Connect with us

Spread & Containment

Regeneron brings its antibody chops to gene editing’s biggest problem

TARRYTOWN, NY — For over three decades, Regeneron has been synonymous with one thing in the drug industry: antibodies. Blockbusters like Dupixent, Eylea,…

Published

on

TARRYTOWN, NY — For over three decades, Regeneron has been synonymous with one thing in the drug industry: antibodies. Blockbusters like Dupixent, Eylea, and Covid-19 antibodies have transformed what started as a scrappy startup into one of biotech’s biggest names.

But the billionaire co-founders who still run the $91 billion giant, CEO Leonard Schleifer and CSO George Yancopoulos, have spent nearly the last decade working on the company’s next act. They have partnered, built, and bought their way into genetic medicine, going beyond antibodies into CRISPR, RNA interference, and other technologies that manipulate the genetic code of life.

It’s an audacious bet on the future of the drug industry. And even though Regeneron’s success has come from antibodies, its leaders believe new therapies may dominate its next age.

Not only is the biotech co-developing the most clinically advanced in vivo CRISPR therapy with Intellia Therapeutics and an Alzheimer’s RNA interference drug candidate with Alnylam Pharmaceuticals, it’s also quietly working on — and increasingly excited about — some earlier, less heralded research that could change the field. Its leaders believe it can crack the delivery problem that holds back the entire space. Doing so would bring genetic medicines beyond the liver to reach more parts of the body, in the process greatly expanding the medical — and commercial — possibilities of the technology.

“While everybody else was so hyped and giving Nobel Prizes for CRISPR and all that, we realized those weren’t really the limitations,” Yancopoulos, Regeneron’s chief scientific officer, told Endpoints News during an interview at the company’s Tarrytown headquarters. “The limitations were really delivery.”

Regeneron is tapping its decades-long expertise in antibodies, attaching these proteins to standard viral vectors so they hunt for specific types of cells in the body. Research is early, with no timetable on reaching the clinic, but results in mice and non-human primates have emboldened the company’s scientific leaders on the promise of the idea. If it works, Regeneron could crack the delivery challenge that has held the entire field back for years, ultimately bringing technological breakthroughs like CRISPR and RNAi to far more diseases.

“We believe we’ve become leaders in that space,” Yancopoulos said of the delivery idea. “We will hopefully be announcing programs where we’re using biologicals to deliver genetic payloads, which we think has the chance to really continue to change the field.”

There’s still a long journey ahead into making this reality. Academics first tried the idea of attaching antibodies to viral vectors in the 1990s with moderate success, but challenges in making such a complex product have deterred industry interest. Before this idea reaches the clinic, Regeneron will need to convince regulators it has the manufacturing chops to attach these antibodies to viruses in a consistent way so batches look the same. Gene therapy experts said scaling up will be a key challenge.

Still, Regeneron carries unique credibility with its deep pockets and decades of antibody experience.

“Regeneron has certainly been the leader in designing and producing specific antibodies that could be used for this purpose,” said Barry Byrne, director of the University of Florida’s gene therapy center. “They’re the ones who will probably make this work.”

***

Whether using a hollowed-out virus or a lipid nanoparticle, delivering genetic cargo in the body is frustratingly hard. These carriers predominantly wind up in the liver, the body’s clearinghouse organ.

While that can address diseases caused by genes expressed in liver cells, that’s not most illnesses. The brute force approach, upping doses to try to reach other organs, comes at the expense of the liver, leading to patient deaths in some gene therapy clinical studies.

Christos Kyratsous

“You have to give so much vector that you’re overwhelming your liver, and your liver enzymes go crazy,” said Christos Kyratsous, co-head of Regeneron’s genetic medicines team. “That becomes the major limitation for delivering the interesting payloads.”

The delivery problem has caused the field to crowd into the same liver-based targets, such as PCSK9, to slash cholesterol. Other efforts, like the sickle cell CRISPR gene-editing program now being reviewed by the FDA, avoid delivery altogether by using an ex vivo process closer to arduous transplant surgery than a typical drug.

The delivery work is one part of a sprawling genetics strategy at Regeneron, which started in 2014 with the launch of its Regeneron Genetics Center. That has become one of the world’s largest DNA-reading efforts, having sequenced 2 million genomes and counting, leading to over 10 new genetic targets tied to diseases like obesity or liver disease.

Walking around the RGC, sequencing machines tower over and outnumber white-coated scientists toiling at lab benches. It’s far more common for its 170 employees to log on remotely to check experiments or let robotic systems whiz around to handle routine tasks like pipetting.

Regeneron has inked collaborations with Decibel Therapeutics and Alnylam over the past few years, respectively working on CRISPR gene editing, gene therapy, and RNA interference to advance that RGC research. In August, Regeneron made an extraordinarily rare M&A move, agreeing to buy Decibel and its gene therapy work.

Regeneron now has six genetic medicines in its pipeline and more than 30 preclinical programs. But even as the field has generated excitement with the first US approvals for gene therapies, RNAi drugs, and mRNA vaccines all since 2017, its potential still dwarfs its current impact. The pesky delivery problem looms over the entire field.

Regeneron hopes its antibody idea can reach more organs, starting with the muscle and the brain. Preclinical data are encouraging, independent experts told Endpoints.

Regeneron’s most advanced program attaches an antibody targeting a protein found in muscle cells called CACNG1 to a viral vector. Mice and non-human primate studies showed massive boosts in reaching muscle cells, alongside big drops in entering the liver and heart compared to an unmodified version of the virus, according to data presented at this year’s American Society of Gene & Cell Therapy meeting.

“This is unlocking an entirely new space in terms of delivery and what you can actually do with all these genetic medicines,” Kyratsous said.

Christina Pacak, a University of Minnesota gene therapy researcher, called the data exciting, adding she’s hopeful for the approach.

“If we can increase safety, reduce costs, and just lower what patients are exposed to, that’s an enormous advantage,” said Pacak, who’s not involved with Regeneron’s research.

***

For Regeneron’s early results, other experts said they are encouraging but not industry-shaking.

“Super-beautiful data. It’s impressive,” said Nicole Paulk, CEO of the gene therapy startup Siren Biotechnology. “But it doesn’t look different magnitude-wise on either purposeful targeting or detargeting to any of the novel capsids. Competitive, but not different.”

Startups like Dyno Therapeutics, Solid Biosciences, Capsida Biotherapeutics, and Apertura Gene Therapy are all tinkering with AAVs, or adeno-associated viruses, to get beyond the liver. (Paulk sits on Dyno’s scientific advisory board.) Outside of AAVs, other startups focused on delivery include Aera Therapeutics, Ensoma, and ReCode Therapeutics.

Even as more startups take on delivery, Regeneron stands alone with its antibody idea. In a sign of its progress, its AAV-focused team has grown from the single digits about seven years ago to now several hundred people.

Outside experts repeatedly mentioned scaling up production as the key challenge to watch. Siren’s Paulk said manufacturing challenges have limited the idea’s potential for decades, as attaching antibodies can be inconsistent and finicky. Paulk said Regeneron would need to have a production trick up its sleeve to address those challenges.

“Every lot becomes a snowflake, and that becomes a challenge for the FDA,” Paulk said. “I don’t see a way this moves forward. I hope I’m dead wrong.”

David Schaffer, a bioengineering researcher at UC Berkeley, called Regeneron’s results “interesting” but noted in an email it may be “technically challenging to scale reproducibly and robustly.”

Regeneron’s leaders said they are confident in meeting that challenge. Kyratsous said they are advancing two methods of attaching antibodies to viruses, adding they’ve seen consistent results in scaling both ideas so far.

“We don’t want to over-engineer something and make something that is very cool on paper or works very well in small animal models, and you cannot scale it up for human use,” he added.

Regeneron’s leaders pointed to their experience in mass-producing antibodies and the expanding AAV team.

“We’re moving toward clinical-scale virus production,” said Leah Sabin, executive director of Regeneron’s genetic medicines unit.

Sabin said they are debating what muscle diseases to prioritize for the clinic, while a brain-targeting program is now being tested in non-human primates. The team is already mulling what tissues to target next.

“The current capsids are not good enough,” Sabin said. “They’re fine, but what would be industry-altering is having this completely new, way more efficient way to get them there.”

Read More

Continue Reading

Spread & Containment

Glimpse Of Sanity: Dartmouth Returns Standardized Testing For Admission After Failed Experiment

Glimpse Of Sanity: Dartmouth Returns Standardized Testing For Admission After Failed Experiment

In response to the virus pandemic and nationwide…

Published

on

Glimpse Of Sanity: Dartmouth Returns Standardized Testing For Admission After Failed Experiment

In response to the virus pandemic and nationwide Black Lives Matter riots in the summer of 2020, some elite colleges and universities shredded testing requirements for admission. Several years later, the test-optional admission has yet to produce the promising results for racial and class-based equity that many woke academic institutions wished.

The failure of test-optional admission policies has forced Dartmouth College to reinstate standardized test scores for admission starting next year. This should never have been eliminated, as merit will always prevail. 

"Nearly four years later, having studied the role of testing in our admissions process as well as its value as a predictor of student success at Dartmouth, we are removing the extended pause and reactivating the standardized testing requirement for undergraduate admission, effective with the Class of 2029," Dartmouth wrote in a press release Monday morning. 

"For Dartmouth, the evidence supporting our reactivation of a required testing policy is clear. Our bottom line is simple: we believe a standardized testing requirement will improve—not detract from—our ability to bring the most promising and diverse students to our campus," the elite college said. 

Who would've thought eliminating standardized tests for admission because a fringe minority said they were instruments of racism and a biased system was ever a good idea? 

Also, it doesn't take a rocket scientist to figure this out. More from Dartmouth, who commissioned the research: 

They also found that test scores represent an especially valuable tool to identify high-achieving applicants from low and middle-income backgrounds; who are first-generation college-bound; as well as students from urban and rural backgrounds.

All the colleges and universities that quickly adopted test-optional admissions in 2020 experienced a surge in applications. Perhaps the push for test-optional was under the guise of woke equality but was nothing more than protecting the bottom line for these institutions. 

A glimpse of sanity returns to woke schools: Admit qualified kids. Next up is corporate America and all tiers of the US government. 

Tyler Durden Mon, 02/05/2024 - 17:20

Read More

Continue Reading

Spread & Containment

From Colombia to Laos: protecting crops through nanotechnology

In a recent breakthrough, DNA sequencing technology has uncovered the culprit behind cassava witches’ broom disease: the fungus genus Ceratobasidium….

Published

on

In a recent breakthrough, DNA sequencing technology has uncovered the culprit behind cassava witches’ broom disease: the fungus genus Ceratobasidium.

Credit: Alliance of Bioversity and CIAT / A. Galeon

In a recent breakthrough, DNA sequencing technology has uncovered the culprit behind cassava witches’ broom disease: the fungus genus Ceratobasidium.

The cutting-edge nanopore technology used for this discovery was first developed to track the COVID-19 virus in Colombia, but is equally suited to identifying and reducing the spread of plant viruses. The findings, published in Scientific Reports, will help plant pathologists in Laos, Cambodia, Vietnam and Thailand protect farmers’ valued cassava harvest.

“In Southeast Asia, most smallholder farmers rely on cassava: its starch-rich roots form the basis of an industry that supports millions of producers. In the past decade, however, Cassava Witches’ Broom disease has stunted plants, reducing harvests to levels that barely permit affected farmers to make a living,” said Wilmer Cuellar, Senior Scientist at the Alliance of Bioversity and CIAT.

Since 2017, researchers at the Alliance of Bioversity International and CIAT have incorporated nanotechnology into their research, specifically through the Oxford Nanopore DNA/RNA sequencing technology. This advanced tool provides insight into the deeper mysteries of plant life, accurately identifying pathogens such as viruses, bacteria and fungi that affect crops.

“When you find out which pathogen is present in a crop, you can implement an appropriate diagnostic method, search for resistant varieties and integrate that diagnosis into variety selection processes,” said Ana Maria Leiva, Senior Researcher at the Alliance.

Nanotechnology, in essence, is the bridge between what we see and what we can barely imagine. This innovation opens a window into the microscopic world of plant life and pathogens, redefining the way we understand and combat diseases that affect crops.

For an in-depth look at the technology being used in Laos and Colombia, please explore this link.


About the Alliance of Bioversity International and CIAT

The Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT) delivers research-based solutions that harness agricultural biodiversity and sustainably transform food systems to improve people’s lives. Alliance solutions address the global crises of malnutrition, climate change, biodiversity loss, and environmental degradation.

With novel partnerships, the Alliance generates evidence and mainstreams innovations to transform food systems and landscapes so that they sustain the planet, drive prosperity, and nourish people in a climate crisis.

The Alliance is part of CGIAR, a global research partnership for a food-secure future. www.alliancebioversityciat.org


Read More

Continue Reading

International

Public Health from the People

There are many ways to privately improve public health. Such responses make use of local knowledge, entrepreneurship, and civil society and pursue standard…

Published

on

There are many ways to privately improve public health. Such responses make use of local knowledge, entrepreneurship, and civil society and pursue standard goals of public health like controlling the spread of infectious diseases. Moreover, private responses improve overall welfare by lowering the total costs of a disease and limiting externalities. If private responses can produce similar outcomes as standard, governmental public health programs—and more—perhaps we should reconsider when and where we call upon governments to improve public health.

Two Kinds of Private Responses

Following Vernon Smith and his distinction between constructivist and ecological rationality, private actors can engage in two general kinds of public health improvements. They can engage in concerted efforts to improve public health, and they can engage in emergent responses through myriad interactions.1 Three stories below—about William Walsh, Martha Claghorn, and Edwin Gould—indicate concerted efforts to improve public health.

Walsh, a Catholic priest and President of the Father Matthew Society in Memphis, Tennessee, used the society to organize a refugee camp outside of the city and helped hundreds of people avoid yellow fever during the 1878 epidemic—one of the worst yellow fever epidemics in the country.2 Shortly after learning mosquitos carried diseases prior to 1901, Claghorn chaired the Civics committee of the Twentieth Century Club in the Richmond Hill area of Long Island and led a community-wide anti-mosquito campaign, which rid the area of potentially infectious mosquitos.3 After realizing that many of his employees were sick with malaria, Gould—president of the St. Louis Southwestern Railway—used his wealth and business firm to finance and develop an anti-mosquito campaign throughout Texas.4

These stories show how individuals recognize a public health problem given their circumstances and use their knowledge and available resources to resolve the problem. More recently, we might all be familiar with private, constructivist responses to Covid-19. We all made plans to avoid others and produce our desired amount of exposure. Many people made facemasks from old clothes or purchased them from facemask producers. Businesses, retailers, restaurants, and many others adapted in various ways to limit exposure for their workers and customers. My favorite example, albeit not relevant for most, is the so-called bubble that was implemented by the NBA, which housed teams, encouraged play, and limited infection. The NBA finished their season and crowned a 2020 champion only because of the privately designed and implemented bubble solution. The key is that the bubble pursued all of those objectives, not just one of them. All of these responses indicate how private interactions among people can minimize their exposure, through negotiation, discussion, and mutually beneficial means.

In addition to privately designed solutions, emergent public health responses are also important, perhaps even more so. Long-term migration and settlement patterns away from infectious diseases, consumption to improve nutrition, hygiene, sanitation, and the development of social norms to encourage preventative behavior are all different kinds of emergent public health responses. Each of these responses—developed through the actions of no one person—are substantial ways to improve public health.

First, consider how common migration operates as a means of lowering prevalence rates. As soon as people realized that living near stagnant bodies of water increased the probability of acquiring diseases like malaria, they were more likely to leave those areas and subsequently avoid them. Places with such features became known as places to avoid; people also developed myths to dissuade visitors and inhabitants.5 Such myths and associations left places like the Roman Campagna desolate for centuries. These kinds of cultural associations are also widespread; for example, many people in North and South Carolina moved to areas with higher elevation and took summer vacations to avoid diseases like malaria. East End and West End, in London, also developed because of the opportunities people had to migrate away from (and towards) several diseases.6

While these migration patterns might develop over decades, movement and migration also help in more acute public health crises. During the 1878 yellow fever epidemic throughout the southern United States, for example, thousands of people fled their cities to avoid infection. They took any means of transportation they could find. While some fled to other, more northern cities, many acquired temporary housing in suburbs, and many formed campsites and refugee camps outside of their city. The refugee camps outside of Memphis—like the one formed by William Walsh—helped hundreds and thousands of people avoid infection throughout the Fall of 1878.

Second, more mundane public health improvements—like improvements in nutrition, hygiene, and sanitation—are also emergent. These improvements arise from the actions of individuals and entrepreneurs, often closely associated with voluntary consumption and markets. According to renowned medical scientist Thomas McKeown, that is, rising incomes encouraged voluntary changes in consumption, which helped improve nutrition, sanitation, and lowered mortality rates.7 These effects were especially pertinent for women and mothers as they often selected more nutritious food and altered household sanitation practices. With advancing ideas about germs, moreover, historian Nancy Tomes argues that private interests advanced the campaign to improve house-hold sanitation and nutrition—full of advice and advertisements in newspapers, magazines, manuals, and books.8 Following Tomes, economic historians Rebecca Stein and Joel Mokyr substantiate these ideas and show that people changed their hygiene, sanitation, house-hold cleaning habits, and diets as they learned more about germs.9 Such developments helped people to provide their desired exposure to germs according to their values.

Obviously, there were concerted public health improvements during this time that also explain falling mortality rates. For example, waterworks were conscious efforts to improve public health and were provided publicly and privately, with similar, positive effects on health.10 The point is that while we might be quick to connect the health improvements associated with a public water system, we should also recognize emergent responses like gradual changes in voluntary consumption.

Finally, social norms or rules that encourage preventative behavior might also be relevant kinds of emergent public health responses. Such rules identify behavior that should or should not be allowed, they are enforced in a decentralized way, and if they follow from the values of individuals in a community.11 If such rules pertain to public health, they can raise the cost of infectious behavior or the benefits of preventative behavior. Covering one’s mouth when sneezing is not only beneficial from a public health perspective, it also helps avoid earning disapproval.

The condom code during the height of the HIV/AIDS epidemic is another example of an emergent public health rule that reduced infectiousness by encouraging safer behavior.12 People who adopted safer sexual practices were seen to be doing the right thing—akin to taking care of a brother. People who refrained from adopting safer sexual practices were admonished. No single person or entity announced the rule; rather, it emerged from the actions and interactions of individuals within various communities to pursue their goals regarding maintaining sexual activity and limiting the spread of disease. Indeed, such norms were more effective in communities where people used their social capital resources to determine which behaviors should be changed and where they can more easily monitor and enforce infractions. This seems like a relevant factor where many gay men and men who have sex with men live in dense urban areas like New York and Los Angeles that foster LGBTQ communities.

Covid-19 provides additional examples where social norms encouraged the use of seemingly appropriate behavior, e.g., social distancing, the use of facemasks, and vaccination. Regardless of any formal rule in place, many people adapted their behavior because of social norms that encouraged social distancing, the use of facemasks, and vaccination. In communities that valued such behaviors, people that wore face masks and vaccinated were praised and were seen as doing the right thing; people that did not were viewed with scorn. Indeed, states and cities that have higher levels of social capital and higher values for public health tend to have higher Covid-19 vaccine uptakes.13

Improving Public Health and More

“Private approaches tend to lower the total costs of diseases and they limit externalities.”

While these private approaches can improve public health, can they do more than typical public health approaches cannot? Private approaches tend to lower the total costs of diseases and they limit externalities. Each aspect of private responses requires additional explanation.

Responding to infectious diseases and disease prevention is doubly challenging because not only do we have to worry about being sick, we also have to consider the costs imposed by our preventative behaviors and the rules we might impose. Thus, the total costs of an infectious disease include 1) the costs related to the disease—the pain and suffering of a disease and the opportunity costs of being sick—and 2) the costs associated with preventative and avoidance behavior. While disease costs are mostly self-explanatory, the costs of avoiding infection warrant more explanation. Self-isolation when you have a cold, for example, entails the loss of potentially valuable social activities; and wearing condoms to prevent sexually transmitted diseases forfeits the pleasures of unprotected sexual activity. Diseases for which vaccines and other medicines are available are less worrisome, perhaps, because these are diseases with lower prevention costs than diseases where those pharmaceutical interventions are not available. Governmental means of prevention also add relevant costs. Many readers might be familiar with the costs imposed by our private and public responses to Covid—from isolation to learning loss, and from sharp decreases in economic activity to increased rates of depression and spousal abuse.14 Long before Covid, moreover, people bemoaned wearing masks during the Great Flu,15 balked at quarantine against yellow fever,16 and protested bathhouse closings with the onset of HIV.17

Figure 1 shows the overall problem: diseases are harmful but our responses to those diseases might also be harmful.

Figure 1. The Excess Burden of Infectious Diseases

This figure follows Bhattacharya, Hyde, and Tu (2013) and Philipson (2000), who refer to the difference between total costs and disease costs as the excess burden of a disease. That is, excess burden depends on how severely we respond to a disease in private and in public. The excess burden associated with the common cold tends to be negligible as we bear the minor inconvenience of a fever, a sore throat perhaps, or a couple days off work; moreover, most people don’t go out of their way to avoid catching a cold. The excess burden of plague, however, is more complicated; not only are the symptoms much worse—and include death—people have more severe reactions. Note too that disease costs rise with prevalence and with worsening symptoms but eventually decline as more severe diseases tend to be less prevalent. Still, no one wants to be infected with a major disease, and severe precautions are likely. We might shun all social interactions, and we might use government to impose strict quarantine measures. As disease severity rises along the horizontal axis, it might be the case that the cure is worse than the disease.

The private responses indicated above all help to lower the total costs of a disease because people choose their responses and they use their local knowledge and available resources to select cheaper methods of prevention. Claghorn used her neighborhood connections and the social capital of her civics association to encourage homeowners to rid their yards of pools of water; as such she lowered the costs of producing mosquito control. Similarly, Gould used the organizational structure of his firm to hire experts in mosquito control and build a sanitation department. These are cheap methods to limit exposure to mosquitos.

Emergent responses also help to lower the total costs of a disease because such responses indicate the variety of choices people face and their ability to select cheaper options. People facing diseases like malaria might be able to move away and, for some, it is cheaper than alternative means of prevention. Many people now are able to limit their exposure to mosquitos with screens, improved dwellings, and air conditioning.18 Consider the variety of ways people can limit their exposure to sexually transmitted diseases like HIV. If some people would rather use condoms to limit HIV transmission, they are better off doing so than if they were to refrain from sexual activity altogether. Similarly, some people would be better off having relatively risky sexual activity if they were in monogamous relationships or if they knew about their partner’s sexual history. That people can choose their own preventative measures indicates lower total costs compared with blunt, one-rule-for-all, governmental public health responses.

Negative and positive externalities of spreadable diseases indicate too much infectious behavior and too little preventative behavior, respectively. Hosting a party is fun, but it also incurs the internal costs of the drinks and appetizers and, more importantly, perhaps the external costs of raising the probability that people get sick. Attending a local cafe can be relaxing, but you have to pay for a cup of coffee and you might also transmit a disease to other coffee drinkers. The same could be said for many other public and social activities that might spread diseases like attending a class or a basketball game, transporting goods and people, and sexual behaviors. Our preventative behaviors from taking a vaccine to covering your mouth and from isolation to engaging in safer sexual practices emits positive externalities. If left unchecked, negative and positive externalities lead to higher rates of infection.

Overall, we should continue to think more critically about delineating how private and public actors can improve public health and overall welfare. More importantly, we should recognize that private actors are more capable than we often realize, especially in light of conscious efforts to improve public health and those efforts that emerge from people’s actions and interactions. These private efforts might be better at advancing some public health goals than public actors do. Individuals, for example, have more access to local knowledge and can discover novel solutions that serve multiple ends—often ends they value—rather than the ends of distant officials. Such cases and possibilities indicate cheaper ways to improve public health.


Footnotes

[1] Smith (2009), Rationality in Economics: Constructivist and Ecological Forms, Cambridge University Press.

[2] For more on Walsh, see Carson (forthcoming), “Prevention Externalities: Private and Public Responses to the 1878 Yellow Fever Epidemic,” Public Choice.

[3] For more on Claghorn, see Carson (2020), “Privately Preventing Malaria in the United States, 1900-1925,” Essays in Economics and Business History.

[4] For more on Gould, see Carson (2016), “Firm-led Malaria Prevention in the United States, 1910-1920,” American Journal of Law and Medicine.

[5] On the connection between malarial diseases, dragons, and dragon-slaying saints, see Horden (1992), “Disease, Dragons, and Saints: the management of epidemics in the dark ages,” in Epidemics and Ideas by Ranger and Slack.

[6] For more on migration and prevalence rates, see Mesnard and Seabright (2016), “Migration and the equilibrium prevalence of infectious disease,” Journal of Demographic Economics.

[7] The American Journal of Public Health published several commentaries on McKeown in 2002: https://www.ncbi.nlm.nih.gov/pmc/issues/130602/

[8] Tomes (1990), “The Private Side of Public Health: Sanitary Science, Domestic Hygiene, and the Germ Theory, 1870-1990,” Bulletin of the History of Medicine.

[9] Mokyr and Stein (1996), “Science, Health, and Household Technology: The Effect of the Pasteur Revolution on Consumer Demand,” in The Economics of New Goods, NBER.

[10] See Werner Troesken’s work on public and private waterworks in the U.S. around the turn of the 20th century. See Galiani, Gertler, and Shargrodsky (2005), “Water for Life,” Journal of Political Economy.

[11] Brennan et al., (2013), Explaining Norms, Oxford University Press.

[12] For more on the condom code, see Carson (2017), “The Informal Norms of HIV Prevention: The emergence and erosion of the condom code,” Journal of Law, Medicine and Ethics.

[13] Carilli, Carson, and Isaacs (2022), “Jabbing Together? The complementarity between social capital, formal public health rules, and covid-19 vaccine rates in the U.S.,” Vaccine.

[14] Leslie and Wilson, “Sheltering in Place and Domestic Violence: Evidence from Calls for Service During Covid-19.” Journal of Public Economics 189, 104241. Mulligan, “Deaths of Despair and the Incidence of Excess Mortality in 2020,” NBER, https://www.nber.org/papers/w28303. Betthauser, Bach-Mortensen, and Engzell, “A systematic review and meta-analysis of the evidence on learning during the Covid-19 Pandemic,” Nature Human Behavior, https://www.nature.com/articles/s41562-022-01506-4

[15] On the great influenza epidemic, see CBS News, “During the 1918 Flu pandemic, masks were controversial for ‘many of the same reasons they are today’.” Oct. 30, 2020. https://www.cbsnews.com/news/mask-1918-flu-pandemic-controversial/

[16] On yellow fever quarantine in Mississippi, see Deanne Nuwer (2009), Plague Among the Magnolias: The 1878 Yellow Fever Epidemic in Mississippi.

[17] On these closures, see Trout (2021), “The Bathhouse Battle of 1984.” https://www.sfaf.org/collections/beta/the-bathhouse-battle-of-1984/

[18] Tusting et al. (2017), “Housing Improvement and Malaria Risk in Sub-Saharan Africa: a multi-country analysis of survey data.” PLOS Medicine.


*Byron Carson is an Associate Professor of Economics and Business at Hampden-Sydney College in Virginia, where he teaches courses on introductory economics, money and banking, health economics, and urban economics. Byron earned his Ph.D. in Economics from George Mason University in 2017, and his research interests include economic epidemiology, public choice, and Austrian economics.


This article was edited by Features Editor Ed Lopez.


(0 COMMENTS)

Read More

Continue Reading

Trending