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These are the most-read science news stories of 2021.

The International Space Station spotted the origins of a bizarre type of upside-down lightning called a blue jet (illustrated) zipping up from a thundercloud into the stratosphere in 2019. The discovery ranked among  Science News ' most-read stories of 2021.

DTU SPACE, DANIEL SCHMELLING/MOUNT VISUAL

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By Science News Staff

December 23, 2021 at 9:00 am

Science News drew over 21 million visitors to our website this year. Here’s a rundown of the most-read news stories and long reads of 2021.

Top news stories

1. space station detectors found the source of weird ‘blue jet’ lightning.

Instruments on the International Space Station detected the origins of an odd type of lightning called a blue jet. The bizarre bolt is sparked by a “blue bang” — a flash of bright blue light that may be brought on by the turbulent mixing of oppositely charged regions within a thundercloud ( SN: 2/13/21, p. 14 ).

2. A newfound quasicrystal formed in the first atomic bomb test

The first atomic bomb test, in 1945, forged a peculiar, glassy material called trinitite — and within it, a rare form of matter called a quasicrystal . Quasicrystals’ atoms are arranged in an orderly structure like normal crystals, but the structure’s pattern doesn’t repeat ( SN: 6/19/21, p. 12 ).

3. An Indigenous people in the Philippines have the most Denisovan DNA

The Ayta Magbukon people in the Philippines set the record for the highest known level of Denisovan ancestry — about 5 percent of their DNA comes from the ancient hominids . The finding suggests that several Denisovan populations independently reached Southeast Asia and interbred with Homo sapiens groups that arrived thousands of years later ( SN: 9/11/21, p. 16 ).

4. Astronomers may have seen a star gulp down a black hole and explode

In a first, astronomers caught a glimpse of a rare double cosmic cannibalism : A star swallowed a black hole or neutron star, which then gobbled that star from within, resulting in an astonishing explosion ( SN: 10/9/21 & 10/23/21, p. 6 ).

5. Frog skin cells turned themselves into living machines

Skin stem cells plucked from frog embryos organized themselves into miniature living robots, dubbed “xenobots,” that can swim, move around debris and even self-heal . Xenobots may one day serve a useful purpose, but ethical questions need to be considered ( SN: 4/24/21, p. 8 ).

Favorite video

Acrobatic rabbits bewitched online readers in our most-viewed YouTube video posted this year. The video — accompanying the story “ A gene defect may make rabbits do handstands instead of hop ” ( SN: 4/24/21, p. 13 ) — shows a sauteur d’Alfort rabbit walking on its front paws (below). Such hop-less bunnies may have adopted the odd gait because of a mutation in a gene called RORB , scientists discovered.

Top feature stories

1. new drugs that block a brain chemical are game changers for some migraine sufferers.

A class of drugs that inhibits a neurotransmitter called calcitonin gene-related peptide is helping some patients who suffer from chronic, debilitating migraines ( SN: 3/27/21, p. 16 ).

2. Einstein’s theory of general relativity unveiled a dynamic and bizarre cosmos

Albert Einstein’s general theory of relativity has served as the bedrock of our understanding of the cosmos. In the last 100 years, scientists have confirmed its most radical predictions, including black holes, gravitational waves and an expanding universe ( SN: 2/13/21, p. 16 ).

3. Chemists are reimagining recycling to keep plastics out of landfills

No matter people’s dedication to sorting and recycling plastics, most still end up in landfills because the materials are too difficult to transform into useful new products. Some chemists are trying to change that ( SN: 1/30/21, p. 20 ).

4. Psychology has struggled for a century to make sense of the mind

In the last 100 years, psychologists and other social scientists have dug into the muddy “science of us” and developed conflicting theories about human thought and behavior. From the messy, contentious research bloomed insights into what makes humans tick ( SN: 8/14/21, p. 18 ).

5. Fossils and ancient DNA paint a vibrant picture of human origins

From the Taung Child to Lucy, the last century of paleoanthropology has sketched a rough timeline of how humans came to be. Scientists now agree that human evolution has its roots in Africa, but many mysteries in our history remain to be solved ( SN: 9/25/21, p. 20 ).

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Science News

17th-century pirate 'corsair' shipwreck discovered off Morocco's Barbary Coast

By Tom Metcalfe published 5 August 24

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By Emily Cooke published 5 August 24

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By Robert Lea published 5 August 24

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By Jennifer Nalewicki published 5 August 24

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By Alice Sun published 5 August 24

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By Jamie Carter published 4 August 24

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By Andrea Thompson published 4 August 24

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By Patrick Pester published 3 August 24

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By Samantha Mathewson published 3 August 24

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By Ashley Hamer published 3 August 24

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3 remarkable trees: A living fossil, a deadly canopy, and the world's biggest seeds that were once mounted in gold by royals

By Christina Harrison, Tony Kirkham published 3 August 24

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A tiny extinct penguin from New Zealand is key to understanding penguin wing evolution, researchers say.

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Articles on Scientific research

Displaying 1 - 20 of 91 articles.

Giant waves, monster winds and Earth’s strongest current: here’s why the Southern Ocean is a global engine room

Luke Bennetts , University of Adelaide ; Callum Shakespeare , Australian National University , and Catherine Vreugdenhil , The University of Melbourne

Federal funding for major science agencies is at a 25-year  low

Chris Impey , University of Arizona

Is scientific discovery driven by great individuals or by great teams?

Denisa Mindruta , HEC Paris Business School

Early COVID-19 research is riddled with poor methods and low-quality results − a problem for science the pandemic worsened but didn’t create

Dennis M. Gorman , Texas A&M University

Netflix’s You Are What You Eat uses a twin study. Here’s why studying twins is so important for science

Nathan Kettlewell , University of Technology Sydney

Fact-bombing by experts doesn’t change hearts and minds. But good science communication can

Tom Carruthers , The University of Western Australia ; Heather Bray , The University of Western Australia , and Matthew Nurse , Australian National University

Talking about science and technology has positive impacts on research and society

Ashley Rose Mehlenbacher , University of Waterloo ; Donna Strickland , University of Waterloo , and Mary Wells , University of Waterloo

Tenacious curiosity in the lab can lead to a Nobel Prize – mRNA research exemplifies the unpredictable value of basic scientific research

André O. Hudson , Rochester Institute of Technology

Pigs with human brain cells and biological chips: how lab-grown hybrid lifeforms bamboozle scientific ethics

Julian Koplin , Monash University

When Greenland was green: Ancient soil from beneath a mile of ice offers warnings for the future

Paul Bierman , University of Vermont and Tammy Rittenour , Utah State University

10 reasons humans kill animals – and why we can’t avoid it

Benjamin Allen , University of Southern Queensland

Hurricanes push heat deeper into the ocean than scientists realized, boosting long-term ocean warming, new research shows

Noel Gutiérrez Brizuela , University of California, San Diego and Sally Warner , Brandeis University

Colonialism has shaped scientific plant collections around the world – here’s why that matters

Daniel Park , Purdue University

You shed DNA everywhere you go – trace samples in the water, sand and air are enough to identify who you are, raising ethical questions about privacy

Jenny Whilde , University of Florida and Jessica Alice Farrell , University of Florida

Nigeria needs to take science more seriously - an agenda for the new president

Oyewale Tomori , Nigerian Academy of Science

Two decades of stagnant funding have rendered Canada uncompetitive in biomedical research. Here’s why it matters, and how to fix it.

Stephen L Archer , Queen's University, Ontario

How tracking technology is transforming our understanding of animal behaviour

Louise Gentle , Nottingham Trent University

What the world would lose with the demise of Twitter: Valuable eyewitness accounts and raw data on human behavior, as well as a habitat for trolls

Anjana Susarla , Michigan State University

There are 8 years left to meet the UN Sustainable Development Goals, but is it enough time?

Rees Kassen , L’Université d’Ottawa/University of Ottawa and Ruth Morgan , UCL

‘Gain of function’ research can create experimental viruses. In light of COVID, it should be more strictly regulated – or banned

Colin D. Butler , Australian National University

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Scientific understanding in biomedical research

• Original Research
• Open access
• Published: 02 August 2024
• Volume 204 , article number  66 , ( 2024 )

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• Somogy Varga   ORCID: orcid.org/0000-0001-9383-7843 1 , 2  

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Motivated by a recent trend that advocates a reassessment of the aim of medical science and clinical practice, this paper investigates the epistemic aims of biomedical research. Drawing on contemporary discussions in epistemology and the philosophy of science, along with a recent study on scurvy, this paper (1) explores the concept of understanding as the aim of scientific inquiry and (2) establishes a framework that will guide the examination of its forms in biomedical research. Using the case of Tuberculosis (TB), (3) it is argued that grasping a mechanistic explanation is crucial for reaching a threshold of understanding at which we may speak of an objectual, biomedical understanding of TB.

Avoid common mistakes on your manuscript.

Within just a few years, multiple editorials in prominent medical journals have issued a call to reflect on the aim of clinical medicine and medical science. Focusing on the latter matter, in a 2013 editorial, the editors of The Lancet clarified that they frequently confront not only queries about the rationale behind specific scientific studies but also broader inquiries regarding the overarching aim of medical science, which includes both clinical and medical laboratory research. They contend that the moment has come to rethink our approach to conducting and incentivizing research, and for this, “we need to remind ourselves about the real purpose of research” (The Lancet, 2013 , p. 347; see also Thornton, 2013 ). The authors express concern that a significant portion of the vast sums allocated annually to biomedical research fails to meet its true objectives. This shortfall is attributed not only to deficiencies in research design and methodology but also to a lack of “clinical meaningfulness.” Specifically, they highlight that many research projects pose questions that are not sufficiently aligned with clinical medicine and relevant to the treatment, control, prevention, or prediction of diseases. The authors note that the issues extend beyond merely reducing the potential impact of biomedical research; they suggest a fundamental misunderstanding of the very purpose of biomedical research, implying that such studies may not truly qualify as medical . Footnote 1

This short Lancet piece highlights significant, yet often overlooked, questions concerning the epistemic aim of medical research. This paper will address these questions, positing that medical science is fundamentally engaged in inquiries aimed at achieving what we shall refer to as biomedical understanding . To investigate and clarify what such understanding amounts to, the paper takes inspiration from two sources. On the one hand, it draws on contemporary discussions in philosophy of science and epistemology, which have seen a renewed interest in understanding as a distinct cognitive accomplishment (Grimm, 2021 ; Baumberger et al., 2017 ), as the epistemic aim of scientific inquiry, and the measure of progress (see e.g., Potochnik, 2015 ; De Regt & Dieks, 2005 ; Elgin, 2017 ). Acknowledging that what constitutes proper understanding can depend on the field, as noted by scholars in the field (Strevens, 2010 ; De Regt et al., 2009 ), this paper aims to specifically articulate what understanding entails within medical science. On the other hand, this paper draws on and employs several distinctions from a recent study on scurvy (Varga, 2023 ). However, while that study focused on a noncommunicable condition stemming from severe dietary deficiencies, this paper shifts our focus to Tuberculosis (TB), a multifaceted and emblematic infectious disease often accompanied by stigma (WHO, 2023 ). TB, which is one of the oldest known infectious diseases, is caused by the bacterium Mycobacterium tuberculosis (Kapur et al., 1994 ; Daniel, 2006 ). The bacteria are transmitted when an infected individual coughs, sneezes, or speaks, allowing another person to breathe in the pathogens. Symptoms of TB can include coughing, chest pain, fatigue, fever, and night sweats and although the condition is treatable with antibiotics it remains a major global health concern.

The paper is organized as follows. It (1) explores the idea of understanding as the aim of scientific inquiry and (2) lays down a framework of understanding that will subsequently guide our exploration of its forms in medicine. Using the case of Tuberculosis (TB), (3) it is argued that grasping a mechanistic explanation is crucial for reaching a threshold of understanding at which we may speak of an objectual, biomedical understanding of TB. If evidence can be gathered to support this argument, it would align with the previously mentioned research on a noncommunicable disease (scurvy), suggesting a recurring pattern across various contexts of medical research.

1 The aim of scientific inquiry: constitutive aim and truth

Scientific inquiries can be viewed as extensions of our day-to-day endeavors to gather information albeit executed in a more systematic manner (see e.g., Kelp, 2021 ). They are goal-directed activities, implying that there is some aim that inquiry strives to accomplish. It is quite natural to assume that this description also fits medical science; however, before delving into the question of what constitutes the epistemic aim of medical science, it is crucial to first briefly clarify what medical science refers to. What sets medical science apart and qualifies something as specifically medical science, rather than just science in general?

Medical science, which includes clinical research and laboratory research in medicine, is fundamentally based on the life sciences. Over the past two centuries, it has extensively leveraged discoveries in biology that have identified cellular, genetic, and molecular entities and processes that help explain the development and course of diseases. While some aspects of medical science may not differ essentially from laboratory sciences within contributing disciplines such as biology, biochemistry, and physiology, medical science cannot simply be reduced to the sum of these fields. One reason is that medical research is only deemed properly medical when it has a specific practical orientation—that is, when it is driven by the goal of contributing to clinical medicine, which primarily focuses on the diagnosis, prevention, and treatment of disease. Without this practical focus, research might be more accurately described as biological rather than medical. Take, for example, large-scale laboratory research that aims to chart the functions of specific limbic structures in the brain. Without a practical focus on clinical applications or health outcomes, such research might be more accurately described as neurobiological rather than medical. Of course, this research could potentially yield benefits for clinical medicine in the future, but without a direct and immediate practical orientation, it would not be classified as medical research. Moreover, if we were to classify such research as medical merely based on potential future benefits, the distinction between medical and non-medical research would collapse.

Of course, this practical orientation toward health outcomes is a characteristic that biomedical research shares with related fields such as public health. However, their epistemic aims are directed towards different objectives: biomedical research typically focuses on the biological and physiological aspects of diseases at a molecular or cellular level, aiming to elucidate disease mechanisms and develop new treatments, whereas public health is primarily concerned with improving the health of populations through prevention strategies, health education, surveillance, and improving access to health care. Public health aims encompass a wide array of objectives: ensuring safe environments by controlling hazards in air, water, and food, enhancing host resistance through balanced nutrition and immunization, promoting health-supportive behaviors, and improving equitable access to health and social services (White et al., 2013 ; Munthe, 2008 ). Footnote 2

Although both fields are dedicated to conducting research with the final aim to improve health outcomes, they operate with different priorities and methodologies, each aligned with their distinct epistemic goals. A biomedical researcher might delve into the genetic factors that contribute to the resistance of TB to antibiotics, focusing on molecular and cellular details. In contrast, public health initiatives may not require such knowledge; instead, they often concentrate on understanding societal or other health factors that hinder the implementation of vaccination programs or public campaigns aimed at increasing awareness and prevention of TB.

Having briefly clarified at least some of the aspects that set medical science apart, we can now turn to the question of its aim. As we begin to explore this, it is worth considering how plausible it is to claim that scientific inquiries in medicine are driven by a single aim. This consideration is crucial because the diversity of methods, approaches, and priorities within medical science suggests that its objectives might not be unified under a single overarching aim. In response, it is important to clarify that for the purposes of this paper, we do not assert that medical science is driven by a single aim. Instead, among potentially other aims, our objective is to explore the nature of medical science’s epistemic aim , which also determines what counts as progress at least in this limited sense. Thus, very roughly, if A is the aim of inquiry, then medical science makes progress when A accumulates or increases (for a discussion, see Bird, 2007 ; Varga, 2024 ).

So what is the epistemic aim of scientific inquiry in medicine? According to a plausible suggestion, the aim is simply to discover truths about health and disease and correct past errors (e.g., false beliefs about diseases like scurvy or depression being caused by humoral imbalance) that were based on tradition, cognitive errors, ideologies, or religious dogma. Correspondingly, progress consists in a cumulative acquisition of true beliefs. For example, until the nineteenth century, the prevailing belief was that TB was inherited or caused by environmental factors such as bad air or poor living conditions. But already in 1720, the English physician Benjamin Marten hypothesized that TB and its symptomatic lesions in the lungs are caused by “species of Animalcula or wonderfully minute living Creatures” that can be transmitted “by very frequently conversing so nearly as to draw inpart of the breath he emits from the lungs” (cited in Cambau & Drancourt, 2014 ; Daniel, 2006 ). Supporting this hypothesis, in 1865, the French physician Jean-Antoine Villemin provided experimental evidence that TB could be transmitted. He observed that TB was more prevalent in people living close and in poorly ventilated buildings, and he noted that while TB was common among troops in barracks, it decreased during military campaigns when soldiers were not housed (Daniel et al., 1994 ). Thus, Marten and Villemin unearthed truths regarding TB, rectified previous mistakes, and aided in the ongoing accumulation of accurate beliefs, which constitutes progress.

On its face, the suggestion that the aim of medical research is simply to discover truths is plausible. After all, it is often said that scientific inquiries are in the “truth business” (Pennock, 2019 ; Lipton, 2004 ), and it is difficult to imagine that contemporary medical science would be able to achieve what it does if its claims would not at least roughly correspond to how the world actually is. Nonetheless, the acquisition of true beliefs does not seem sufficient to constitute progress. Footnote 3 Take, for instance, a scenario where Marten and Villemin arrived at the same conclusion through unreliable methods and, coincidentally, the theory they came to accept happened to be true. In that case, Marten and Villemin would have acquired a true belief, but it would not have counted as genuine progress. What would be lacking is suitable justification for holding the relevant belief. In other words, the belief that they would have acquired would not qualify as knowledge .

1.1 Knowledge and understanding

What we learn from these considerations is that progress not only requires that our beliefs and theories be true but that we have attained adequate reasons for forming them. If this is correct, then it seems safe to conclude that the aim of inquiry is not merely truth, but knowledge (achieved by reliable means), which would mean that progress consists in the increase not of true beliefs, but of knowledge. Although this correction marks an improvement, it is necessary to supply some clarifications and caveats.

First, the aim of inquiry cannot simply be the mere accumulation of knowledge. Medical science has an expansive range of questions at its disposal, and it could potentially attain a vast pool of knowledge, but much of this potential knowledge might be trivial or inconsequential, lacking the impact or significance to be deemed progress. Imagine that researchers could come to know everything about some minor and transient symptom (e.g., a slight, transient change in nail coloration or longitudinal nail ridging) observed in a small subset of TB patients that are known not to have bearing on the disease’s diagnosis, progression, or response to treatment. While detailed knowledge of these symptoms might add to the clinical descriptions of TB, the reason this gained knowledge is not considered significant or constitutive of true progress likely stems from its limited impact on key areas of TB research and clinical management. It lacks the potential to advance our understanding of TB (or indeed other medically relevant conditions), uncover new treatment targets, enhance diagnostic methods, or deepen our understanding of disease transmission and resistance mechanisms.

If we accept this line of reasoning, then the aim of inquiry in medicine cannot be simply to amass knowledge, but rather a selective process that prioritizes the acquisition of certain kinds of significant knowledge. Hence, part of the scientific endeavor involves a critical evaluation process to identify which pieces of knowledge are significant and worth pursuing. This selection process is fundamental to progress, ensuring that scientific efforts are directed toward areas of genuine importance and potential impact (Kitcher, 2001 ; Dupré, 2016 ). Identifying and focusing on significant knowledge, therefore, becomes a crucial aspect of the scientific method, guiding researchers in making meaningful advancements rather than merely expanding the repository of human knowledge.

While the aim of inquiry is significant knowledge, the selection process to identify which pieces of knowledge count as significant cannot be extracted from nature and is largely relative to specific interests. As Kitcher ( 2001 , 61) stated regarding scientific inquiry in general, “significant science must be understood in the context of a particular group with particular practical interests and a particular history”. In the context of TB, it is far more plausible to suggest that what constitutes significant knowledge is closely interwoven with practical concerns related to the understanding and treatment of TB.

Having discussed the issue of significance, we are now faced with a final challenge that questions the notion that the goal of inquiry in medical science is best described as the pursuit of knowledge. In recent years, numerous philosophers of science have contended that framing the aim of inquiry in terms of understanding offers significant benefits over viewing progress merely as an accumulation of knowledge. The advantage with comprehending progress in terms of increased understanding is that it avoids the challenges faced by accounts measuring scientific progress in terms of knowledge (see e.g., Elgin, 2007 , 2017 ; De Regt & Dieks, 2005 ; Potochnik, 2017 ). Footnote 4 First, traditional accounts have problems explaining the significance of certain pragmatic virtues (e.g., simplicity) that do not affect the truth of claims, theories, and explanations. In contrast, an account of progress based on the notion of understanding does not face this problem, as these pragmatic virtues clearly affect the ability to understand (Dellsén, 2016 ). Second, traditional accounts of progress as knowledge accumulation have problems explaining abstractions, approximations, and idealizations. For example, in medicine, physiological accounts often offer idealized and simplified descriptions of organs and their functions (Ereshefsky, 2009 ). These provide computational tractability and improve understanding, but they also include aspects that are, strictly taken, inaccurate or false. However, such falsehoods are, as Elgin ( 2017 ) puts it, “felicitous”: although they involve false representations, they also exemplify significant aspects of phenomena in a tractable manner. Several philosophers have argued that science can increase understanding and contribute to progress even if it involves departing from the truth (e.g., Elgin, 2009a , b ; Strevens, 2017 ; Potochnik, 2015 ).

On an account of progress in terms of knowledge, the presence of manifest falsehoods seems incompatible with progress. However, an account of progress in terms of understanding fares better here, since understanding is compatible with a limited number of falsehoods, which are outweighed by practical advantages. Strevens argues that idealized models can provide understanding, but in a somewhat more limited way, showing why some causal factors are difference-makers and others are not (Strevens, 2017 ). Potochnik ( 2017 , 102; 2015 ) holds that while idealizations cannot be true or approximately true, they can be epistemically acceptable. Because such idealizations are rampant in science and they always detract from the truth, truth does not seem to be a good candidate for describing the aim of science. However, given that idealizations can support understanding, it is more adequate to suppose that understanding is what science aims at.

The latter is not susceptible to such worries, because, in contradistinction to knowledge, understanding is only quasi-factive: it can survive false beliefs if they are not absolutely vital to the phenomenon in question. For example, Marten hypothesized that TB was caused by “species of Animalcula or wonderfully minute living Creatures” (Doetsch, 1978 ; Daniel et al., 1994 ). Strictly taken, this is false: TB was not caused by such small creatures, but by the Mycobacterium tuberculosis bacteria, which Marten had no knowledge of. Nevertheless, it is hard to deny that some progress occurred and an increase in the (objectual) understanding of TB had been obtained.

In all, as opposed to truth or knowledge, the epistemic aim of scientific inquiry is best comprehended as understanding. Comprehending progress in terms of increased understanding dovetails more closely with the pragmatic nature of medicine and has the advantage of being resistant to some of the problems that haunt accounts that comprehend progress as knowledge accumulation. If the epistemic goal of inquiry is best framed as seeking understanding, this raises questions about what understanding is in medical research. The following sections will initially delve into theories of understanding, followed by an examination of the specific nature of understanding within the realm of medicine.

2 Forms of understanding

The debates on understanding have focused on three types of understanding: propositional understanding (understanding that something is the case), explanatory understanding (understanding why something is the case), and objectual understanding (understanding a particular topic or subject matter) (see e.g., Kvanvig, 2003 ; Hannon, 2021 ; Grimm, 2021 ). Footnote 5 In what follows, we are going to be focusing on explanatory and objectual understanding, in part because propositional understanding is often largely reducible to propositional knowledge or explanatory understanding. For example, saying “he understands that he needs to come to TB screening” could amount to the attribution of propositional knowledge (“he knows that he needs to come to TB screening”) or to explanatory understanding (“he understands why it is important for him to come to TB screening”). Of course, there are many other examples of how the term “understanding” is used. But many of them are either reducible to claims about knowledge, objectual understanding or explanatory understanding. For example, when we say that a person really understands how x works, then we are attributing to this person some degree of objectual understanding of x.

To illustrate the difference between knowledge and understanding, consider the example of TB. A student of medicine may attend a lecture on infectious diseases and come to know from a reliable source that TB is caused by Mycobacterium tuberculosis. Accepting the testimony from a reliable source and even double checking it in an encyclopedia of infectious diseases, the student gains causal knowledge. But while the student now knows a proposition that picks out the cause of TB, that is not enough for explanatory understanding, which not only requires knowledge of what caused the effect, but also grasping how that cause brings about the effect (Kvanvig, 2003 ; Pritchard, 2010a ), which many take to involves a type of “skill” (see e.g., De Regt, 2017 ). Understanding does not only require the possession of a theory or model, but also the skill or ability to use it to discern the causal relationship involved. One way to comprehend the difference is that unless explanatory understanding about how cause and effect are related is attained, she will be unable to address what-if-things-had-been-different questions or predict the outcomes of potential interventions (Grimm, 2011 ).

For another example, consider an utterly false theory leading to correct results. Charles Locock’s mid-19th century discovery of the anticonvulsant effect of potassium bromide. Locock, a physician working in London, shared the widely accepted theory among his contemporaries of a causal relationship between masturbation, convulsions, and epilepsy (Ban, 2006 ). As bromides were known to reduce the sex drive, Locock reasoned that the ingestion of potassium bromides would control convulsions by reducing the rate of masturbation. His account of the drug’s effectiveness was published in The Lancet in 1857, and subsequent independent studies confirmed potassium bromide’s antiepileptic efficacy, albeit evidently not by reducing masturbation frequency. Through observations and inference to the best explanation, Locock had attained knowledge that potassium bromide reduced convulsions, and such knowledge allowed the introduction of a relatively effective antiepileptic treatment into medical practice.

Still, in an important sense, such causal knowledge does not properly close the inquiry, which would require grasping a correct explanation and attaining understanding of what happens and how cause and effect are related. Locock did not understand why potassium bromide was effective, why it failed to be effective in some people, and so on. This meant that he lacked the ability to improve the efficiency of the intervention, since he was unable to counterfactually anticipate the effects of changes he could have made with respect to the treatment. More precisely, the lack of understanding means that Locock was unable to (i) predict the changes that would occur if the factors cited as explanatory were different and (ii) to draw correct inferences about similar situations under slightly varied conditions.

2.1 Explanatory and objectual understanding

Objectual and explanatory understanding differ in several ways (Kvanvig, 2003 , 2009 ; Hannon, 2019 , 2021 ). Explanatory understanding involves grasping why something is the case (e.g., uncovering the causal mechanisms or reasons behind phenomena) and its scope is less expansive than that of objectual understanding (Hannon, 2021 ). Objectual understanding, usually expressed using the verb “understands”, followed by a noun, as in the phrase “she understands TB”, entails a comprehensive grasp of a particular topic or subject matter, which includes incorporating these causal explanations into a broader context. While explanatory understanding is often necessary, it is not sufficient for objectual understanding, which requires integrating these explanatory insights within a larger framework.

To illustrate the difference, imagine that our student has now acquired knowledge of a vast number of isolated facts about TB, such that her peers would not hesitate to say that she has knowledge about TB. Nonetheless, this would not imply that the student understands TB, which would attribute to the student a more profound penetration of TB, a sort of epistemic acquaintance that is more profound than knowing particular propositions (Kvanvig, 2003 , p. 191; Strevens, 2017 ). Her objectual understanding of TB is gradable and can always become more profound along various dimensions (Bengson, 2017 ).

Often, achieving (full) objectual understanding is the aim of inquiry, and reaching it justifiably concludes the investigation of the topic (Kvanvig, 2013 ). If we think of medical research, objectual understanding seems to better capture the primary aim of inquiry and the conditions under which it can be concluded. To take the example of TB, researchers not only want to understand why it arises or why certain characteristic biochemical reactions occur but also why it leads to the characteristic symptoms, why it has varied effects on individuals, how it relates to other conditions, and so on. Even though single research projects cannot take on such a large task, the ultimate goal seems to go beyond obtaining explanatory understanding of features of TB to systematically understanding TB , which means attaining some level of coherence and completeness in terms of knowledge, as well as in taxonomies and classifications.

A prevalent perspective posits that achieving objectual understanding marks the endpoint of inquiry and legitimately closes the investigation into the subject (Kvanvig, 2013 ; Carter and Gordon 2014). This perspective aligns well with medicine, where an objectual understanding of a condition, rather than just its explanation, is often the ultimate aim. In their pursuit of understanding TB, researchers aim to grasp not just its origins, but also its manifestations, correlations with other conditions, its varied effects on individuals, and the most useful systematic categorization of its characteristic symptoms and signs.

Some argue that objectual understanding is not merely a subset of explanatory understanding, in part because it is possible to achieve objectual understanding of indeterministic systems where explanatory relations do not obtain (Kvanvig, 2009 ). But even if this turns out to be false (see e.g., Khalifa, 2013 , ch. 4), maintaining this distinction conserves the intuition that when we attribute to somebody objectual understanding of a subject matter (as opposed to explanatory understanding), we imply that the agent’s epistemic commitments relevant to the subject matter form a coherent network. Also, the distinction upholds the idea that objectual understanding’s factivity requirement is more lenient, making it less susceptible to peripheral falsehoods compared to explanatory understanding (see e.g., Elgin, 2017 ; Bamberger, Beisbart, & Brun 2017; Kvanvig, 2009 ).

2.2 Grasping explanations and context-dependency

Both explanatory and objectual understanding go beyond mere knowledge by encompassing an additional cognitive achievement, often referred to as a form of “grasping” (e.g., de Regt, 2009 ; Strevens, 2017 ; Grimm, 2014 ; Elgin, 2017 ; for a critique, see Khalifa, 2013 , ch. 3). The objects of grasping are “explanatory and other coherence-making relationships” (Kvanvig, 2003 , p. 192). There is no clear agreement on the precise meaning of “grasping” (Hannon, 2019 ), but for our purposes we might conceptualize it as a form of cognitive control that agents develop through the active engagement of their epistemic agency in delineating conceptual and explanatory links. Importantly, while grasping enables agents to mentally map a relational assembly (Grimm, 2014 ), it is not reducible to the experience of understanding (e.g., an “aha” moment): good explanations do not necessarily trigger a sense of understanding, while inadequate explanations sometimes do (Trout, 2002 ). While philosophers commonly concur that what is being grasped are explanations, aligning with the notion that the primary purpose of scientific explanation is to foster understanding (Lipton, 2001 ), opinions differ on what kind of explanations lead to understanding, such as deductive-nomological explanations (Hempel & Oppenheim, 1948 ), or mechanistic explanations, which explain phenomena by specifying the mechanisms that produce them (Salmon, 1984 ; Machamer et al., 2000 ). Footnote 6

Importantly, what counts as understanding, is – at least in a limited sense – context-sensitive . This can be interpreted in several ways. First, some argue that understanding is context-sensitive in the sense that the criteria for understanding can evolve even within a single scientific discipline (for historical examples, see De Regt, 2017 ; De Regt et al., 2009 ). This is in part because the capacity of an explanation to lead to understanding is partially contingent upon the disciplinary background and knowledge of individuals seeking to understand.

Second, and more importantly for our aims here, some hold that context-sensitivity is linked to the nature and aim of the particular scientific inquiry. For example, Craver ( 2013 ; Kendler et al., 2011 ) contends that mechanistic explanations are inherently contextual and “perspectival”, as they are framed within a specific explanatory framework that is chosen based on explanatory interests. While this point may be limited to mechanistic explanations, there are indications that objectual understanding displays some context-sensitivity across scientific fields. To illustrate this with a medical example, consider the study of cholesterol metabolism in medical science and chemistry. In medical science, a significant level of objectual understanding of cholesterol metabolism arguably encompasses an understanding of how cholesterol levels are regulated (e.g., by diet, genetics) and how they can be modified through interventions or lifestyle changes to reduce the risk of disease. From the perspective of chemistry, objectual understanding of cholesterol metabolism does not necessarily relate to cardiovascular health but instead focuses on explaining the biochemical pathways of cholesterol breakdown and synthesis, elucidating the precise molecular interactions involved. Thus, what constitutes some sufficient level of objectual understanding in medicine might differ from that in chemistry, primarily because the explanatory goals and interests in medicine are intrinsically tied to practical applications and clinical medicine. There is no inherent tension between context-sensitivity and objectual understanding: even if the threshold for sufficient objectual understanding can be consistent across disciplines, the kinds of explanations needed to reach this understanding vary according to the specific context and the explanatory, practical and other goals of each field.

3 Biomedical understanding

While the presented account of understanding does not purport to capture the intricacies of philosophical debates on the topic, it serves as a basis for exploring what it means to possess objectual understanding of a disease within the medical field. This will be referred to as biomedical understanding (see Varga, 2023 , 2024 ). To grasp what biomedical understanding entails, let us revisit the history of TB research.

Before the 19th century, tuberculosis (TB) was thought to result from heredity or environmental causes like bad air. Marten’s initial hypothesis that “minute living creatures” could spread TB was later validated by Villemin, who in 1865 provided experimental evidence of TB’s transmissibility. He linked its higher incidence to crowded, inadequately ventilated environments and noted a decrease in TB cases among soldiers when they were not confined to cramped barracks (Daniel et al., 1994 ; Bynum, 2012 ). Moreover, by removing liquid from tuberculous cavities of individuals who had died of TB and injecting it into healthy animals, Villemin successfully transmitted the disease from humans to rabbits, from cows to rabbits, and from rabbits to rabbits. Throughout his studies, he used the same amount of liquid and animals of similar origin, age, and habitat conditions, such that “everything indeed other than inoculation, were identical” (Villemin 1868/2015 , 257). While not all animals developed symptoms, autopsies three months later revealed that the vast majority developed extensive TB with massive dissemination of tubercles to the organs (Villemin 1868/2015 ; Barnes, 2000 ).

Clearly, Villemin’s findings helped distinguish between variables that had a direct effect on the development of TB and those that were correlated with it (e.g., certain professions, poverty, poor living conditions). However, while Villemin attained an important piece of explanatory understanding, it would be unwarranted to say that he obtained objectual understanding of TB in any noteworthy sense. Given that the explanatory goals and interests in medicine are closely tied to practical applications, such a claim might seem excessive because the explanatory understanding Villemin obtained did not form a coherent network that would have allowed him to consider how possible medical interventions could limit control the progression and spread of TB. After all, Villemin did not understand under what conditions TB developed, how it transmitted, and what the agent of the disease was, except that the tubercle (nodular lesion) contained it.

Let us now look closer at some shortcomings that could have prevented him from attaining objectual understanding of TB in any substantial sense. The first shortcoming stems from an incomplete understanding of the causal agent. Villemin lacked comprehension with respect to two critical aspects of the causal connection: stability and specificity (see Woodward, 2010 ). A causal link between the injected substance and TB is considered stable if the counterfactual dependence remains consistent across various background situations. Villemin’s studies did not provide much evidence with respect to stability, because they did not involve testing under different background circumstances. In addition, specificity refers to the grain level of counterfactual dependencies between the inoculated substance and TB. Because Villemin inoculated the same amount of substance in each case, his studies offered no knowledge about the extent to which the intensity of tuberculization depends on the amount of substance inoculated. Villemin had no way of determining whether the counterfactual dependencies between the inoculated substance and TB are fine-grained, in which case intervention on the inoculated substance would enable more precise control over how TB develops.

Moreover, Villemin’s incomplete understanding of the causal agent prevented him from ruling out the possibility that experimentally induced tuberculosis might follow a different pathway from ordinary TB or could even be a distinct disease altogether. When injecting liquids from organisms that succumbed from TB, one could argue that the effects obtained were not due to TB, but to the injection containing some “cadaveric material.” Although Villemin could show that the number and extent of lesions on the lungs are not correlated with the number and extent of lesions developed at the injection site, he himself noted a crucial limitation: “should we consider the entire chain of phenomena observed in experimental tuberculosis as the result of a traumatism due to inoculation? This is an enigma that we cannot resolve” (Villemin 1868/2015 , 259).

The second shortcoming concerns a lack of knowledge about the relevant mechanism. The causal knowledge Villemin attained did not permit “tracing” the causal process (Steel, 2008 ), which would have assisted grasping coherence-making relationships and comprehending how the elements of TB are configured. This seems to necessitate some degree of explanatory understanding and discerning the mechanism that is responsible for linking cause and effect. A mechanism for phenomenon P consists of parts and processes that are structured in a way such that they are responsible for P (Glennan et al., 2021 ). Explanations in the biomedical sciences are most frequently mechanistic, explaining a disease by identifying the spatiotemporal structure of a mechanism that is responsible for that disease and its symptoms (Thagard, 2005 ; Darrason, 2018 ; Williamson, 2019 ). Villemin’s study establishes a coarse-grained difference-making relationship, but it does not amount to biomedical understanding because it fails to discern the correct mechanism.

We could say that the lack of such a mechanism has crucially impacted Villemin’s ability to gather sufficient evidence for explanatory understanding. There are two possibilities here, depending on which thesis one subscribes to regarding the role of mechanisms in establishing causal claims (for discussions, see Russo & Williamson, 2007 ; Illari, 2011 ; Williamson, 2019 ). According to a strong thesis, establishing a causal relationship requires not only difference-making evidence but also evidence of a mechanism composed by entities (such as proteins) and processes (such as protein expression) that together link cause and effect. If one accepts the strong thesis, then Villemin has not met the criteria for establishing a causal relationship because he had no knowledge of the mechanism. According to a weaker thesis, difference-making can serve as evidence for a causal relationship. However, evidence of a mechanism, combined with difference-making evidence, significantly increases certainty that the observed correlation is not merely spurious and that the effect can be attributed to the experimental intervention rather than to confounding variables.

Having examined these two shortcomings, it appears likely that each has contributed to the failure to attain objectual understanding. However, it is unclear whether any of these factors are essential for achieving objectual understanding. In the sections that follow, we will explore the historical development of tuberculosis research to further investigate this issue.

3.1 Koch and beyond

A significant breakthrough with respect to the first two shortcomings came with Robert Koch’s 1882 discovery of the bacterium Mycobacterium tuberculosis (MTB) as the causative agent of TB (Keshavjee & Farmer, 2012 ). Footnote 7 Koch formalized a set of “postulates” for establishing causation, which required (a) coincidence of bacteria and disease, (b) isolation of bacteria in a pure culture, and (c) induction of disease by inoculation with bacteria from pure culture. As to (a), Koch was able to show that the MTB were always present in TB (but not in normal states), that they preceded tubercle formation, and that their number covaried with TB being progressive or quiescent. As to (b), Koch managed to isolate individual colonies of MTB in pure culture that allowed studying their growth characteristics. As to (c), he inoculated animals with MTB obtained from various origins (induced disease, spontaneous disease, and artificial culture). Koch found that injections led to the formation of tubercles with similar characteristics, and the number of tubercles corresponded to the amount of the inoculum used (Blevins & Bronze, 2010 ).

While Koch’s postulates can be interpreted in various ways (e.g., Broadbent, 2009 ), some have argued that Koch’s experimental distinction of causal from correlational relationships are best captured by the interventionist account of causation (Ross & Woodward, 2016 ). Interventionism posits that causal relationships are those that can be potentially harnessed for manipulation and control: very roughly, if intervening on C reliably leads to changes in E, then C is the cause of E. Woodward ( 2003 ) outlines the necessary and sufficient criteria for establishing causation as follows: C causes E if and only if (i) there is some possible intervention on C such that (ii) were this intervention to occur, there would be an association or correlation between C and E. The account highlights idealized experimental intervention as appropriate for the purposes of determining whether C causes E, as it eliminates possibility of confounding. As the induced change is not correlated with potential confounders, the presence of a correlation between C and E upon intervention on C means that C has a causal influence on E.

Interventionism fits Koch’s postulates, particularly his emphasis on (c), i.e., the induction of disease into a healthy animal by inoculation with bacteria from pure culture. In fact, Koch clearly maintains that determining causality between MTB and TB “can only be decided by inoculating pure bacilli,” thus step (c) (quoted in Ross & Woodward, 2016 , p. 44). Footnote 8 Of course, (b) can be seen as a procedure to ensure that (c) obtains the characteristics of a proper intervention: it excludes the possibility that confounding factors are contained in the inoculated material. Causal claims can only be established if the intervention is associated with a change in the incidence of TB (e.g., its presence, absence, rate of occurrence). In accordance with (M), if the inoculation of substances had not led to the occurrence of disease, Koch would not have identified them as the cause of the disease.

Although the discovery of the causal agent addressed the first shortcoming in Villemin’s research, it alone was insufficient to resolve the second shortcoming concerning the mechanism. However, this is clearly a significant issue, in part because it connects with important questions from a clinical perspective. Without an understanding of the mechanism, questions about what holds together the symptoms of TB, whether certain characteristics (e.g., diarrhea) are parts of TB or caused by TB, how MTB is disseminated to other organs, why most individuals with latent infection do not develop the disease, cannot be answered.

3.2 Twentieth-century discoveries

In the twentieth century, a notable breakthrough came with the identification of the mechanism through which MTB interacts intricately with the host’s immune system, leading to TB. Roughly, when MTB reaches the lungs, it is taken up by macrophages, which are immune cells that engulf and destroy foreign particles. However, MTB is able to survive and replicate within the macrophages, which leads to the formation of granulomas that surround the infected macrophages to contain the infection. MTB is sometimes able to resist destruction and containment, eventually causing the macrophages to burst and release more bacteria into the surrounding tissue. The infected tissue becomes inflamed, leading to the formation of the characteristic lesions, or granulomas, in the lungs and other organs. The granulomas can restrict the infection, leading to a latent TB infection, or they can break down, releasing MTB into the lungs, where it can be coughed up and spread to others (for reviews, see Delogu et al., 2013 ; Yan et al., 2022 ).

The mechanism was elucidated over several decades through the significant contributions of numerous researchers. Therefore, it is challenging to pinpoint exactly when and by which researchers a threshold was crossed, marking a stage at which we may speak of researchers having attained objectual understanding of TB. However, once a mechanistic explanation became available that referenced the configuration and activities of component entities, and identified both the normal functioning of macrophages and how MTB disrupts this process, it seems quite intuitive to say that researchers had achieved a significant level of objectual, biomedical understanding of TB. Researchers have progressed beyond merely explaining various aspects of TB; they have crossed a threshold into systematically, objectually understanding TB .

Of course, while this assertion may seem intuitively appealing, it alone raises a crucial question: what is it about mechanistic explanations that renders them necessary for achieving a significant level of objectual understanding? In what follows, the aim will be to show that mechanistic explanations have enabled achieving a level of coherence and integration, offering clear potential to refine theoretical frameworks and clinical practices, and to facilitate the development of more comprehensive taxonomies and classifications. But before doing so, it is worth emphasizing that a sufficient level of objectual biomedical understanding of TB has been achieved, not merely by grasping the relevant mechanistic explanations, but also by integrating this with other pieces of knowledge and understanding already obtained.

For this, we may start by noting how a mechanistic explanation not only overcomes the second shortcoming observed in the research of Villemin and Koch but also enables new insights that carry profound implications for diagnosis, treatment, and prevention strategies, directly affecting patient care and public health initiatives. This underscores an earlier argument that what constitutes a sufficient level of objectual understanding in medicine is context-sensitive and closely linked to a practical orientation. Let us now review a couple of important implications for research and clinical settings.

First, grasping the relevant mechanistic explanation, researchers were able to chart a much more fine-grained intricate web of counterfactual dependencies, which paves the road towards enhanced intervention possibilities concerning TB. Researchers can formulate new hypotheses around potential interventions, such as enhancing the macrophages’ capability to eradicate MTB or inhibiting MTB’s ability to prevent acidification within macrophages (for a review of current research, see e.g., Bo et al., 2023 ).

Second, comprehending the mechanism significantly enhances the ability to interpret and address a range of clinically relevant issues. It provides a unified view of TB, clarifying how its various elements are interrelated, and explaining how seemingly disparate symptoms are interconnected through a common cause. This comprehensive insight into the relationships between TB symptoms and the disease process improves diagnostic accuracy and aids in refining diagnostic criteria. It enables healthcare providers to more effectively differentiate TB from other conditions with similar symptoms, thereby reducing the risk of misdiagnosis. Moreover, this understanding is crucial in explaining why some individuals with latent TB infections do not progress to active disease, a key factor in managing public health risks.

Overall, comprehending the mechanism of TB has facilitated a significant milestone, crossing a threshold into what we may describe as an objectual, biomedical understanding of TB. This had key implications for identifying new treatment targets, enhancing diagnostic methods, and deepening our knowledge of disease transmission and resistance mechanisms—all of which are vital for improving clinical interventions and formulating effective public health strategies. Crossing this threshold is an important milestone, but it is entirely consistent with recognizing that further exploration and deeper understanding may still be necessary. It does not in any way imply that researchers have reached a final stage in their inquiry that would conclude investigation into TB. Indeed, as researcher recognize, many questions remain (for a recent review, see e.g., Bloom, 2023 ; WHO, 2023 ), driving increasingly detailed and nuanced insights to continuously refine existing approaches to treatment and prevention.

4 Concluding remarks

In light of the recent calls to reexamine the foundational aims of medicine, both in research and clinical practice, this paper emphasizes the importance of understanding as a unifying aim in these domains. As underscored by recent editorials cited in the introduction, there is an imperative to revisit not only the practical aims that medicine seeks, but also its epistemic aims. This is particularly salient in a time when the very essence of what constitutes medical science and clinical medicine is under scrutiny. Accordingly, this paper concentrated on the relevant epistemic aims. By exploring different forms of understanding, the paper uses TB as a focal point to argue that a grasp of mechanistic explanations is crucial for reaching a threshold of understanding at which we may speak of an objectual understanding of TB.

An important limitation of this paper is its focus on a single case: TB. Consequently, there are notable constraints on the breadth of conclusions that can be drawn. However, there are at least some reasons to believe that the findings may have broader applicability. One such reason is that an earlier study on noncommunicable diseases (Varga, 2023 ) have reached similar conclusion. That study revealed that in the case of scurvy, a mechanistic explanation of the condition is necessary for biomedical understanding, but this is not sufficient for understanding in a clinical setting. This earlier study, which examined an emblematic noncommunicable disease, reached a similar conclusion to the current study that focuses on a representative communicable disease. This suggests a potential pattern across various contexts of biomedical research. That said, additional research is required to reinforce this point by investigating whether these conclusions are applicable across a wide spectrum of diseases, including those that are rarer and less prominent. Additionally, it is worth noting that this might differ significantly for conditions where mechanistic explanations have proven challenging to establish. Mental disorders could serve as critical test cases to explore the applicability of our findings in contexts where the underlying mechanisms are less understood.

Interestingly, in an editorial published by the British Medical Journal (Marshall et al., 2018 ) the editors prompt a similar reflection on the purpose of clinical medicine. They challenge the prevailing emphasis on disease-centric care and encourage contemplation of whether a holistic therapeutic relationship with patients might better align with the true aim of medical practice. Though published separately, these editorials collectively highlight a growing movement towards a critical reevaluation of the aims and priorities of both medical science and clinical medicine. The question has sparked considerable interest, with various competing accounts proposing that there is a single, overarching aim (e.g., Broadbent, 2019 ) whereas others suggesting that medicine has multiple aims (e.g., Boorse, 2016 ; Brody & Miller, 1998 ; Schramme, 2017 ).

Munthe ( 2008 ) advocates for an integrated, multidimensional model, highlighting that recent decades have seen the introduction of new objectives focusing on autonomy and equality.

See Bird ( 2019 ) for a helpful discussion of an example from physics.

Other accounts maintain that progress in science occurs when theories come nearer to the truth or when it accumulates solutions to scientific puzzles that are neutral about questions of truth. For a critical review, see Bird ( 2007 ).

Practical understanding (“understanding-how”) typically involves skillful behaviors, relies often on non-propositional knowledge, and is neither explanatory nor susceptible to Gettier-style objections (Bengson, 2017 ). For example, a person may lack the resources to explain the workings of a device but may understand how the device works by way of her skill to adeptly use it.

A mechanism is typically defined as “a structure performing a function in virtue of its component parts, component operations, and their organization” (Bechtel & Abrahamsen, 2005 , p. 423).

For his research, Koch earned the Nobel Prize in 1905.

It makes sense to think that had Koch adhered to a view of causation as merely regularities involving necessary and sufficient conditions that could be discerned through observation, he would not have emphasized (c).

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Varga, S. Scientific understanding in biomedical research. Synthese 204 , 66 (2024). https://doi.org/10.1007/s11229-024-04694-w

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How to Conduct Scientific Research?

United Nations Educational, Scientific and Cultural Organization (UNESCO) defines research as systematic and creative actions taken to increase knowledge about humans, culture, and society and to apply it in new areas of interest. Scientific research is the research performed by applying systematic and constructed scientific methods to obtain, analyze, and interpret data.

Scientific research is the neutral, systematic, planned, and multiple-step process that uses previously discovered facts to advance knowledge that does not exist in the literature. It can be classified as observational or experimental with respect to data collection techniques, descriptive or analytical with respect to causality, and prospective, retrospective, or cross-sectional with respect to time ( 1 ).

All scientific investigations start with a specific research question and the formulation of a hypothesis to answer this question. Hypothesis should be clear, specific, and directly aim to answer the research question. A strong and testable hypothesis is the fundamental part of the scientific research. The next step is testing the hypothesis using scientific method to approve or disapprove it.

Scientific method should be neutral, objective, rational, and as a result, should be able to approve or disapprove the hypothesis. The research plan should include the procedure to obtain data and evaluate the variables. It should ensure that analyzable data are obtained. It should also include plans on the statistical analysis to be performed. The number of subjects and controls needed to get valid statistical results should be calculated, and data should be obtained in appropriate numbers and methods. The researcher should be continuously observing and recording all data obtained.

Data should be analyzed with the most appropriate statistical methods and be rearranged to make more sense if needed. Unfortunately, results obtained via analyses are not always sufficiently clear. Multiple reevaluations of data, review of the literature, and interpretation of results in light of previous research are required. Only after the completion of these stages can a research be written and presented to the scientific society. A well-conducted and precisely written research should always be open to scientific criticism. It should also be kept in mind that research should be in line with ethical rules all through its stages.

Actually, psychiatric research has been developing rapidly, possibly even more than any other medical field, thus reflecting the utilization of new research methods and advanced treatment technologies. Nevertheless, basic research principles and ethical considerations keep their importance.

Ethics are standards used to differentiate acceptable and unacceptable behavior. Adhering to ethical standards in scientific research is noteworthy because of many different reasons. First, these standards promote the aims of research, such as knowledge, truth, and avoidance of error. For example, prohibitions against fabricating, falsifying, or misrepresenting research data promote truth and minimize error. In addition, ethical standards promote values that are essential to collaborative work, such as trust, accountability, mutual respect, and fairness. Many ethical standards in research, such as guidelines for authorship, copyright and patenting policies, data-sharing policies, and confidentiality rules in peer review, are designed to protect intellectual property interests while encouraging collaboration. Many ethical standards such as policies on research misconduct and conflicts of interest are necessary to ensure that researchers can be held accountable to the public. Last but not the least, ethical standards of research promote a variety of other important moral and social values, such as social responsibility, human rights, animal welfare, compliance with the law, and public health and safety ( 2 ). In conclusion, for the good of science and humanity, research has the inevitable responsibility of precisely transferring the knowledge to new generations ( 3 ).

In medical research, all clinical investigations are obliged to comply with some ethical principles. These principles could be summarized as respect to humans, respect to the society, benefit, harmlessness, autonomy, and justice. Respect to humans indicates that all humans have the right to refuse to participate in an investigation or to withdraw their consent any time without any repercussions. Respect to society indicates that clinical research should seek answers to scientific questions using scientific methods and should benefit the society. Benefit indicates that research outcomes are supposed to provide solutions to a health problem. Harmlessness describes all necessary precautions that are taken to protect volunteers from potential harm. Autonomy indicates that participating in research is voluntary and with freewill. Justice indicates that subject selection is based on justice and special care is taken for special groups that could be easily traumatized ( 4 ).

In psychiatric studies, if the patient is not capable of giving consent, the relatives have the right to consent on behalf of the patient. This is based on the idea of providing benefit to the patient with discovery of new treatment methods via research. However, the relatives’ consent rights are under debate from an ethical point of view. On the other hand, research on those patients aim to directly get new knowledge about them, and it looks like an inevitable necessity. The only precaution that could be taken to overcome this ambivalence has been the scrupulous audit of the Research Ethic Committees. Still, there are many examples that show that this method is not always able to prevent patient abuse ( 5 ). Therefore, it is difficult to claim autonomy when psychiatric patients are studied, and psychiatric patients are considered among patients to require special care.

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Paper on creating friendly color maps for color vision deficiency accepted for publication.

Elizabeth Blackwell

Timothy Lang (ST11) is a co-author on an article titled “Effective Visualization of Radar Data for Users Impacted by Color Vision Deficiency”, which was recently accepted for publication in Bulletin of the American Meteorological Society. The article is led by Zachary Sherman of Argonne National Laboratory (ANL), and it is an outgrowth of a long-standing collaboration on open science between ANL, MSFC, and other institutions that predates NASA Science Policy Directive (SPD) 41a and the Transform to Open Science (TOPS) campaign. Color Vision Deficiency (CVD) affects up to 8% of genetic males and 0.5% of genetic females, and traditional color maps used in radar meteorology and other Earth sciences often lack perceptual accuracy and clarity when viewed by those affected by CVD. The article reviews new color maps that convey useful and clear scientific information whether viewed by those with normal color perception or those with CVD. These color maps are available in open-source repositories like cmweather ( https://github.com/openradar/cmweather ) and pyart ( http://arm-doe.github.io/pyart/ ). The article and the open-source CVD-friendly color maps are excellent examples of the greater inclusivity fostered when open science is practiced. Read the paper at: https://journals.ametsoc.org/view/journals/bams/aop/BAMS-D-23-0056.1/BAMS-D-23-0056.1.xml .

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Researchers discover a new form of scientific fraud: Uncovering 'sneaked references'

by Lonni Besançon and Guillaume Cabanac, The Conversation

A researcher working alone—apart from the world and the rest of the wider scientific community—is a classic yet misguided image. Research is, in reality, built on continuous exchange within the scientific community: First you understand the work of others, and then you share your findings.

Reading and writing articles published in academic journals and presented at conferences is a central part of being a researcher. When researchers write a scholarly article, they must cite the work of peers to provide context, detail sources of inspiration and explain differences in approaches and results. A positive citation by other researchers is a key measure of visibility for a researcher's own work.

But what happens when this citation system is manipulated? A recent Journal of the Association for Information Science and Technology article by our team of academic sleuths—which includes information scientists, a computer scientist and a mathematician—has revealed an insidious method to artificially inflate citation counts through metadata manipulations: sneaked references.

Hidden manipulation

People are becoming more aware of scientific publications and how they work, including their potential flaws. Just last year more than 10,000 scientific articles were retracted . The issues around citation gaming and the harm it causes the scientific community, including damaging its credibility, are well documented.

Citations of scientific work abide by a standardized referencing system: Each reference explicitly mentions at least the title, authors' names, publication year, journal or conference name, and page numbers of the cited publication. These details are stored as metadata, not visible in the article's text directly, but assigned to a digital object identifier, or DOI—a unique identifier for each scientific publication.

References in a scientific publication allow authors to justify methodological choices or present the results of past studies, highlighting the iterative and collaborative nature of science.

However, we found through a chance encounter that some unscrupulous actors have added extra references, invisible in the text but present in the articles' metadata, when they submitted the articles to scientific databases. The result? Citation counts for certain researchers or journals have skyrocketed, even though these references were not cited by the authors in their articles.

Chance discovery

The investigation began when Guillaume Cabanac, a professor at the University of Toulouse, wrote a post on PubPeer , a website dedicated to post-publication peer review, in which scientists discuss and analyze publications. In the post, he detailed how he had noticed an inconsistency: a Hindawi journal article that he suspected was fraudulent because it contained awkward phrases had far more citations than downloads, which is very unusual.

The post caught the attention of several sleuths who are now the authors of the JASIST article . We used a scientific search engine to look for articles citing the initial article. Google Scholar found none, but Crossref and Dimensions did find references. The difference? Google Scholar is likely to mostly rely on the article's main text to extract the references appearing in the bibliography section, whereas Crossref and Dimensions use metadata provided by publishers.

A new type of fraud

To understand the extent of the manipulation, we examined three scientific journals that were published by the Technoscience Academy, the publisher responsible for the articles that contained questionable citations.

Our investigation consisted of three steps:

• We listed the references explicitly present in the HTML or PDF versions of an article.
• We compared these lists with the metadata recorded by Crossref, discovering extra references added in the metadata but not appearing in the articles.
• We checked Dimensions, a bibliometric platform that uses Crossref as a metadata source, finding further inconsistencies.

In the journals published by Technoscience Academy, at least 9% of recorded references were "sneaked references." These additional references were only in the metadata, distorting citation counts and giving certain authors an unfair advantage. Some legitimate references were also lost, meaning they were not present in the metadata.

In addition, when analyzing the sneaked references, we found that they highly benefited some researchers. For example, a single researcher who was associated with Technoscience Academy benefited from more than 3,000 additional illegitimate citations. Some journals from the same publisher benefited from a couple hundred additional sneaked citations.

We wanted our results to be externally validated, so we posted our study as a preprint , informed both Crossref and Dimensions of our findings and gave them a link to the preprinted investigation. Dimensions acknowledged the illegitimate citations and confirmed that their database reflects Crossref's data. Crossref also confirmed the extra references in Retraction Watch and highlighted that this was the first time that it had been notified of such a problem in its database. The publisher, based on Crossref's investigation, has taken action to fix the problem.

Implications and potential solutions

Why is this discovery important? Citation counts heavily influence research funding, academic promotions and institutional rankings. Manipulating citations can lead to unjust decisions based on false data. More worryingly, this discovery raises questions about the integrity of scientific impact measurement systems, a concern that has been highlighted by researchers for years. These systems can be manipulated to foster unhealthy competition among researchers, tempting them to take shortcuts to publish faster or achieve more citations.

To combat this practice we suggest several measures:

• Rigorous verification of metadata by publishers and agencies like Crossref.
• Independent audits to ensure data reliability.
• Increased transparency in managing references and citations.

This study is the first, to our knowledge, to report a manipulation of metadata. It also discusses the impact this may have on the evaluation of researchers. The study highlights, yet again, that the overreliance on metrics to evaluate researchers, their work and their impact may be inherently flawed and wrong.

Such overreliance is likely to promote questionable research practices, including hypothesizing after the results are known, or HARKing ; splitting a single set of data into several papers, known as salami slicing; data manipulation; and plagiarism. It also hinders the transparency that is key to more robust and efficient research. Although the problematic citation metadata and sneaked references have now been apparently fixed, the corrections may have, as is often the case with scientific corrections , happened too late.

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July 24, 2024

China-U.S. Science Collaborations Are Declining, Slowing Key Research

The U.S. and China are collaborating less on projects across scientific disciplines amid a culture of fear in both countries

By Gemma Conroy & Nature magazine

Manuel Augusto Moreno/Getty Images

China’s scientific collaboration with other countries has declined since the pandemic, driven by falling partnerships with the United States, an analysis shows.

Scientists have been warning that political tensions between China and the United States, combined with the pandemic, have affected research collaborations between the two countries. But it takes time for evidence of this sort of decline to accumulate in research databases.

The latest evidence comes from an analysis conducted by Springer Nature’s team in China. ( Nature ’s news team is editorially independent of its publisher, Springer Nature.) The authors used InCites, a tool owned by publishing-analytics firm Clarivate, based in London, to analyse internationally co-authored articles that were published between 2013 and 2023. InCites draws on papers indexed in the science-citation database Web of Science.

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They found that in 2022, the total number papers co-authored by researchers from China and their international peers declined for the first time since 2013 (See 'Research Powerhouse').

The proportion of research papers with Chinese and international co-authors has been falling for even longer. At its peak, in 2018, 26.6% — roughly 110,000 articles — of China’s output in the InCites database was co-authored with international colleagues. By 2023, the proportion of the country’s articles with international peers had dropped by 7.2%, despite China’s overall number of articles almost doubling to 759,000 over the same period.

The drop in internationally co-authored papers is mainly due to China’s declining share of papers published with US researchers, which fell by 6.4% between its peak in 2017 and 2023 — the largest decline of any country included in the analysis. The findings were presented at the Zhongguancun Forum in Beijing on 25 April.

The decline in US-China collaborations echoes findings from a 2022 analysis conducted for Nature , which found that the number of researchers with dual US and China affiliations on research articles in Elsevier’s Scopus database had fallen by more than 20% between 2019 and 2021.

Although the latest analysis shows that the share of US–China articles has been slowly declining over the past six years, the pandemic exacerbated the downward trend, says Marina Zhang, an innovation researcher who focuses on China at the University of Technology Sydney in Australia.

Political tensions

Zhang says that ongoing geopolitical tensions between the United States and China have also fuelled the decline. “This is especially worrying for researchers,” says Zhang. The US Department of Justice’s controversial China Initiative — which was launched in 2018 to tackle espionage in research and industry — ended in 2022. The crackdown resulted in several scientists being arrested over their ties to collaborators or institutions in China, and has stoked fear among researchers of Chinese descent. Since then, the US government has adopted a range of policies focused on tightening research security . And in July 2023, the Chinese government implemented its revised counter-espionage law, which broadened the definition of what constitutes spying.

The crackdown on perceived foreign interference in both the United States and China is making researchers more cautious about collaborating, says Zhang. Restrictive policies and the climate of fear could end up driving talent away from certain countries and fields, leading to a “brain drain and a loss of valuable human capital”, she says.

This “chilling effect” on US–China collaborations is already hindering influential research, says Tang Li, a researcher who specializes in science and innovation policy at Fudan University in Shanghai, China. For instance, a 2024 study examined the effect that the foreign-interference investigations at the US National Institutes of Health (NIH) had on researchers and found that those in the United States with collaborators in China were less productive during this period than were their colleagues with scientific partners in other countries.

Zhang says that the faltering collaborative ties between the United States and China could also result in the countries pursuing the same types of research separately, instead of joining forces to tackle global problems such as climate change , pandemics and food security.

Turning inwards

More worryingly, the countries might increasingly prioritize domestic interests over international cooperation, which could make scientific research a more nationalistic endeavour, says Zhang.

China’s collaborations with other countries have also tapered off since 2020, but not as markedly as those with the United States. Tang says that reviving US–China collaborations is crucial because such scientific partnerships could help to bridge the gap between the two countries. “Given the increasing global disasters and uncertainties, humanity cannot afford to waste time on nationalistic rivalries,” she says.

This article is reproduced with permission and was first published on July 19, 2024 .

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Picture a Scientist—Diverse Role Models Show that Science is for Everyone

Who do you picture when you think of the word “scientist”? Do you fit that image? Although science should be for everyone, some groups, including girls, people of color, the LGBTQ+ community, people with disabilities, and more are often discouraged from becoming scientists. Research shows that girls in particular start to lose interest in pursuing science careers during middle school. But part of the problem for every group is that you cannot be what you cannot see. So how do we change who students picture as scientists? We tested whether a playful STEAM (science, technology, engineering, art, math) program that uses comic books, trading cards featuring a variety of female role models, games, and outdoor exploration could change students’ minds. Our data shows that after the In Their Eyes: Conservation + Comics program, more students think that girls can be scientists, too!

Learning, Belief, and Ideas About Who Can Be a Scientist

Picture a scientist: who do you imagine? Go ahead and draw your scientist on a piece of paper or in a journal. Once you are finished, put your pencil down and read on. We will come back to your drawing later.

Have you ever wondered how you know what you know? How does your brain understand that, by combining certain letters together, you spell a specific word? Or how do you know how to make a bowl of cereal in the morning? Have you ever wondered why you think the way you do? Scientists in the fields of psychology and cognitive science are working hard to answer questions like these. They study something called cognition , which is the process of learning and understanding through thought, experiences, and using the senses (touch, taste, sound, smell, sight, kinesthetic, proprioceptive, etc.). Humans know what they know because of cognition, and our brains use various cognitive processes to help us understand ourselves and the world around us. Some examples of cognitive processes are solving problems, making decisions, or using memory [ 1 ]. The processes used by our brains to learn things like math or language are different than the brain processes used to form the beliefs we hold about ourselves—these beliefs are called our self-concept .

Science shows us that there is a link between people’s self-concepts and who they grow up to be [ 2 ]. How do we know what we can be if we never see anyone like us doing the job? How do we believe we belong somewhere without role models that we identify with? One area of scientific study involves people’s beliefs about who can be a scientist. Historically, only white men were allowed to be scientists and women, people of color, individuals with disabilities, and other minority groups (like people in the LGBTQ+ community) were intentionally excluded from science [ 3 ]. This caused two problems: first, there were very few scientists who were not white and male; and second, because there was a lack of diverse scientists, the belief that a person must be white and male to be a scientist was reinforced. In other words, there were very few diverse scientific role models, which reinforced people’s beliefs that women, people of color, and others did not belong in science.

We wanted to see if providing diverse scientific role models to students could influence their beliefs about who a scientist could be.

STEM to STEAM

Research shows that girls start to lose interest in science around middle school, and that interest in a subject is a strong predictor of career choice [ 4 , 5 ]. So, we created a STEM (science, technology, engineering, math) lesson for middle school students, called the In Their Eyes: Conservation + Comics program [ 6 ]. Teaching STEM in creative ways—such as with comic books—has been shown to be a fun and effective way to learn [ 7 ]. To do so, our lesson added art to change STEM to STEAM (science, technology, engineering, ART, math)!

Every part of our lesson featured diverse, real-world scientists as role models: first, there was a classroom lesson in which students read scientific comic books and won scientist trading cards through a vocabulary game ( Figure 1 ). Next, students took a virtual fieldtrip to a national park, for a lesson on biology and conservation taught by a female scientist. After learning about these topics, the students made their own scientific comic books to tell their conservation stories. Lastly, the students took everything they learned and created posters to show to their classes, friends, teachers, families, and 16 diverse guest scientists.

• Figure 1 - Two scientist trading cards used as part of our STEAM lesson.
• (A) The front of Dr. Kristen Lear’s trading card tells you her preferred pronouns and what type of scientist she is—a bat conservationist. (B) The front of Earyn McGee’s trading card tells you her preferred pronouns and what type of scientist she is—a herpetologist.

Did They Change Their Minds?

To understand if people’s ideas have changed over time, scientists must gather information both before the experiment (like our STEAM lesson) and after the experiment. Then, they compare before (pre-experiment) to after (post-experiment). This tells them if their experiment had any impact on what the person thought, knew, or believed. To test whether our lesson changed the students’ ideas about who could be a scientist, we used something called the Draw a Scientist Test (DAST) both before and after the lesson ( Figure 2 ).

• Figure 2 - An example of the DAST from our experiment, which uses drawings and questions to learn who a student thinks a scientist can be.
• Instructions direct the student to draw a scientist and include a caption about what their scientist is saying to them about the work the scientist is doing; students are instructed not to draw themselves, their teacher, or to use the internet. This drawing is of a scientist the student met during the lesson. The drawing caption states, “The scientist is talking to me about all the cool sea life she gets to see at work”.

The DAST is a method that has been used by scientists and education researchers to study people’s perceptions of scientists since the 1980s [ 8 ]. It has been updated many times over the years and is widely respected. The DAST asks students to “draw a picture of a scientist”. The student is also asked follow-up questions, such as: “Was the scientist you drew a man or woman?”, “Was the scientist working outdoors or indoors?”, and “What was the scientist doing in your picture?”.

The drawings and answers from this study were collected and examined to uncover stereotypical ideas of scientists. A stereotype is an oversimplified belief about a person that is often wrong, such as “only men can be scientists”. Stereotypes like this demonstrate a limited idea of who can be a scientist and what a scientist does. For example, a drawing with facial hair indicates a male scientist, and a person wearing a white lab coat shows only one type of scientist (many scientists do not wear lab coats at all). After analyzing the DASTs, we then compared the number of stereotypes pre-experiment and post-experiment to see if there was a change.

Mind Detectives

Studying people’s beliefs, thoughts, and knowledge is like being a mind detective! So, did we solve the mystery about how to change people’s perceptions about who can be scientists by using diverse role models?

After reviewing the pre-DASTs and the post-DASTs, we found that students drew fewer stereotypic images in the post-DASTs. Out of the 33 students that completed both pre- and post-DASTS, 22 of them drew traditional scientific equipment (such as beakers and flasks) before the lesson, yet only 12 of them drew this type of equipment after the lesson. In addition, 14 students drew protective gear like lab coats before the lesson, and only 6 students drew protective gear afterward. Lastly, before the lesson, an equal number of students drew men and women as scientists; but after the lesson, 19 students drew women, 10 students drew men, and three students drew non-binary scientists.

We also found that students shifted some of their ideas about science. Our lesson featured diverse women in the field of biology, and the number of drawings that featured biologists increased from 16 to 25. In fact, six students drew scientists they had been introduced to from the lesson ( Figure 3 )!

• Figure 3 - A bar graph of student perceptions of scientists before and after the lesson.
• The bars show student DAST responses pre- (green) and post- (orange) lesson. You can see that there were changes in student perceptions—for example, female and non-binary representation increased while male representation decreased.

Picture a Scientist

Why does all of this matter? These numbers show us that our lesson could be breaking harmful stereotypes about what a scientist is and who a scientist can be! By peeking into students’ beliefs about science and scientists, we were able to determine one part of a solution to the lack of diversity in STEM fields. It will take a lot of work to make STEM equal for everyone, but this could be one important step toward future success.

Now, picture a scientist again—who do you imagine this time?

Psychology : ↑ The field of science that studies human minds and behaviors.

Cognitive Science : ↑ The field of science that studies specific processes in the brain, like memory, perception, and language.

Cognition : ↑ The mental action or process of gaining knowledge and understanding through thought, experience, and the senses.

Self-Concept : ↑ The image we have of ourselves and our behaviors.

Role Models : ↑ People looked up to by others as examples to be imitated.

Diverse : ↑ Very different or variety. In this context, people from a range of different social and ethnic backgrounds and of different genders, sexual orientations, etc.

Perceptions : ↑ Ways of thinking, understanding, or believing something; mental impressions.

Stereotypical : ↑ A widely held, oversimplified idea that is often biased, prejudiced, or wrong.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

Funding for this project provided by the IF/THEN ® She Can Change the World grant.

Original Source Article

↑ Meaders, C., Gardiner, J., Wynns, S., Nigam, S., and Harris, J. 2023. A comic-based conservation lesson plan diversifies middle school student conceptions of scientists. J. Res. STEM Educ. 9:20–45. doi: 10.51355/jstem.2023.127

[1] ↑ Wyer, R. S., and Srull, T. K. 1986. Human cognition in its social context. Psychol. Rev. 93:322–59. doi: 10.1037/0033-295X.93.3.322

[2] ↑ Wang, D., Liu, X., and Deng, H. 2022. The perspectives of social cognitive career theory approach in current times. Front Psychol . 13:1023994. doi: 10.3389/fpsyg.2022.1023994

[3] ↑ O'Brien, L. T., Bart, H. L., and Garcia, D. M. 2020. Why are there so few ethnic minorities in ecology and evolutionary biology? Challenges to inclusion and the role of sense of belonging. Soc. Psychol. Educ. 23:449–77. doi: 10.1007/s11218-019-09538-x

[4] ↑ Sadler, P. M., Sonnert, G., Hazari, Z., and Tai, R. 2012. Stability and volatility of STEM career interest in high school: a gender study. Sci. Educ. 96:411–27. doi: 10.1002/sce.21007

[5] ↑ Blotnicky, K. A., Franz-Odendaal, T., French, F., and Joy, P. 2018. A study of the correlation between STEM career knowledge, mathematics self-efficacy, career interests, and career activities on the likelihood of pursuing a STEM career among middle school students. IJ STEM Ed . 5:22. doi: 10.1186/s40594-018-0118-3

[6] ↑ Meaders, C., Gardiner, J., Wynns, S., Nigam, S., and Harris, J. (2023). A comic-based conservation lesson plan diversifies middle school student conceptions of scientists. J. Res. STEM Educ. 9:20–45. doi: 10.51355/jstem.2023.127

[7] ↑ Spiegel, A. N., McQuillan, J., Halpin, P., Matuk, C., and Diamond, J. 2013. Engaging teenagers with science through comics. Res. Sci. Educ. 43:2309–26. doi: 10.1007/s11165-013-9358-x

[8] ↑ Chambers, D. W. 1983. Stereotypic images of the scientist: the draw-a-scientist test. Sci. Educ. 67:255–65. doi: 10.1002/sce.3730670213

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Collection  12 March 2021

2020 Top 50 Life and Biological Sciences Articles

We are pleased to share with you the 50 most downloaded Nature Communications articles* in the life and biological sciences published in 2020. (Please note we have a separate collection on the Top 50 SARS-CoV-2 papers .) Featuring authors from around the world, these papers highlight valuable research from an international community.

Browse all Top 50 subject area collections here .

* Data obtained from SN Insights (based on Digital Science's Dimensions) and has been normalised to account for articles published later in the year.

Vitamin D metabolites and the gut microbiome in older men

Here, the authors investigate associations of vitamin D metabolites with gut microbiome in a cross-sectional analysis of 567 elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and find larger alpha-diversity correlates with high 1,25(OH)2D and high 24,25(OH)2D and higher ratios of activation and catabolism.

• Robert L. Thomas
• Lingjing Jiang
• Deborah M. Kado

The misuse of colour in science communication

The accurate representation of data is essential in science communication, however, colour maps that visually distort data through uneven colour gradients or are unreadable to those with colour vision deficiency remain prevalent. Here, the authors present a simple guide for the scientific use of colour and highlight ways for the scientific community to identify and prevent the misuse of colour in science.

• Fabio Crameri
• Grace E. Shephard
• Philip J. Heron

Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.

• Grégoire Chevalier
• Eleni Siopi
• Pierre-Marie Lledo

The default network of the human brain is associated with perceived social isolation

Here, using pattern-learning analyses of structural, functional, and diffusion brain scans in ~40,000 UK Biobank participants, the authors provide population-scale evidence that the default network is associated with perceived social isolation.

• R. Nathan Spreng
• Emile Dimas
• Danilo Bzdok

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test

Patients whose disease is diagnosed in its early stages have better outcomes. In this study, the authors develop a non invasive blood test based on circulating tumor DNA methylation that can potentially detect cancer occurrence even in asymptomatic patients.

• Xingdong Chen
• Jeffrey Gole

Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure

Regulatory and coding regions of genes are shaped by evolution to control expression levels. Here, the authors use deep learning to identify rules controlling gene expression levels and suggest that all parts of the gene regulatory structure interact in this.

• Christoph S. Börlin
• Aleksej Zelezniak

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

• Angkana T. Huang
• Bernardo Garcia-Carreras
• Derek A. T. Cummings

Biomineral armor in leaf-cutter ants

Biomineral armour is known in a number of diverse creatures but has not previously been observed in insects. Here, the authors report on the discovery and characterization of high-magnesium calcite armour which overlays the exoskeletons of leaf-cutter ants.

• Chang-Yu Sun
• Cameron R. Currie

Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation

Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

• Jasper Iske
• Midas Seyda
• Stefan G. Tullius

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

Preclinical evidence suggests that a fasting mimicking diet (FMD) can make cancer cells more vulnerable to chemotherapy, while protecting normal cells. In this randomized phase II clinical trial of 131 patients with HER2 negative early stage breast cancer, the authors demonstrate that FMD is safe and enhances the effects of neoadjuvant chemotherapy on radiological and pathological tumor response.

• Stefanie de Groot
• Rieneke T. Lugtenberg
• Dutch Breast Cancer Research Group (BOOG)

Aerobic microbial life persists in oxic marine sediment as old as 101.5 million years

The discovery of aerobic microbial communities in nutrient-poor sediments below the seafloor begs the question of the mechanisms for their persistence. Here the authors investigate subseafloor sediment in the South Pacific Gyre abyssal plain, showing that aerobic microbial life can be revived and retain metabolic potential even from 101.5 Ma-old sediment.

• Yuki Morono
• Fumio Inagaki

The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice

Auxin-inducible degron systems can be leaky and require high doses of auxin. Here the authors establish AID2 which uses an OsTIR1 mutant and the ligand 5-Ph-IAA to overcome these problems and establish AID-mediated target depletion in mice.

• Aisha Yesbolatova
• Yuichiro Saito
• Masato T. Kanemaki

Origin and cross-species transmission of bat coronaviruses in China

Bats are a likely reservoir of zoonotic coronaviruses (CoVs). Here, analyzing bat CoV sequences in China, the authors find that alpha-CoVs have switched hosts more frequently than betaCoVs, identify a bat family and genus that are highly involved in host-switching, and define hotspots of CoV evolutionary diversity.

• Alice Latinne
• Peter Daszak

Multivariate genomic scan implicates novel loci and haem metabolism in human ageing

Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

• Paul R. H. J. Timmers
• James F. Wilson
• Joris Deelen

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Mircobial symbionts of mosquitoes can affect transmission of human pathogens. Here, Herren et al . identify a microsporidian symbiont in Anopheles gambiae that impairs transmission without affecting mosquito fecundity or survival.

• Jeremy K. Herren
• Lilian Mbaisi
• Steven P. Sinkins

Gene editing and elimination of latent herpes simplex virus in vivo

Herpes simplex virus establishes lifelong latency in ganglionic neurons, which are the source for recurrent infection. Here Aubert et al. report a promising antiviral therapy based on gene editing with adeno-associated virus-delivered meganucleases, which leads to a significant reduction in ganglionic HSV loads and HSV reactivation.

• Martine Aubert
• Daniel E. Strongin
• Keith R. Jerome

A predictive index for health status using species-level gut microbiome profiling

A biologically-interpretable and robust metric that provides insight into one’s health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, the authors introduce a species-level index that predicts the likelihood of having a disease.

• Vinod K. Gupta
• Jaeyun Sung

Bacterial nanotubes as a manifestation of cell death

Bacterial nanotubes and other similar membranous structures have been reported to function as conduits between cells to exchange DNA, proteins, and nutrients. Here the authors provide evidence that bacterial nanotubes are formed only by dead or dying cells, thus questioning their previously proposed functions.

• Jiří Pospíšil
• Dragana Vítovská
• Libor Krásný

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.

• Zhigang Liu
• Xiaoshuang Dai

Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells

Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

• Tapash Jay Sarkar
• Marco Quarta
• Vittorio Sebastiano

Mitochondrial TCA cycle metabolites control physiology and disease

Mitochondrial metabolites contribute to more than biosynthesis, and it is clear that they influence multiple cellular functions in a variety of ways. Here, Martínez-Reyes and Chandel review key metabolites and describe their effects on processes involved in physiology and disease including chromatin dynamics, immunity, and hypoxia.

• Inmaculada Martínez-Reyes
• Navdeep S. Chandel

A deep learning model to predict RNA-Seq expression of tumours from whole slide images

RNA-sequencing of tumour tissue can provide important diagnostic and prognostic information but this is costly and not routinely performed in all clinical settings. Here, the authors show that whole slide histology slides—part of routine care—can be used to predict RNA-sequencing data and thus reduce the need for additional analyses.

• Benoît Schmauch
• Alberto Romagnoni
• Gilles Wainrib

Circadian regulation of mitochondrial uncoupling and lifespan

Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

• Matt Ulgherait
• Mimi Shirasu-Hiza

Circadian control of brain glymphatic and lymphatic fluid flow

Glymphatic function is increased during the rest phase while more cerebrospinal fluid (CSF) drains directly to the lymphatic system during the active phase. The water channel aquaporin-4 supports these endogenous, circadian rhythms in CSF distribution.

• Lauren M. Hablitz
• Virginia Plá
• Maiken Nedergaard

Brain-inspired replay for continual learning with artificial neural networks

One challenge that faces artificial intelligence is the inability of deep neural networks to continuously learn new information without catastrophically forgetting what has been learnt before. To solve this problem, here the authors propose a replay-based algorithm for deep learning without the need to store data.

• Gido M. van de Ven
• Hava T. Siegelmann
• Andreas S. Tolias

Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy

Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.

• Charles P. Couturier
• Shamini Ayyadhury
• Kevin Petrecca

Deep learning for genomics using Janggu

Deep learning is becoming a popular approach for understanding biological processes but can be hard to adapt to new questions. Here, the authors develop Janggu, a python library that aims to ease data acquisition and model evaluation and facilitate deep learning applications in genomics.

• Wolfgang Kopp
• Altuna Akalin

Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues

Tissue clearing has revolutionised histology, but limited penetration of antibodies and stains into thick tissue segments is still a bottleneck. Here, the authors characterise optically cleared tissue as an electrolyte gel and apply this knowledge to stain the entirety of thick tissue samples.

• Etsuo A. Susaki
• Chika Shimizu
• Hiroki R. Ueda

Sestrins are evolutionarily conserved mediators of exercise benefits

Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

• Myungjin Kim
• Alyson Sujkowski
• Jun Hee Lee

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers

Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.

• Maira Di Tano
• Franca Raucci
• Valter D. Longo

Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.

• Nayoung Kim
• Hong Kwan Kim
• Hae-Ock Lee

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

• Gurnit Atwal
• PCAWG Consortium

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression

Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

• Anna S. E. Cuomo
• Daniel D. Seaton
• Oliver Stegle

Trajectory-based differential expression analysis for single-cell sequencing data

Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models.

• Koen Van den Berge
• Hector Roux de Bézieux
• Lieven Clement

Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome

Here, Pasolli et al. perform a large-scale genome-wide comparative analysis of publicly available and newly sequenced food and human metagenomes to investigate the prevalence and diversity of lactic acid bacteria (LAB), indicating food as a major source of LAB species in the human gut.

• Edoardo Pasolli
• Francesca De Filippis
• Danilo Ercolini

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia

Ancient DNA analysis of early European farmers has found a high level of genetic affinity with present-day Sardinians. Here, the authors generate genome-wide capture data for 70 individuals from Sardinia spanning the Middle Neolithic to Medieval period to reveal relationships with mainland European populations shifting over time.

• Joseph H. Marcus
• Cosimo Posth
• John Novembre

Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome

Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

• Matthias Arnold
• Kwangsik Nho
• Gabi Kastenmüller

Integrative pathway enrichment analysis of multivariate omics data

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

• Marta Paczkowska
• Jonathan Barenboim

Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice

Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

• Stephanie J. Alexopoulos
• Sing-Young Chen
• Kyle L. Hoehn

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects.

• Yann W. Yap
• Patricia M. Rusu
• Adam J. Rose

Multiplexed CRISPR technologies for gene editing and transcriptional regulation

Multiplexed CRISPR technologies have recently emerged as powerful approaches for genetic editing and transcriptional regulation. Here the authors review this emerging technology and discuss challenges and considerations for future studies.

• Nicholas S. McCarty
• Alicia E. Graham
• Rodrigo Ledesma-Amaro

Determining sequencing depth in a single-cell RNA-seq experiment

For single-cell RNA-seq experiments the sequencing budget is limited, and how it should be optimally allocated to maximize information is not clear. Here the authors develop a mathematical framework to show that, for estimating many gene properties, the optimal allocation is to sequence at the depth of one read per cell per gene.

• Martin Jinye Zhang
• Vasilis Ntranos

Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels

Ceramides are a type of sphingolipid (SL) that have been shown to play a role in several metabolic disorders. Here, the authors investigate the effect of SL-production by gut Bacteroides on host SL homeostasis and show that microbiome-derived SLs enter host circulation and alter ceramide production.

• Elizabeth L. Johnson
• Stacey L. Heaver
• Ruth E. Ley

Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland

European populations underwent strong genetic changes during the Neolithic. Here, Furtwängler et al. provide ancient nuclear and mitochondrial genomic data from the region of Switzerland during the end of the Neolithic and the Early Bronze Age that reveal a complex genetic turnover during the arrival of steppe ancestry.

• Anja Furtwängler
• A. B. Rohrlach
• Johannes Krause

Brain insulin sensitivity is linked to adiposity and body fat distribution

Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

• Stephanie Kullmann
• Vera Valenta
• Martin Heni

Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

• Filipa C. Simões
• Thomas J. Cahill
• Paul R. Riley

Sexual-dimorphism in human immune system aging

Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

• Eladio J. Márquez
• Cheng-han Chung

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

• Tatsuya Tsukui
• Kai-Hui Sun
• Dean Sheppard

Pathway and network analysis of more than 2500 whole cancer genomes

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

• Matthew A. Reyna

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4 + T cells to cytokines

Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an ‘effectorness gradient’ is depicted by a transcriptional continuum, which shapes the downstream genetic programs.

• Eddie Cano-Gamez
• Blagoje Soskic
• Gosia Trynka

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