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How do viruses spread?
Not by individual virus particles
An individual virus particle is unbelievably tiny.
Since they are so lightweight they can float in the air for relatively long distances. So that makes them airborne, right?
Yet these airborne individual virus particles are almost never a problem. Studies show that people are not at risk of being infected by single viral particle.
Why not? We’re likely always inhaling single viral particles here and there. But they quickly break down, or if they persist then our immune system quickly wipes them out.
So if that ain’t the problem then what is? The problem is when we encounter a drop of fluid, or a solid surface, which may have many hundreds or thousands of such viral particles.
Try not to touch people who may be infected! If you do touch someone then wash your hands first.
When it comes to this novel coronavirus (its formal name is SARS-CoV-2) we have to be very careful: An infected person can leave viral particles behind on anything they touch or breathe on.
Infectious material could be left behind on a table, supermarket cart, keypad on an ATM machine, a computer keyboard, on a phone, etc.
A healthy person might touch one of those surfaces, and then touch their face, which then lets those virus particles get in to your airway. That’s a problem, but we can avoid danger: Be careful of what you touch and wash your hands!
Viruses spread exponentially
How does the likelihood of death from any common cause compare to the likelihood of death from something that spreads exponentially? The important difference is that for any other cause of death, that cause is (a) usually not transmissible, and (b) the rate of death stays (more or less) the same over time.
But for deaths caused by a virus the situation is different – (c) it is transmissible from one person to another, and (d) the number of people infected grows exponentially over time.
Droplets from sneezing and coughing
Sneezing or coughing sends out lots of tiny, snotty water droplets. Each droplet could hold thousands of viral particles. If we inhaled some of these drops then that is enough to make us sick.
Most droplets are short range. The larger ones only go about six feet before they fall to the ground. That’s why it is important to practice social distancing. Stay at least six feet away from people outside of your home.
But read on – with this novel coronavirus (SARS-CoV-2) there is a bit more danger:
Smaller droplets remain in the air longer
The big particles fall quickly, but the small particles float in the air longer – and then they dehydrate (they lose water molecules.) That leaves an even tinier, lighter particle.
These super tiny particles are almost like a gel. Some call these droplet nuclei, or an aerosol, or a bioaerosol. The danger is that these very tiny globs remain airborne much longer, and can travel a further distance. They can float over 20 feet!
That isn’t quite far enough for a virus to technically be called “airborne,” but it still is super dangerous. So if you are indoors – like in a supermarket – the air could become saturated with lots of these tiny droplet nuclei, making the location unsafe.
So when people were saying “this is new coronavirus is bad, but at least it isn’t airborne,” we now know that they were partially incorrect. When indoors this virus is somewhat airborne (6 to 20 feet), and that’s why one needs to avoid supermarkets unless necessary.
Health authorities suggest wearing a mask if you have to do so. Even an imperfect mask is better than none at all.
Truly airborne viruses
An airborne virus is one that can float in very tiny aerosol drops, less than 5 microns across, for hours and still remain infectious.
A micron is 0.001 millimeters , or 0.000039 inch.
Its symbol is μm
We now have evidence that this novel coronavirus, SARS-CoV-2, is an airborne virus.
The National Academy of Sciences (NAS) has given a boost to an unsettling idea: that the novel coronavirus can spread through the air—not just through the large droplets emitted in a cough or sneeze. Though current studies aren’t conclusive, “the results of available studies are consistent with aerosolization of virus from normal breathing,”
researchers reported earlier this year in The New England Journal of Medicine that SARS-CoV-2 can float in aerosol droplets—less than 5 microns across—for up to 3 hours, and remain infectious
You may be able to spread coronavirus just by breathing, new report finds, Science, AAAS, Robert F. Service, 4/2/2020
Yes, wearing cloth face masks works!
Cloth masks can help stop the spread of COVID-19, save lives and restore jobs. About 95% of the world lives in countries where the government and leading disease experts both agree that masks are effective at reducing the spread of COVID-19.
Anyone not wearing a cloth mask in public puts everyone at risk of getting infected and they hurt our economy by increasing the chances of a second lockdown.
Why? The U.S. CDC and most experts agree that many infected and contagious people don’t know they’re sick because they don’t have symptoms. Wearing a mask significantly reduces the chances of spreading COVID-19 from you to others.
“Some people have said that covering their faces infringes on their rights, but…it’s about protecting your neighbors…Spreading this disease infringes on your neighbors’ rights.” –Larry Hogan, Governor of Maryland (Republican)
“If everybody’s wearing a mask, it will dramatically reduce the opportunity and possibility of spread.” –Charlie Baker, Governor of Massachusetts (Republican)
Countries that have contained major COVID-19 outbreaks have close to 100% mask usage. An international review of the scientific research on masks by 19 experts (from Stanford, MIT, Oxford, UPenn, Brown, UNC, UCLA, and USF) concluded that:
Near-universal adoption of non-medical masks in public (in conjunction with other measures like test & trace) can reduce effective-R below 1.0 and stop the community spread of the virus.
Laws appear to be highly effective at increasing compliance and slowing or stopping the spread of COVID-19.
There are “34 scientific papers indicating basic masks can be effective in reducing virus transmission in public — and not a single paper that shows clear evidence that they cannot.” –The Washington Post
Flight of the aerosol, Ian M Mackay et al. Virology Down Under, 2/9/2020
Jeremy Howard writes
When historians tally up the many missteps policymakers have made in response to the coronavirus pandemic, the senseless and unscientific push for the general public to avoid wearing masks should be near the top.
The evidence not only fails to support the push, it also contradicts it. It can take a while for official recommendations to catch up with scientific thinking. In this case, such delays might be deadly and economically disastrous.
It’s time to make masks a key part of our fight to contain, then defeat, this pandemic. Masks effective at “flattening the curve” can be made at home with nothing more than a T-shirt and a pair of scissors. We should all wear masks — store-bought or homemade — whenever we’re out in public.
At the height of the HIV crisis, authorities did not tell people to put away condoms. As fatalities from car crashes mounted, no one recommended avoiding seat belts. Yet in a global respiratory pandemic, people who should know better are discouraging Americans from using respiratory protection.
… There are good reasons to believe DIY masks would help a lot. Look at Hong Kong, Mongolia, South Korea and Taiwan, all of which have covid-19 largely under control. They are all near the original epicenter of the pandemic in mainland China, and they have economic ties to China.
Yet none has resorted to a lockdown, such as in China’s Wuhan province. In all of these countries, all of which were hit hard by the SARS respiratory virus outbreak in 2002 and 2003, everyone is wearing masks in public.
George Gao, director general of the Chinese Center for Disease Control and Prevention, stated, “Many people have asymptomatic or presymptomatic infections. If they are wearing face masks, it can prevent droplets that carry the virus from escaping and infecting others.”
My data-focused research institute, fast.ai, has found 34 scientific papers indicating basic masks can be effective in reducing virus transmission in public — and not a single paper that shows clear evidence that they cannot.
Studies have documented definitively that in controlled environments like airplanes, people with masks rarely infect others and rarely become infected themselves, while those without masks more easily infect others or become infected themselves.
Masks don’t have to be complex to be effective. A 2013 paper tested a variety of household materials and found that something as simple as two layers of a cotton T-shirt is highly effective at blocking virus particles of a wide range of sizes.
Oxford University found evidence this month for the effectiveness of simple fabric mouth and nose covers to be so compelling they now are officially acceptable for use in a hospital in many situations. Hospitals running short of N95-rated masks are turning to homemade cloth masks themselves; if it’s good enough to use in a hospital, it’s good enough for a walk to the store.
The reasons the WHO cites for its anti-mask advice are based not on science but on three spurious policy arguments.
First, there are not enough masks for hospital workers.
Second, masks may themselves become contaminated and pass on an infection to the people wearing them.
Third, masks could encourage people to engage in more risky behavior.
None of these is a good reason to avoid wearing a mask in public.
Yes, there is a shortage of manufactured masks, and these should go to hospital workers. But anyone can make a mask at home by cutting up a cotton T-shirt, tying it back together and then washing it at the end of the day. Another approach, recommended by the Hong Kong Consumer Council, involves rigging a simple mask with a paper towel and rubber bands that can be thrown in the trash at the end of each day.
… the idea that masks encourage risky behavior is nonsensical. We give cars anti-lock brakes and seat belts despite the possibility that people might drive more riskily knowing the safety equipment is there. Construction workers wear hard hats even though the hats presumably could encourage less attention to safety. If any risky behavior does occur, societies have the power to make laws against it.
About the author – Jeremy Howard is a distinguished research scientist at the University of San Francisco, founding researcher at fast.ai and a member of the World Economic Forum’s Global AI Council.
More reason to wear face masks:
Experts said the choir outbreak is consistent with a growing body of evidence that the virus can be transmitted through aerosols — particles smaller than 5 micrometers that can float in the air for minutes or longer.
The World Health Organization has downplayed the possibility of transmission in aerosols, stressing that the virus is spread through much larger “respiratory droplets,” which are emitted when an infected person coughs or sneezes and quickly fall to a surface.
But a study published March 17 in the New England Journal of Medicine found that when the virus was suspended in a mist under laboratory conditions it remained “viable and infectious” for three hours — though researchers have said that time period would probably be no more than a half-hour in real-world conditions.
Nell Greenfieldboyce writes
the question of whether or not the coronavirus can be “airborne” is extremely contentious right now — and it’s a question that has real implications for what people should do to avoid getting infected.
… a committee of independent experts convened by the National Academies of Sciences, Engineering, and Medicine has weighed in, in response to a question from the White House Office of Science and Technology Policy about whether the virus “could be spread by conversation in addition to sneeze/cough-induced droplets.”
“Currently available research supports the possibility that SARS-CoV-2 could be spread via bioaerosols generated directly by patients’ exhalation,” says a letter from the committee chair. By bioaerosols, they are referring to fine particles emitted when someone breathes that can be suspended in the air rather than larger droplets produced through coughs and sneezes.
Even if additional research shows that any virus in such tiny particles is viable, researchers still won’t how much of it would need to be inhaled to make someone sick. But the committee experts also caution that uncertainty about all this is almost a given—because there’s currently no respiratory virus for which we know the exact proportion of infections that come from breathing the virus in versus coming into contact with droplets in the air or on surfaces.
“I personally think that transmission by inhalation of virus in the air is happening,” says Linsey Marr, an aerosol scientist at Virginia Tech. But she says so far, health experts have largely discounted the possibility of transmitting this coronavirus in this way.
“From an infection prevention perspective, these things are not 100% black and white. The reason why we say ‘droplet’ versus ‘airborne’ versus ‘contact’ is to give overall guidance on how to manage patients who are expected to be infectious with a specific pathogen,” said Dr. Hanan Balkhy, assistant director-general for antimicrobial resistance at WHO, in an interview with NPR earlier this week.
As an expert who worked to contain an outbreak of the deadly MERS coronavirus in Saudi Arabia, she believes that this new virus should behave similarly to other severe coronaviruses — and that means, unless health-care workers are doing invasive procedures like putting in breathing tubes, the virus is expected to primarily spread through droplets.
Droplets are larger respiratory particles that are 5 to 10 micrometers in size. Those are considered “big,” even though a 5 micrometer particle would still be invisible to the naked eye. Traditionally, those droplets are thought to not travel more than about three feet or so after exhalation. That would mean the virus can only spread to people who get close to an infected person or who touch surfaces or objects that might have become contaminated by these droplets. This is why public health messages urge people to wash their hands and stand at least 6 feet away from other people.
An “airborne” virus, in contrast, has long been considered to be a virus that spreads in exhaled particles that are tiny enough to linger in the air and move with air currents, letting them be breathed in by passersby who then get sick. Measles is a good example of this kind of virus — an exhaled measles pathogen can hang suspended in a room for a couple hours after an infected person leaves.
The reality of aerosol generation, however, is far more complex than this “droplet” versus “airborne” dichotomy would suggest, says Marr. People produce a wide range of different-sized particles of mucus or saliva. These particles get smaller as they evaporate in the air and can travel different distances depending on the surrounding air conditions.
“The way the definitions have been set up, this “droplet” vs “airborne” distinction, was first established in the 1950s or even earlier,” says Marr. “There was a more limited understanding of aerosol science then.”
Even a 5 micrometer droplet can linger in the air. “If the air were perfectly still, it would take a half hour to fall from a height of 6 feet down to the ground. And, of course, the air isn’t perfectly still,” says Marr. “So it can easily be blown around during that time and stay in the air for longer or shorter.”
What’s more, coughs and sneezes create turbulent clouds of gas that can propel respiratory particles forward.
“For symptomatic, violent exhalations including sneezes and coughs, then the droplets can definitely reach much further than the 1 to 2 meter [3 to 6 feet] cutoff,” says Lydia Bourouiba, an infectious disease transmission researcher at MIT, referring to the distance typically cited as safe for avoiding droplet-carried diseases.
In fact, studies show that “given various combinations of an individual patient’s physiology and environmental conditions, such as humidity and temperature, the gas cloud and its payload of pathogen-bearing droplets of all sizes can travel 23 to 27 feet,” she wrote in a recent article published online by the Journal of the American Medical Association.
…. Some of the strongest evidence that an airborne route of transmission might be possible for this virus comes from a report published last month by the New England Journal of Medicine that described mechanically generating aerosols carrying the SARS-CoV-2 virus in the laboratory. It found that the virus in these little aerosols remained viable and infectious throughout the duration of the experiment, which lasted 3 hours.
WHO mentioned this study in its recent review of possible modes of transmission and noted that “this is a high-powered machine that does not reflect normal human cough conditions … this was an experimentally induced aerosol-generating procedure.”
It may have been artificial, says Marr, but “the conditions they used in that laboratory study are actually less favorable for survival compared to the real world. So it’s more likely that the virus can survive under real world conditions.”
Reference: Turbulent Gas Clouds and Respiratory Pathogen Emissions: Potential Implications for Reducing Transmission of COVID-19
Lydia Bourouiba, JAMA insights, March 26, 2020. doi:10.1001/jama.2020.4756
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1
March 17, 2020 , DOI: 10.1056/NEJMc2004973
A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic. We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.
… We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic.
Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed).
These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, and they provide information for pandemic mitigation efforts.
Neeltje van Doremalen, Ph.D., Trenton Bushmaker, B.Sc.
National Institute of Allergy and Infectious Diseases, Hamilton, MT
Dylan H. Morris, M.Phil., Princeton University, Princeton, NJ, Myndi G. Holbrook, B.Sc.
National Institute of Allergy and Infectious Diseases, Hamilton, MT
Amandine Gamble, Ph.D.
University of California, Los Angeles, Los Angeles, CA
Brandi N. Williamson, M.P.H.
National Institute of Allergy and Infectious Diseases, Hamilton, MT
Azaibi Tamin, Ph.D., Jennifer L. Harcourt, Ph.D.
Natalie J. Thornburg, Ph.D., Susan I. Gerber, M.D.
Centers for Disease Control and Prevention, Atlanta, GA
James O. Lloyd-Smith, Ph.D.
University of California, Los Angeles, Los Angeles, CA, Bethesda, MD
Emmie de Wit, Ph.D., Vincent J. Munster, Ph.D.
National Institute of Allergy and Infectious Diseases, Hamilton, MT
Due to the likely imminent arrival of coronavirus outbreaks in America, many school districts are preparing to fight the pandemic with the most effective tool: social distancing. This may include cancelling school, and other public events, for up to 2 weeks in affected areas.
As such, teachers may be asked to prepare 2 weeks worth of lessons for students to do at home as stand alone work. How do we efficiently prepare for this? I have been uploading resources to my website and creating worksheets based on them. In a pinch I could email our students 2 weeks worth of worksheets in PDF format, and print out packets for students with little or no internet access.
Teachers can supplement the work they assign by creating a YouTube channel with daily mini-lectures. Students could listen & ask questions from their homes.
Teachers of course don’t need their own website. They can use any of their favorite science websites, such as The Physics Classroom.
However, we shouldn’t need something like the coronavirus to begin preparing. It is just good practice for teachers to create a library of ready-to-go, self-contained lesson plans for each topic. Instead of waiting for an emergency, make this part of your weekly schedule: Each week pick your best lesson, and write a self-contained worksheet for it.
As you create handouts (whether destined for PDF or paper) please think about readability, and about students who are slow readers or who have IEPs:
Have a brief, clear introduction so the student knows what we are learning and why. See below for details.
Use a large enough font.
Have some space between each section.
Break long paragraphs into a smaller paragraphs.
Add a color graphic to help explain the concept in each section.
A packed page is a poorly-designed page. Trying to shove a class onto just a page or two is especially irrelevant since we are no longer limited by paper. Students can view as many pages as we need on their PCs, tablets, or phones.
Writing a brief, clear introduction
* Content objective:
Briefly discuss what we are learning, and/or why we are learning this. This may involve teaching new ideas, procedures, or skills.
* Vocabulary objective – What are the critical words in this lesson?
These include not only new terms that you introduce, but supposedly “common” words that one assumes the students “already know.” (The problem is that many students don’t always know what these terms means. Please click the link for more information.)
– Tier II vocabulary words: High frequency words used across content areas. They are key to understanding directions, understanding relationships, and for making inferences.
– Tier III vocabulary words: Low frequency, domain specific terms.
* Build on what we already know.
Very few lessons start completely from scratch. Most will include some vocabulary & scientific concepts that were learned in earlier grades. So in this section of your introduction, briefly make connections to prior concepts.
How are you preparing for this?
Reliable sources of information
What is a pandemic?
A pandemic is an epidemic occurring on a scale which crosses international boundaries, usually affecting a large number of people. Pandemics can also occur in important agricultural organisms (livestock, crop plants, fish, tree species) or in other organisms.
The World Health Organization (WHO) has a classification – starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people, and ends with a pandemic when infections from the new virus have spread worldwide.
A disease is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, cancer is responsible for many deaths but is not a pandemic because the disease is not infectious or contagious.
(Intro adapted from Wikipedia article, Pandemic)
Viruses spread exponentially
How does the likelihood of death from any common cause compare to the likelihood of death from something that spreads exponentially? The important difference is that for any other cause of death, that cause is (a) usually not transmissible, and (b) the rate of death stays (more or less) the same over time.
But for deaths caused by a virus the situation is different – (c) it is transmissible from one person to another, and (d) the number of people infected grows exponentially over time.
How would we respond to a pandemic?
What happens if a pandemic hits? Jon Evans, Techcrunch, 2/23/2020
Don’t get all disaster-movie here. Some people seem to have the notion that a pandemic will mean shutting down borders, building walls, canceling all air travel and quarantining entire nations indefinitely. That is incorrect. Containment attempts can slow down an outbreak and buy time to prepare, but if a pandemic hits, by definition, containment has failed… [so] the focus will switch from containment to mitigation: slowing down how fast the virus spreads through a population in which it has taken root.
Mitigation can occur via individual measures, such as frequent hand washing, and collective measures, such as “social distancing” — cancellations of mass events, closures, adopting remote work and remote education wherever possible, and so forth.
The slower the pandemic moves, the smoother the demands on health-care systems will be; the less risk those systems will have of becoming overloaded; the more they can learn about how best to treat the virus; and the greater the number of people who may ultimately benefit from a vaccine, if one is developed.
How dangerous is the Coronavirus (COVID-19) pandemic?
How should we respond to a pandemic?
Past Time to Tell the Public: “It Will Probably Go Pandemic, and We Should All Prepare Now” by Jody Lanard and Peter M. Sandman
1. Tell friends and family to try to get ahead on their medical prescriptions if they can, in case of very predictable supply chain disruptions, and so they won’t have to go out to the pharmacy at a time when there may be long lines of sick people. This helps them in a practical sense, but it also makes them visualize – often for the first time – how a pandemic may impact them in their everyday lives, even if they don’t actually catch COVID-19….
2. We also recommend that people might want to slowly (so no one will accuse them of panic-buying) start to stock up on enough non-perishable food to last their households through several weeks of social distancing at home during an intense wave of transmission in their community. This too seems to get through emotionally, as well as being useful logistically.
3. Three other recommendations that we feel have gone over well with our friends and acquaintances: Suggesting practical organizational things they and their organizations can do to get ready, such as cross-training to mitigate absenteeism. Suggesting that people make plans for childcare when they are sick, or when their child is sick.
4. Right now, today, start practicing not touching your face when you are out and about! You probably won’t be able to do it perfectly, but you can greatly reduce the frequency of potential self-inoculation. …
How should we respond to a pandemic?
Josh Michaud, Associate Director Global Health at Kaiser Family Foundation, John Hopkins School of Advanced International Studies, writes:
CDC guidance urges flexibility in implementing mitigation measures, and continual re-assessment of their effectiveness as new information comes in. A “targeted, layered” approach that addresses current circumstances is the best practice. The ultimate goal of such measures is to reduce the intensity of an outbreak, flattening out the epidemic curve and therefore reducing strain on the health system, and on social economic well-being (see this graphic representation).
With community transmission of #COVID19 in multiple countries it appears that containment of the virus in China will not happen (this outcome was not unexpected). Emphasis in many places could turn from containment to “mitigation”. What does mitigation mean?
First, to be clear: it’s not either/or, because containment efforts and mitigation efforts encompass a spectrum of activities, are complementary and can occur at the same time.
Still, we can contrast their goals: containment is meant to halt transmission, while mitigation is meant to reduce negative impacts of transmission.
For the U.S., CDC has long had recommendations for how communities can use mitigation to address pandemic influenza. A revision to this guidance came in 2017, incorporating lessons learned from the 2009 H1N1 influenza pandemic.
“Community Mitigation Guidelines to Prevent Pandemic Influenza — United States, 2017”
Not all guidance from pandemic influenza is applicable to #COVID19 because the epidemiology and circumstances differ, but countries face similar challenges with both.
For example, both are highly transmissible, and in both cases we have no specific countermeasures available at first (e.g. vaccines). Containment is difficult if not impossible in both cases.
The 2009 H1N1 pandemic is often remembered as being “mild”, but there was a quite a significant health impact: an estimated 43-89 million people in the US were infected and 12,000 people died between Apr2009-Apr2010.
CDC talks about mitigation in three buckets: 1) individuals behaviors (hand hygiene, staying at home, avoiding ill people); 2) “social distancing” (closing schools and public gatherings, and 3) environmental mitigation (surface cleaning efforts). Let’s focus in 1 and 2.
Encouraging better individual hygiene behaviors is cornerstone of mitigation. Good hand hygiene (wash those hands!), and voluntary home isolation when ill (and even home quarantine when potentially exposed) are recommended.
Many studies show the effectiveness of hand hygiene; one study on H1N1 from Egypt highlighted by CDC showed 47% fewer cases of influenza occurred after twice-daily hand washing and health hygiene instruction was provided in elementary schools.
Studies of the US public during H1N1 found that people actually did change their hygiene behaviors: in one survey 59% of Americans reported washing hands more frequently and 25% said they avoided public places like sporting events, malls, and public transportation.
CDC guidelines also support social distancing in some cases, including school closures, canceling public gatherings, and workplace closures/telework.
During H1N1, CDC recommended communities with confirmed cases consider closing child care facilities and schools. From Aug–Dec 2009, communities in 46 states implemented 812 dismissals (in a single school or all schools in a district), affecting 1,947 schools.
This number of schools represented 0.7% and 3.3% of all urban and rural schools, respectively, in the U.S. Evidence from TX indicated school closures there reduced acute respiratory illness in households with school-age children by 45%–72%.
Interestingly, surveys of parents whose children were affected by school closures found strong support for, and belief in the effectiveness of these measures: 90% of parents agreed with dismissal decisions, and 85% believed dismissals reduced transmission.
Even so, closing schools was disruptive, and a systematic review of US school closures during H1N1 was not able to determine whether the benefits outweighed the cost in this “mild” epidemic, though they did recommend such measures during a “severe” pandemic.
CDC guidelines also note there are practical obstacles to asking people to stay home from school and work: in 2009 a major difficulty was that many people did not have access to paid leave, and therefore had a hard time following guidance.
Another challenge for mitigation in the U.S. is that while CDC can offer recommendations and guidance, implementation of these policies mostly occurs at local district, county, & state levels. This can lead to a patchwork of different mitigation approaches across locations.
A recent publication looked at US local health department decision-making around social distancing during outbreaks, and concluded resources available and actions implemented are inconsistent and unpredictable across the country. https://journals-sagepub-com.proxy1.library.jhu.edu/doi/pdf/10.1177/0033354918819755
CDC guidance urges flexibility in implementing mitigation measures, and continual re-assessment of their effectiveness as new information comes in. A “targeted, layered” approach that addresses current circumstances is the best practice.
The ultimate goal of such measures is to reduce the intensity of an outbreak, flattening out the epidemic curve and therefore reducing strain on the health system, and on social economic well-being (see this graphic representation).
Reliable sources of information
Autism Shares Brain Signature with Schizophrenia and Bipolar Disorder, By Nicholette Zeliadt, Spectrum, Scientific American, February 8, 2018
Gene expression patterns in the brains of people with these conditions, new research finds
Gene expression patterns in the brains of people with autism are similar to those of people who have schizophrenia or bipolar disorder, according to a large study of postmortem brain tissue. The findings appear today in Science.
All three conditions show an activation of genes in star-shaped brain cells called astrocytes, and suppression of genes that function at synapses, the junctions between neurons. The autism brains also show a unique increase in the expression of genes specific to immune cells called microglia.
“This study demonstrates for the first time that [gene expression] can be used to robustly define cross-disorder phenotypes that are shared and distinct,” says lead investigator Daniel Geschwind, professor of neurology, psychiatry and human genetics at the University of California, Los Angeles. “And these phenotypes are related to the molecular and cellular pathways that likely have gone awry.”
People who have one of these conditions may have features in common, such as language problems, irritability and aggression. They also share certain genetic variants that raise the risk of the conditions.
The new work shows that the overlap among risk variants is related to the commonality in their gene expression patterns. This hints that the variants raise risk in part by turning on or off certain sets of genes in the brain.
“We’re seeing all these studies coming out finding links between genetic variants and psychiatric [conditions], but how do we go from genetic risk to mechanisms?” says Emma Meaburn, senior lecturer of psychological sciences at Birkbeck University of London, who was not involved in the study. “This paper begins to fill that gap.”
By Nicholetter Zeliadt, Spectrum News, 1/13/2020
Some of the inherited variants implicated in autism also increase the odds of other conditions, including schizophrenia, bipolar disorder, depression and attention deficit hyperactivity disorder (ADHD), according to a new study1.
The results come from an international effort called the Psychiatric Genomics Consortium, which involves more than 800 scientists. “These disorders, which we think of as very clinically different, might be related at the level of their genetic basis,” says lead investigator Jordan Smoller, associate chief for research in psychiatry at Massachusetts General Hospital in Boston.
Smoller and his colleagues analyzed data from 727,126 people, about one-third of whom have one or more of eight psychiatric conditions. The team focused on so-called common variants — single-letter changes to DNA that appear in 1 percent or more of the population.
The team linked 146 variants to least one condition, and most of them to multiple conditions. Variants in the latter group tend to affect genes that are highly expressed throughout life, starting during the second trimester of fetal development, and may be key to brain development.
“More and more, the picture that’s emerging is that there are multiple [variants] associated with, let’s say, a psychiatric vulnerability that is not specific to one disorder,” says Tinca Polderman, assistant professor of complex trait genetics at Vrije Universiteit Amsterdam in the Netherlands, who was not involved in the work. “Whether it develops into autism or [something else] may have to do with other factors.”
Reference – Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders, There are 606 authors, collectively referred to as the Cross-Disorder Group of the Psychiatric Genomics Consortium. Cell. 2019 Dec 12; 179(7):1469-1482.e11. doi: 10.1016/j.cell.2019.11.020.
The Same Genes May Underlie Different Psychiatric Disorders: A distinct set of genes may underlie several psychiatric conditions. By Mark Fischetti, Scientific American, July 1, 2018
People who have autism, schizophrenia and bipolar disorder may have different challenges, but the ailments might arise from a common set of genes. Researchers compared genetic analyses of 700 human brains from deceased individuals who had one of those three disorders, major depression or alcoholism (columns) with brains of individuals who had none of the conditions. They examined 13 groups of genes thought to function together (rows).
The scientists found that five groups had a pattern of overactivity or underactivity across at least three of the five conditions (blue and gray panels). Bipolar disorder, for example, was more similar to schizophrenia than to major depression even though clinicians may link bipolar disorder and depression, based on their symptoms.
These insights could possibly reveal new treatments, says neurogeneticist Daniel Geschwind of the University of California, Los Angeles, one of the investigators. He adds that one path to that result, which has not yet been tested, could be to “put the different groups of genes in lab dishes and see which drugs reverse any overexpression or underexpression of the genes.”
Graphic by Martin Krzywinski; Source: “Shared Molecular Neuropathology across Major Psychiatric Disorders Parallels Polygenic Overlap,” by Michael J. Gandal et al., in Science. Vol. 359; February 9, 2018
At the moment this is a placeholder article,
What if the Placebo Effect Isn’t a Trick? New research is zeroing in on a biochemical basis for the placebo effect — possibly opening a Pandora’s box for Western medicine.
The New York Times Magazine, Gary Greenberg, Nov 7, 2018
Give people a sugar pill, they have shown, and those patients — especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence — will improve. Tell someone a normal milkshake is a diet beverage, and his gut will respond as if the drink were low fat. Take athletes to the top of the Alps, put them on exercise machines and hook them to an oxygen tank, and they will perform better than when they are breathing room air — even if room air is all that’s in the tank. Wake a patient from surgery and tell him you’ve done an arthroscopic repair, and his knee gets better even if all you did was knock him out and put a couple of incisions in his skin. Give a drug a fancy name, and it works better than if you don’t.
You don’t even have to deceive the patients. You can hand a patient with irritable bowel syndrome a sugar pill, identify it as such and tell her that sugar pills are known to be effective when used as placebos, and she will get better, especially if you take the time to deliver that message with warmth and close attention. Depression, back pain, chemotherapy-related malaise, migraine, post-traumatic stress disorder: The list of conditions that respond to placebos — as well as they do to drugs, with some patients — is long and growing.
But as ubiquitous as the phenomenon is, and as plentiful the studies that demonstrate it, the placebo effect has yet to become part of the doctor’s standard armamentarium — and not only because it has a reputation as “fake medicine” doled out by the unscrupulous to the credulous. It also has, so far, resisted a full understanding, its mechanisms shrouded in mystery. Without a clear knowledge of how it works, doctors can’t know when to deploy it, or how.
Not that the researchers are without explanations. But most of these have traditionally been psychological in nature, focusing on mechanisms like expectancy — the set of beliefs that a person brings into treatment — and the kind of conditioning that Ivan Pavlov first described more than a century ago. These theories, which posit that the mind acts upon the body to bring about physical responses, tend to strike doctors and researchers steeped in the scientific tradition as insufficiently scientific to lend credibility to the placebo effect.
“What makes our research believable to doctors?” asks Ted Kaptchuk, head of Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter. “It’s the molecules. They love that stuff.” As of now, there are no molecules for conditioning or expectancy — or, indeed, for Kaptchuk’s own pet theory, which holds that the placebo effect is a result of the complex conscious and nonconscious processes embedded in the practitioner-patient relationship — and without them, placebo researchers are hard-pressed to gain purchase in mainstream medicine.
But as many of the talks at the conference indicated, this might be about to change. Aided by functional magnetic resonance imaging (f.M.R.I.) and other precise surveillance techniques, Kaptchuk and his colleagues have begun to elucidate an ensemble of biochemical processes that may finally account for how placebos work and why they are more effective for some people, and some disorders, than others. The molecules, in other words, appear to be emerging. And their emergence may reveal fundamental flaws in the way we understand the body’s healing mechanisms, and the way we evaluate whether more standard medical interventions in those processes work, or don’t. Long a useful foil for medical science, the placebo effect might soon represent a more fundamental challenge to it.
In a way, the placebo effect owes its poor reputation to the same man who cast aspersions on going to bed late and sleeping in. Benjamin Franklin was, in 1784, the ambassador of the fledgling United States to King Louis XVI’s court. Also in Paris at the time was a Viennese physician named Franz Anton Mesmer. Mesmer fled Vienna a few years earlier when the local medical establishment determined that his claim to have cured a young woman’s blindness by putting her into a trance was false, and that, even worse, there was something unseemly about his relationship with her.
By the time he arrived in Paris and hung out his shingle, Mesmer had acquired what he lacked in Vienna: a theory to account for his ability to use trance states to heal people. There was, he claimed, a force pervading the universe called animal magnetism that could cause illness when perturbed. Conveniently enough for Mesmer, the magnetism could be perceived and de-perturbed only by him and people he had trained.
Mesmer’s method was strange, even in a day when doctors routinely prescribed bloodletting and poison to cure the common cold. A group of people complaining of maladies like fatigue, numbness, paralysis and chronic pain would gather in his office, take seats around an oak cask filled with water and grab on to metal rods immersed in the water. Mesmer would alternately chant, play a glass harmonium and wave his hands at the afflicted patients, who would twitch and cry out and sometimes even lose consciousness, whereupon they would be carried to a recovery room. Enough people reported good results that patients were continually lined up at Mesmer’s door waiting for the next session.
It was the kind of success likely to arouse envy among doctors, but more was at stake than professional turf. Mesmer’s claim that a force existed that could only be perceived and manipulated by the elect few was a direct challenge to an idea central to the Enlightenment: that the truth could be determined by anyone with senses informed by skepticism, that Scripture could be supplanted by facts and priests by a democracy of people who possessed them. So, when the complaints about Mesmer came to Louis, it was to the scientists that the king — at pains to show himself an enlightened man — turned. He appointed, among others, Lavoisier the chemist, Bailly the astronomer and Guillotin the physician to investigate Mesmer’s claims, and he installed Franklin at the head of their commission.
To the Franklin commission, the question wasn’t whether Mesmer was a fraud and his patients were dupes. Everyone could be acting in good faith, but belief alone did not prove that the magnetism was at work. To settle this question, they designed a series of trials that ruled out possible causes of the observed effects other than animal magnetism. The most likely confounding variable, they thought, was some faculty of mind that made people behave as they did under Mesmer’s ministrations. To rule this out, the panel settled upon a simple method: a blindfold. Over a period of a few months, they ran a series of experiments that tested whether people experienced the effects of animal magnetism even when they couldn’t see.
One of Mesmer’s disciples, Charles d’Eslon, conducted the tests. The panel instructed him to wave his hands at a part of a patient’s body, and then asked the patient where the effect was felt. They took him to a copse to magnetize a tree — Mesmer claimed that a patient could be treated by touching one — and then asked the patient to find it. They told patients d’Eslon was in the room when he was not, and vice versa, or that he was doing something that he was not. In trial after trial, the patients responded as if the doctor were doing what they thought he was doing, not what he was actually doing.
It was possibly the first-ever blinded experiment, and it soundly proved what scientists today call the null hypothesis: There was no causal connection between the behavior of the doctor and the response of the patients, which meant, as Franklin’s panel put it in their report, that “this agent, this fluid, has no existence.” That didn’t imply that people were pretending to twitch or cry out, or lying when they said they felt better; only that their behavior wasn’t a result of this nonexistent force. Rather, the panel wrote, “the imagination singly produces all the effects attributed to the magnetism.”
When the panel gave d’Eslon a preview of its findings, he took it with equanimity. Given the results of the treatment (as opposed to the experiment), he opined, the imagination, “directed to the relief of suffering humanity, would be a most valuable means in the hands of the medical profession” — a subject to which these august scientists might wish to apply their methods. But events intervened. Franklin was called back to America in 1785; Louis XVI had bigger trouble on his hands and, along with Lavoisier and Bailly, eventually met with the short, sharp shock of the device named for Guillotin.
The panel’s report was soon translated into English by William Godwin, the father of Mary Shelley. The story spread fast — not because of the healing potential that d’Eslon had suggested, but because of the implications for science as a whole. The panel had demonstrated that by putting imagination out of play, science could find the truth about our suffering bodies, in the same way it had found the truth about heavenly bodies.
Hiving off subjectivity from the rest of medical practice, the Franklin commission had laid the conceptual foundation for the brilliant discoveries of modern medicine, the antibiotics and vaccines and other drugs that can be dispensed by whoever happens to possess the prescription pad, and to whoever happens to have the disease. Without meaning to, they had created an epistemology for the healing arts — and, in the process, inadvertently conjured the placebo effect, and established it as that to which doctors must remain blind.
It wouldn’t be the last time science would turn its focus to the placebo effect only to quarantine it. At a 1955 meeting of the American Medical Association, the Harvard surgeon Henry Beecher pointed out to his colleagues that while they might have thought that placebos were fake medicine — even the name, which means “I shall please” in Latin, carries more than a hint of contempt — they couldn’t deny that the results were real. Beecher had been looking at the subject systematically, and he determined that placebos could relieve anxiety and postoperative pain, change the blood chemistry of patients in a way similar to drugs and even cause side effects. In general, he told them, more than one-third of patients would get better when given a treatment that was, pharmacologically speaking, inert.
If the placebo was as powerful as Beecher said, and if doctors wanted to know whether their drugs actually worked, it was not sufficient simply to give patients the drugs and see whether they did better than patients who didn’t interact with the doctor at all. Instead, researchers needed to assume that the placebo effect was part of every drug effect, and that drugs could be said to work only to the extent that they worked better than placebos. An accurate measure of drug efficacy would require comparing the response of patients taking it with that of patients taking placebos; the drug effect could then be calculated by subtracting the placebo response from the overall response, much as a deli-counter worker subtracts the weight of the container to determine how much lobster salad you’re getting.
In the last half of the 1950s, this calculus gave rise to a new way to evaluate drugs: the double-blind, placebo-controlled clinical trial, in which neither patient nor clinician knew who was getting the active drug and who the placebo. In 1962, when the Food and Drug Administration began to require pharmaceutical companies to prove their new drugs were effective before they came to market, they increasingly turned to the new method; today, virtually every prospective new drug has to outperform placebos on two independent studies in order to gain F.D.A. approval.
Like Franklin’s commission, the F.D.A. had determined that the only way to sort out the real from the fake in medicine was to isolate the imagination. It also echoed the royal panel by taking note of the placebo effect only long enough to dismiss it, giving it a strange dual nature: It’s included in clinical trials because it is recognized as an important part of every treatment, but it is treated as if it were not important in itself. As a result, although virtually every clinical trial is a study of the placebo effect, it remains underexplored — an outcome that reflects the fact that there is no money in sugar pills and thus no industry interest in the topic as anything other than a hurdle it needs to overcome.
When Ted Kaptchuk was asked to give the opening keynote address at the conference in Leiden, he contemplated committing the gravest heresy imaginable: kicking off the inaugural gathering of the Society for Interdisciplinary Placebo Studies by declaring that there was no such thing as the placebo effect.
When he broached this provocation in conversation with me not long before the conference, it became clear that his point harked directly back to Franklin: that the topic he and his colleagues studied was created by the scientific establishment, and only in order to exclude it — which means that they are always playing on hostile terrain. Science is “designed to get rid of the husks and find the kernels,” he told me.
Much can be lost in the threshing — in particular, Kaptchuk sometimes worries, the rituals embedded in the doctor-patient encounter that he thinks are fundamental to the placebo effect, and that he believes embody an aspect of medicine that has disappeared as scientists and doctors pursue the course laid by Franklin’s commission. “Medical care is a moral act,” he says, in which a suffering person puts his or her fate in the hands of a trusted healer.
“I don’t love science,” Kaptchuk told me. “I want to know what heals people.” Science may not be the only way to understand illness and healing, but it is the established way. “That’s where the power is,” Kaptchuk says. That instinct is why he left his position as director of a pain clinic in 1990 to join Harvard — and it’s why he was delighted when, in 2010, he was contacted by Kathryn Hall, a molecular biologist. Here was someone with an interest in his topic who was also an expert in molecules, and who might serve as an emissary to help usher the placebo into the medical establishment.
Hall’s own journey into placebo studies began 15 years before her meeting with Kaptchuk, when she developed a bad case of carpal tunnel syndrome. Wearing a wrist brace didn’t help, and neither did over-the-counter drugs or the codeine her doctor prescribed. When a friend suggested she visit an acupuncturist, Hall balked at the idea of such an unscientific approach. But faced with the alternative, surgery, she decided to make an appointment. “I was there for maybe 10 minutes,” she recalls, “when she stuck a needle here” — Hall points to a spot on her forearm — “and this awful pain just shot through my arm.” But then the pain receded and her symptoms disappeared, as if they had been carried away on the tide. She received a few more treatments, during which the acupuncturist taught her how to manipulate a spot near her elbow if the pain recurred. Hall needed the fix from time to time, but the problem mostly just went away.
“I couldn’t believe it,” she told me. “Two years of gross drugs, and then just one treatment.” All these years later, she’s still wonder-struck. “What was that?” she asks. “Rub the spot, and the pain just goes away?”
Hall was working for a drug company at the time, but she soon left to get a master’s degree in visual arts, after which she started a documentary-production company. She was telling her carpal-tunnel story to a friend one day and recounted how the acupuncturist had climbed up on the table with her. (“I was like, ‘Oh, my God, what is this woman doing?’ ” she told me. “It was very dramatic.”) She’d never been able to understand how the treatment worked, and this memory led her to wonder out loud if maybe the drama itself had something to do with the outcome.
Her friend suggested she might find some answers in Ted Kaptchuk’s work. She picked up his book about Chinese medicine, “The Web that Has No Weaver,” in which he mentioned the possibility that placebo effects figure strongly in acupuncture, and then she read a study he had conducted that put that question to the test.
Kaptchuk had divided people with irritable bowel syndrome into three groups. In one, acupuncturists went through all the motions of treatment, but used a device that only appeared to insert a needle. Subjects in a second group also got sham acupuncture, but delivered with more elaborate doctor-patient interaction than the first group received. A third group was given no treatment at all. At the end of the trial, both treatment groups improved more than the no-treatment group, and the “high interaction” group did best of all.
Kaptchuk, who before joining Harvard had been an acupuncturist in private practice, wasn’t particularly disturbed by the finding that his own profession worked even when needles were not actually inserted; he’d never thought that placebo treatments were fake medicine. He was more interested in how the strength of the treatment varied with the quality and quantity of interaction between the healer and the patient — the drama, in other words. Hall reached out to him shortly after she read the paper.
The findings of the I.B.S. study were in keeping with a hypothesis Kaptchuk had formed over the years: that the placebo effect is a biological response to an act of caring; that somehow the encounter itself calls forth healing and that the more intense and focused it is, the more healing it evokes. He elaborated on this idea in a comparative study of conventional medicine, acupuncture and Navajo “chantway rituals,” in which healers lead storytelling ceremonies for the sick. He argued that all three approaches unfold in a space set aside for the purpose and proceed as if according to a script, with prescribed roles for every participant. Each modality, in other words, is its own kind of ritual, and Kaptchuk suggested that the ritual itself is part of what makes the procedure effective, as if the combined experiences of the healer and the patient, reinforced by the special-but-familiar surroundings, evoke a healing response that operates independently of the treatment’s specifics. “Rituals trigger specific neurobiological pathways that specifically modulate bodily sensations, symptoms and emotions,” he wrote. “It seems that if the mind can be persuaded, the body can sometimes act accordingly.” He ended that paper with a call for further scientific study of the nexus between ritual and healing.
When Hall contacted him, she seemed like a perfect addition to the team he was assembling to do just that. He even had an idea of exactly how she could help. In the course of conducting the study, Kaptchuk had taken DNA samples from subjects in hopes of finding some molecular pattern among the responses. This was an investigation tailor-made to Hall’s expertise, and she agreed to take it on. Of course, the genome is vast, and it was hard to know where to begin — until, she says, she and Kaptchuk attended a talk in which a colleague presented evidence that an enzyme called COMT affected people’s response to pain and painkillers. Levels of that enzyme, Hall already knew, were also correlated with Parkinson’s disease, depression and schizophrenia, and in clinical trials people with those conditions had shown a strong placebo response. When they heard that COMT was also correlated with pain response — another area with significant placebo effects — Hall recalls, “Ted and I looked at each other and were like: ‘That’s it! That’s it!’ ”
It is not possible to assay levels of COMT directly in a living brain, but there is a snippet of the genome called rs4680 that governs the production of the enzyme, and that varies from one person to another: One variant predicts low levels of COMT, while another predicts high levels. When Hall analyzed the I.B.S. patients’ DNA, she found a distinct trend. Those with the high-COMT variant had the weakest placebo responses, and those with the opposite variant had the strongest. These effects were compounded by the amount of interaction each patient got: For instance, low-COMT, high-interaction patients fared best of all, but the low-COMT subjects who were placed in the no-treatment group did worse than the other genotypes in that group. They were, in other words, more sensitive to the impact of the relationship with the healer.
The discovery of this genetic correlation to placebo response set Hall off on a continuing effort to identify the biochemical ensemble she calls the placebome — the term reflecting her belief that it will one day take its place among the other important “-omes” of medical science, from the genome to the microbiome. The rs4680 gene snippet is one of a group that governs the production of COMT, and COMT is one of a number of enzymes that determine levels of catecholamines, a group of brain chemicals that includes dopamine and epinephrine. (Low COMT tends to mean higher levels of dopamine, and vice versa.) Hall points out that the catecholamines are associated with stress, as well as with reward and good feeling, which bolsters the possibility that the placebome plays an important role in illness and health, especially in the chronic, stress-related conditions that are most susceptible to placebo effects.
Her findings take their place among other results from neuroscientists that strengthen the placebo’s claim to a place at the medical table, in particular studies using f.M.R.I. machines that have found consistent patterns of brain activation in placebo responders. “For years, we thought of the placebo effect as the work of imagination,” Hall says. “Now through imaging you can literally see the brain lighting up when you give someone a sugar pill.”
One group with a particularly keen interest in those brain images, as Hall well knows, is her former employers in the pharmaceutical industry. The placebo effect has been plaguing their business for more than a half-century — since the placebo-controlled study became the clinical-trial gold standard, requiring a new drug to demonstrate a significant therapeutic benefit over placebo to gain F.D.A. approval.
That’s a bar that is becoming ever more difficult to surmount, because the placebo effect seems to be becoming stronger as time goes on. A 2015 study published in the journal Pain analyzed 84 clinical trials of pain medication conducted between 1990 and 2013 and found that in some cases the efficacy of placebo had grown sharply, narrowing the gap with the drugs’ effect from 27 percent on average to just 9 percent. The only studies in which this increase was detected were conducted in the United States, which has spawned a variety of theories to explain the phenomenon: that patients in the United States, one of only two countries where medications are allowed to be marketed directly to consumers, have been conditioned to expect greater benefit from drugs; or that the larger and longer-duration trials more common in America have led to their often being farmed out to contract organizations whose nurses’ only job is to conduct the trial, perhaps fostering a more placebo-triggering therapeutic interaction.
Whatever the reason, a result is that drugs that pass the first couple of stages of the F.D.A. approval process founder more and more frequently in the larger late-stage trials; more than 90 percent of pain medications now fail at this stage. The industry would be delighted if it were able to identify placebo responders — say, by their genome — and exclude them from clinical trials.
That may seem like putting a thumb on the scale for drugs, but under the logic of the drug-approval regime, to eliminate placebo effects is not to cheat; it merely reduces the noise in order for the drug’s signal to be heard more clearly. That simple logic, however, may not hold up as Hall continues her research into the genetic basis of the placebo. Indeed, that research may have deeper implications for clinical drug trials, and for the drugs themselves, than pharma companies might expect.
Since 2013, Hall has been involved with the Women’s Health Study, which has tracked the cardiovascular health of nearly 40,000 women over more than 20 years. The subjects were randomly divided into four groups, following standard clinical-trial protocol, and received a daily dose of either vitamin E, aspirin, vitamin E with aspirin or a placebo. A subset also had their DNA sampled — which, Hall realized, offered her a vastly larger genetic database to plumb for markers correlated to placebo response. Analyzing the data amassed during the first 10 years of the study, Hall found that the women with the low-COMT gene variant had significantly higher rates of heart disease than women with the high-COMT variant, and that the risk was reduced for those low-COMT women who received the active treatments but not in those given placebos. Among high-COMT people, the results were the inverse: Women taking placebos had the lowest rates of disease; people in the treatment arms had an increased risk.
These findings in some ways seem to confound the results of the I.B.S. study, in which it was the low-COMT patients who benefited most from the placebo. But, Hall argues, what’s important isn’t the direction of the effect, but rather that there is an effect, one that varies depending on genotype — and that the same gene variant also seems to determine the relative effectiveness of the drug. This outcome contradicts the logic underlying clinical trials. It suggests that placebo and drug do not involve separate processes, one psychological and the other physical, that add up to the overall effectiveness of the treatment; rather, they may both operate on the same biochemical pathway — the one governed in part by the COMT gene.
Hall has begun to think that the placebome will wind up essentially being a chemical pathway along which healing signals travel — and not only to the mind, as an experience of feeling better, but also to the body. This pathway may be where the brain translates the act of caring into physical healing, turning on the biological processes that relieve pain, reduce inflammation and promote health, especially in chronic and stress-related illnesses — like irritable bowel syndrome and some heart diseases. If the brain employs this same pathway in response to drugs and placebos, then of course it is possible that they might work together, like convoys of drafting trucks, to traverse the territory. But it is also possible that they will encroach on one another, that there will be traffic jams in the pathway.
What if, Hall wonders, a treatment fails to work not because the drug and the individual are biochemically incompatible, but rather because in some people the drug interferes with the placebo response, which if properly used might reduce disease? Or conversely, what if the placebo response is, in people with a different variant, working against drug treatments, which would mean that a change in the psychosocial context could make the drug more effective? Everyone may respond to the clinical setting, but there is no reason to think that the response is always positive. According to Hall’s new way of thinking, the placebo effect is not just some constant to be subtracted from the drug effect but an intrinsic part of a complex interaction among genes, drugs and mind. And if she’s right, then one of the cornerstones of modern medicine — the placebo-controlled clinical trial — is deeply flawed.
When Kathryn Hall told Ted Kaptchuk what she was finding as she explored the relationship of COMT to the placebo response, he was galvanized. “Get this molecule on the map!” he urged her. It’s not hard to understand his excitement. More than two centuries after d’Eslon suggested that scientists turn their attention directly to the placebo effect, she did exactly that and came up with a finding that might have persuaded even Ben Franklin.
But Kaptchuk also has a deeper unease about Hall’s discovery. The placebo effect can’t be totally reduced to its molecules, he feels certain — and while research like Hall’s will surely enhance its credibility, he also sees a risk in playing his game on scientific turf. “Once you start measuring the placebo effect in a quantitative way,” he says, “you’re transforming it to be something other than what it is. You suck out what was previously there and turn it into science.” Reduced to its molecules, he fears, the placebo effect may become “yet another thing on the conveyor belt of routinized care.”
“We’re dancing with the devil here,” Kaptchuk once told me, by way of demonstrating that he was aware of the risks he’s taking in using science to investigate a phenomenon it defined only to exclude. Kaptchuk, an observant Jew who is a student of both the Torah and the Talmud, later modified his comment. It’s more like Jacob wrestling with the angel, he said — a battle that Jacob won, but only at the expense of a hip injury that left him lame for the rest of his life.
Indeed, Kaptchuk seems wounded when he complains about the pervasiveness of research that uses healthy volunteers in academic settings, as if the response to mild pain inflicted on an undergraduate participating in an on-campus experiment is somehow comparable to the despair often suffered by people with chronic, intractable pain. He becomes annoyed when he talks about how quickly some of his colleagues want to move from these studies to clinical recommendations. And he can even be disparaging of his own work, wondering, for instance, whether the study in which placebos were openly given to irritable bowel syndrome patients succeeded only because it convinced the subjects that the sugar was really a drug. But it’s the prospect of what will become of his findings, and of the placebo, as they make their way into clinical practice, that really seems to torment him.
Kaptchuk may wish “to help reconfigure biomedicine by rejecting the idea that healing is only the application of mechanical tools.” He may believe that healing is a moral act in which “caring in the context of hope qualitatively changes clinical outcomes.” He may be convinced that the relationship kindled by the encounter between a suffering person and a healer is a central, and almost entirely overlooked, component of medical treatment. And he may have dedicated the last 20 years of his life to persuading the medical establishment to listen to him. But he may also come to regret the outcome.
After all, if Hall is right that clinician warmth is especially effective with a certain genotype, then, as she wrote in the paper presenting her findings from the I.B.S./sham-acupuncture study, it is also true that a different group will “derive minimum benefit” from “empathic attentions.” Should medical rituals be doled out according to genotype, with warmth and caring withheld in order to clear the way for the drugs? And if she is correct that a certain ensemble of neurochemical events underlies the placebo effect, then what is to stop a drug company from manufacturing a drug — a real drug, that is — that activates the same process pharmacologically? Welcomed back into the medical fold, the placebo effect may raise enough mischief to make Kaptchuk rue its return, and bewilder patients when they discover that their doctor’s bedside manner is tailored to their genes.
For the most part, most days, Kaptchuk manages to keep his qualms to himself, to carry on as if he were fully confident that scientific inquiry can restore the moral dimension to medicine. But the precariousness of his endeavors is never far from his mind. “Will this work destroy the stuff that actually has to do with wisdom, preciousness, imagination, the things that are actually critical to who we are as human beings?” he asks. His answer: “I don’t know, but I have to believe there is an infinite reserve of wisdom and imagination that will resist being reduced to simple materialistic explanations.”
The ability to hold two contradictory thoughts in mind at the same time seems to come naturally to Kaptchuk, but he may overestimate its prevalence in the rest of us. Even if his optimism is well placed, however, there’s nothing like being sick to make a person toss that kind of intelligence aside in favor of the certainties offered by modern medicine. Indeed, it’s exactly that yearning that sickness seems to awaken and that our healers, imbued with the power of science, purport to provide, no imagination required. Armed with our confidence in them, we’re pleased to give ourselves over to their ministrations, and pleased to believe that it’s the molecules, and the molecules alone, that are healing us. People do like to be cheated, after all.
Gary Greenberg is the author, most recently, of “The Book of Woe: The DSM and the Unmaking of Psychiatry.” He is a contributing editor for Harper’s Magazine. This is his first article for the magazine.
A version of this article appears in print on Nov. 11, 2018, on Page 50 of the Sunday Magazine with the headline: Why Nothing Works.
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Possible causes of Alzheimer’s diseases
We currently don’t know the cause of Alzheimer’s disease. There may be more than one cause.
Two proteins central to the pathology of Alzheimer’s disease act as prions—misshapen proteins that spread through tissue like an infection by forcing normal proteins to adopt the same misfolded shape—according to new UC San Francisco research.
Using novel laboratory tests, the researchers were able to detect and measure specific, self-propagating prion forms of the proteins amyloid beta (A-β) and tau in postmortem brain tissue of 75 Alzheimer’s patients. In a striking finding, higher levels of these prions in human brain samples were strongly associated with early-onset forms of the disease and younger age at death.
by University of California, San Francisco
Alzheimer’s disease: mounting evidence that herpes virus is a cause, The Conversation US, Oct 19, 2018
Ruth Itzhaki, Professor Emeritus of Molecular Neurobiology, University of Manchester
More than 30m people worldwide suffer from Alzheimer’s disease – the most common form of dementia. Unfortunately, there is no cure, only drugs to ease the symptoms. However, my latest review, suggests a way to treat the disease. I found the strongest evidence yet that the herpes virus is a cause of Alzheimer’s, suggesting that effective and safe antiviral drugs might be able to treat the disease. We might even be able to vaccinate our children against it.
The virus implicated in Alzheimer’s disease, herpes simplex virus type 1 (HSV1), is better known for causing cold sores. It infects most people in infancy and then remains dormant in the peripheral nervous system (the part of the nervous system that isn’t the brain and the spinal cord). Occasionally, if a person is stressed, the virus becomes activated and, in some people, it causes cold sores.
We discovered in 1991 that in many elderly people HSV1 is also present in the brain. And in 1997 we showed that it confers a strong risk of Alzheimer’s disease when present in the brain of people who have a specific gene known as APOE4.
The virus can become active in the brain, perhaps repeatedly, and this probably causes cumulative damage. The likelihood of developing Alzheimer’s disease is 12 times greater for APOE4 carriers who have HSV1 in the brain than for those with neither factor.
Later, we and others found that HSV1 infection of cell cultures causes beta-amyloid and abnormal tau proteins to accumulate. An accumulation of these proteins in the brain is characteristic of Alzheimer’s disease.
We believe that HSV1 is a major contributory factor for Alzheimer’s disease and that it enters the brains of elderly people as their immune system declines with age. It then establishes a latent (dormant) infection, from which it is reactivated by events such as stress, a reduced immune system and brain inflammation induced by infection by other microbes.
Reactivation leads to direct viral damage in infected cells and to viral-induced inflammation. We suggest that repeated activation causes cumulative damage, leading eventually to Alzheimer’s disease in people with the APOE4 gene.
Presumably, in APOE4 carriers, Alzheimer’s disease develops in the brain because of greater HSV1-induced formation of toxic products, or less repair of damage.
New treatments? The data suggest that antiviral agents might be used for treating Alzheimer’s disease. The main antiviral agents, which are safe, prevent new viruses from forming, thereby limiting viral damage.
In an earlier study, we found that the anti-herpes antiviral drug, acyclovir, blocks HSV1 DNA replication, and reduces levels of beta-amyloid and tau caused by HSV1 infection of cell cultures.
It’s important to note that all studies, including our own, only show an association between the herpes virus and Alzheimer’s – they don’t prove that the virus is an actual cause. Probably the only way to prove that a microbe is a cause of a disease is to show that an occurrence of the disease is greatly reduced either by targeting the microbe with a specific anti-microbial agent or by specific vaccination against the microbe.
Excitingly, successful prevention of Alzheimer’s disease by use of specific anti-herpes agents has now been demonstrated in a large-scale population study in Taiwan. Hopefully, information in other countries, if available, will yield similar results.
Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease
Ruth F. Itzhaki, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
Front. Aging Neurosci., 19 October 2018, https://doi.org/10.3389/fnagi.2018.00324
Strong evidence has emerged recently for the concept that herpes simplex virus type 1 (HSV1) is a major risk for Alzheimer’s disease (AD). This concept proposes that latent HSV1 in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4) is reactivated intermittently by events such as immunosuppression, peripheral infection, and inflammation, the consequent damage accumulating, and culminating eventually in the development of AD….
How an outsider in Alzheimer’s research bucked the prevailing theory — and clawed for validation
Sharon Begley, Stat News, 10/29/2018
Robert Moir was damned if he did and damned if he didn’t. The Massachusetts General Hospital neurobiologist had applied for government funding for his Alzheimer’s disease research and received wildly disparate comments from the scientists tapped to assess his proposal’s merits.
It was an “unorthodox hypothesis” that might “fill flagrant knowledge gaps,” wrote one reviewer, but another said the planned work might add little “to what is currently known.” A third complained that although Moir wanted to study whether microbes might be involved in causing Alzheimer’s, no one had proved that was the case.
As if scientists are supposed to study only what’s already known, an exasperated Moir thought when he read the reviews two years ago.
He’d just had a paper published in a leading journal, providing strong data for his idea that beta-amyloid, a hallmark of Alzheimer’s disease, might be a response to microbes in the brain. If true, the finding would open up vastly different possibilities for therapy than the types of compounds virtually everyone else was pursuing.
But the inconsistent evaluations doomed Moir’s chances of winning the $250,000 a year for five years that he was requesting from the National Institutes of Health. While two reviewers rated his application highly, the third gave him scores in the cellar. Funding rejected.
Complaints about being denied NIH funding are as common among biomedical researchers as spilled test tubes after a Saturday night lab kegger. The budgets of NIH institutes that fund Alzheimer’s research at universities and medical centers cover only the top 18 percent or so of applications. There are more worthy studies than money.
Moir’s experience is notable, however, because it shows that, even as one potential Alzheimer’s drug after another has failed for the last 15 years (the last such drug, Namenda, was approved in 2003), researchers with fresh approaches — and sound data to back them up — have struggled to get funded and to get studies published in top journals. Many scientists in the NIH “study sections” that evaluate grant applications, and those who vet submitted papers for journals, have so bought into the prevailing view of what causes Alzheimer’s that they resist alternative explanations, critics say.
“They were the most prominent people in the field, and really good at selling their ideas,” said George Perry of the University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer’s Disease. “Salesmanship carried the day.”
Dating to the 1980s, the amyloid hypothesis holds that the disease is caused by sticky agglomerations, or plaques, of the peptide beta-amyloid, which destroy synapses and trigger the formation of neuron-killing “tau tangles.” Eliminating plaques was supposed to reverse the disease, or at least keep it from getting inexorably worse. It hasn’t. The reason, more and more scientists suspect, is that “a lot of the old paradigms, from the most cited papers in the field going back decades, are wrong,” said MGH’s Rudolph Tanzi, a leading expert on the genetics of Alzheimer’s.
Even with the failure of amyloid orthodoxy to produce effective drugs, scientists who had other ideas saw their funding requests repeatedly denied and their papers frequently rejected. Moir is one of them.
For years in the 1990s, Moir, too, researched beta-amyloid, especially its penchant for gunking up into plaques and “a whole bunch of things all viewed as abnormal and causing disease,” he said. “The traditional view is that amyloid-beta is a freak, that it has a propensity to form fibrils that are toxic to the brain — that it’s irredeemably bad. In the 1980s, that was a reasonable assumption.”
But something had long bothered him about the “evil amyloid” dogma. The peptide is made by all vertebrates, including frogs and lizards and snakes and fish. In most species, it’s identical to humans’, suggesting that beta-amyloid evolved at least 400 million years ago. “Anything so extensively conserved over that immense span of time must play an important physiological role,” Moir said.
What, he wondered, could that be?
In 1994, Moir changed hemispheres to work as a postdoctoral fellow with Tanzi. They’d hit it off over beers at a science meeting in Amsterdam. Moir liked that Tanzi’s lab was filled with energetic young scientists — and that in cosmopolitan Boston, he could play the hyper-kinetic (and bone-crunching) sport of Australian rules football. Tanzi liked that Moir was the only person in the world who could purify large quantities of the molecule from which the brain makes amyloid.
Moir initially focused on genes that affect the risk of Alzheimer’s — Tanzi’s specialty. But Moir’s intellectual proclivities were clear even then. His mind is constantly noodling scientific puzzles, colleagues say, even during down time. Moir took a vacation in the White Mountains a decade ago with his then-6-year-old son and a family friend, an antimicrobial expert; in between hikes, Moir explained a scientific roadblock he’d hit, and the friend explained a workaround.
Moir’s inclination toward unconventional thinking took flight in 2007. He was (and still is) in the habit of spending a couple of hours Friday afternoons on what he calls “PubMed walkabouts,” casually perusing that database of biomedical papers. One summer day, a Corona in hand, he came across a paper on something called LL37. It was described as an “antimicrobial peptide” that kills viruses, fungi, and bacteria, including — maybe especially — in the brain.
What caught his eye was that LL37’s size and structure and other characteristics were so similar to beta-amyloid, the two might be twins.
Moir hightailed it to Tanzi’s office next door. Serendipitously, Tanzi (also Corona-fueled) had just received new data from his study of genes that increase the risk of Alzheimer’s disease. Many of the genes, he saw, are involved in innate immunity, the body’s first line of defense against germs. If immune genetics affect Alzheimer’s, and if the chief suspect in Alzheimer’s (beta-amyloid) is a virtual twin of an antimicrobial peptide, maybe beta-amyloid is also an antimicrobial, Moir told Tanzi.
If so, then the plaques it forms might be the brain’s last-ditch effort to protect itself from microbes, a sort of Spider-Man silk that binds up pathogens to keep them from damaging the brain. Maybe they save the brain from pathogens in the short term only to themselves prove toxic over the long term.
Tanzi encouraged Moir to pursue that idea. “Rob was trained [by Marshall] to think out of the box,” Tanzi said. “He thinks so far out of the box he hasn’t found the box yet.”
Moir spent the next three years testing whether beta-amyloid can kill pathogens. He started simple, in test tubes and glass dishes. Those are relatively cheap, and Tanzi had enough funding to cover what Moir was doing: growing little microbial gardens in lab dishes and then trying to kill them.
Day after day, Moir and his junior colleagues played horticulturalists. They added staph and strep, the yeast candida, and the bacteria pseudomonas, enterococcus, and listeria to lab dishes filled with the nutrient medium agar. Once the microbes formed a thin layer on top, they squirted beta-amyloid onto it and hoped for an Alexander Fleming discovery-of-penicillin moment.
Autoimmune diseases occur when the body’s immune system targets and damages the body’s own cells.
Our bodies have an immune system: a network of special cells and organs that defends the body from germs and other foreign invaders.
At the core of the immune system is the ability to tell the difference between self and nonself: between what’s you and what’s foreign.
If the system becomes unable to tell the difference between self and nonself then the body makes autoantibodies (AW-toh-AN-teye-bah-deez) that attack normal cells by mistake.
At the same time, we always have regulatory T cells. They keep the rest of our immune system in line. If they fail to work correctly then other white blood cells can mistakenly attack parts of our body. This causes the damage we know as autoimmune disease.
The body parts that are affected depend on the type of autoimmune disease. There are more than 100 known types.
Overall, autoimmune diseases are common, affecting more than 23.5 million Americans. They are a leading cause of death and disability. Some autoimmune diseases are rare, while others, such as Hashimoto’s disease, affect many people.
(Intro adapted from U.S. Department of Health & Human Services, Office on Women’s Health)
There are many different auto-immune diseases. Each one has a separate cause. In fact, each particular autoimmune disorder itself may have several different causes.
Medical researchers are still learning how auto-immune diseases develop. They seem to be a combination of genetic mutations and some trigger in the environment.
TBA: The hygiene hypothesis
Diabetes (Type 1 diabetes mellitus)
Inflammatory bowel disease (IBD)
Lupus (Systemic lupus erythematosus)
Multiple sclerosis (MS)
Many autoimmune disorders can now be partially treated with biologics (artificial biological molecules.) These biologics modulate the immune system. These can treat – but not cure – some auto-immune diseases.
Infliximab, etanercept, adalimumab, etc.
Students will gain the knowledge and skills to select a diet that supports health and reduces the risk of illness and future chronic diseases. PreK–12 Standard 4
Through the study of Prevention students will
8.1 Describe how the body fights germs and disease naturally and with medicines and immunization.
Through the study of Signs, Causes, and Treatment students will
8.2 Identify the common symptoms of illness and recognize that being responsible for individual health means alerting caretakers to any symptoms of illness
8.5 Identify ways individuals can reduce risk factors related to communicable and chronic diseases
8.13 Explain how the immune system functions to prevent and combat disease
The immune system functions to protect against microscopic organisms and foreign substances that enter from outside the body and against some cancer cells that arise within. 6C/H1*
Some allergic reactions are caused by the body’s immune responses to usually harmless environmental substances. Sometimes the immune system may attack some of the body’s own cells. 6E/H1
Antibiotics are chemicals that disrupt and kill bacteria.
Note that they don’t kill viruses, fungi, or parasites.
For example, influenza (“the flu”) is a virus, not a bacteria. Therefore antibiotics can’t help fight the influenza virus.
Antibiotics work by blocking vital processes in bacteria, killing the bacteria or stopping them from multiplying.
This helps the body’s natural immune system to fight the infection.
Different antibiotics work against different types of bacteria.
Antibiotics that affect a wide range of bacteria are called broad spectrum antibiotics (eg, amoxicillin and gentamicin).
Antibiotics that affect only a few types of bacteria are called narrow spectrum antibiotics (eg, penicillin).
Different types of antibiotics work in different ways.
For example, penicillin destroys bacterial cell walls, while other antibiotics can affect the way the bacterial cell works.
Doctors choose an antibiotic according to the bacteria that usually cause a particular infection.
Sometimes your doctor will do a test to identify the exact type of bacteria causing your infection and its sensitivity to particular antibiotics.
Antibiotic medicines may contain one or more active ingredients and be available under different brand names. The medicine label should tell you the active ingredient and the brand name.
Simple animation showing how an antibiotic disrupts the building of a cell wall.
Once the cell wall is disrupted, water can enter, making the cell swell, and eventually burst.
Ways that antibiotics can disrupt bacteria
You can right-click on each image to expand it, or click here for the original page. It shows us several different types of antibiotics. Each has a different way of disrupting a bacteria,
This image is from “Mechanisms of Bacterial Resistance to Aminoglycoside Antibiotics”, 2019 RCSB PDB Video Challenge for High School Students. from the PDB-101 website. This is an educational portal of the RCSB PDM (protein data bank.)
8.1 Describe how the body fights germs and disease naturally and with medicines and
8.5 Identify ways individuals can reduce risk factors related to communicable and chronic diseases
8.6 Describe the importance of early detection in preventing the progression of disease
8.7 Explain the need to follow prescribed health care procedures given by parents and health care providers
8.13 Explain how the immune system functions to prevent and combat disease
8.19 Explain the prevention and control of common communicable infestations, diseases, and infections
Inoculations use weakened germs (or parts of them) to stimulate the body’s immune system to react. This reaction prepares the body to fight subsequent invasions by actual germs of that type. Some inoculations last for life. 8F/H4
If the body’s immune system cannot suppress a bacterial infection, an antibacterial drug may be effective—at least against the types of bacteria it was designed to combat. Less is known about the treatment of viral infections, especially the common cold. However, more recently, useful antiviral drugs have been developed for several major kinds of viral infections, including drugs to fight HIV, the virus that causes AIDS. 8F/M6** (SFAA)
Pasteur found that infection by disease organisms (germs) caused the body to build up an immunity against subsequent infection by the same organisms. He then produced vaccines that would induce the body to build immunity to a disease without actually causing the disease itself. 10I/M3*
Investigations of the germ theory by Pasteur, Koch, and others in the 19th century firmly established the modern idea that many diseases are caused by microorganisms. Acceptance of the germ theory has led to changes in health practices. 10I/M4*
Current health practices emphasize sanitation, the safe handling of food and water, the pasteurization of milk, isolation, and aseptic surgical techniques to keep germs out of the body; vaccinations to strengthen the body’s immune system against subsequent infection by the same kind of microorganisms; and antibiotics and other chemicals and processes to destroy microorganisms. 10I/M7** (BSL)
He Got Schizophrenia. He Got Cancer. And Then He Got Cured.
A bone-marrow transplant treated a patient’s leukemia — and his delusions, too. Some doctors think they know why.
By Moises Velasquez-Manoff
Mr. Velasquez-Manoff is a science writer.
The man was 23 when the delusions came on. He became convinced that his thoughts were leaking out of his head and that other people could hear them. When he watched television, he thought the actors were signaling him, trying to communicate. He became irritable and anxious and couldn’t sleep.
Dr. Tsuyoshi Miyaoka, a psychiatrist treating him at the Shimane University School of Medicine in Japan, eventually diagnosed paranoid schizophrenia. He then prescribed a series of antipsychotic drugs. None helped. The man’s symptoms were, in medical parlance, “treatment resistant.”
A year later, the man’s condition worsened. He developed fatigue, fever and shortness of breath, and it turned out he had a cancer of the blood called acute myeloid leukemia. He’d need a bone-marrow transplant to survive. After the procedure came the miracle. The man’s delusions and paranoia almost completely disappeared. His schizophrenia seemingly vanished.
Years later, “he is completely off all medication and shows no psychiatric symptoms,” Dr. Miyaoka told me in an email. Somehow the transplant cured the man’s schizophrenia.
A bone-marrow transplant essentially reboots the immune system. Chemotherapy kills off your old white blood cells, and new ones sprout from the donor’s transplanted blood stem cells. It’s unwise to extrapolate too much from a single case study, and it’s possible it was the drugs the man took as part of the transplant procedure that helped him. But his recovery suggests that his immune system was somehow driving his psychiatric symptoms.
At first glance, the idea seems bizarre — what does the immune system have to do with the brain? — but it jibes with a growing body of literature suggesting that the immune system is involved in psychiatric disorders from depression to bipolar disorder.
The theory has a long, if somewhat overlooked, history. In the late 19th century, physicians noticed that when infections tore through psychiatric wards, the resulting fevers seemed to cause an improvement in some mentally ill and even catatonic patients.
Inspired by these observations, the Austrian physician Julius Wagner-Jauregg developed a method of deliberate infection of psychiatric patients with malaria to induce fever. Some of his patients died from the treatment, but many others recovered. He won a Nobel Prize in 1927.
One much more recent case study relates how a woman’s psychotic symptoms — she had schizoaffective disorder, which combines symptoms of schizophrenia and a mood disorder such as depression — were gone after a severe infection with high fever.
Modern doctors have also observed that people who suffer from certain autoimmune diseases, like lupus, can develop what looks like psychiatric illness. These symptoms probably result from the immune system attacking the central nervous system or from a more generalized inflammation that affects how the brain works.
Indeed, in the past 15 years or so, a new field has emerged called autoimmune neurology. Some two dozen autoimmune diseases of the brain and nervous system have been described. The best known is probably anti-NMDA-receptor encephalitis, made famous by Susannah Cahalan’s memoir “Brain on Fire.” These disorders can resemble bipolar disorder, epilepsy, even dementia — and that’s often how they’re diagnosed initially. But when promptly treated with powerful immune-suppressing therapies, what looks like dementia often reverses. Psychosis evaporates. Epilepsy stops. Patients who just a decade ago might have been institutionalized, or even died, get better and go home.
Admittedly, these diseases are exceedingly rare, but their existencesuggests there could be other immune disorders of the brain and nervous system we don’t know about yet.
Dr. Robert Yolken, a professor of developmental neurovirology at Johns Hopkins, estimates that about a third of schizophrenia patients show some evidence of immune disturbance. “The role of immune activation in serious psychiatric disorders is probably the most interesting new thing to know about these disorders,” he told me.
Studies on the role of genes in schizophrenia also suggest immune involvement, a finding that, for Dr. Yolken, helps to resolve an old puzzle. People with schizophrenia tend not to have many children. So how have the genes that increase the risk of schizophrenia, assuming they exist, persisted in populations over time? One possibility is that we retain genes that might increase the risk of schizophrenia because those genes helped humans fight off pathogens in the past. Some psychiatric illness may be an inadvertent consequence, in part, of having an aggressive immune system.
Which brings us back to Dr. Miyaoka’s patient. There are other possible explanations for his recovery. Dr. Andrew McKeon, a neurologist at the Mayo Clinic in Rochester, Minn., a center of autoimmune neurology, points out that he could have suffered from a condition called paraneoplastic syndrome. That’s when a cancer patient’s immune system attacks a tumor — in this case, the leukemia — but because some molecule in the central nervous system happens to resemble one on the tumor, the immune system also attacks the brain, causing psychiatric or neurological problems. This condition was important historically because it pushed researchers to consider the immune system as a cause of neurological and psychiatric symptoms. Eventually they discovered that the immune system alone, unprompted by malignancy, could cause psychiatric symptoms.
Another case study from the Netherlands highlights this still-mysterious relationship. In this study, on which Dr. Yolken is a co-author, a man with leukemia received a bone-marrow transplant from a schizophrenic brother. He beat the cancer but developed schizophrenia. Once he had the same immune system, he developed similar psychiatric symptoms.
The bigger question is this: If so many syndromes can produce schizophrenia-like symptoms, should we examine more closely the entity we call schizophrenia?
Some psychiatrists long ago posited that many “schizophrenias” existed — different paths that led to what looked like one disorder. Perhaps one of those paths is autoinflammatory or autoimmune.
If this idea pans out, what can we do about it? Bone marrow transplant is an extreme and risky intervention, and even if the theoretical basis were completely sound — which it’s not yet — it’s unlikely to become a widespread treatment for psychiatric disorders. Dr. Yolken says that for now, doctors treating leukemia patients who also have psychiatric illnesses should monitor their psychiatric progress after transplantation, so that we can learn more.
And there may be other, softer interventions. A decade ago, Dr. Miyaoka accidentally discovered one. He treated two schizophrenia patients who were both institutionalized, and practically catatonic, with minocycline, an old antibiotic usually used for acne. Both completely normalized on the antibiotic. When Dr. Miyaoka stopped it, their psychosis returned. So he prescribed the patients a low dose on a continuing basis and discharged them.
Minocycline has since been studied by others. Larger trials suggest that it’s an effective add-on treatment for schizophrenia. Some have argued that it works because it tamps down inflammation in the brain. But it’s also possible that it affects the microbiome — the community of microbes in the human body — and thus changes how the immune system works.
Dr. Yolken and colleagues recently explored this idea with a different tool: probiotics, microbes thought to improve immune function. He focused on patients with mania, which has a relatively clear immunological signal. During manic episodes, many patients have elevated levels of cytokines, molecules secreted by immune cells. He had 33 mania patients who’d previously been hospitalized take a probiotic prophylactically. Over 24 weeks, patients who took the probiotic (along with their usual medications) were 75 percent less likely to be admitted to the hospital for manic attacks compared with patients who didn’t.
The study is preliminary, but it suggests that targeting immune function may improve mental health outcomes and that tinkering with the microbiome might be a practical, cost-effective way to do this.
Watershed moments occasionally come along in medical history when previously intractable or even deadly conditions suddenly become treatable or preventable. They are sometimes accompanied by a shift in how scientists understand the disorders in question.
We now seem to have reached such a threshold with certain rare autoimmune diseases of the brain. Not long ago, they could be a death sentence or warrant institutionalization. Now, with aggressive treatment directed at the immune system, patients can recover. Does this group encompass a larger chunk of psychiatric disorders? No one knows the answer yet, but it’s an exciting time to watch the question play out.
Moises Velasquez-Manoff, the author of “An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases” and an editor at Bay Nature magazine, is a contributing opinion writer.