Structural racism is a form of racism that is embedded in the laws, policies, institutions, and practices that provide advantages to certain racial groups while disadvantaging others.1 Although structural racism is well documented as an important contributor to health care inequities, its effects on medical students, trainees, and faculty have received less attention. We believe aversive racism is a critical and overlooked contributor to structural racism in academic medicine.
“We want diversity, but we also want qualified people.”
Aversive racism, an established construct in social psychology, is defined as exhibiting racist tendencies while denying that one’s thoughts, behaviors, or motives are racist.2 According to John Dovidio and Samuel Gaertner, who defined the concept in the 1990s, aversive racism occurs when people endorse egalitarian values in principle, but when faced with ambiguous situations or unclear guidelines, discriminate against people from historically marginalized groups while rationalizing or justifying their actions on the basis of factors other than race.2 Aversive racism is pervasive in both academic medicine and society at large. In areas ranging from medical school admissions decisions to executive leadership appointments, aversive racism in academic medicine impedes diversity, equity, and inclusion efforts. Understanding this construct and developing strategies for combating aversive racism will help diversify academic medicine and reduce health disparities.
“If he just kept his head down and stayed under the radar, he would be a lot more successful.”
Aversive racism undermines the substantial investments in antiracism initiatives that many institutions have made to combat structural racism. One manifestation of aversive racism in academic medicine is ongoing inequalities in the promotion of faculty from historically marginalized groups.3 Although Asian students and students from groups that are underrepresented in medicine (URM) made up 31% of U.S. medical school graduating classes in 2018, Asian and URM faculty accounted for only 18 to 19% of full professors in perioperative and primary care specialties.3
The residency application process is another area where aversive racism has substantial effects. Program directors may unwittingly rationalize the selection of a less-diverse incoming residency class by lamenting the lack of qualified applicants from diverse backgrounds, rather than acknowledging the barriers facing URM applicants in the selection process.4 URM students are less likely to receive honors grades on their clinical clerkships and are awarded fewer honor-society memberships upon graduation than White students.4 The grades assigned during third- and fourth-year clerkships are more subjective and more susceptible to bias than the pass–fail grades commonly used during the preclinical years.4 This system impedes URM students’ chances of matching into competitive residency programs, thereby perpetuating disparities in academic medicine.
The same mechanisms are at play when URM candidates for leadership positions are evaluated less favorably than their equally qualified White peers. Using subjective phrases such as “not a good fit,” “not what we’re looking for,” or “I’m going with my gut on this” allows an evaluator’s biases to hold sway when guidelines are ambiguous.
“She was a promising candidate, but she just wasn’t the right fit for our department.”
In the language of social psychology and sociology, aversive racism results from the interplay of normal cognitive processes, including social dominance, implicit bias, and in-group favoritism.1,2,5 Aversive racism flourishes when decisions are left to judgment calls by people who don’t recognize the effects of intergroup dynamics on their thought processes. Social dominance theory explains the mechanisms behind the inevitability of group-based hierarchies. According to this theory, society and social systems have at least two groups — the dominant or top group, which has the most of whatever attributes or resources society deems valuable (e.g., power or money), and the less-dominant group or groups.5
When it comes to race, the hierarchy is upheld by institutional racism (racial discrimination within financial, legal, and education systems, among others); interpersonal racism (discrimination, overt or aversive, by members of the dominant group against members of less-dominant groups); and internalized racism (conscious or unconscious acceptance of the racial hierarchy by members of less-dominant groups).1 To avoid sanctions or to move up the hierarchy, members of less-dominant groups tend to show deference to members of the dominant group, a process that reinforces and perpetuates this hierarchy, whereas people at the top often deny that a group-based hierarchy exists.5
The hierarchy is maintained in part by societal myths that legitimize inequity. People at the top of the hierarchy not only have a stronger preference for hierarchical societies than members of less-dominant groups, but they are more likely to endorse such legitimizing myths.5 In academic medicine, myths that legitimize inequity include the concept of a meritocracy — the idea that success is based primarily on a person’s abilities, which ignores the effects of structural racism on opportunities. Implicit bias — the unconscious, automatic association of negative stereotypes or attitudes with a particular group — also helps maintain inequality.2
Implicit bias works in concert with in-group favoritism, which entails preferring members of one’s own group to outsiders.2 When faculty members interview residency applicants, for example, in-group favoritism manifests when an interviewer ranks students from a school they personally attended higher than they otherwise would have, thereby disadvantaging other applicants. Aversive racism occurs when people fail to recognize the influence of these forces on their judgments. Social dominance, implicit bias, and in-group favoritism intersect within academic medicine, resulting in aversive racism that affects the judgments of decision makers and contributes to structural racism in medicine.
“They are clearly qualified for the job, but they’re too ‘in your face’; I’m worried people won’t respect their opinions.”
Behaviors that reflect aversive racism are harmful to people from historically marginalized groups but maintain the positive self-image of the people carrying them out.2 For example, Dovidio and colleagues had White college students evaluate hypothetical university applicants.2 Participants had previously completed a questionnaire, which was used to stratify them into high-prejudice and low-prejudice groups (although even the high-prejudice students ranked low on measures of prejudice as compared with the general population). Participants then evaluated admissions packets of Black and White applicants that were constructed to reflect high, low, or ambiguous academic achievement. There was no difference between high- and low-prejudice participants’ evaluations of high- or low-achieving applicants, regardless of the applicant’s race. When evaluating applicants with ambiguous achievement records, however, high-prejudice participants rejected Black applicants significantly more often than they rejected White applicants. The investigators concluded that the ambiguity in the records allowed participants to justify their admissions decisions to themselves by focusing on the application’s weaknesses.
“But I voted for Obama.”
The Covid-19 pandemic unmasked the structural racism that exists throughout the United States. Academic medicine isn’t immune to the scourge of White supremacy and structural racism. No matter how many institutional statements are made condemning racist acts, we cannot expect to overcome structural racism within academic medicine until we acknowledge the reality of aversive racism. In addition to examining their role in upholding a race-based hierarchy, members of the academic medicine community must do the difficult work required to challenge their own conscious and subconscious thoughts and actions that contribute to aversive racism.2 This work includes unlearning implicit biases, countering negative stereotypes and legitimizing myths, and eliminating the use of automatic, biased judgments to make decisions, all of which will require extensive and deliberate practice.2
Future work will involve developing evidence-based anti–aversive-racism programs to break down academic medicine’s unspoken racial hierarchy, which contributes to structural racism in health care.1,2,5 Effective programs would help normalize antiracist attitudes; provide continuous and effective antiracism education for trainees, faculty, executive leaders, and staff; and refashion existing systems that favor the “in group.” Finally, academic institutions could capitalize on the good intentions and desires of progressive academic leaders to overcome their aversive racist thoughts and actions.2 We hope academic leaders will lead the charge by acknowledging the need to openly address aversive racism within broader efforts to dismantle structural racism in medicine.
Along-standing tradition in American medicine is to mention a patient’s race or ethnicity at the beginning of oral case presentations or written chart notes, particularly those by medical students or trainees. For example, an oral presentation might begin, “A 50-year-old Black man presents with intermittent chest pain” or “This 70-year-old White woman presents with increasing dyspnea.” Given persistent racism in medicine and the growing recognition that racial and ethnic categories are socially constructed and not biologically coherent, the practice of mentioning race or ethnicity immediately in case presentations — alongside age and sex — is worth revisiting.
According to a survey that one of us conducted more than a decade ago, medical schools varied considerably in their perspectives on mentioning race or ethnicity at the beginning of case presentations.1 Overall, 11% of schools taught students to mention race routinely, 63% taught them to include it selectively, 9% discouraged the practice, and 18% simply did not address the issue. Most schools (62%), however, acknowledged that residents at their institutions frequently mentioned race in the first sentence of case presentations, regardless of the school’s stated position. Whether the prevalence of this practice has changed substantially is unclear; recent discussions with medical educators lead us to believe that it has decreased somewhat, but that the practice remains common at some institutions.
What are the fundamental objectives of oral presentations and written notes? Oral case presentations are tools for communication with other clinicians who are or will be involved in the patient’s care; their content generally unfolds in a standardized sequence that is anticipated by listeners and intended to facilitate accurate understanding of the case. Particularly when patients have new clinical problems, the initial portion of the presentation triggers the process of diagnostic clinical reasoning: almost instantly, listening clinicians begin to formulate diagnostic hypotheses, some of which are perceived as more likely than others. Written chart notes serve a similar purpose and also provide a historical record, so that clinical teams need not rely on memory. For students and residents, there is an additional educational objective: oral and written case presentations are evaluated by supervising clinician-educators to assess skills in information gathering, clinical reasoning, and communication.
The question at hand is whether mentioning race or ethnicity at the beginning of an oral presentation or chart note enhances or undermines these objectives. Some proponents may argue that this information suggests initial biologic probabilities that are immediately relevant for hypothesis generation, diagnosis, and treatment. For example, proponents may cite genetic examples such as sickle cell disease (far more prevalent among Black Americans than in other U.S. racial or ethnic groups) and hemochromatosis (far more prevalent among White populations than in other racial or ethnic groups). Other proponents may argue that race or ethnicity should be acknowledged immediately even if it has little diagnostic or therapeutic relevance for most patients — that there is a benefit to processing an individual patient’s history and physical findings through the lens of race or ethnicity, given the impact of racism on health.
We believe these arguments are problematic, for reasons that fall into two main categories. First, routine inclusion of race or ethnicity at the beginning of a case presentation reinforces the still-prevalent but mistaken belief that race or ethnicity is a robust surrogate for genetic or innate biologic predisposition to disease.2,3 Racial and ethnic groups are not static, uncontroversial categories; because they are socially constructed, they are fluid and evolve over time. Moreover, commonly used racial and ethnic categories are often confusing mixtures of skin color, geographic location, ancestry, culture, and religion. Although there may be a strong statistical correlation between patient-identified race or ethnicity and a particular clinical diagnosis in a specific geographic area at a given point in time, these rare exceptions — which are often mediated by ancestry4 — should not drive the standard template for case presentations. Moreover, immediately mentioning race or ethnicity may predispose clinicians to premature diagnostic closure, a cognitive error in clinical reasoning. The subliminal effect of classifying a patient by race or ethnicity before hearing or reading about the patient’s illness history and physical findings may result in incorrect inclusion or exclusion of diagnostic hypotheses.
Second, immediately mentioning race or ethnicity may result in conscious or unconscious demographic or cultural stereotyping. Differences in demographic features such as socioeconomic status often reflect systemic racism, but they are statistical constructs that do not necessarily apply to an individual patient. Similarly, immediately mentioning race or ethnicity may trigger implicit and potentially inaccurate inferences about a patient’s beliefs or values, based on stereotypical assumptions about the patient’s cultural background. Even if certain beliefs are prevalent in certain groups at a given point in time, they are not necessarily held by all members of a given group.
In our view, the arguments against inclusion of race or ethnicity at the beginning of case presentations are more persuasive than arguments for including it. Avoiding the routine use of race or ethnicity as an immediate cognitive framing device increases the probability that the listener or reader — and perhaps even the person presenting the case — will initiate clinical reasoning and clinical decision making in an unbiased fashion. Later in the case presentation, clinicians can review strong associations between suspected diagnoses and ancestral groups and can propose appropriate testing for genetic or biologic markers — on the basis of all clinically relevant information and not simply race or ethnicity. Some clinicians may nevertheless choose to include racial, ethnic, or ancestral categories at the beginning of case presentations in carefully selected clinical scenarios, usually when the category is thought to suggest a specific diagnosis with near certainty. These exceptions, however, do not undermine the fundamental point that in general, diagnostic probabilities associated with race, ethnicity, or even ancestry are not decisive and that these labels are often entangled with biases and stereotypes.2
We are not advocating a “color blind” approach to clinical decision making and health care, which would most likely reinforce existing biases and health inequities.2 To omit racial and ethnic labels early in the case narrative is not to ignore the growing recognition that racism can affect health through biologic mechanisms or to downplay the influence of systemic racism on the provision of medical care. Accordingly, clinically relevant and patient-specific socioeconomic considerations, cultural beliefs, and race-related barriers to high-quality health care should be acknowledged and addressed later in the case presentation.
In a recent article, a multidisciplinary group of authors enumerated the ways in which preclinical curricula in medical schools misrepresent race and propagate physician bias.3 Their examples included inaccurate conflation of race and ancestry, pathologizing race and presenting race-based differences in disease rates without providing proper context, and teaching race-based clinical guidelines without acknowledging their controversial elements. Mentioning race or ethnicity at the beginning of case presentations represents a similar problem in the clinical years of medical training: it reinforces the misrepresentations of race or ethnicity to which students are exposed in the preclinical years.
In his thought-provoking book Black Man in a White Coat, physician Damon Tweedy describes his reaction when, during his residency, a colleague began an oral case presentation with, “Mr. Gary Warren is a fifty-five-year-old African American male.” Tweedy writes, “This three-pronged age-race-gender description was the traditional way to present a case. Once again the only black person in the room, I wondered if anyone else there had ever given thought to this method and shared any of my concerns. … [W]hy did it matter so much whether the patient was white, black, or something else? Did this way of presenting cases assume that race should automatically color the way a doctor approached a patient’s chest pain or achy stomach?”5
Tweedy appears troubled by the inclusion of race at the beginning of case presentations; we share his concern. We believe that in medical schools and residency programs where this practice remains prevalent, clinician-educators should acknowledge its potentially problematic impact on clinical reasoning and use it as a springboard for discussions of stereotyping and racism in medical practice.
Human behaviour is at the heart of the climate crisis. Never before has changing this behaviour been quite so important. Drastic reductions in the release of greenhouse gas (GHG) emissions within the next decade is essential. This will require behaviour change within governments, organisations, communities and individuals to transform our existing patterns of production and consumption. Given the scale of the collective changes required, it can be tempting to believe that our own individual choices and behaviours will make a negligible difference. In fact, changes in personal choice behaviours can accumulate to have sizeable beneficial consequences for the climate, especially from the majority of us who lead carbon-intensive lifestyles. This raises the question – how can we harness psychology to change our own behaviour and help others do the same?
The first step is to focus on changing behaviours that have the highest impact. If we narrow our attention to individual actions, those that can most substantially decrease a person’s annual carbon footprint include following a plant-based diet (saves 0.8 tonnes of CO2-equivalents per year), reducing air travel (each return transatlantic flight avoided saves 1.6 tonnes), living car-free (saves 2.4 tonnes) and having smaller families (saves 58.6 tonnes per child). Switching to a green energy supplier and home insulation can also have a modest influence. For a sense of perspective, consider that if everyone in the UK were to switch just one beef or lamb meal a week to a plant-based option, this would result in an 8 per cent reduction in domestic GHG emissions.
Of course, knowing the most impactful personal changes is only part of the story. The next step is to carry them out. From years of unkept new year’s resolutions or diets that haven’t quite gone to plan, we can all appreciate that acting on even the best intentions is not easy. In psychology, this conundrum is referred to as the value-action gap. It refers to the phenomenon whereby our actions do not necessarily correlate with our attitudes (eg, a person might have a positive attitude toward protecting the environment, and yet not be doing anything about it). Much research in promoting pro-environmental behaviour has gone into trying to shift values through increased education and awareness. These interventions inform people about the dangers or costs of a given behaviour, similar to the information I presented above about the impact of different lifestyle choices. Unfortunately, because of the value-action gap, this type of information alone has been largely unsuccessful at convincing individuals to actually change their behaviour. To reduce the gap, we must delve deeper into the root causes of human behaviour.
As social animals, one of our strongest sources of motivation is the people around us. This has been best demonstrated by work examining eating behaviours, which has found that a person’s chance of becoming obese increases by 57 per cent following one of their friends becoming obese. These ‘social contagion’ effects occur because our social worlds create norms or standards that guide our own behaviour. We can leverage these social influences on people’s motivation to help implement long-lasting pro-environmental behaviour change. One way of doing this is through public commitments or ‘pledges’ to undertake a certain behaviour. A popular example is Veganuary where individuals pledge to eat vegan food for the first month of the year. Pledges work best when they are active: ie, when they require a positive action, such as a written statement, and when they are made to people with whom we identify most, known as our ingroup. So, if you would like to try switching to a plant-based diet, why not consider the Veganuary workplace pledge (or a similar initiative involving a public commitment), where you, alongside your office mates, take up the challenge of a meat-free January; even better, why not share your intentions on social media?
Do you need to improve your vegetarian cooking skills, or learn new walking and cycling routes for journeys you commonly take?
Yet, there is often more to behaviour change than increasing motivation. As laid out in a leading theory called the COM-B model of behaviour change, motivation on its own is not enough – rather, to adopt a new behaviour successfully, an individual also requires capacity and opportunity. Here ‘capacity’ refers to the knowledge and skills needed to support a new course of action. For example, in the case of being able to live car-free, this might mean having the ability to confidently ride a bicycle. Meanwhile, ‘opportunity’ relates to the external factors (often beyond a person’s control) that make execution possible. For example, in deciding whether to avoid flying to a holiday destination, opportunity factors would relate to the time and cost constraints of alternative travel options, such as taking the train.
So, if you are determined to make more pro-environmental choices, consider whether there is anything you could learn to help make these changes. Do you need to improve your vegetarian cooking skills, or learn new walking and cycling routes for journeys you commonly take? If you are a manager or run an organisation, you might wish to think through the ways you can increase the opportunity your members have to act pro-environmentally. This could include ensuring there are accessible showers at work for cyclists, and bicycle racks to allow safe storage. Can you organise international meetings via Zoom to help reduce unnecessary air travel? Thinking through the practicalities and gaining new skills that make pro-environmental behaviours possible is as important as the effort one is willing to put in.
Nudges have been shown to be particularly effective at helping people make more environmentally friendly food choices when shopping. An example in this context is by manipulating ‘default options’, which is a way to capitalise on human laziness. This approach involves designing the decision-making scenario so that the desired behaviour requires the least amount of effort, and the undesirable behaviour requires an effortful ‘opt-in’. You can apply this logic to your own behaviour. For example, if you wanted to reduce the amount of meat you eat, you could save your online repeat weekly shopping order so that it contains only plant-based food by default, meaning that extra time and effort will always be needed to add meat to your basket, thus making that behaviour less likely.
The problem comes as the climate-virtuous choice (the donation) is used to morally justify the carbon-intensive behaviour (flying)
Other types of pro-environmental behaviours are underpinned by different psychological processes because they involve infrequent, one-off decisions, such as making the switch to a green energy supplier or opting to avoid air travel. These types of decisions rely more heavily on our slower, rational and deliberative type of reasoning. You might think this would make it easier to avoid temptation and to take the pro-environmental option. However, sometimes the deliberation can lead us astray – for instance, once we have made a climate-virtuous choice, we might use this to justify reductions in our other pro-environmental behaviours, a psychological excuse process that is known as the moral licensing effect.
This effect explains a problematic issue with being able to purchase ‘carbon offsets’. Carbon offsets sell us the opportunity to make a donation to compensate for a carbon-intensive behaviour, such as taking a flight. By financing efforts that will remove emissions from the atmosphere, such as planting trees, these offsets claim to make the initial behaviour carbon-neutral. The impact of these initiatives on emissions are widely disputed but, moreover, these offsets have unintended psychological consequences in that they increase acceptability of the environmental harmful behaviour. The problem comes as the climate-virtuous choice (the donation) is used to morally justify the carbon-intensive behaviour (flying). In other words, by removing the moral burden of these behaviours, they give us the most convenient excuse of all to continue as we are. If you find yourself bargaining or justifying actions with previous good behaviour, you might be succumbing to the moral licensing effect.
All in all, insights from psychology can help ween us off our high-carbon lifestyles. By focusing on non-trivial personal behaviours, as well as understanding the roots of these behaviours, we can more effectively change our own behaviours. Leaders and policymakers too can use psychological insights to devise interventions to help promote long-lasting change. Social pressure, nudges, new skills, as well as practically implementable solutions will all contribute toward achieving these shifts.
It is important to remember, though, that the scope of our behaviour as individuals extends far beyond being consumers. We are also members of communities, employees of companies and part of the electorate. Therefore, voting for political candidates with environmental agendas, joining local lobbying groups and engaging with well-targeted campaigns – especially those directed at the 100 companies responsible for 71 per cent of GHG emissions – are ways we can all as individuals influence societal-level decision-making and build pressure towards much-needed regulation. After all, individual choices do not occur in a vacuum, but are shaped by industry and government regulations, and organisational management. Using our collective power to hold these actors to account is therefore also crucial if we are to succeed in averting climate chaos.
Cities are bastions of opportunity. They are filled with vast numbers of people meeting friends and family, visiting restaurants, museums, concert halls and sporting events, and travelling to and from jobs. Yet many of us who live in cities have occasionally been overwhelmed by the activity. At other times, we might feel ‘alone in the crowd’. For decades, the conflicting experiences of city living have led urbanites and scholars to ask: are cities bad for mental health?
The conventional wisdom and scientific answer for more than half a century has been ‘yes’. This question is becoming increasingly important as global urbanisation unfolds: around two-thirds of the world’s population will live in cities by 2050. Bigger cities, which have more of what makes a city a city, would seem to be particularly bad for mental health. A typical explanation invokes factors such as noise, crime and short, callous social interactions (think about New York City’s reputation for rudeness) to argue that big cities create sensory and social burdens that city dwellers constantly have to combat psychologically. While this explanation appears to be supported by some evidence that rural areas might, on the whole, have lower depression rates than cities, there is scantevidence that these particular factors cause higher depression rates in cities, and no investigation of how bigger cities compare with smaller cities.
As it turns out, the relationship between cities and mental health is more complex than conventional explanations suggest. A study that I recently conducted with my colleagues at the University of Chicago demonstrates that larger cities in the United States actually have substantially lower rates of depression than smaller cities. Our team looked at depression rates calculated by the Centers for Disease Control and Prevention, other depression rates from the Substance Abuse and Mental Health Services Administration, and additional rates estimated by us, using geolocated Twitter posts and a machine-learning algorithm. Despite the fact that differing methods were used to assess depression rates – some were based on clinical criteria, one involved phone surveys, etc – and each source included different (though overlapping) sets of US cities, we found a consistent result. Specifically, a doubling of city population was associated with a 12 per cent decrease in depression rates, on average.
Lower rates of depression in larger cities seem to be a consequence of how cities are built and can be explained by a new scientific view of cities called urban scaling theory. Urban scaling theory has helped us understand why some experiences are common to all urbanites and provides us with new perspectives on how these collective experiences influence innovation, crime, economic productivity and, now, mental health.
For me, the hustle and bustle of life in the biggest cities became especially salient when I first travelled from my hometown of New York City to Chicago for college. When I stepped off the plane, the slower pace and midwestern ease of Chicago seemed to hang in the air. I found myself immediately slowing down and acclimatising to the somewhat more relaxed lifestyle of a metropolitan area of 9.6 million (compared with the New York metro area’s 20.1 million).
The infrastructure networks of cities are similar to the human circulatory system, and the branching patterns of trees
This experience was, in all likelihood, due to my internalisation of the fact that the pace of life is faster in bigger cities, a fact that is predicted quantitatively and precisely by urban scaling theory. In particular, a city with twice as many people as another city will have an approximately 12 per cent faster pace of life (the same percentage by which depression rates decrease). What does this mean concretely? Research shows that people literally walk faster in larger cities. People in towns with around 10,000 inhabitants tend to walk at a leisurely pace of 3.5 km per hour, while people in cities of around 1 million tend to walk at a pace of 5.8 km per hour, almost a jog.
In addition to walking speed, studies have found evidence that invention, job diversity, social interactions, restaurant diversity and crime also increase in bigger cities, and also follow the 12 per cent rule. There is some variability from city to city, but the average increase is 12 per cent per doubling of the population. These studies show that, in general, cities foster greater social interaction (both positive and negative), diversity, culture and generation of ideas. These principles are summarised by the 12 per cent rule (and a few others) and seem to apply across cultures and over time, as far back as 1150 BCE.
How is it possible that we can make such precise predictions given all the factors that make each city and neighbourhood unique? At its core, urban scaling theory is a collection of mathematical models explaining how cities are organised. These models, to borrow a phrase from Plato, ‘bring together in one idea the scattered particulars’ of modern city living, and explain and contextualise some of the experiences that city dwellers have every day. One key insight is that the physical layouts of cities follow simple rules. Cities have layered infrastructure networks – made up of electrical lines, streets, railway lines, etc – with larger components branching off into smaller ones that serve smaller groups of people. In this sense, the infrastructure networks of cities are similar to the human circulatory system’s network of branching arteries, veins and capillaries, and the branching patterns of trees. To add to this, people’s semirandom movement through cities is constrained by these infrastructure networks. This means that we can borrow some mathematical tools from physics to construct equations that describe how people move through cities.
With a few additional considerations, the equations of urban scaling theory ask what happens when we balance the costs and benefits associated with the movement of individuals, goods and information over cities’ infrastructure networks. While the maths is complicated, the results are simple relationships between the size of a city’s population and a variety of urban metrics. This is where the prediction of a 12 per cent increase in social metrics such as crime and innovation with a doubling of city size comes from: it is the result of how cities’ infrastructure networks are built and facilitate interactions between the people who move through them.
With regard to depression, the most important insight is that larger cities facilitate more social interactions. And yes, this too follows the 12 per cent rule. To ground this in some hypothetical numbers, if residents of a city of 1 million people averaged 43 social contacts within the same city, then residents of a city of 10 million people would be expected to average 63 social contacts. Why is this important for depression? For about 10 years, we have known that the number of social contacts people have is strongly associated with the risk for depression: the more people you interact with, the lower your risk of experiencing depressive symptoms. Given this, it makes sense that we have found that depression rates are lower in larger cities, and that this reduction in depression rates follows the 12 per cent rule.
The character of a city, the collective influence of its inhabitants, hangs in the air
This observation has profound implications for how we think about depression. In the context of an ongoing global pandemic, a notable one is that depression within cities can be partly understood as a collective ecological phenomenon. Individual factors are of course important for any one person’s experience with depression, but so is the larger social network in which people are embedded. Unfortunately, we still do not fully understand the exact dynamics that connect social interactions to depression. However, my research suggests that the effect of social interactions is cumulative: close, supportive friendships and family relationships might be more important than passing interactions with strangers, but it is likely that there is more of both (and every other type of social interaction) in bigger cities.
Importantly, the physical environment of the city – its roads, train and bus lines, sidewalks and bike paths – shapes these social networks. Specifically, at the level of entire cities, infrastructure facilitates the delivery of goods, services and information, which help support all of the opportunities that cities have to offer. At the same time, these infrastructure networks allow people to move throughout the city to access these opportunities and, as a result, they also facilitate opportunities for a greater diversity and number of social interactions.
In this sense, it is true that the character of a city, the collective influence of its inhabitants, hangs in the air, ready to have an effect on whoever is around to breathe it in.
This analogy takes on a more concrete meaning with respect to COVID-19 – which, unsurprisingly (since social contact facilitates airborne transmission), follows the same 12 per cent rule in the speed at which it spreads through cities. As is the case with infectious diseases such as COVID-19, there is a strong rationale for frequent, local measurements of depression rates. Depressive disorders appear to be increasingly prevalent, are extremely debilitating, and cost the global economy billions of dollars each year in lost economic production. I suspect such a tracking effort for depression would reveal better ways of distributing mental healthcare access to the communities that need it most.
In addition, repeated local tracking could pave the way for better understanding other mental health conditions. Some of these, such as anxiety, are highly comorbid with depression and probably follow similar patterns. Others, such as schizophrenia or autism, might show different patterns across cities of differing sizes. Such tracking might also help us understand why depression rates are lower in some rural areas despite the fact that social networks are generally smaller. Perhaps in rural areas, higher-quality social interactions make up for a lack of quantity, while in large cities quantity makes up for reduced quality?
Cities have historically had a bad reputation for mental and physical health. However, in a fast-urbanising world, the higher social connectivity of larger cities could have positive influences on city dwellers’ mental health. While more social contacts make containing epidemics such as COVID-19 harder, they also lead to greater economic opportunity, more political and technological innovation, and, apparently, lower rates of depression. As more people live in cities every year, it is important that we acknowledge, measure and internalise how the physical places we inhabit – and the people we share those spaces with – influence our wellbeing in ways we might not expect.
The molecular signaling systems of complex cells are nothing like simple electronic circuits. The logic governing their operation is riotously complex — but it has advantages.6
Biologists often try to understand how life works by making analogies to electronic circuits, but that comparison misses the unique qualities of cellular signaling systems.Olena Shmahalo/Quanta Magazine
Back in 2000, when Michael Elowitz of the California Institute of Technology was still a grad student at Princeton University, he accomplished a remarkable feat in the young field of synthetic biology: He became one of the first to design and demonstrate a kind of functioning “circuit” in living cells. He and his mentor, Stanislas Leibler, inserted a suite of genes into Escherichia coli bacteria that induced controlled swings in the cells’ production of a fluorescent protein, like an oscillator in electronic circuitry.
It was a brilliant illustration of what the biologist and Nobel laureate François Jacob called the “logic of life”: a tightly controlled flow of information from genes to the traits that cells and other organisms exhibit.
But this lucid vision of circuit-like logic, which worked so elegantly in bacteria, too often fails in more complex cells. “In bacteria, single proteins regulate things,” said Angela DePace, a systems biologist at Harvard Medical School. “But in more complex organisms, you get many proteins involved in a more analog fashion.”
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Biologists thought that the regulatory systems in cells might obey something like the simple binary logic of electronic circuits. Then experiments showed that the versatility of the real “logic of life” lies in its graded complexity.
Recently, by looking closely at the protein interactions within one key developmental pathway that shapes the embryos of humans and other complex animals, Elowitz and his co-workers have caught a glimpse of what the logic of complex life is really like. This pathway is a riot of molecular promiscuity that would make a libertine blush, where the component molecules can unite in many different combinations. It might seem futile to hope that this chaotic dance could convey any coherent signal to direct the fate of a cell. Yet this sort of helter-skelter coupling among biomolecules may be the norm, not some weird exception. In fact, it may be why multicellular life works at all.
“Biological cell-cell communication circuits, with their families of promiscuously interacting ligands and receptors, look like a mess and use an architecture that is the opposite of what we synthetic biologists might have designed,” Elowitz said.
Yet this apparent chaos of interacting components is really a sophisticated signal-processing system that can extract information reliably and efficiently from complicated cocktails of signaling molecules. “Understanding cells’ natural combinatorial language could allow us to control [them] with much greater specificity than we have now,” he said.
In this time-lapse video, bacteria in the channels of a microfluidics chip produce an orderly succession of fluorescent proteins under the control of a “repressilator,” an inserted genetic circuit. This kind of genetic control is much harder to establish in complex cells because their molecular signaling is more elaborate.
The emerging picture does more than reconfigure our view of what biomolecules in our cells are up to as they build an organism — what logic they follow to create complex life. It might also help us understand why living things are able to survive at all in the face of an unpredictable environment, and why that randomness permits evolution rather than frustrating it. And it could explain why molecular medicine is often so hard: why many candidate drugs don’t do what we hoped, and how we might make ones that do.
Messengers, Not the Messages
If you were designing a machine or an electronic circuit, it would be folly to model it after a cell. The components of cells are for the most part not carefully arranged and assembled, but are instead just floating and mixing inside the cell membrane like an unruly, jostling crowd. Yet somehow, it works.
The tidy, traditional explanation is that although the protein molecules that make up most of a cell’s working parts are constantly bumping into one another, they treat nearly all of these encounters with indifference. Only when a protein meets another molecule that meshes exactly with an exquisitely sculpted part of its surface do the two lock together and interact. These processes of precise molecular recognition maintain clear lines of communication within cells and keep them running.
Michael Elowitz, a systems biologist at the California Institute of Technology, sees evidence that combinatorial rules might be a “design principle” of the molecular wiring of cells.Jeff Lewis/AP Images for HHMI
The only problem with this story is that it is wrong. Although many proteins do exhibit selective molecular recognition, some of the ones most central to the workings of our eukaryotic cells are far less picky.
Take the growth factor proteins called BMPs, which regulate how cells proliferate and differentiate into various tissues by directing them to turn sets of genes on and off. Their name comes from “bone morphogenetic protein,” because the first-known gene for one was originally thought to encode a protein involved in bone formation.
But although it is indeed involved in that — malfunctions in BMP production are implicated in bone-growth diseases — the idea that bone growth is the function of BMP proteins has long since proved illusory. One type of BMP is involved in the developmental process called gastrulation, which happens around 14 days after fertilization in human embryos, when cells start to specialize into different tissue types and the embryo changes from a clump of cells into a far more complex structure. Later, BMPs are also expressed in cartilage, the kidneys, the eyes and the early brain, and they guide the development of those tissues.
The reality is that the function of BMPs cannot be defined by their effects on the phenotype (that is, on traits). They mediate communications between cells, but what that communication triggers can be totally different in different types of cells, or in the same cell type at a different stage of development. BMPs are messengers, not the messages.
What Elowitz and others are now bringing to light is how BMPs pull off this trick of being so mercurial while also behaving predictably enough for organisms to stake their lives on them. These qualities seem to emerge from the layers upon layers of complexity in the composition of the BMP system, and the flexible, variable affinities of those elements for one another. Paradoxically, the complexity makes the system both more precise and more reliable.
Biological cell-cell communication circuits … use an architecture that is the opposite of what we synthetic biologists might have designed.
Michael Elowitz, California Institute of Technology
Mammals have genes that encode 11 or more distinct BMP proteins, each with a slightly different structure. BMPs act in bound pairs, or dimers, of the same or different proteins, and in some cases these dimers pair up too, further multiplying the variations. The family of BMP proteins sticks to an associated family of receptor proteins — and those receptors are also made from subunits that fit together in small groups, typically four at a time. It’s this whole cluster of molecules that activates the transcription factors turning genes on and off and triggering a downstream effect on the host cell.
It’s not simply the case, however, that each BMP dimer has designated receptors to which it binds like a lock and key. In fact, these molecules aren’t terribly choosy: Each BMP dimer may stick to several different pairs of receptor subunits with varying degrees of avidity. It’s a combinatorial system, in which the components can be assembled in many ways: less like locks and keys, more like Lego bricks.
Samuel Velasco/Quanta Magazine; source: Michael Elowitz and Yaron Antebi
The possible permutations are exhausting to contemplate. How can the BMP pathway ever deliver a specific directive to guide a cell’s fate? With so much complexity, “it took a little unconventional thought to approach the problem,” said James Linton, a research scientist in Elowitz’s group.
The Caltech team, along with Yaron Antebi, a former postdoc with Elowitz who is now at the Weizmann Institute of Science in Israel, undertook experimental and computational studies to characterize the binding propensities between 10 major mammalian forms of BMPs and seven receptor subunits in two types of mouse cells. That involved studying a lot of combinations, but an automated robotic system for carrying out the reactions in cell cultures made it possible.
The interactions, although promiscuous, were far from “anything goes.” Certain BMPs had nearly interchangeable effects, but others did not. In some cases, one BMP plus two receptor subunits worked as well as an assembly of three different components. An assembly might work as well with one BMP swapped for another, but only if the receptor stayed the same. Sometimes two swapped components had independent effects, and their combined effect was a simple sum. Sometimes the effects mutually reinforced one another or canceled each other out.
In general, the BMPs could be sorted into groups of equivalents. “We classified two BMPs as equivalent if they have the same pattern of interactions with all other BMPs,” said Elowitz. But those equivalence relationships weren’t fixed — they varied with the cell types and the configuration of receptors that the cells expressed. A pair of BMPs might substitute for each other in one type of cell but not in another. This finding tallied with the observations of other researchers that, for example, the BMP9 protein can substitute for BMP10 in the pathway for blood vessel formation but not in the pathway for heart development.
More Specificity From Fewer Signals
Why does BMP signaling work in a way that seems so unnecessarily complicated? The Caltech team speculates that it might give organisms more for less. Mathematical modeling by members of the group — Christina Su at Caltech, Antebi in Israel and Arvind Murugan at the University of Chicago — showed that a promiscuous system of interactions offers a range of potential advantages over one-to-one molecular interactions.
In particular, in systems where ligands bind uniquely to receptors, the number of types of ligands limits how many different cell types or targets can be uniquely addressed. In a combinatorial system, different pairings between a small number of ligands and receptors can specify a much larger number of targets. The differences between the pairings also permit graded effects rather than an all-or-nothing response.
Yaron Antebi, a biologist now at the Weizmann Institute of Science, contributed to the modeling work that showed how promiscuous systems of molecular interactions could offer advantages over one-to-one sets of interactions.Ohad Herches, Weizmann Institute of Science
“Our working hypothesis is that these ligand-receptor combinations have the potential to be more cell-type-specific than individual molecules,” said Elowitz.
A combinatorial system therefore offers more options for addressing cells and can produce more complex cell patterning. This versatility matters for building organisms containing many cell types in precise configurations. Even with a small repertoire of signaling molecules, one group of cells in the embryo can be instructed to become cartilage, say, while another group becomes bone, and others get other fates.
The many possible combinations might create some fuzziness at boundaries between regions, but Linton speculates that these might be sharpened by operating in conjunction with other signaling systems. A pathway involving the family of proteins called Wnt, for example, often seems to operate alongside BMP signaling. “If you find BMP at work somewhere, it’s very likely that you’ll find Wnt,” Linton said. Sometimes the pathways are mutually antagonistic and sometimes they enhance each other. If the Wnt pathway follows similar combinatorial rules — a possibility that still needs to be explored experimentally, Elowitz stresses — then BMP and Wnt might help to refine each other’s signaling.
Elowitz and his colleagues think that in this way, these kinds of combinatorial rules could represent a widespread “design principle” of the molecular wiring of cells.
It’s a combinatorial system, in which the components can be assembled in many ways: less like locks and keys, more like Lego bricks.
The systems biologist Galit Lahav of Harvard Medical School agrees that such a system makes a lot of sense. She wonders if something similar might apply to the gene p53, which is central to controlling cells’ cycles of replication and division and is often implicated in cancers. The p53 protein plays several different roles in cell signaling, and it binds to many other molecules.
The combinatorial principle might also extend to situations beyond cell growth and development. Linton sees a loose parallel with what seems to happen in the olfactory system: Humans have around 400 types of receptor proteins lining the membranes of the olfactory bulb in the nose, and these receptors can collectively discriminate vast numbers of odors. That wouldn’t be possible if each odorant molecule had to be uniquely recognized by its own dedicated receptor. Instead, the receptors seem to bind promiscuously to odorants with different affinities, and the output signal sent to the brain’s smell center is then determined by combinatorial rules.
Using Noise to Their Advantage
The evidence that interactions of proteins, RNA molecules and DNA genomic sequences involved in cell regulation are flexible and promiscuous has become ever more prevalent in the past decade or so. They turn up in a wide range of systems throughout biology. “Given that promiscuity did not have to exist, but is ubiquitous, the simplest and most reasonable assumption is that it is providing some functional capability,” Elowitz said.
He thinks that capability is, at root, information processing. “Just as neurons wired together through axons and dendrites can perform complex information processing, so too can proteins wired together through biochemical interactions,” he said. It’s an insight that other scientists have also drawn from their studies of biochemical networks.
Heidi Klumpe, a member of Elowitz’s group who conducted much of the experimental work on the BMP system, compares it to the way neural networks work: not by assigning fixed roles to given components of the network, but by letting the roles emerge from many connections. “We think the cells are doing a more complex computation than previously thought,” she said.
Our working hypothesis is that these ligand-receptor combinations have the potential to be more cell-type-specific than individual molecules.
Michael Elowitz, California Institute of Technology
“What we are trying to do now is figure out precisely what kinds of functions these systems actually compute,” Elowitz said, “and what higher-level capabilities these computations then enable.”
The evolutionary biologist Andreas Wagner of the University of Zurich agrees that the idea that a promiscuous system like this has been selected because it confers some advantage is “right on the mark.” That this benefit may lie in its versatility is “an intriguing possibility that has probably crossed the mind of anybody who seriously thought about this problem,” he said.
But he adds that “there is another, more mundane possibility”: Perhaps this is the only way a complicated system like the cells of multicellular organisms can work at all. “Cellular systems are highly noisy,” Wagner said; molecular encounters in the crowded, jostling environment inside cells are unpredictable, and the amounts of proteins produced from moment to moment fluctuate randomly. A cell in which each component is wired specifically to another would be highly vulnerable to those uncontrollable variations. It would behave as though circuit elements kept dropping randomly in and out of the network.
Moreover, every time a cell divides, there’s no guarantee that circuits will get exactly reproduced because of random copying errors in DNA replication. “A system like that might be exquisitely sensitive to mutations that alter its properties,” Wagner said. “Taken together, all these costs might well be prohibitive.”
Consequently, cells may have evolved adaptations that use noise to their advantage, and Elowitz’s model of the combinatorial logic of regulatory networks “may be one example of such adaptation,” Wagner said. “Cells may have sloppy systems whose power emerges from the right kind of combinatorics.”
“Biological systems are generally much more robust than we imagine,” said Meng Zhu, a developmental biologist at Harvard Medical School. Researchers often find that when they experimentally disable a gene that appears critical to survival, the organism barely seems to notice: It readjusts the interactions and pathways in its gene and protein networks to compensate. The redundancy and the compensatory function of related proteins, as seen in the BMP system, might be a key part of that ability, she says.
Zhu thinks that promiscuous, highly interconnected protein networks might also promote the ability of organisms to acquire useful new capacities through evolution. “A system that has higher connectivity tends to evolve new functions more easily,” she said, because it can better tolerate deleterious mutations in its component parts.
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Conversely, if all the interactions between the molecular components are very finely tuned, “it’s very hard to do something new,” said Ard Louis, a physicist who works on problems of biological complexity at the University of Oxford. Any change in those components, even one that seems advantageous, is likely to disrupt some existing, possibly vital function.
Promiscuous binding that allows one protein to substitute for another might therefore enable the network to acquire new functions without losing the old ones. Wagner, working with Joshua Payne at the Swiss Federal Institute of Technology Zurich, has found support for this idea: They have shown that the promiscuous binding of transcription factors can promote both robustness to mutations and the ability to evolve new functions.
So it could be that a combinatorial system of ligand binding both creates more options for cells and gives organisms more evolvability and robustness against noise. Evolution may have organized much of the cell’s biochemistry to be far less sensitive to the details than researchers thought.
“I think noisy, evolved biological systems are full of details, but a lot of them are irrelevant,” Klumpe said. “Moreover, it may not be a specific detail that matters, but rather the conservation of some higher-level function” — such as the requirement that transcription factors bind with some level of strength to turn on gene expression.
Circuitry Is Too Simple
This kind of “sloppiness” in biomolecular networks may have important consequences for drug development. “One of the challenges in ordinary medicine is that drugs can be very specific for a target protein, but that target protein may be nonspecific in terms of the cell types in which it is expressed,” Elowitz said. You might be able to hit a protein target very accurately but still not know what effect that will have in different tissues — if any. The work of Elowitz’s team suggests that drugs may need to be more than single-molecule “magic bullets”: They might have to hit different combinations of tissue-specific targets to induce the desired response.
Whatever the reason for its combinatorial principles, the BMP signaling system shows that cells are not like the machines we humans make. “And it might be that that’s true for many biological systems,” Linton said. “If you make simple analogies to electronics, you’re going to come up short.”
This makes it challenging not just to talk about biological systems but to understand and engineer them. Electronic analogies might be appropriate for relatively simple systems such as the bacteria that Elowitz and Leibler worked on 20 years ago, but when living organisms get more complicated — and in particular when they become multicellular, with genetically identical cells that work together in diverse, specialized states — different rules may apply.
The operating principle exemplified by the BMP system might be “something that emerged in nature as a way to give rise to multicellularity and more complex tissues,” Linton said. It’s even possible, he suggests, that “this was the innovation that allowed organisms such as us to emerge.”
Perhaps, then, the most useful analogies for how cells work are themselves biological, such as olfaction or cognition. Maybe the only way to truly understand life is with reference to itself.
One of the first articles Quanta Magazine published in 2021 described a cosmic surprise: A long-puzzling smudge of X-ray light was not, as most believed, a nearby cloud of gas, the remnant of some long-ago stellar explosion. Instead, it was the edge of a truly enormous structure, a bubble that towered over our Milky Way galaxy. The revelation was the product of a unique space telescope that was never designed to find galaxy-size X-ray towers — after all, no one knew they existed. But it keeps with the tradition, going back to when the four Jovian moons materialized in Galileo’s eyepiece, of looking closer, with better instruments, and seeing unimagined spectacles.
In three days, the James Webb Space Telescope is scheduled to launch into space. To find a worthy comparison, we might have to go back all the way to Galileo. Its capabilities are so unlike those of anything that has come before, its powers so vastly superior, that it has the potential to do what Galileo’s inch-wide refractor once did: forever alter humanity’s relationship to the wider universe. Astronomers have a long wish list for what Webb might investigate, as my colleague Natalie Wolchover detailed in “The Webb Space Telescope Will Rewrite Cosmic History. If It Works.” The list includes the first galaxies at the beginning of time and the coruscating skies of Earth-like exoplanets. But everyone suspects it will be the unimagined revelations that Webb will be known for.
Given enough time and data, most anomalies turn out to be attractive statistical artifacts, false fodder for physicists’ daydreams. Rare are the hints of new phenomena that stand up to decades of investigation. But this April, physicists announced the first results of an experiment designed specifically to chase just such an anomaly, one involving the intrinsic magnetism of a particle called the muon. They found that the experimental value differs from the predictions of the Standard Model of particle physics by a wide margin, confirming an anomaly first hinted at in 2001. The result suggests that there might be extra particles flying around that we don’t yet know about — or, better yet, entirely new physical laws. The result dovetails with decades’ worth of strange neutrino behaviors — results that have led physicists to suggest an entirely new “dark sector” of particles and forces largely inaccessible to us.
At first glance, a time crystal would appear to violate one of nature’s most sacred commandments: Nothing comes for free. This object, first conceived (in a slightly different form) in 2012, would flip back and forth between two distinct states forever, with no energy lost or gained. (A laser triggers the change, but the time crystal does not absorb any net energy from the laser.) This summer, researchers announced that they had finally created it using one of Google’s quantum computers. In doing so, they forged a novel phase of matter — the first out-of-equilibrium phase, and the first object to spontaneously break time-translation symmetry. That’s in addition to appearing to violate one of nature’s most cherished laws. “The consequence is amazing,” said Roderich Moessner, a co-author on the paper. “You evade the second law of thermodynamics.” Maxwell’s demon would be proud.
One problem with studying the Milky Way galaxy is that we’re stuck inside it. That makes it hard to tell if a smear on the night sky is a truly enormous galaxy-size structure or a star-size smudge viewed relatively close up. For decades, astronomers assumed that just such a smear was coming from a nearby object — perhaps the remnant of a long-ago supernova. But a recent analysis of X-ray data found a matching smear on the other side of the Milky Way, one that helps to trace out a pair of galaxy-size bubbles 45,000 light-years tall. Astronomers suspect that the bubbles might be evidence of an eruption from millions of years ago — the detritus of a half-eaten cloud of gas that ventured too close to the Milky Way’s supermassive black hole.
Quantum computing is infamously difficult, as the individual quantum bits (or qubits) that make up a quantum processor are remarkably fragile. That’s why many have been excited about a potential approach to quantum computing that uses sturdy “topological” qubits — quantum bits whose information is inexorably braided into their physical structure. In recent years, various teams of researchers have published papers claiming to have created these qubits in the lab. But now controversy has engulfed the field. Other phenomena can convincingly masquerade as one of these topological qubits, and independent researchers aren’t convinced of anything they’ve seen. Retractions have followed. The field of topological quantum computing still has promise, but the task has shown itself to be even more difficult than researchers first imagined.
A new and even more detailed image of the black hole at the center of galaxy M87 has put to rest a decades-old question: How do supermassive black holes, those galaxy-anchoring anomalies, launch jets of matter and energy thousands of light-years into space? The M87 images revealed a powerful spiral magnetic field around the black hole — a key ingredient in a 44-year-old model of jet formation called the Blandford-Znajek process. Researchers this year also made one of the first convincing discoveries of a midsize black hole, one smaller than supermassive anchors but larger than a star-size shell. Equipped with a new search strategy, researchers hope that the 55,000-solar-mass discovery will be the first of many.
Three decades and $10 billion in the making, the James Webb Space Telescope is scheduled to launch on Christmas Day. For the next month or so, the telescope will perform an intricate and perilous unfolding process as it heads to its distant destination — one far beyond the moon, and beyond any hope of human repair. But if it succeeds — the fingers of every astrophysicist are crossed — it will expose cosmic secrets 13 billion years in the making.
The detailed understanding of brains and multicellular bodies reached new heights this year, while the genomes of the COVID-19 virus and various organisms yielded more surprises.1
Three and a half billion years of evolution have given life on Earth plenty of time to explore the margins of what’s possible, so biological science has a lot of catching up to do. Biologists have identified some fundamental principles and mechanisms that govern their field, like natural selection, the cellular nature of organisms and the central dogma of molecular biology. They have toiled to catalog not only the diversity of what Charles Darwin called “endless forms most beautiful and most wonderful” but also the microscopic galaxies of complexity at the cellular level inside those species. They have even made headway in understanding the complex chemical give-and-take that animates cells, organisms and ecosystems.
Still, the living world never runs out of surprises. Things as mundane as soil and sleep harbor secrets, and some discoveries tear up scientists’ old assumptions about what is even biologically possible.
It’s been a long-standing tenet of biochemistry, for example, that the useful properties of protein molecules largely depend on how they fold their amino acid chains into a precise shape. But one of the hottest topics in protein science these days is the study of malleable proteins and blobby masses of protein molecules called condensates that control a wide range of vital processes in cells, and that work precisely because they are fluid rather than fixed in a single conformation.
In 2021, Quanta articles covered many of these surprising turns involving studies of genomes, the brain, and the dynamic interactions of organisms with one another and their environment. Some of our most ambitious journalism also looked at the ongoing struggle by science and society to deal with the COVID-19 pandemic.
With the wider distribution of vaccines against COVID-19 in 2021, parts of the world briefly began to creep out from under the pandemic even as the rise of the delta variant and other forms of the SARS-CoV-2 virus emphasized that the crisis isn’t over. For epidemiologists, a hard lesson of the past two years was that the statistical tools, public health systems and communication protocols they relied on were not entirely ready to cope with a virus as challenging as this one. They discovered that even cornerstone variables like the real-time reproduction number, Rt, and the generation interval were hard to assess, which made modeling the trajectory of the pandemic exceptionally challenging. Even now, there are concerns that viral surveillance systems around the globe may be inadequate for monitoring the rise of potentially dangerous new variants of SARS-CoV-2 — in no small part because public health systems are still stretched thin with the burden of caring for COVID-19 patients.
An extraordinary parasitic plant native to Southeast Asia spends most of its life as a thread of cells growing inside other plants, then blooms as a giant flower that weighs as much as a small child and smells like rotting meat. But the most astonishing fact about this species of “corpse flower” might be what is — and isn’t — in its genome, which was published early this year. Sapria himalayana is missing almost half of the genes highly conserved in other plants, including some that biologists considered essential. Despite those reductions, its genome is still unexpectedly huge because it is what one scientist called “a huge graveyard of DNA” stolen from other species and inflated by massive numbers of copies of the mobile genetic elements called transposons.
Weird as Sapria is, its freaky DNA embodies several recent trends in genomic discoveries. It’s increasingly clear that by making copies of themselves and jumping around within and between chromosomes, transposons can rewire an organism’s genome and facilitate the horizontal transfer of DNA between species. In both plants and animals, horizontal transfers seem to be much more common than was once believed, and researchers are still trying to fathom their significance in evolution.
The lush, abundant complexity of life on Earth owes its existence to the lineages of single-celled organisms that made fateful hops to multicellularity dozens of times in the past 3.5 billion years. Researchers are still trying to understand how and why those transitions occurred, given that the evolutionary advantages of multicellularity are often not apparent in its early stages. Experimental studies with algae, yeast and other single-celled species have shown, however, that if clumping together gives them even a small consistent benefit, such as making them less vulnerable to predation, it can nudge them to become multicellular in a stunningly short time.
Developing a multicellular body is only the first step, though. The other major challenge lies in making the cooperating cells differentiate into distinct tissues with specialized functions. Important clues to that process emerged from new work that reconstructed how a defensive gland evolved in a beetle.
In introductory neuroscience textbooks, the brain is often drawn like a lopsided globe of the world, with its surface divided sharply into distinct regions for perception, memory, speech, awareness and other faculties. These neat partitions reflect a wealth of clinical and experimental data, but they also point to our subjective experience of these processes as separable categories of mental function.
Yet experience can be deceiving. Mounting evidence suggests that it’s a mistake to believe that our capacities are split into separate pathways in anatomically distinct brain areas. On closer examination, parts of the brain strongly associated with specific functions are sometimes also linked to unexpectedly different functions as well: Most of the activity in the brain’s perception centers, for example, is tied to body movements. Neuroscientists are still sorting out the significance of that discovery, but it helps to explain observations that the background “noise” measured in the brain’s electrical signals encodes information about what the body is doing.
Surprises also came to light this year in another brain system that researchers thought they had demystified decades ago. Researchers had shown that a network of “grid cells” in the brain enables us to map where we are in space and also seems to help us keep track of memories and abstract concepts. Now it appears that this elegant grid system only works for mapping in two dimensions; we and other mammals seem to rely on a more complex, less well-understood system for knowing where we are in 3D.
For a long time, scientists studied sleep primarily as a neurological phenomenon: Our consciousness and behavior obviously changed when we went to sleep, but our physiology seemed to be about the same as when we were relaxed and motionless. That view changed significantly during the past few decades, however, when experiments detected subtle chemical shifts in the body during slumber and found evidence that even creatures with rudimentary brains sleep. This trend reached its peak this year with the discovery that the hydra, a tiny animal so simple that it lacks a centralized nervous system, spends a part of every four hours asleep. It now appears that when the first snooze occurred a billion years ago, it may have served a metabolic function that helped cells repair themselves.
Olena Shmahalo for Quanta Magazine; source: Daniel Berger and Jeff Lichtman/Lichtman Lab at Harvard University
Back in the 1970s, neuroscientists undertook an ambitious effort to define how all the neurons in a very simple animal, the roundworm Caenorhabditis elegans, are wired together. In theory, the resulting “connectome” should be the cornerstone for understanding all of the worm’s potential behaviors and responses. Five decades later, researchers do have a complete and refined connectome for the worm — but it’s still the only animal for which that can be said.
In 2021, however, neuroscientists released partial connectomes for several creatures, including humans, that showed how rapidly the field of connectomics is expanding. Harvard University and Google researchers shared a connectome for one cubic millimeter of human brain tissue that revealed unique types of neurons and other surprises. Researchers also published information about the connectome of fruit flies that included their navigational circuitry. Yet some researchers think the most important advance might be the advent of large-scale or comparative connectomics: the ability to fold information from multiple individuals into the connectome of a species, which may reveal some of the rules governing how neurons are wired together and how variations in those neural circuits affect organisms.
We are going to need all the help we can get to minimize the effects of greenhouse gas-driven climate change in the decades ahead. And unfortunately, climatologists may have overestimated how much help we can expect from one process in nature. The amount of carbon dioxide in the atmosphere at any time represents the summed effect of carbon sources such as burning fossil fuels and “carbon sinks” that pull it out of circulation. An example of the latter is the way plants can sequester carbon in the soil as long carbohydrate chains called humus. Because humus seemed to endure a long time, many global climate models have counted on it to tie up sizable amounts of excess carbon. But over the past decade or so, interdisciplinary studies quietly revolutionizing soil science have established that in warmed natural soils, humus routinely breaks down much sooner than expected. Untended soils in forests around the world probably can’t be expected to hold onto much of the excessive carbon dioxide at all. Researchers are still investigating whether some organisms can be modified to trap carbon more permanently.
A study conducted in the United Kingdom says there’s no evidence the Omicron variant causes less severe reactions than the Delta variant.
“The study finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection,” says a blog post by researchers from the U.K.’s Imperial College London. “However, hospitalization data remains very limited at this time.”
Researchers looked at data gathered by the U.K. Health Security Agency and the U.K.’s health service for COVID cases confirmed by PCR tests between Nov. 29 and Dec. 11.
Researchers estimate the risk of reinfection by Omicron is 5.4 times greater than for the Delta.
“This implies that the protection against reinfection by Omicron afforded by past infection may be as low as 19%,” the blog said, adding that researchers estimated protection would be between 0-20% after two doses of vaccine and would be 55-80% after a booster shot.
“This study provides further evidence of the very substantial extent to which Omicron can evade prior immunity given by both infection or vaccination. This level of immune evasion means that Omicron poses a major, imminent threat to public health.” wrote Professor Neil Ferguson, the leader of the research team.
“Quantifying reinfection risk and vaccine effectiveness against Omicron is essential for modelling the likely future trajectory of the Omicron wave and the potential impact of vaccination and other public health interventions,” Professor Azra Ghani of the Imperial College London wrote in the blog post.
There were only 24 known cases of hospitalization caused by Omicron, the study said, meaning more research will be needed in that area.
Health authorities in the United Kingdom worry that Omicron cases will overwhelm hospitals because the variant is spreading so fast and Omicron cases are doubling every two days.
“Whatever the eventual percentage of people with Omicron who will need NHS care, the absolute number seeking care will also double every two days,” Christina Pagel, director of UCL’s Clinical Operational Research Unit, wrote in an opinion piece for TheGuardian.
“So the question is not whether it will be bad for the NHS, but whether it will be just dreadful or catastrophic.”
Named after the man who oversaw NASA through most of its formative decade of the 1960s, Webb is about 100 times more sensitive than Hubble and is expected to transform scientists’ understanding of the universe and our place in it.
NASA’s James Webb Space Telescope, built to give the world its first glimpse of the universe as it existed when the earliest galaxies formed, was launched by rocket early Saturday from the northeastern coast of South America, opening a new era of astronomy.
The revolutionary $9 billion infrared telescope, described by NASA as the premiere space-science observatory of the next decade, was carried aloft inside the cargo bay of an Ariane 5 rocket that blasted off at about 7:20 a.m. EST (1220 GMT) from the European Space Agency’s (ESA) launch base in French Guiana.
The flawless Christmas Day launch, with a countdown conducted in French, was carried live on a joint NASA-ESA webcast. The liftoff capped a project decades in the making, coming to fruition after years of repeated delays and cost over-runs.
“From a tropical rain forest to the edge of time itself, James Webb begins a voyage back to the birth of the universe,” a NASA commentator said as the two-stage launch vehicle, fitted with double solid-rocket boosters, roared off its launch pad into cloudy skies.
After a 27-minute, hypersonic ride into space, the 14,000-pound instrument was released from the upper stage of the French-built rocket about 865 miles above the Earth, and should gradually unfurl to nearly the size of a tennis court over the next 13 days as it sails onward on its own.
Live video captured by a camera mounted on the rocket’s upper stage showed the Webb gliding gently away after it was jettisoned, drawing cheers and applause from jubilant flight engineers in the mission control centre.
Flight controllers confirmed moments later, as the Webb’s solar-energy array was deployed, that its power supply was working.
Coasting through space for two more weeks, the Webb telescope will reach its destination in solar orbit 1 million miles from Earth – about four times farther away than the moon. And Webb’s special orbital path will keep it in constant alignment with the Earth as the planet and telescope circle the sun in tandem.
By comparison, Webb’s 30-year-old predecessor, the Hubble Space Telescope, orbits the Earth from 340 miles away, passing in and out of the planet’s shadow every 90 minutes. Named after the man who oversaw NASA through most of its formative decade of the 1960s, Webb is about 100https://df2d4dc256f043f3fbe2eb509defa701.safeframe.googlesyndication.com/safeframe/1-0-38/html/container.html
times more sensitive than Hubble and is expected to transform scientists’ understanding of the universe and our place in it.
NASA Administrator Bill Nelson, striking a spiritual tone as he addressed the launch webcast by video link, quoted the Bible and hailed the new telescope as a “time machine” that will “capture the light from the very beginning of the creation.”
Webb mainly will view the cosmos in the infrared spectrum, allowing it to peer through clouds of gas and dust where stars are being born, while Hubble has operated primarily at optical and ultraviolet wavelengths.
The new telescope’s primary mirror – consisting of 18 hexagonal segments of gold-coated beryllium metal – also has a much bigger light-collecting area, enabling it to observe objects at greater distances, thus farther back into time, than Hubble or any other telescope.
That, astronomers say, will bring into view a glimpse of the cosmos never previously seen – dating to just 100 million years after the Big Bang, the theoretical flashpoint that set in motion the expansion of the observable universe an estimated 13.8 billion years ago.
Hubble’s view reached back to roughly 400 million years following the Big Bang, a period just after the very first galaxies – sprawling clusters of stars, gases and other interstellar matter – are believed to have taken shape.
While Hubble caught glimmers of “toddler” galaxies, Webb will reveal those objects in greater detail while also capturing even fainter, earlier “infant” galaxies, astrophysicist Eric Smith, NASA’s Webb program scientist, told Reuters hours before the launch.
Aside from examining the formation of the earliest stars and galaxies, astronomers are eager to study super-massive black holes believed to occupy the centers of distant galaxies.
Webb’s instruments also make it ideal to search for evidence of potentially life-supporting atmospheres around scores of newly documented exoplanets – celestial bodies orbiting distant stars – and to observe worlds much closer to home, such as Mars and Saturn’s icy moon Titan.
The telescope is an international collaboration led by NASA in partnership with the European and Canadian space agencies. Northrop Grumman Corp (NOC.N) was the primary contractor. The Arianespace launch vehicle is part of the European contribution
“The world gave us this telescope, and we handed it back to the world today,” Gregory Robinson, Webb program director for NASA told reporters at a post-launch briefing.
Webb was developed at a cost of $8.8 billion, with operational expenses projected to bring its total price tag to about $9.66 billion, far higher than planned when NASA was previously aiming for a 2011 launch. read more Astronomical operation of the telescope, to be managed from the Space Telescope Science Institute in Baltimore, is expected to begin in the summer of 2022, following about six months of alignment and calibration of Webb’s mirrors and instruments.
It is then that NASA expects to release the initial batch of images captured by Webb. Webb is designed to last up to 10 years.
Local governments, businesses, and universities are imposing COVID-19 safety protocols again as cases increase across the U.S. due to the Omicron variant.
Since the beginning of December, both U.S. cases and deaths have risen about 50%, and hospitalizations have increased 26%, according to a Reuters tally. The jump in infections has led to a number of closures and last-minute changes as the holidays approach.
New York set records for reporting the highest number of infections in a single day during the pandemic, with 21,000 cases on Friday and 22,000 on Saturday, according to The New York Times.
The surge is a “reminder that the pandemic is not over yet and we must take extra care to keep ourselves and each other safe,” Gov. Kathy Hochul said on Friday.
The National Football League has postponed three games, and nine National Basketball Association players entered safety protocols The National Hockey League also announced that at least six teams would have games postponed.
Entertainment venues and restaurants in several states are closing again as staff and customers test positive, including spots in New York, Texas, Indiana, Maine, and Minnesota. Some restaurants are taking precautions by canceling indoor dining for the holidays or shifting to to-go service for the rest of the year.
Universities are shifting their plans, too. Harvard University announced Saturday that it would move to remote learning for the first three weeks of January, The New York Times reported. Middlebury College in Vermont, DePaul University in Chicago, and Southern New Hampshire University announced similar changes for next semester. Cornell University canceled graduation ceremonies and moved finals online after more than 900 students tested positive.
Major workplaces are beginning to consider fully remote options again as well. CNN is closing its U.S. offices to all nonessential employees, the network said Saturday in an internal staff memo seen by The Wall Street Journal. CNN, which is part of AT&T’s Warner Media division, will close for all employees who don’t have to work in the office.
The network, which returned to using full-scale studios for its shows, will use “flash studios” again that can be operated remotely by fewer people. The network will also make changes to studios and control rooms to reduce the number of people needed on site.
“We are doing this out of an abundance of caution,” Jeff Zucker, president of CNN, said in the memo. “And it will also protect those who will be in the office by minimizing the number of people who are there.”
President Joe Biden will address the country on Tuesday to discuss the Omicron variant and new steps the administration will take to help vulnerable communities, The New York Times reported. He’s expected to encourage vaccinations, booster shots, and testing.
The WHO reported Saturday that the Omicron variant has been detected in 89 countries, and cases are doubling every 1.5 to 3 days in places with community transmission. Some countries are returning to tougher measures to slow the spread of the virus, particularly in Europe.
The Netherlands began a nationwide lockdown on Sunday, with all non-essential stores, bars and restaurants closed until Jan. 14 and schools closed until Jan. 9. The lockdown will affect holiday celebrations as well, the AP reported. Residents in the Netherlands will only be allowed to have two visitors except for Christmas and New Year’s, when they can host four people.
Officials in Austria and France have tightened travel restrictions, and Paris canceled its New Year’s Eve fireworks celebration. Denmark has closed theaters, concert halls, and museums, and Ireland imposed an 8 p.m. curfew on pubs and limited attendance at events.
“None of this is easy,” Micheal Martin, the prime minister for Ireland, said Friday night.
“We are all exhausted with COVID and the restrictions it requires,” he said. “The twists and turns, the disappointments and the frustrations take a heavy toll on everyone. But it is the reality that we are dealing with.”
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