawking’s travel experience left such a lasting impression on him that he wanted to take to the grave a memory of which he was particularly proud. For this reason, the equation describing the temperature of black holes has been engraved on his tombstone at Westminster Abbey:

This formula, which relates the five fundamental constants of nature,^[5] is the map of his most famous discovery: the black holes of the universe are not entirely black, but emit a glow that is known as Hawking radiation.

The mind as the final frontier

Ultimately, Stephen Hawking’s journey reveals a profound truth about our species: we are not prisoners of our biology. While evolution endowed us with limited senses—those necessary to ensure our survival in the bush—it also bequeathed us a mind with the amazing ability to advance our understanding of the cosmos.

Manuel Ribes

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

References:

[1] Stephen Hawking Brief Answers to the Big Questions  Editorial Planeta S.A., 2018 ISBN: 978-84-9199-058-1 (epub)

[2]https://quoteinvestigator.com/2016/09/09/language/#7b00d116-d3e2-4149-a739-f8913649a3d1-link

[3] Marie Amalric and Stanislas Dehaene  Origins of the brain networks for advanced mathematics in expert mathematicians   PNAS | May 3, 2016 | vol. 113 | no. 18 |

[4] Stanislas Dehaene The Number Sense [How the Mind Creates Mathematics] Oxford University Press 1997 ISBN 0-19-511004-8

[5]  T_H: Hawking Temperature (Kelvin).

    ħ: Reduced Planck constant (quantum world).

    c: Speed of light (relativity).

    π: Pi (geometry).

    G: Gravitational constant (gravity).

    M: Mass of the black hole.

    k_B: Boltzmann constant (thermodynamics).

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Through comparative analysis of the DNA of large populations, these studies allow scientists to locate small genetic variations associated with diseases such as Alzheimer’s disease, Parkinson’s disease, and diabetes, fostering the development of personalized medicine and new therapeutic strategies.

However, while GWAS have important biomedical applications, they also raise significant bioethical concerns, especially when their findings are used to genetically select embryos or to evaluate complex human traits. This calls for ethical reflection on the limits of these technologies.

GWAS are one of the most influential methodologies in modern genetics. These studies consist of comparative analysis of the entire genomes of a large number of individuals in order to identify statistically significant associations between genetic variants and certain traits or diseases.

The fundamental objective of GWAS is to detect small differences in the DNA sequence that distinguish people who have a certain trait—for example, a disease—from those who do not have it. In other words, the goal is to identify the genetic variants that appear most frequently in individuals who share a specific biological trait, within the vast “sea” of DNA sequences.

This involves analyzing the frequencies of genomic variants in large population samples. Individuals can be classified into two groups: those who have a certain genetic variant and the associated trait (for example, a disease); and those who lack that variant and do not present that trait. Statistical comparison between the two groups allows regions of the genome potentially involved in expression of the trait under study to be identified.

More than 20 years after their introduction into genomic research, GWAS have become a fundamental tool for identifying genetic variants associated with numerous human traits and complex diseases. Their capacity for detection increases notably as the analyzed sample size grows, resulting in the creation of large biobanks and international consortia of genomic data.

Accordingly, they are making a substantial contribution to our understanding of key areas in population genetics, evolutionary genetics, and conservation genetics, and especially in biomedical research for application in personalized medicine, pharmacogenomics, and gene therapy. GWAS also play a role in agriculture and livestock farming for the improvement of cultivated plants and domestic animals. In this article, we will look at the fundamentals of this technology and its applications in functional genomics in man.

Major genes, polygenes, and heritability

To better understand the significance of GWAS results, it may be helpful to review some basic concepts of genetics.

In higher organisms, two types of systems for determining traits can be distinguished: “major” genes and “polygenes”.

Major genes are those that determine well-defined qualitative traits, in which there is a direct relationship between the genotype (the DNA sequence) and the phenotype (the observable manifestation of the trait it encodes). Classic examples are the color of flowers in many plants, the SRY gene involved in the determination of male sex in humans, and the blood groups of the ABO system, etc.

Polygenes, or minor genes, determine traits through the joint action of multiple units distributed throughout the genome, each of which contributes to the additive effect to a varying degree. Polygenic systems are related to quantitative traits such as height, body weight, mental illness, cancer, etc.

In polygenic traits, the phenotype depends not only on genes, but also on environmental factors. Therefore, the total phenotypic variation (V_P) can be expressed as the sum of three components: V_P=V_G+V_E+V_GE, where: V_G represents the variation in the trait due to genes; V_E the variation in the trait due to environmental factors; and V_GE the variation due to the interaction between genes and the environment. From these components, the parameter “heritability” (h²) is calculated; this estimates the proportion of the phenotypic variation of a trait due to genetic factors, where h²=V_G/V_P. It is a central concept in quantitative genetics that allows us to evaluate the relative contribution of genetics and the environment in the manifestation of traits.

The human genome and the molecular basis of genes

The genome is the complete set of genetic information contained in the DNA molecules of an organism. It is made up of one or more DNA molecules, the chromosomes, which in turn consist of tens, hundreds, or thousands of genes and non-coding intergenic regions. The concept of gene has evolved as knowledge about the structure and function of DNA has advanced. Today, we understand that a gene is a DNA sequence that contains the information necessary to produce a functional RNA molecule, which in many cases will be subsequently translated into a protein.

The human genome contains approximately 3.2 billion base pairs, distributed over 23 chromosomes in the haploid set. There are an estimated 21,000 protein-coding genes in this genetic material. Regions of the genome that directly encode proteins are called exons. All of them together constitute the “exome”, which accounts for approximately 1.5% of the human genome. Despite this small proportion, the exome plays a fundamental role in determining the phenotypic traits of each individual. However, the rest of the genome is not a simple set of “junk DNA”, which was the initial assumption after the completion of the Human Genome Project in 2003.

Soon afterwards, thanks to the international ENCODE (ENCcyclopedia Of DNA Elements) project, it would be shown that many of the non-coding regions of the human genome contain regulatory elements that control when, where, and to what extent genes are expressed. ENCODE is a large-scale project involving numerous research groups, which was launched in 2003 by the National Human Genome Research Institute (NHGRI) in the United States with the aim of identifying all the functional elements of the human genome.^[1] The functionality of the entire genome varies from one cell to another, depending on the developmental stage, cell type (specialization), or tissue to which they belong, so that, although they share the same genome, the part that is expressed in each of them varies. The complete set of RNA molecules, especially messenger RNA, present in a cell or tissue at any given time is known as the “transcriptome”.

Fundamentals of GWAS

GWAS are based on the systematic comparison of the DNA of thousands—or even millions—of individuals to detect genetic variations associated with biological traits or diseases.

Most of these analyses focus on single nucleotide polymorphisms (SNPs), which involve the substitution of a single nucleotide base for another (A, T, C, or G) at a specific position in the DNA. An SNP is considered important when it occurs in at least 1% of the population and naturally contributes to phenotypic variation. It is the most frequent type of genetic variation and is mainly found in non-coding DNA. When SNPs appear in a gene or regulatory area of gene expression, they can alter the function or expression of the gene. They are used to locate and map polygenes related to quantitative traits, also called quantitative trait loci (QTLs).

GWAS analysis is based on the development of SNP arrays that enable hundreds of thousands or even millions of these genetic markers to be analyzed simultaneously in each individual DNA sample. These arrays typically contain between 200,000 and over two million SNPs, allowing much of human genetic variability to be explored. In addition to SNPs, there are other forms of genetic variation that can also influence the phenotype. These include “indels”, which are insertions or deletions of nucleotides in the DNA sequence, and “structural variants” (SV), which involve larger changes in the genome, generally greater than 50 base pairs. These variants can play an important role in a number of diseases, including some neurodegenerative disorders.

Once SNPs or other genomic variants have been identified, they are generally used to search for nearby variants that directly contribute to the disease or trait whose genetic basis is under investigation. The analysis consists of determining whether the presence of a certain SNP or any other variation at the same location in the genome is statistically associated with the same phenotype.

Functionality of genetic variants

Analyses derived from the ENCODE project have shown that only about 12% of SNPs are located within coding regions of the genome. In fact, disease-associated SNPs are more likely to be found in non-coding regulatory regions, such as “promoter” or “enhancer” regions, which are usually located outside the gene sequence and are critical for regulating gene expression. This suggests that many diseases are not necessarily due to changes in the protein encoded by a gene, but to alterations in the mechanisms that regulate its expression.

Genomic studies have also revealed that each individual carries more than 10,000 genetic variants—one every 17 nucleotides—of which an estimated 300 may affect protein function. While common variants are often shared among different human populations, many rare variants are characteristic of specific population groups. Therefore, GWAS also have a special interest in population genetics and evolutionary genetics.^[2]

Technological evolution and biomedical applications of GWAS

In the early years of GWAS, so-called “microarrays” were used to detect SNPs and other genetic variations. These systems compared the DNA of individuals to a standard reference sequence in the human genome. However, this approach oversimplified the complexity of genetic variation. In recent years, new mass sequencing technologies have been developed along with the use of multiple reference genomes and more sophisticated bioinformatics tools that allow the direct analysis of individual DNA sequences and more accurate detection of genetic diversity and integration with gene expression data.^[3]

The UK Biobank is a large-scale GWAS database and has contributed significantly to research into the genetic basis of many diseases. Samples in this large biobank come almost entirely from the United Kingdom, which means that GWAS results are based on specific regions and ethnicities. European ancestry is generally overrepresented in GWAS applications, while data based ​​on other regions or ethnicities are more limited.

GWAS have identified thousands of genetic variants associated with complex diseases, including neurodegenerative diseases, schizophrenia, type 2 diabetes (T2D), high blood pressure, and various types of cancer. These studies allow the identification of relevant genes and intergenic interactions, and offer very valuable information about the mechanisms involved in the traits studied and about the underlying mechanisms involved in their expression. These analyses have contributed significantly to the development of personalized medicine, pharmacogenomics, and the design of new therapeutic strategies.

Another fundamental resource for this type of study is the GWAS Catalog. This compendium of GWAS analyses was founded by the NHGRI in 2008, in response to the rapid increase in the number of studies using this technology. The EMBL (European Molecular Biology Laboratory), the world’s leading provider of biological data resources and tools, has also been collaborating since 2010. The Catalog offers an unprecedented opportunity to investigate the impact of common variants on complex diseases. In addition, it greatly facilitates the knowledge and systematic summary of the observed associations. Based on published studies, it is a consistent, searchable, and freely accessible database of SNP-trait associations, which is easily integrated with other resources and accessed by scientists, clinicians, and other users worldwide. It is also one of the largest repositories of full genome-wide summary statistics, which researchers can submit directly.

In recent decades, many research studies have been published on the application of GWAS to determine the genetic basis of several neurodegenerative diseases. These diseases, such as Alzheimer’s disease, Parkinson’s disease, ALS, multiple sclerosis, etc., are characterized by their complex genetic and regulatory patterns. For example, one GWAS study successfully identified approximately 75 genetic risk loci for Alzheimer’s disease dementia,^[4,5] while another identified 90 independent genome-wide significant signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci for Parkinson’s disease.^[6]

Despite these promising results, we are still far from fully understanding the current state of research and future trends in the development of GWAS for these types of diseases. Therefore, in order to better understand their causes, GWAS are being complemented with transcriptome-wide association studies (TWAS), which provide additional insights by allowing the genetic basis of these disorders to be correlated with their functional and physiological aspects.

GWAS face several limitations since, as noted above, they either fail to identify the causal genes, or most of the genetic variants identified are assigned to non-coding regions or have limited power to detect rare variants or small-effect polygenic signals, particularly in small population samples. TWAS studies, on the other hand, integrate tissue-specific QTL data, which makes it easier to locate genetically-regulated gene expression in the tissues in which the disease manifests. Nevertheless, there is still a long way to go since, in the case of Alzheimer’s disease for example, the GWAS carried out so far are either too few or lack samples from non-European populations.

Regarding Parkinson’s disease, in a GWAS published in 2025 that included around 63,000 patients and approximately 1.7 million control samples, a total of 134 risk loci were identified in European, Icelandic, Finnish, and Ashkenazi Jewish populations.^[6] This study also provided a follow-up analysis, aiming to facilitate precision medicine with the aim of advancing research on Parkinson’s disease.

GWAS have been used for many other health-related traits. In the case of T2D, a meta-analysis that included genomic data from more than 2.5 million individuals, of whom 428,452 had T2D, is notable. This study identified 1,289 significant signals in the genome related to an increased risk of this disease, which were mapped to 611 loci.^[7] It also included data on coronary artery disease, peripheral artery disease, and end-stage diabetic nephropathy, and linked obesity and vascular problems to the progression of T2D.

Bioethical assessment

Although GWAS have mostly focused on analyzing disease-related genetic variation, they are equally applicable to any type of quantitative traits governed by polygenic systems. Consequently, they are being applied for traits such as height, IQ, obesity, eye and skin color, etc. Some of these applications are ethically questionable due to their neo-eugenic nature, such as when they are used in preimplantation genetic diagnosis to select certain traits in embryos created through in vitro fertilization. Thus, in a previous article we saw the use of GWAS for analysis of the factors involved in the genetic causes of infertility due to embryonic inviability.^[8,9]  It would also be unethical to apply GWAS for the detection and selection of embryos based on their genetic characteristics related to diseases or other hereditary traits. Regardless of the findings of GWAS or other more or less informative analyses on the genetic traits of the samples, destroying human embryos—whose dignity must be respected at all times—cannot constitute a legitimate means that makes these applications ethically acceptable.

Nicolás Jouve

Professor Emeritus of Genetics at the University of Alcalá

Member of the Bioethics Observatory of the Catholic University of Valencia

References

[1] The ENCODE (Encyclopedia of DNA Elements) Project. Science. 306, 5696 (2004): 636-640.

[2] The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 491(2012):56–65.

[3] Genomic Inequality. To successfully use a patient’s genetic makeup in a clinical setting, we must better understand the incredible diversity of human genomes. The Scientist. Dec 1 (2012).

[4] Andrews, S.J., Renton, A.E., Fulton-Howard, B. et al. The complex genetic architecture of Alzheimer’s disease: novel insights and future directions. EBioMedicine 90(2023):104511.

[5] Bellenguez, C., Küçükali, F. Jansen, I.E. et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 54 (2022):412-436.

[6] The Global Parkinson’s Genetic Program, Leonard, H.L.  Novel Parkinson’s Disease Genetic Risk Factors Within and Across European Populations. MedRxiv. DOI:  https://doi.org/10.1101/2025.03.14.24319455

[7] Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X, Lorenz KM, et al. Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications. MedRxiv DOI: 10.1101/2023.03.31.23287839

[8] Carioscia, S.A., Biddanda, A., Starostik, M.R. et al. Common variation in meiosis genes shapes human recombination and aneuploidy. Nature (2026). https://doi.org/10.1038/s41586-025-09964-2

[9] JOUVE, N. and TUDELA, J. “A genetic study on embryo inviability reopens the bioethical debate after using 139,000 human embryos” In Bioethics Observatory, Catholic University of Valencia, 2 February 2026.

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The study, published in Nature Immunology, shows that after two doses administered to rhesus macaques, antibodies capable of neutralizing different strains of the virus are generated.

This breakthrough represents a significant step towards the development of a preventive vaccine that is more effective and faster than the strategies tested to date, although clinical trials in humans will still be necessary to confirm its safety and efficacy.

The trial has successfully activated a specific immune response related to human immunodeficiency virus (HIV) infection after a single dose of the new drug.

Researcher Amelia Escolano leads a research group at the Wistar Institute in Philadelphia, where they design vaccines and immunization strategies to induce antibodies against HIV.

The experiment was conducted using rhesus macaques, which, after receiving a dose of WIN332 immunization, were able to produce antibodies against HIV within three weeks. A second dose further intensified the immune response.

The study proposes a new classification of neutralizing antibodies against HIV. Type I antibodies are dependent on the viral glycan, while type II antibodies are not. WIN332 is the first immunogen designed to induce type II antibodies. These new antibodies target a critical region of the virus known as V3-glycan.

The vaccination protocol involves two doses, and neutralizing activity can be observed three weeks after the first dose. After the second dose, the antibodies are able to neutralize and block different strains of the virus.

Previous HIV vaccine trials required five to ten doses to produce an effective response, with the process lasting months or years, which significantly limited their efficacy. This study therefore represents a major advance in terms of both the effectiveness and speed of the protective effect.

The next step is to find funding to conduct clinical trials of the vaccine in humans.

Background

As we have previously published in our Bioethics Observatory, advances in HIV treatment have come from antiretroviral drugs, which limit the replication of the virus in infected people.

Thus, in 2024 the drug Lenacapavir managed to prevent 100% of AIDS infections in women with a dose of two injections per year.

This new drug for the treatment of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection was approved in 2024 by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

Lenacapavir, in combination with other antiretroviral drugs, is indicated for the treatment of adults with HIV-1 who cannot be treated with currently available drugs due to resistance, intolerance, or safety considerations.

The results of the trial, conducted on women from South Africa and Uganda, were presented at the 25th International AIDS Conference held in Munich and were published in The New England Journal of Medicine.

During the International AIDS Conference, the case of the seventh patient cured of the disease was also presented. This patient, known as the “second Berlin patient,” had been living with HIV since 2009 and was diagnosed with acute myeloid leukemia in 2015.

As treatment for this disease, she received chemotherapy and a stem cell transplant. The genetic characteristics of the transplanted cells conferred immunity to the infection.

Previously, in 2022, the case of the first woman cured of HIV with umbilical cord stem cells was presented, who was treated for 4 years for the acute myeloid leukemia she suffered from.

In 2009 the “Berlin patient” was the first person in the world to be cured of HIV also thanks to a stem cell transplant.

Prevalence and future perspectives of new therapeutic approaches

According to the UNAIDS report, the prevalence of HIV among adults (aged 15 to 49) was 0.7% worldwide.

Among the risk factors and behaviors that determine the spread of infection are homosexual practices (7.6%), sex workers (2.7%), intravenous drug users (7.1%), transgender people (8.5%), and prisoners (1.4%).

Advances in the treatment of HIV infection have managed to turn into a chronic infection that was fatal for many years after its emergence.

The first advances, thanks to antiretroviral drugs, managed to stop the replication of the virus, making it undetectable in infected patients and preventing its transmission.

Findings related to the case of the “Berlin patient” showed that the perfusion of stem cells with certain genetic characteristics conferred immunity to infection after proliferating in the transplanted individual.

The current finding opens up new therapeutic possibilities in the prevention of HIV infection, potentially offering more effective results than current treatments after human trials.

More importantly, it would come at a lower cost, so its application would be extended to populations that currently do not offer the available treatments.

This is especially relevant in Third World countries where the prevalence is extremely high.

It should be remembered that, according to the UNAIDS report, in 2024, 4,000 adolescents and young women between the ages of 15 and 24 were infected with HIV every week. More than 80% of all cases (3,300) were in sub-Saharan Africa.

However, therapeutic measures should be combined with prophylactic measures, which help to curb the spread of the disease specifically in high-risk groups, as well as the generalization of preventive diagnoses, which should be standardized in primary care.

Julio Tudela and Ester Bosch

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

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Scientific knowledge, technological development, and human progress

Throughout history, the well-being of humanity has been strongly connected to scientific and technological development. Although this connection is neither mechanical nor unambiguous, it can be argued that science and technology have been one of the most decisive drivers of human progress in terms of health, longevity, and prosperity.  As Nobel laureate Robert Solow established, technological progress is the main driver of economic growth.^[1] In keeping with this, scientist Richard Klausner said that “Over the past 100 years, humanity has witnessed the capacity to improve health that dwarves all of the advances of the entire history of our species. This amazing progress was the result, quite simply, of science and technology”.^[2]

It is often debated whether we should prioritize basic research or technological development; however, this is an artificial distinction, as there is a constant feedback dialogue between the two. There are instances where technology drives science: tools like the telescope allowed Galileo to prove heliocentrism, and the microscope revealed the cellular world. Today, particle accelerators and the CRISPR-Cas9 system have expanded the frontiers of our knowledge. Nevertheless, the reverse process is equally common. Electricity, semiconductors, biotechnology, and computing were born of theoretical curiosity with no immediate applications, but the generation of electricity, as well as electric motors, would have been unthinkable without Faraday’s law of induction; semiconductors rely on quantum mechanics; biotechnology rests on the foundations of molecular biology, genetics, and biochemistry; and the modern computer is inconceivable without Boolean algebra.

The belief that scientific and technological progress is one of the main drivers of progress and the well-being of mankind has led to sustained growth in global investment in research and development (R&D) in recent decades. In fact, global R&D investment has tripled over the last 30 years, reaching $2.7 trillion in 2023.

The result is an undeniable growth in global well-being so far this century. According to information from Our World in Data, a publication founded by economist Max Roser^[3] at the University of Oxford, extreme poverty has been reduced by 73% and maternal mortality by 33%; literacy, considering the proportion of adults who can read and write, has increased by 57%; and the world GDP per capita has grown by 70%.

Although there are dozens of disruptive technologies (robotics, synthetic biology, quantum computing, etc.), each with the potential to radically transform our daily lives, there are three that promise to elevate human well-being to a new level: Artificial Intelligence, Gene Editing, and Nuclear Fusion.

Artificial intelligence

The growing relevance of AI at the World Economic Forum in Davos, the most recent edition of which was attended by over a hundred officially appointed technology pioneers, along with large delegations from leading AI companies, clearly reflects global awareness of the central role this technology already plays in economic and social development. Beyond the media debate about the eventual arrival of a “superintelligence”, what really matters is to understand the degree to which AI is permeating today’s socio-economic fabric.

As Klaus Schwab, founder of the Forum, predicted, we are immersed in the so-called “Fourth Industrial Revolution”^[4]: adoption by business is accelerating, business models based on AI services are expanding, and generative tools have gone from being experimental to being integrated into fundamental operational processes.

Recent research from the McKinsey Global Institute sheds light on this shift.^[5] The immediate future is characterized not so much by the replacement of human labor as by an ever closer collaboration between people, intelligent agents, and robots.^[6] Although the study focuses on the United States, its findings can be extrapolated to other advanced economies. According to the analysis, the technologies currently available could theoretically automate activities that account for around 57% of current working hours. At the same time, as technologies take on more complex sequences of tasks, the human role becomes more crucial in ensuring coherence, oversight, and decision-making.

This signals the emergence of a paradigm shift. In this new scenario, workers will spend less time on routine tasks, such as preparing documents or searching for information, and more on asking relevant questions, interpreting results, and exercising critical judgment.

The economic potential is staggering: in an intermediate scenario of adopting automation by 2030, AI-powered agents and robots could generate around $2.9 trillion annually for the US economy. Reaching this potential will depend less on new technological advances than on the ability of organizations to extensively redesign their workflows. Most current processes were designed for a pre-AI world; the challenge now is to rebuild that organizational “backbone” to adapt it to smooth collaboration between humans and machines.

However, the impact of AI transcends the economy and the labor market. As Stanford University professor Fei-Fei Li notes, “For the first time in history, we’re poised to build machines so in tune with the physical world that we can rely on them as true partners in the greatest challenges we face. […] [W]e’re on the cusp of technology that elevates the aspects of life we care about most”.^[7]

Gene editing

For just over a decade, mankind has had an extraordinarily precise tool to intervene in the genetic material of living beings: so-called CRISPR-Cas9 “genetic scissors”. Its origin lies in research initiated in the eighties on repeat sequences of bacterial DNA, later called CRISPR by Francisco Juan Martínez Mojica. The conversion of this natural mechanism into a universally applicable biotechnological tool became possible thanks to the work of Emmanuelle Charpentier and Jennifer Doudna, who managed to reprogram the defense system of Streptococcus pyogenes, an achievement for which both were awarded the Nobel Prize in Chemistry in 2020.

The way in which the system works is as simple as it is effective: the CRISPR component precisely identifies a specific DNA sequence, while the Cas9 protein acts as “molecular scissors” that cut the genome at that exact site, allowing genetic information to be removed, corrected, or inserted. This precision marked a turning point over previous gene therapy methods, which were much more difficult to control. As Jennifer Doudna stated, “The original gene therapy approaches were not using as precise a way to introduce information into genomes. They relied on viral integration where the virus decided where it was going, not the experimenter”.^[8]

Although still evolving, CRISPR-Cas9 has already profoundly transformed biotechnology and promises significant advances in both human health and agricultural productivity on a global scale. At the same time, its ease of use raised the possibility of intervening in the human genome from the very beginning. In view of this scenario, the scientific community reacted quickly: in 2015, the world’s leading academies called for a moratorium on hereditary modifications of the human genome, while supporting basic research and non-heritable applications.

The Pontifical Academy for Life – both – has warned that “any application of this technique must be carefully evaluated with regard to the method used and with consideration of the scientific as well as the social consequences. Furthermore, it is necessary to reflect particularly on the application of this technique to the human germinal line, as it would make it possible to “design” a human being, eliminating defects or favoring specific characteristics, and would consequently produce hereditary alterations in the human population”.^[9]

Nuclear fusion

There is broad scientific consensus that access to energy is a key driver of economic growth and human progress. As Václav Smil, professor emeritus at the University of Manitoba, points out, “Other things being equal, the degree of cultural development varies directly as the amount of energy per capita per year harvested and put to work”.^[10]

Under this premise, mankind is tirelessly pursuing abundant, cheap, clean energy. The hope for achieving this goal is to replicate the way the stars and our sun produce energy. Although we have studied this process, known as nuclear fusion, for more than 70 years, we have not yet managed to reproduce it on an industrial scale. This is because we are playing at a clear disadvantage. A fusion reaction is the process by which two light atomic nuclei combine to form a single heavier one, releasing a huge amount of energy. In the Sun, hydrogen nuclei fuse to form helium thanks to the enormous gravitational pressure inside it, at a temperature of about 15 million degrees Celsius. We do not have that pressure on Earth, so to ignite an equivalent reaction, we need to reach temperatures ten times higher, of the order of 150 million degrees.

At this temperature, matter becomes a plasma that no solid material can confine. To isolate it, we use powerful magnetic fields that keep the plasma levitating, preventing it from touching the walls of the reactor. The main obstacle until now has been to achieve a positive energy balance: that the energy produced clearly exceeds that required to maintain the reaction.

The important thing is that these barriers are beginning to be overcome. More progress has been made in the last 5 years than in all the previous decades. In late 2022, the Lawrence Livermore National Laboratory achieved, albeit for nanoseconds, a reaction with net energy gain. More recently, laboratories in France and China have demonstrated the feasibility of stable reactions sustained for more than 15 minutes.

This progress has fueled intense private work: more than 40 companies are currently competing in the development of fusion technologies. Some have set ambitious timelines, such as Helion Energy, which plans to connect its first commercial plant to the grid in 2028, and Commonwealth Fusion Systems, in collaboration with MIT, which aims to build a 400 MW plant by the early 2030s. If these milestones are met, the deployment of nuclear fusion could accelerate exponentially.

An MIT study^[11]  estimates that the cumulative economic benefits of the fusion could range between $68 and $175 trillion by 2050. Like any emerging technology, its efficiency will improve over time, helping to secure and lower the costs of the energy supply required by an increasingly complex, high-tech society.

It should also be remembered that one of the main fuels of fusion is deuterium, an isotope of hydrogen present in water. The deuterium contained in a single liter of water has an energy potential equivalent to about 1,700 kWh, enough to cover the electrical needs of an average household for months.

Mankind’s real challenge

The convergence of AI, gene editing, and nuclear fusion promises not only an exponential leap in material well-being, but a qualitative transformation of the human condition. By delegating the burden of work to machines, intervening in the biological foundations of life, and accessing a potentially limitless source of energy, humanity is approaching a historic threshold: the end of survival as a central issue.

It is precisely at this point that the most profound challenge arises. For the first time, a civilization capable of generating unlimited abundance must learn to justify its future not by the urgency of need, but by the conscious choice of its own purpose. This challenge transcends the technical to enter into the ethical, cultural, and metaphysical realms.

Nevertheless, the search for a meaning that sustains existence beyond circumstances is not uncharted territory; it is a path that has already been travelled from various perspectives. Viktor Frankl, an Austrian psychiatrist who survived the horror of the Nazi concentration camps, left to posterity the conviction that the search for meaning is the major motivating force of human beings. According to Frankl, this meaning is not invented, but is discovered as a vital response to the questions the world presents to us.

In line with this view, Joseph Ratzinger, Pope Benedict XVI, emphasized that meaning is not an artifact of our engineering, but a foundation that one receives: “[M]eaning is not created by us but is given by God […] Meaning is something that carries us, that goes ahead of us and beyond all our ideas and discoveries-and only in this way has it the strength to sustain our lives”.^[12]

Both perspectives, from psychiatry and theology, converge on a fundamental warning for the 21st century: technological abundance will only reach its fullness if we are able to anchor it in a purpose that transcends us.

Manuel Ribes

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

References

[1] Robert M. Solow Technical Change and the Aggregate Production Function The Review of Economics and Statistics, Vol. 39, No. 3 (Aug., 1957), pp. 312-320   The MIT Press  http://www.jstor.org/stable/1926047 .

[3]  Max Roser (2021) – “Why do we need to know about progress if we are concerned about the world’s largest problems?” Published online at OurWorldinData.org. Retrieved from: ‘https://archive.ourworldindata.org/2025 1125-173858/problems-and-progress.html’ [Online Resource] (archived on November 25, 2025).

[4] Gloria Shkurti Özdemir WEF 2026 showed us AI will rule the future Daily Sabah JAN 28, 2026

[5] Lareina Yee et al. Agents, Robots, and us: Skill partnerships in the age of AI McKinsey Global Institute November 2025

[6] In this research, “agents” and “robots” are used as broad, practical terms to describe all machines that can automate non-physical and physical work, respectively.

[7]  Fei-Fei Li From Words to Worlds: Spatial Intelligence is AI’s Next Frontier  Substack Oct 20, 2025

[8]  Jan Witkowski  A Conversation with Jennifer Doudna

doi:10.1101/sqb.2015.80.030072 Cold Spring Harb Symp Quant Biol 2015. 80: 314-315 Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved

[9]  Pontifical Academy for Life Human Genome Editing Scientific perspectives and ethical and social implications

 https://www.academyforlife.va/content/pav/en/projects/human-genome-editing.html

[10] Vaclav Smil Energy and Civilization The MIT Press November 13, 2018   ISBN: 9780262536165

[11]  Bob Mumgaard and Vinod Khosla Is the world ready for the transformational power of fusion?  World Economic Forum Annual Meeting  Jan 7, 2025

[12]  Elena Álvarez La respuesta de Ratzinger a la crisis de sentido Nueva Revista  3 July 2018

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The patient, who lost his sight due to an injury to the optic nerve caused by a “bilateral non-arteritic anterior ischemic optic neuropathy”, has partially recovered his vision.

The breakthrough, published in Brain Communications, opens new therapeutic possibilities in the field of neurotechnology, while also raising important ethical questions about the limits and uses of brain stimulation.

The lead author of the study is Eduardo Fernández Jover, director of the Institute of Bioengineering of the Miguel Hernández University of Elche (UMH) and head of the Bioengineering, Biomaterials and Nanomedicine area of ​​CIBER (CIBER BBN).

In 2022, the patient volunteered to participate in an experimental clinical trial at UMH, in which he had an implant placed in his brain to stimulate the cortex, which would allow him to reproduce visual perceptions.

The procedure involved implanting an array of 100 microelectrodes in the patient’s primary visual cortex. The researchers then electrically stimulated the brain to produce artificial visual perceptions.

After a series of tests, the doctors confirmed that the patient had recovered some of his vision.

The case has surprised researchers because the patient had been blind for three years and has continued to retain some visual function after the brain implant was removed three years ago. Other cases of vision recovery involved patients with recent optic nerve damage.

The recovery of his vision allowed him to perceive light, detect movement, and even read large characters.

For six months, he and the other participants in the trial trained the system and established thresholds. The training consisted of tasks to assess light, spatial localization, movement, visual acuity, and contrast sensitivity.

Given that visual improvement only occurred in one of the four participants in the clinical trial, future studies will determine whether it is an isolated case or if it could occur again in other patients.

Previously, in 2021, the Biomedical Engineering laboratory at UMH had already implanted a brain chip in a blind patient, enabling him to perceive letters and shapes of objects.

Background

As we have previously reported, other brain implant interventions have offered promising results so far.

There are numerous experiences with a brain-computer interface (BCI) such as the Neuralink brain chip, or in China the Beinao No. 1 chip implanted in three human patients.

In addition to achieving the recovery of bilingual communicative ability in a patient after a stroke or the possibility for ALS patients to communicate again with their environment.

Advances in the fields of neuroscience and computing offer therapeutic hopes, but also bioethical dilemmas.

Bioethical assessment

The use of brain stimulation, whether invasive (via microchips) or non-invasive (via electrostimulation), is a promising option in the recovery of patients after strokes or pathologies that severely affect their ability to communicate, move, or perceive the environment, as well as other cognitive processes.

The application of these advances to therapeutics is commendable, ethically acceptable, and should be promoted to make them accessible to all patients who need them. However, their high cost may pose a significant barrier given the current state of research.

But alongside this indication, other enhancements can be proposed, which do not seek to restore lost functions but rather to implement new capabilities. These include improving sensory perception, memory, or other brain functions that confer an advantage over natural human abilities.

The possibility of inducing moods through these procedures, or altering individuals’ perceptions or behavior, presents high-risk scenarios that could constitute a violation of human dignity, freedom, and free will. This could contribute to the subjugation of some, the weakest, by others, the “enhanced.”

As always, bioethics must accompany the new possibilities that scientific advances in neuroscience offer in understanding the human brain. Neuroethics is therefore an essential discipline today, ensuring that these new possibilities in the field contribute to progress rather than becoming a threat to it.

Julio Tudela and Ester Bosch

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

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This court ruling highlights the negligence of doctors who ignored pre-existing conditions such as autism or anxiety. It also reinforces the need for a paradigm shift in medical protocols: scientific evidence and bioethical prudence must prevail in the face of the growing number of people who detransition after undergoing premature interventions.

The Varian Case

Fox Varian, 22, sued the doctors who performed her gender reassignment surgery when she was a minor, alleging negligence. After winning the case, she received a $2 million settlement.

When the young woman was only 16 years old, and despite being a minor, psychologist Kenneth Einhorn authorized the transition and Dr. Simon Chin performed the surgery in which he removed her breasts.

During the trial, held in New York State, Varian’s lawyers argued that the psychologist and surgeon failed to follow the necessary protocols to save her from trauma and surgery. They also stated that it was the psychologist who proposed the idea of ​​transitioning the young woman after diagnosing her with gender dysphoria.

Varian’s mother has stated that she felt intimidated by the psychologist into authorizing her daughter’s surgery because he told her that otherwise she would commit suicide.

The lawyers also argued that other mental health issues such as depression, anxiety, social phobia, and autism were not taken into account before deciding whether to perform the operation.

Furthermore, the doctor who performed the double mastectomy only met briefly with the young woman twice before the surgery. Three years after the operation, Fox Varian detransitioned.

Background

As we have previously published in our Observatory, in 2022 we already warned of the growing number of transgender people who regretted undergoing gender transition treatments.

Cases like that of Keira Bell, who sued the hospital that prescribed her hormone blockers at the age of 16 for failing to objectively inform her of the potential consequences of this treatment. Or the case of a repentant transgender person who exposed the lies of gender ideology.

As an example of the growing trend opposing the widespread adoption of gender transition procedures, the case of the British National Health Service (NHS) should be mentioned. In 2024, it announced that it would stop prescribing puberty blockers in its hospitals to minors wishing to undergo gender transition.

New Trends in the United States

Recently, in February 2026, both the American Medical Association (AMA) and the American Society of Plastic Surgeons (ASPS) expressed doubts about the efficacy and appropriateness of gender transition treatments. Based on the accumulating clinical results, they propose delaying related surgeries until at least age 19.

In this regard, the American Society of Plastic Surgeons warns about the lack of a positive risk-benefit balance in these interventions, specifically when analyzing the long-term consequences.

The studies that support the suitability of these interventions, now questioned, have been denounced for offering serious limitations in their quality, consistency and patient follow-up, which is fundamental for the correct assessment of long-term side effects.

Countries such as Sweden, Norway, Finland, France, England, the United States, and Australia have long warned of a need to modify the application of the so-called Dutch Protocol in the treatment of people with gender dysphoria.

Bioethical assessment

There are already many court rulings that condemn health professionals and related entities to compensate patients who have reported not having been correctly diagnosed and properly informed about the consequences of gender reassignment therapies, suffering their consequences.

The surgical procedures performed for this purpose and hormone treatments have numerous physical and psychological side effects that worsen the quality of life of patients who undergo them.

Intervention in adolescents, as in the case at hand, presents greater risks, associated with hormonal blockers and their consequences on their normal physical and mental development.

Many of the countries that began applying these therapies more than 20 years ago have drastically modified their protocols, limiting access to hormone-blocking treatments and pharmacological and surgical reassignment.

In a previous report, we already showed evidence of how counterproductive pharmacological and surgical gender transition interventions can be in patients with dysphoria, reinforcing the need to provide psychological or psychiatric treatments to those affected.

Many of the laws that regulate these interventions, such as the Spanish one, continue to propose exactly the opposite of what the most recent studies show.

They warn of the destructive effects of these interventions and their limited ability to address the suicidal tendencies of many of those affected.

As a recent study shows, they require psychological and psychiatric treatments, which are not provided to them in many cases.

On the contrary, gender transition is being promoted through pharmacological or surgical interventions.

If appropriate psychological or psychiatric interventions have been previously applied, these operations are not shown to be effective in reducing suicide rates.

However, the administration of treatments with hormonal blockers or surgical interventions presents numerous side effects and complications that contribute to worsening the quality of life of these patients.

The accumulated scientific evidence on these interventions should promote a paradigm shift in intervention protocols in these cases, not the accumulation of court rulings filed by those who have suffered their negative consequences, which are irreversible in many cases.

Julio Tudela and Ester Bosch

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

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The most critical period of human embryonic development begins 14 days after fertilization. Following implantation of the embryo in the blastocyst state (composed of around 100 cells), the primary germ layers begin to form and most of the genes in the genome are activated, so that cell differentiation and organ and tissue organization can take place in the new being.

The fact is that only about 30% of embryos produced by IVF and implanted in the uterus successfully pass this stage, a rate comparable to that of those conceived naturally. Many embryos are expelled or their development collapses for no known reason. In a previous article, we reported on efforts to learn more about the causes of this great loss of embryonic viability through the creation of synthetic embryos, embryoids, or embryo models, in an attempt to circumvent the technical, ethical, and legal restrictions on studies on the development of human embryos from 14 days onwards.

During the early stages of human embryonic development, a large proportion of viability is therefore lost. Research into its causes is not permitted, which in turn hinders progress in the investigation of this important factor in human infertility. Since it is well established that all embryonic development is genetically regulated in space and time, genetic factors must explain the high loss of viability. Nonetheless, regardless of the explanation, the analysis must consider the influence of genes in the formation of the gametes that combine to create each new being.

Human gametogenesis

Before discussing a study that analyzes the causes of embryonic inviability, it is worth recalling some fundamental aspects about the formation of gametes, the creation of the zygote, and the early stages of embryonic development.

Female gametogenesis, or “oogenesis”, takes place in the germline tissue from very early stages of embryonic-fetal development. Once this tissue is formed, the germ cells begin female meiosis to generate the eggs, arresting the process in meiotic prophase I, in a state known as “dictyotene”. They remain in this state for years, until sexual maturity is reached. At puberty, meiosis resumes from the point where it had arrested and the eggs are produced asynchronously, one per menstrual cycle.^[1]

In contrast, male gametogenesis or “spermatogenesis” takes place in the male germline tissue in adulthood, beginning at sexual maturity, without temporary interruption of meiosis of the spermatogonial stem cells.

It is important to remember that, during meiosis, the 23 pairs of chromosomes (23 maternal and 23 paternal) pair up longitudinally to form 23 bivalents. Once their chromatids—the lateral elements of each chromosome—are aligned, breakages and reciprocal exchanges between homologous paternal and maternal regions occur. This process is called “crossing-over” and gives rise to genetic recombination, which is the main source of non-mutational variation in sexually reproducing species. The points of exchange between chromatids, which can be observed microscopically, are called “chiasmata”.

Following this genetic exchange, the 46 chromosomes are aligned and separated into two sets of 23, which are passed to each daughter cell during the first meiotic division. The second meiotic division involves a further division of these cells, so that each of the four resulting cells contains a set of 23 chromatids. Another difference between female and male gametogenesis is that, in the former, only one of the four resulting cells matures into an egg, while in males, all four cells give rise to functional sperm.

The search for genes causing embryonic inviability

Recently, researchers from Johns Hopkins University in New York (USA) published a paper in Nature that seeks to unravel the causes of high embryonic inviability and pregnancy loss in human reproduction, based on genetic regulation during meiosis.^[2] In the study, specific genetic variations in maternal genes were identified as a cause of embryos presenting chromosomal abnormalities incompatible with life.

New evidence was also provided that supports previous knowledge: the leading cause of inviability in embryonic-fetal development is aneuploidy, i.e., alterations in the number of chromosomes—either an extra or missing chromosome—that combine in the gametes. It is estimated that only about half of human conceptions survive to birth, mainly due to the abundance of inviable aneuploidies in the early stages of gestation.^[4] The imbalance in the number of chromosomes leads to genetic instability that, in many cases, is incompatible with life. This is not always the case, however, since there are situations in which the presence of one chromosome more or one less is tolerated, albeit with phenotypic consequences. Examples include trisomy 21, which causes Down syndrome (2n = 47); monosomy of the sex chromosomes, responsible for Turner syndrome (2n = 45:22’’ + X0); and trisomy of the sex chromosomes, causing Klinefelter syndrome (2n = 47:22’’ + XXY).

We also know that many chromosomal abnormalities are passed down through the female line and that their frequency increases with maternal age. The study discussed herein provides new evidence in this regard and also demonstrates the influence of a genetic component that determines embryonic viability or inviability. To address this factor, the researchers conducted a large-scale analysis of common and rare genetic combinations in 139,000 IVF-derived embryos from 23,000 couples, using a combined study of embryonic DNA—similar to preimplantation genetic diagnosis (PGD)—and parental DNA.

Comparative analysis of the data was carried out using computing tools, enabling the identification of associations between maternal DNA variants and embryos that failed to complete their developmental cycle, in which major genes and molecular markers like single nucleotide polymorphisms (SNPs) were involved.

PGD data from IVF-derived embryos provide information on recombination and the incidence of aneuploidy when compared to parental data. Thus, it was observed that aneuploidies largely involved the gain or loss of chromosomes of maternal origin compared to those of paternal origin.

Among the major genes implicated, a variant of the SMC1B gene was detected; this encodes a family of proteins necessary for cohesion of the chromatids of the maternal and paternal chromosomes and DNA recombination during meiosis and mitosis. This gene is involved in the maintenance of homologous chromosome pairs during female meiosis through structures that keep them together. The deterioration of these structures increases over time, which, as mentioned, in the case of female gametogenesis, is several decades. This would explain the increase in the frequency of aneuploidies, their particular incidence through the maternal line, and their relationship with the mother’s age. The longer the time spent in prophase of meiosis I, the greater the likelihood of deterioration of the molecular machinery responsible for keeping the chromosome pairs together.

Statistical analysis also revealed that the number of crossovers was lower in aneuploid versus euploid embryos, which is consistent with the fundamental role of these structures in chromosome pairing and correct segregation.

The SMC1B gene is located on human chromosome 22 and had already been identified in mice and other species. ^[3] According to researcher Rajiv McCoy, co-author of the paper, “the genes that emerged from our study in humans are exactly the ones that experimental biologists have detailed over decades as critical for recombination and chromosome cohesion in model organisms like mice and worms”.

The statistical analysis, which compared the parental genotypes with the viable and inviable embryonic ones, also implicated another genetic factor located on human chromosome 14: the C14orf39 gene, responsible for a meiotic protein that localizes to the central element of the “synaptonemal complex”. This is a structure that is needed for the precise pairing of homologous chromosomes during prophase and for their proper segregation at the end of meiosis I.

These findings highlight the dual role of recombination: on the one hand, in the generation of genetic diversity and, on the other, in ensuring the fidelity of chromosome distribution in meiosis.

The authors also conducted a genome-wide association study (GWAS) considering maternal meiotic aneuploidies affecting any chromosome. They identified, among others, two significant associations at the genomic level: SNP rs9351349, located within an intergenic region of chromosome 6; and SNP rs6006737, located on chromosome 22, whose incidence in the samples analyzed was associated with lower rates of female recombination.

The findings of this study suggest that there are variants of certain genes or genomic regions that affect meiotic stability and, consequently, a balanced constitution of the chromosome number in the offspring. Therefore, the authors pose the evolutionary paradox of the high incidence of aneuploidy in human reproduction. Given the severity of its effects, one would expect that natural selection would have eliminated the allelic combinations responsible for this instability over the course of generations. However, the authors speculate on the reasons for this paradox, which is difficult to explain from an evolutionary perspective, and point out the lack of association between the aneuploidy risk variant and fertility phenotypes such as number of live-born children and infertility.

Finally, it should be noted that one of the most positive aspects of finding genes involved in any phenotypic manifestation—and in this case, in the incidence of aneuploidies as a cause of embryonic inviability—is the possibility of seeking solutions through drugs that act on the molecular mechanisms responsible for these alterations.

Bioethical assessment

The research discussed herein did not meet the requirements to be considered research with human participants since, as stated in the paper, “[it] does not obtain information or biospecimens through intervention or interaction with a human participant”; therefore, it did not require federally regulated approval according to the Johns Hopkins University Homewood IRB.

However, as explained, it involved 139,000 human embryos, obtained through IVF from 23,000 couples.

The vast majority of these embryos are surplus embryos from assisted reproduction techniques, i.e., embryos that were not implanted, which were either cryopreserved or discarded due to having some type of abnormality.

The study does not report on the fate of these embryos, although in most cases they are destroyed.

The Johns Hopkins University IRB considers that the more than 130,000  human embryos used and discarded—destroyed—in the study are not “human participants”, and do not require regulatory intervention by the aforementioned committee.

The human nature of the embryo today constitutes scientific evidence that is undisputed by experts. However, the human embryo continues to be acted upon as if it were not, as if it were a pre-embryo, an obsolete and outdated concept proposed in the 1980s.

Research aimed at identifying genetic causes that could help treat cases of infertility by detecting chromosomal abnormalities in conceived embryos is considered, a priori, a legitimate objective.

Nevertheless, the methods to be used in this type of research must also be evaluated bioethically, in order to determine whether the entire process is ethically legitimate.

Sacrificing more than 130,000 human embryos after their genetic diagnosis in an attempt to establish a correlation with the information obtained from the parental genome can never be considered a licit and bioethically acceptable means to justify research of this nature.

For the same paper to talk about human embryos and then justify not requiring ethical validation because it does not include human participants is unacceptable for an institution like Johns Hopkins University, as well as for a journal like Nature, which should also uphold the ethics of the research it publishes.

On previous occasions we have stressed the need to include strict ethical criteria when experimenting with human embryos, whose dignity must be respected in all circumstances.

Nicolás Jouve

Professor Emeritus of Genetics at the University of Alcalá

Member of the Bioethics Observatory of the Catholic University of Valencia

Julio Tudela

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

References

[1] Bata OY, Kono T. Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J. Biol. Chem. 277 (2002): 5285–5289.

[2] Carioscia, S.A., Biddanda, A., Starostik, M.R. et al. Common variation in meiosis genes shapes human recombination and aneuploidy. Nature (2026). https://doi.org/10.1038/s41586-025-09964-2

[3] Hodges CA, Revenkova E, Jessberger R, Hassold TJ, Hunt PA. SMC1-beta-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction. Nat. Genet. 37 (2005): 1351–1355.

[4] McCoy RC, Summers MC, McCollin A, et al. Meiotic and mitotic aneuploidies drive arrest of in vitro fertilized human preimplantation embryos. Genome Med. 15 (2023): 77.

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According to the organizers, the creation in the laboratory of structures such as embryoids, cerebroids, and other synthetic biological systems opens up therapeutic possibilities, but also generates complex dilemmas that make bioethical reflection more necessary than ever. Synthetic biology not only seeks to design biologically based products, but also to redesign existing natural biological systems and even generate new species outside of natural mechanisms, introducing distorting elements with often unpredictable consequences.

A program focused on regenerative medicine and human dignity

The day will begin with an official opening at 9:30 a.m., followed by a round table discussion analyzing the impact of synthetic biology on regenerative medicine. Among the participating experts are Núria Montserrat, Minister of Research and Universities of the Government of Catalonia and principal investigator at the Institute for Bioengineering of Catalonia (IBEC), who will address the topic of organoids, and Lluís Montoliu, research scientist at the Spanish National Research Council (CSIC) and deputy director of the National Center for Biotechnology (CNB), who will reflect on the temptation and possibility of creating “supermen and superwomen.”

The scientific reflection will be complemented by the genetic and naturalist perspective of Andrés Moya, Professor of Genetics at the University of Valencia. Under the title “Goethe’s Dream: Science and Nature,” Moya will analyze how humankind, a self-intervening species, is progressing toward “transevolution and transhumanization.” His presentation will explore how these processes lead us to construct our own future and that of the “other-natural” as a response to the nihilism imposed by naturalization.

Epistemology, Governance, and the Humanization of Science

The midday session, entitled “Humanizing Synthetic Biology,” will feature a presentation by Nicolás Jouve, Professor Emeritus of Genetics at the University of Alcalá de Henares. Jouve will argue for the need to apply precautionary and responsible principles to prevent technology from manipulating human beings under the “lure of transhumanist enhancement.” His approach proposes not halting progress, but rather humanizing it, guaranteeing respect for genetic heritage and human dignity within the framework of integral ecology.

Then, Marta Bertolaso, Professor of Philosophy of Science at the Campus Bio-Medico University of Rome, will explore the epistemological questions and socio-technical imaginaries of this discipline. Bertolaso ​​will argue that current debates remain too focused on “deterministic and mechanistic paradigms,” and will propose new lines of argumentation based on scientific practice to facilitate a proactive and constructive ethical debate.

Future Challenges and Regulation

In the afternoon, the focus will shift to biomedical challenges and the protection of dignity, with Alfredo Marcos, Professor of Philosophy of Science at the University of Valladolid, presenting “Biomedical Challenges: Between Futurism and the Care of Present Dignity”.

The discussion will also focus on the governance models needed to regulate these practices, a presentation that will be given by Vicente Bellver, Professor of Philosophy of Law at the University of Valencia and president of the Bioethics Committee of the Valencian Community. Bellver will critically review the international legal framework and the ethical reports published by government bodies to offer concrete governance proposals that respond to current scientific developments.

Closing Ceremony

The event will conclude with a closing ceremony by Julio Tudela, Director of the Bioethics Observatory of the Catholic University of Valencia.

The congress will take place in Valencia, Spain, and the presentations will be in Spanish.

For those interested in following the congress online, it will be streamed live on our YouTube channel.

If you want to come to the congress in Valencia, registration (free) is compulsory.

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From a bioethical perspective, the risk of technology and artificial intelligence supplanting real human connections by offering ‘emotional anesthesia’ is examined. This does not resolve the anthropological need for relationships and raises the urgent need to rebuild spaces for authentic coexistence in the face of the threat of normalized loneliness.

Loneliness has become one of the most worrying social and health phenomena of our time, with a particularly intense impact among adolescents and young people.

Far from being a marginal or transitory experience, various recent studies agree that it is a structural problem, linked to mental health, social transformations and the growing use of digital technologies.

An international report based on work promoted by the World Health Organization reveals that adolescents are currently the age group that experiences the most loneliness worldwide.

Around 20.9% of teenagers report feeling lonely, a figure that rises to 24.3% for girls, clearly surpassing other age groups, including those over 60. This data breaks down the stereotype that associates loneliness almost exclusively with old age and highlights a particularly vulnerable stage of life.

Loneliness, technology and digital responses

This context helps to understand recent phenomena such as the success in China of an application designed for young people living alone to periodically confirm that they are still alive, alerting a contact if they do not.

As reported by various media outlets, the app does not respond to a specific emergency, but to a widespread fear of social invisibility: the possibility of suffering an accident or crisis without anyone noticing.

The virality of this tool highlights how technology attempts to compensate, in a limited and ambiguous way, for the lack of stable human connections.

These proposals raise important questions: To what extent can technology replace presence, care, and shared responsibility? Are we normalizing structural loneliness instead of addressing it as a social and relational problem?

The Spanish case: a persistent reality

In Spain, the situation is no less worrying. The Study on Unwanted Loneliness and Youth in Spain shows that one in four young people between the ages of 16 and 29 (25.5%) suffers from unwanted loneliness. In almost half of the cases this situation lasts for more than three years.

In addition, 69% of young people say they have felt lonely at some point, with a higher incidence among women and those aged between 21 and 26.

The study also highlights significant risk factors: loneliness is more common among young people with financial difficulties, people who have suffered bullying, and vulnerable groups.

Furthermore, although the use of social media is not in itself the direct cause, replacing face-to-face relationships with exclusively online connections doubles the risk of loneliness.

A matter of health and social ethics

The consequences are not only emotional. Loneliness has a two-way relationship with mental health: young people who experience it are 2.5 times more likely to suffer psychological problems, and suicidal thoughts increase alarmingly.

These data, provided in the study, make youth loneliness a real public health issue.

This reality directly challenges society. It is not simply a matter of designing individual coping strategies or applications, but of strengthening community ties, emotional education, and inclusion policies, recognizing that human beings are, by nature, relational beings.

Persistent loneliness in young people is not just a generational symptom: it is an indicator of the type of society we are building and of the urgency of ethically rethinking our ways of coexistence and mutual care.

The roots of isolation

To understand the magnitude of youth loneliness, it is necessary to look beyond the statistics and recognize the philosophical underpinnings that fuel it: an exacerbated individualism that has distorted the social nature of the person.

According to Nacho Tornel, PhD in Law and Restorative Family Mediation, “Current culture pushes us towards absolute autonomy, pathologizing interdependence and denying the fundamental anthropological truth that “it is not good for man to be alone.”

This context has given rise to a postmodern youth profile marked by hedonism, consumerism, and frenetic activism that seeks to fill the existential void with noise to avoid internal reflection and self-discovery.”

We are thus experiencing the paradox of the most prosperous and technologically connected society in history, yet one inhabited by the most isolated young people. They often substitute deep connections with a misguided sense of freedom that lacks commitment and a focus on the common good, ultimately damaging their own dignity.

Faced with the proliferation of single-person households and isolated lives, scientific evidence confirms that happiness does not reside in individual success or self-sufficiency, but in the quality of our relationships.

Bioethical Assessment

There are structural factors in modern societies that can be identified as contributing to this crisis of imposed loneliness. The first and most important is the irrelevance attributed to the family institution. The family is a school of human interaction, a place of support, and a privileged environment for socialization.

Marital breakdowns, low birth rates, the proposal of alternative family models, or parents who fail to educate their children, cause contemporary young people to face situations of isolation that can lead to pathological consequences.

In this context, the proliferation of generative Artificial Intelligence (AI), which reproduces forms of communication similar to human communication, is beginning to fill the void left by the absence of parents, siblings, friends, neighbors, or mere acquaintances.

Relationships with virtual characters can become the factor that multiplies isolation in so many young people, disconnected from reality and resigned to “emotional numbing.” Through AI-created avatars, they renounce the most genuinely human dimension: the relational one, which enriches us, allows us to break free from the slavery of self-indulgence, and opens human beings to transcendence, to the other…

We are concerned to witness the fascination with the uncontrolled proliferation of the virtual universe, which, aided by new technologies, seduces so many and deprives them of true human relationships. The alarming inaction in the face of this enormous risk multiplies the chances of isolation and destitution for so many young people and adults who are gradually renouncing the richness of real human relationships, with their risks, discoveries, sacrifices and victories. This is particularly true in the family environment, a privileged ecosystem for human growth.

Julio Tudela and Cristina Castillo

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

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In the 1970s, when the secrets of the molecule of life were already known, laboratory technologies emerged to alter the DNA composition of an organism, so-called “genetic engineering”. These techniques enable the modification of DNA information through base changes (A-T or C-G), deletion of a genomic region, or the addition of a new DNA segment (even an entire gene), with potential applications in microorganisms, plants, and animals for a variety of purposes. The foundations of this technology were established by American biochemists Paul Berg (1926-2023) and Walter Gilbert (b. 1932), and British biochemist Frederick Sanger (1918-2013), Nobel Laureates in Chemistry in 1980.

The “molecular scalpel” revolution: CRISPR-Cas9

The concept of gene modification refers to the potential to alter the natural genetic traits of their carriers, and it is within this applied domain where a vast array of possibilities has opened up, with applications in agricultural and livestock enhancement, as well as in industrial and clinical fields, depending on the species involved.

The CRISPR-Cas9 system is the next generation of genetic engineering that, in a more direct and simple way, enables the modification or deletion of any gene or genomic region with a known DNA sequence. It is based on a natural mechanism of immunity that operates in bacteria and Archaea to degrade and eliminate invading DNA sequences (viruses, plasmids, etc.)^[1]. Briefly, this technique involves introducing two components into the cells of the organisms to be modified: a guide RNA that locates the target region of the genome or the gene by complementary base pairing with the DNA; and an enzyme called Cas9 (or other alternatives), which locates the complex formed between the guide RNA and its target in the DNA and acts by producing a cut. The cut must then be repaired through one of two pathways: an “editing” process that modifies the nucleotide bases with the aid of a template molecule; or inactivation of the expression of the target gene or region (knockout).

Due to the ease with which this system induces cuts and modifications in specific regions of the genome, its use has spread rapidly, with a large number of applications emerging in all types of organisms within a short space of time. This requires knowledge of the sequence of the genomic region or gene targeted for editing or deletion (the Congress on Genetic Research: Possibilities and Risks. An Approach from Bioethics, covered “CRISPR gene editing”).

CRISPR-Cas9 has been employed across all areas to correct or modify traits associated with deficiencies or alterations in the target organism, which, given the universality of DNA, can be any species. Applications include “gene therapy” to correct hereditary diseases in humans and the “improvement” of cultivated plants and domestic animals to enhance their productivity, capacity for environmental adaptability, disease resistance and quality of their by-products.

Food security: The urgent challenge for 2030

As we shall see below, among its many applications, CRISPR-Cas9 offers the possibility of editing the genomes of edible fungal species to modify their dietary properties.

In 2025, the World Health Organization published a report with the participation of five specialized agencies of the United Nations on the State of Food Security and Nutrition in the World 2025 (SOFI 2025). It stated that the world is still above pre-COVID-19 pandemic levels and far from eradicating hunger and food insecurity by 2030. An estimated 8.2% of the world’s population—about 673 million people—faced hunger in 2024, down from 8.5% in 2023 and 8.7% in 2022. However, it noted that this trend is not uniform and that hunger continues to increase across large areas of Africa and Western Asia, which UNICEF has identified as especially affecting many children in countries such as South Sudan, Yemen, Ethiopia, and Madagascar. Similarly, the Food and Agriculture Organization (FAO) of the United Nations has been warning about protein-energy malnutrition as one of the critical issues affecting children in developing countries for decades, urging the need to produce new foods to meet energy and nutrient requirements.

The aforementioned report states that there are resources worldwide to end hunger and malnutrition by 2030, but that economic funds and political will are needed to achieve this. A third key factor is to continue exploring new and more diverse food sources that can reach the most needy communities without relying on imported inputs, which are often expensive and unpredictable.

Fusarium venenatum: The sustainable alternative to meat

The search for new food sources is a necessity even in the most developed countries, where research has been conducted for years on ways to expand the market for alternative nutritional resources to prevent health issues such as iron and micronutrient deficiency, obesity, allergies, diabetes, etc.

Proteins are polymers whose primary structure consists of a sequence of amino acids, of which there are 20 different ones that are linked by peptide bonds. These molecules constitute the structural and functional components of cells. They are therefore part of the cells and tissues of all organisms and, importantly, they are the direct products of gene expression.

Proteins are also the essential components of both animal- and plant-based foods. In the human diet, they are necessary as a source of amino acids for the development and maintenance of the body, to repair and replace worn or damaged tissues, and to promote the synthesis of enzymes, hormones, and all the essential components for growth of the organism.

The search for alternative protein sources has become a priority in recent years, so the production of new sources that supplement or even replace traditional animal- and plant-based proteins has been encouraged. In this regard, the results of the use of so-called “mycoproteins”, or proteins derived from fungi, have recently been published.

Fusarium venenatum (F. venenatum), a filamentous fungus rich in proteins and essential amino acids and low in polyunsaturated fats, has been used for years. This organism can be grown in bioreactors via fermentation, allowing the efficient production of large quantities of fungal biomass. Mycoproteins mimic the fibrous consistency of meat thanks to the fungal mycelia, making them suitable for use in different types of foods like nuggets, hamburgers, and other substitutes (such as those marketed in the United States under the label “Quorn” or similar), particularly useful in vegetarian and flexitarian diets. In addition, mycoproteins can be fermented by bacteria in the human gut microbiota, so they can also act as a beneficial prebiotic. Although extensive studies have not yet been conducted, the rate of allergic reaction to mycoproteins is very low. Manufacturers of this type of food say that its production has a lower environmental impact than meat of animal origin such as chicken or pork, and a carbon footprint up to 10 times lower than that of beef. Therefore, the use of F. venenatum for the production of mycoproteins for human food has become a promising and environmentally sustainable strategy to address the global protein shortage and already has regulatory approval in the European Union, the United States, and Australia^[1].

Science in action: More protein and less chitin

According to an article published last November in Trends in Biotechnology, this microscopic fungus has become a food resource of great interest due to its nutritional properties and digestibility. In the aforementioned study, the researchers used CRISPR-Cas9 to remove a gene that limited the protein yield in order to improve its nutritional profile and production efficiency. The F. venenatum strain obtained (designated FCPD) showed a 32.9% increase in the essential amino acid index, a 44.3% reduction in substrate consumption, and an improved mycoprotein production rate compared to the wild-type (WT) strain. Moreover, the new strain demonstrated considerable environmental performance with respect to cell-cultured meat and chicken meat ^[2].

Despite the excellent prospects of F. venenatum, the efficacy in substrate conversion, protein biosynthesis, and nutrient digestion is limited by some components of the cell wall of this filamentous fungus, such as chitin, a natural polysaccharide that forms one third of the cell mass of the fungal wall and constitutes a natural indigestible, difficult-to-absorb polymer. Chitin is the most abundant polymer in nature after cellulose. Consequently, many studies have been conducted to try to degrade the cell walls of F. venenatum through physicochemical processes, such as high-pressure homogenization, enzyme treatment, and ultrasonication, with little success. New efforts have recently focused on improving F. venenatum by using CRISPR-Cas9 to eliminate the genes responsible for the synthesis of chitin systases (Chs genes), thus making the cell wall more vulnerable to degradation. Chitin is a natural indigestible polymer. Previously, 12 possible Chs genes had been detected in F. venenatum and deletion of one of them enhanced cell wall sensitivity and also produced unexpected beneficial effects, such as promoting protein synthesis. After the application of CRISPR-Cas9, a strain called FC02 was obtained, whose protein content increased from 35.30% to 54.12%, while the chitin content decreased from 8.56% to 6.29%. The published study verifies that the modified strain, F. venenatum FC02, lacks a 3155 bp genomic region in its DNA in comparison to the unmodified strain^[3]. This modification made it easier to extract the proteins from the cell wall of the resulting strain, while also giving the biomass products more desirable digestive characteristics and a significantly higher essential amino acid index.

The future: Highly digestible functional foods

These findings suggest that the mycelial structure of edible fungi can be genetically modified to create functional foods with controlled digestibility, while guiding the production of high-quality mycoproteins. This is another example of how genetic engineering can help to improve food production. In this case, the application of CRISPR-Cas9 to modify the mycelium structure of edible fungi enhances the production of highly digestible functional nutrients. F. venenatum  has become an excellent source of mycoproteins that also provides other nutritional benefits such as essential amino acids and beta-glucans, which are beneficial for gut health and glycemic control, with a low polyunsaturated fat content. It also contributes indirectly to health by aiding weight loss and reducing cholesterol.

Nicolás Jouve

Professor Emeritus of Genetics at the University of Alcalá

Member of the Bioethics Observatory of the Catholic University of Valencia

References:

[1] Mojica FJ, Díez-Villaseñor C, García-Martínez J. Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 2005, 60:174–182.

[2] Ahmad MI, Faroog Sk, Alhamoud Y et al. A review on mycoprotein: history, nutritional composition, production methods, and health benefits. Trends Food Sci Tech. 2022 12:14-29.

[3] Wu X, Wang M, Luo S, et al. Dual enhancement of mycoprotein nutrition and sustainability via CRISPR-mediated metabolic engineering of Fusarium venenatum. Trends Biotechnol. 2025 Nov 19:S0167-7799(25)00404-4.

[4] Wu X, Zhou Z, Luo S, Wang Y et al. Cell wall engineering-guided strategy for high-efficiency biosynthesis of nutrient-fortified Fusarium venenatum mycoprotein. Bioresour Technol. 2025 Nov;436:133005.

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