Friday, March 17, 2023

How I ended up in a high-risk pancreatic cancer screening clinic


Pancreatic cancer is a scary disease. The pancreas (like the brain) is in a difficult to access space.  It is removed from other anatomical structures so that it does not produce symptoms that lead to early detection.  In medical school they taught us two presentations – waking up with painless jaundice and depression.  The painless jaundice is more of a specific give away than the depression. In either case, prognosis at the time of diagnosis is poor and has not improved significantly in the past decades (1,2,7).

I think about discussions I used to have over lunch with several specialists. Our typical group consisted of 3 GI docs, 1 or 2 Infectious Disease docs, a nephrologist and me.  We usually talked about movies but one day it turned to pancreatic cancer.  The question became – if you could screen for it would you?  This discussion happened back in the 1990s and the consensus at that time was no.  One of the pieces of evidence offered was the poor prognosis after surgical intervention – irrespective of the time of diagnosis.

I personally know 10 people who were diagnosed with pancreatic cancer. Four of them are on the paternal side of my family and one is a first degree relative – my sister. My earliest recollection of the disease was visiting my paternal aunt who lived a few blocks from my family.  Back in the 1950s, there was no useful imaging and diagnoses typically depended on exploratory surgery and direct tissue sampling. People who lived in remote areas did not travel to large referral centers to see specialists. You lived and died based on the skill of local physicians – some who had surgical training but were not technically general surgeons. Blood banking also did not exist and my father and uncle had to donate blood for my aunt. Nine of the 10 people I have known with pancreatic cancer are deceased some of them within weeks to months of the diagnosis.  My sister has been a trail blazer.  After a fortuitous diagnosis while being scanned for gallbladder disease, pancreatic cancer was diagnosed and she underwent radiation therapy, chemotherapy, a Whipple procedure, and maintenance therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor.  She saw an oncologist who recommended genetic testing and discovered she had an ATM gene variant. The genetic counselor she was seeing at the time recommended that all her siblings get tested for the same gene and to see if their children also needed to be tested.

ATM stands for “ataxia telangiectasia mutated.”  Ataxia telangiectasia (AT) is a hereditary degenerative ataxia that occurs in 1 in 20K to 100K live births (3,4).  Gait problems and truncal instability occurs in the first decade of life followed by progressive ataxia. Telangiectasias starts at about age 5 and are most evident in the conjunctive but can occur at various sites on the body. Immunodeficiency is noted with frequent respiratory infections.  Humoral and cell mediated immunity are affected as evidenced by decreased immunoglobulins and lymphocytopenia. AT is also associated with an increased frequency of cancers beginning with hematological malignancies in childhood and different malignancies as adults (6).  Lifespan with AT is decreased but is now more than 25 years with supportive measures. 

The mutations causing AT were discovered as mutations in the ATM gene in the late 20th century.  The ATM gene is located on chromosome 11, and the gene product is a serine-threonine kinase involved in DNA repair (5). Like most human genes there are a large number of mutations and single nucleotide polymorphisms (SNPs).  Those mutations associated with AT are insertions, deletions, missense, and truncations.  These mutations can lead to absence or loss of function ATM protein.  In my case the lab report read:

 

Variant Details:

ATM, Exon 10, c.1564_1565del (p.Glu522Ilefs*43), heterozygous, PATHOGENIC

This sequence change creates a premature translational stop signal (p.Glu522Ilefs*43) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).

This premature translational stop signal has been observed in individual(s) with breast cancer and ataxia-telangiectasia (PMID: 9000145, 9463314, 10330348, 10817650, 12497634, 21965147, 27083775).

In order to appreciate how the ATM protein works – a brief review of cell biology is in order.  Cells reproduce according to a cell cycle with various components. The protein components and cell signaling of that cycle were discovered in the past 40 years.  The cell cycle has checkpoints designed to stop the cycle and repair any DNA that is discovered as defective along the way. ATM is one of the proteins that modulates that process.  Functional ATM protein means that it is less likely that damaged DNA is passed along in new cell lines and that reduces the risk of cancer.  ATM mutations are associated with increase risk for pancreatic, ovarian, breast, and prostate cancer and as previously noted – malignancies associated with AT.  That is the mile high version of checkpoint and checkpoint proteins.  If you want a more detailed explanation, put it in the comments section and I will add more.

This mechanism is interesting to consider when thinking about genomic versus environmental effects. Peak incidence for new diagnoses of pancreatic cancer occurs during the 70s. If you have a defective DNA repair mechanism – is this the time where those defects accumulate to the point of creating malignancy?  How is your history of avoiding carcinogens like alcohol and tobacco smoke relevant to that probability?  What about the protective effects of antioxidants and exercise? At some point does a partially functional ATM protein protect against cancer or is the fully functional protein required?

The referral process in my own primary care clinic went smoothly when I told my internist about my sister’s diagnosis. I got an online appointment with a genetic counselor and when the results came back – she told me there was a 10-15% chance of pancreatic cancer and one clinic that did risk surveillance at Mayo.  She asked me if I was interested and why.  She also advised me that there are currently loopholes in the law that allow some companies to discriminate against you based on genetic testing. After discussing what those companies did – I told her I was not concerned about it and she made the referral.  I met with the gastroenterologist who headed the clinic, signed up for additional research protocols, had an MRI scan and just completed an upper GI endoscopy with ultrasound (US).  The ultrasound device is in the head of the gastroscope and it needs to be positioned in various areas of the stomach and duodenum to visualize the entire pancreas. The US procedure was also set up to proceed with a fine needle biopsy of the pancreas – but no lesions were noted and no biopsy was necessary. If a biopsy is required it is done through the wall of the stomach or duodenum.  Current screening is on an annual basis and the orders have already been placed for next year.

Getting back to the answer to the question posed in the title - it comes down to genes. One of the cultural myths in the US is that you always bear some level of responsibility for your disease. Recall any discussion about this with friends or family: “Did you hear that your classmate died last week from X?”  The next question or comment is likely to be – “well he (smoked, drank, never exercised, was obese, didn’t take care of himself, never saw a doctor, etc.”). There always must be an explanation for your old classmate dying prematurely and it is rarely biological.  Even though everybody in town with the same risk factors – outlived him by 20 years.  The stark reality is that it does not take a risk factor-based analysis. All it takes is a gene (or many genes) that code for the disease either directly or indirectly.

 

George Dawson, MD, DFAPA

 

References:

1:  Armstrong SA, Schultz CW, Azimi-Sadjadi A, Brody JR, Pishvaian MJ. ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications. Mol Cancer Ther. 2019 Nov;18(11):1899-1908. doi: 10.1158/1535-7163.MCT-19-0208. PMID: 31676541; PMCID: PMC6830515.

2:  Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol. 2021 Jul;18(7):493-502. doi: 10.1038/s41575-021-00457-x. Epub 2021 May 17. PMID: 34002083; PMCID: PMC9265847.

The risk of death from pancreatic cancer rises dramatically with age from <2 deaths per 100,000 person-years for individuals in the USA aged 35–39 years to >90 deaths per 100,000 person-years for individuals aged >80 years.

3:  Subramony SH, Xia G. Disorders of the cerebellum, including the degenerative ataxias.  In:  Neurology in Clinical Practice (7th edition). RB Daroff, J Jancovic, JC Mazziotta, SL Pomeroy (eds). Elsevier, London, 2016.  p: 1468-1469.

4:  Rothblum-Oviatt, C., Wright, J., Lefton-Greif, M.A. et al. Ataxia telangiectasia: a review. Orphanet J Rare Dis 11, 159 (2016). https://doi.org/10.1186/s13023-016-0543-7

5:  ATM serine/threonine kinase [ Homo sapiens (human) ]

Gene ID: 472, updated on 12-Mar-2023

https://www.ncbi.nlm.nih.gov/gene/472

6:  Hsu F, Roberts NJ, Childs E, et al. Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene. JAMA Oncol. 2021;7(11):1664–1668. doi:10.1001/jamaoncol.2021.3701

The cumulative risk of pancreatic cancer among individuals with a germline pathogenic ATM variant was estimated to be 1.1% (95%CI, 0.8%-1.3%) by age 50 years; 6.3%(95%CI, 3.9%-8.7%) by age 70 years; and 9.5%(95%CI, 5.0%-14.0%) by age 80 years. Overall, the relative risk of pancreatic cancer was 6.5 (95%CI, 4.5-9.5) in ATM variant carriers compared with noncarriers.”

7:  Trikudanathan G, Lou E, Maitra A, Majumder S. Early detection of pancreatic cancer: current state and future opportunities. Curr Opin Gastroenterol. 2021 Sep 1;37(5):532-538. doi: 10.1097/MOG.0000000000000770. PMID: 34387255; PMCID: PMC8494382.

8:  Oh SY, Edwards A, Mandelson MT, Lin B, Dorer R, Helton WS, Kozarek RA, Picozzi VJ. Rare long-term survivors of pancreatic adenocarcinoma without curative resection. World J Gastroenterol. 2015 Dec 28;21(48):13574-81. doi: 10.3748/wjg.v21.i48.13574. PMID: 26730170; PMCID: PMC4690188.

9:  Overbeek KA, Goggins MG, Dbouk M, Levink IJM, Koopmann BDM, Chuidian M, Konings ICAW, Paiella S, Earl J, Fockens P, Gress TM, Ausems MGEM, Poley JW, Thosani NC, Half E, Lachter J, Stoffel EM, Kwon RS, Stoita A, Kastrinos F, Lucas AL, Syngal S, Brand RE, Chak A, Carrato A, Vleggaar FP, Bartsch DK, van Hooft JE, Cahen DL, Canto MI, Bruno MJ; International Cancer of the Pancreas Screening Consortium. Timeline of Development of Pancreatic Cancer and Implications for Successful Early Detection in High-Risk Individuals. Gastroenterology. 2022 Mar;162(3):772-785.e4. doi: 10.1053/j.gastro.2021.10.014. Epub 2021 Oct 19. PMID: 34678218.

10:  Søreide K, Ismail W, Roalsø M, Ghotbi J, Zaharia C. Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery. Cancer Control. 2023 Jan-Dec;30:10732748231154711. doi: 10.1177/10732748231154711. PMID: 36916724; PMCID: PMC9893084.

"The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis."

11:  National Center for Biotechnology Information. ClinVar; [VCV000127340.60], https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000127340.60 (accessed March 19, 2023).


Graphics:

I drew that genogram of my immediate family using EDraw Max.  I am one of the two siblings that tested positive for the ATM variant. My other siblings have not been tested. 

Sunday, March 12, 2023

Endemic ≠ Benign

 


“There is a widespread, rosy misconception that viruses evolve over time to become more benign. This is not the case: there is no predestined evolutionary outcome for a virus to become more benign, especially ones, such as SARS-CoV-2, in which most transmission happens before the virus causes severe disease…”

Aris Katzourakis
Professor of Evolution and Genomics
University of Oxford

 

I typically don’t like to post on a non-psychiatric topic immediately after posting one.  But the current level of misinformation on the pandemic necessitates this. That is obviously not because I am a big influencer with widespread readership – but I like responding to the sea of right wing misinformation on Twitter. And today it was all about how the response to the pandemic was an overreaction with far reaching effects. Nothing about how the virus has killed 1.1 million Americans, the impact of that mortality on families and businesses, the impact on the healthcare system and its workers, and the enduring disability of millions with long COVID.  The evidence is clear that the pandemic was mishandled early on as the Trump administration denied the degree of the problem and then falsely reassured the public that everything was under control. The only way the right wing can rewrite that history is to push a false narrative that there was a conspiracy theory to prevent any investigation of the lab leak theory, that face masks and public health measures don’t work, that school children are irrevocably damaged from online learning, and that all of these unnecessary measures were really an unnecessary infringement on freedom. Unfortunately, pandemic viruses don’t work that way. They do not really care about your political affiliation or what you read on Twitter.

One of the popular myths during the early to mid-pandemic was the idea of herd immunity and how by ignoring all of the public health suggestions up to and including the immunizations (or “jabs” as they are referred to by the right wing) the entire population would build up immunity and the pandemic would fade away. The way that argument was typically presented minimized any death or disability along the way.  Herd immunity would happen and it would happen quickly to resolve the problem.  It also implicitly assumed that writing off the elderly and the 10% of the population that is immunocompromised was morally acceptable.  Not much discussion of how herd immunity would happen without immunizations – since many of the proponents were ideologically sympathetic to the idea that public health measures and immunization were unnecessary.

An associated concept of endemic disease cropped up at one point. The popular usage was  to say: “This is no longer a pandemic, there are no more large outbreaks, therefore we can declare it is an endemic like the common cold viruses.”  Since this was also an ideological rather than scientific argument – it was also a rationale for stopping all of the suggested public health measures and getting things back to normal as soon as possible,

That brings me to a brief essay on endemics written by evolutionary virologist Aris Koutzourakis in Nature (1).  The title speaks for itself.  His definition of endemic is straightforward -  endemic infections mean that the infection rate is static – not rising or falling. The best intuitive example is common cold viruses – there are predictable seasonal fluctuations but the number of viruses and the composition of the pool of common respiratory viruses stays about the same and no one outcompetes the others. Nobody is too worried about common cold viruses because they are not too deadly and don’t commonly overwhelm the healthcare system.  Influenza viruses are somewhat different.  Whether and epidemic or pandemic occurs depends on an elaborate system of guessing the correct components for the influenza vaccine and measures taken to prevent zoonotic transmission of potentially more lethal influenzas viruses – like avian influenza. That backdrop of common cold versus influenza viruses seems like a way to understand endemicity.  It leaves out one important point and that is endemic pathogens can also be lethal and create disability.

Dr. Koutzourakis lists several examples of endemic, but lethal pathogens including malaria, polio, and tuberculosis.  They are all significant causes of mortality and morbidity.  He successfully predicted that unless the pandemic was stopped quickly subsequent evolving variants could be more transmissible and difficult to treat.  That occurred with the subsequent 4 SARS-CoV-2 variants. Viral evolution has also been observed with other pandemic viruses and the occurrence of more dangerous variants. He analyzes the current behavioral situation correctly in the United States.  Even if people are not using the word endemic – they are generally stating that the pandemic is over and that it is time for a return to normal.  Normal typically means no public health measures like masking, social distancing, or even deciding to stay home if you are ill.  The only place that those measures are acceptable is in a medical or dental facility and even then they are no longer universal. To compound the problem, the anti-public health ideologues are either bragging that they were correct all along or actively spreading misinformation about masks, vaccines, or the origin of the virus.

The graphic at the top of this page (click to enlarge) is taken from the CDC web site today.  Even though the area in the red rectangle looks fairly static going back to May of 2022 – the actual number of cases per week ranges from 170 to 900K.  That corresponds with weekly deaths 1,795 to 3,697.   Dr. Katzourakis suggests that there is the potential to see additional spikes of infection and suggests that the direction this pandemic will take at this point depends a lot on continued public health measures, immunizations, antiviral medication, and individual behavior.  One of the critical aspects of science as I explained in my previous post is that scientists look at data supporting or refuting hypotheses in terms of probabilities and also speculate with probability statements. Viral epidemiologists and evolutionary virologists know how viruses work and evolve. Their predictions are much more likely to be accurate than someone with no expertise and no data.  The next time you hear politicians or news personalities talking like this pandemic is over take it as an unfounded opinion. Do the same thing when your neighbor tells you that you don’t need to get any more vaccinations or wear a mask in crowded places.

Don’t let ideology blind you to science.

 

George Dawson, MD, DFAPA

 

References:

1:  Katzourakis A. COVID-19: endemic doesn't mean harmless. Nature. 2022 Jan;601(7894):485. doi: 10.1038/d41586-022-00155-x. PMID: 35075305.

2:  Centers for Disease Control and Prevention. COVID Data Tracker. Atlanta, GA: US Department of Health and Human Services, CDC; 2023, March 12. https://covid.cdc.gov/covid-data-tracker  accessed on 03/12/2023

3:  Callaway E. Beyond Omicron: what's next for COVID's viral evolution. Nature. 2021 Dec;600(7888):204-207. doi: 10.1038/d41586-021-03619-8. PMID: 34876665.


Tuesday, February 28, 2023

The Many Excuses for Ignoring Science – Where Did SARS-CoV-2 Originate?

 


The COVID origins story started off with a bang last weekend.  Woody Harrelson gave the monologue on Saturday Night Live comparing pharmaceutical companies to drug cartels and COVID vaccinations to illicit drugs. He was conveniently able to ignore the fact that these vaccinations have saved an estimated 20 million lives and could have saved more if vaccination goals were met. By way of contrast there are about 30,000 drug related homicides in Mexico every year, several thousand per year in the US, and tens of thousands dead from overdosing on illicit drugs. A stark contrast to the way this monologue was presented. There was plenty of commentary on the monologue – mostly focused on Harrelson’s antivaxx stance in the past including a post that he had to remove at one point. Elon Musk enthusiastically supported the monologue – but didn’t say if it was for the comedic or scientific genius. Harvey Levin praised producer Lorne Michaels for not censoring Harrelson, but didn't comment on editing for comedic content. Nobody recited the simple facts listed above.

The monologue was followed Sunday by a more detailed story without much more scientific credibility in the Wall Street Journal (1).  The authors of that story discuss a 5-page report by the Department of Energy stating the opinion that a lab leak was the likely cause of the pandemic but that theory was given a ‘low confidence’ rating.  They describe the DOE as having many relevant scientists.  Other than controversial headings and fueling partisan debate – what good is a low confidence theory?  The FBI has the same theory with “moderate confidence.” They explain that the US has an 18 agency intelligence community implying that there is adequate expertise there for these low to moderate confidence lab-leak theories. Is this the same intelligence community that was confident that there were weapons of mass destruction in Iraq and who seemed vaguely aware of Chinese balloons invading US air space?  They might have better things to do than speculate about pandemic virus origins and rate those speculations.  Protecting US infrastructure against cyberattacks and criminal activity would seem to be at the top of that list.

I would like to see that 5 page report at this point – to see if there is any reference to a recent consensus statement from the virology community on the origins of SARS-CoV-2 (2).  The full text of that report is available online.  If you read that report a few points jump out at you.  First – these are the professionals with the most expertise in viral genetics and evolution. It is their full-time job and they do active research in the area.  Second – beyond claiming expertise virologists have been very successful at reducing the disease burden through their efforts.  They get results. Third – while emphasizing neutrality they point out that the zoonosis hypothesis (wild origin) has the most supporting data and that there is “no compelling data” to support either a lab leak or intentional contamination hypothesis. Fourth they point out that “gain-of-function” is an inexact term but within the field it also means modification for therapeutic purposes.  The term has been used by some politicians to suggest “nefarious” activity. Fifth – they review the extensive oversight of their research.  They conclude that millions of people are alive today because of their research and that there is adequate oversight. All of that clearly stated before the start of Congressional hearings on these issues.

 There is pre-existing research on viral origins from other groups and wild origin is the most likely scenario (3, 11, 12).

In an interesting twist of events the celebrity gossip show TMZ (10:34 to 18 minute mark) ran with the story.  They started out with the Harrelson monologue followed by Harvey Levin’s characterization that the lab leak theory “blossomed” with the Wall Street journal article.  To their credit they brought on Michael Worobey an evolutionary virologist with a previous description of the wild origins of SARS-CoV-2 in Science (4).  Dr. Worobey pointed out that he wrote a letter in 2021 that the ‘lab leak’ hypothesis had to be taken seriously, but since then then there has been “really strong scientific evidence” of a wild origin of the virus and no real scientific evidence of a lab leak.  Just from a probability standpoint he pointed out that all of the cases were in the area of the Wuhan market, there were animals present that carried coronaviruses, and there is really no other explanation for that degree of localization in a city of 12 million people. He also pointed out the severe social media backlash that he received as a result of following the evidence but encouraged a systematic approach to the research.  He suggested taking the DOE report with a “grain of salt”.

A final comment on the DOE report was made on the public radio show All Things Considered.  Michael Osterholm from CIDRAP was interviewed (5).  He describes himself as being agnostic towards the lab leak versus zoonoses but clearly sees the preponderance of data supporting the wild origin.  He goes on to suggest that people want certainty when a high degree of certainty is not possible and that has led to definitive headlines (about lab leak for example) when hard evidence is lacking. He adds the following characterization and challenges the DOE to present their data:

“…. again, there is a very different type of theater being played out here. It's not one that's based on science.”

He also describes a very plausible scenario of a new virus occurring in the Caribbean and how that could be spun into a ‘lab leak’ from the CDC in Atlanta.

Expect a lot of political demagoguery on the issue with Congressional hearings in the months to follow. Unless there is any data as good as the references I have posted - keep an open mind.  In a postmodern world – people with no or vague expertise make unfounded claims about scientific evidence.  The strongest evidence by far is with the experts and scientists listed in this essay. And that is a wild origin of the virus – just like previous coronaviruses. Anyone suggesting otherwise needs to show up with some data and not excuse making or political theater.

 

George Dawson, MD, DFAPA

 

References:

1:  Gordon MR, Strobel WP. DOE Says Lab Leak Is Likely Origin of Covid-19 ---New intelligence about China outbreak spurs assessment; finding is given 'low confidence'.  Wall Street Journal.  Wall Street Journal.  February 27, 2023.

2:  Goodrum F, Lowen AC, Lakdawala S, Alwine J, Casadevall A, Imperiale MJ, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A. Virology under the Microscope-a Call for Rational Discourse. mSphere. 2023 Jan 26:e0003423. doi: 10.1128/msphere.00034-23. Epub ahead of print. PMID: 36700653.

3:  Garry RF. The evidence remains clear: SARS-CoV-2 emerged via the wildlife trade. Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2214427119. doi: 10.1073/pnas.2214427119. Epub 2022 Nov 10. PMID: 36355862; PMCID: PMC9704731.

4:  Worobey M. Dissecting the early COVID-19 cases in Wuhan. Science. 2021 Dec 3;374(6572):1202-1204. doi: 10.1126/science.abm4454. Epub 2021 Nov 18. PMID: 34793199. (see also the map of SARS-CoV-2 origins)

5:  Contreras G, Brown A, Shapiro A, How an infectious disease expert interprets conflicting reports on COVID-19's origins.  All Things Considered.  February 27, 2023.

https://www.npr.org/2023/02/27/1159821909/how-an-infectious-disease-expert-assessed-how-covid-19-started

6:  Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MUG, Newman C, Koopmans MPG, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science. 2022 Aug 26;377(6609):951-959. doi: 10.1126/science.abp8715. Epub 2022 Jul 26. PMID: 35881010; PMCID: PMC9348750.

7:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

8:  Bloom JD, Chan YA, Baric RS, Bjorkman PJ, Cobey S, Deverman BE, Fisman DN, Gupta R, Iwasaki A, Lipsitch M, Medzhitov R, Neher RA, Nielsen R, Patterson N, Stearns T, van Nimwegen E, Worobey M, Relman DA. Investigate the origins of COVID-19. Science. 2021 May 14;372(6543):694. doi: 10.1126/science.abj0016. PMID: 33986172; PMCID: PMC9520851.

This is an important reference form May of 2021 signed by Dr. Worobey suggesting that a more thorough investigation of the origins of the SARS-CoV-2 virus needs to be done.  Per the above assay and several references - he has concluded that the virus originated in the wild rather than lab leak since this letter. I think this letter also addresses the censorship comments.  Clearly the suggestion by this group that the lab leak had to be reinvestigated illustrates there was no censorship on the science side. 

9:  Chait J.  The Surprisingly Contrarian Case Against Lying About Science.  The Intelligencer.  February 28, 2023  https://nymag.com/intelligencer/2023/02/lab-leak-hypothesis-lying-about-science-is-bad-for-liberals.html 

10: Garry RF. SARS-CoV-2 furin cleavage site was not engineered. Proc Natl Acad Sci U S A. 2022 Oct 4;119(40):e2211107119. doi: 10.1073/pnas.2211107119. Epub 2022 Sep 29. PMID: 36173950; PMCID: PMC9546612. 

11:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

12:  Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MUG, Newman C, Koopmans MPG, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science. 2022 Aug 26;377(6609):951-959. doi: 10.1126/science.abp8715. Epub 2022 Jul 26. PMID: 35881010; PMCID: PMC9348750.

13:  Wu Y, Zhao S. Furin cleavage sites naturally occur in coronaviruses. Stem Cell Res. 2020 Dec 9;50:102115. doi: 10.1016/j.scr.2020.102115. Epub ahead of print. PMID: 33340798; PMCID: PMC7836551.

14:  Xiao, X., Newman, C., Buesching, C.D. et al. Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic. Sci Rep 11, 11898 (2021). https://doi.org/10.1038/s41598-021-91470-2

15:  Lenharo M, Wolf L. US COVID origins hearing renews debate over lab-leak hypothesis. Nature. 2023 Mar 9. doi: 10.1038/d41586-023-00701-1. Epub ahead of print. PMID: 36890328.

"Michael Worobey, an evolutionary biologist at the University of Arizona, Tucson, who has studied genetic evidence from the early days of the pandemic, told Nature that he found the proceedings “shockingly unscientific” and that they do not bode well for the overall investigation. “Not one of those witnesses had any scientific record of investigating and publishing peer-reviewed research on the origins of this virus in quality journals,” he said."

16:  Cohen J.  Science takes a backset to politics in first House hearing on origin of COVID-19 pandemic.  Science.  March 8, 2023.  doi: 10.1126/science.adh5155

Very useful essay that points out little science is occurring and the intelligence is very sketchy.

17:  Rutledge PE. Trump, COVID-19, and the War on Expertise. The American Review of Public Administration. 2020 Aug;50(6-7):505-11.

This is a good reference to keep in mind because it points out that President Trump and his administration actively promoted the lab leak theory of the pandemic dating back as far as May 2020.  All of the pundits decrying censorship of the lab leak hypothesis should ask themselves how censorship is possible when the theory is being actively promoted by the Executive Branch. 

18:  Maxmen A. Wuhan market was epicentre of pandemic's start, studies suggest. Nature. 2022 Mar;603(7899):15-16. doi: 10.1038/d41586-022-00584-8. PMID: 35228730.

This study links to three preprints describing the origin of the virus in the wild with spillover to humans.  As far as I can tell these preprints became the 2 papers listed below as well as reference 12 above:

19:  Pekar JE, Magee A, Parker E, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science. 2022 Aug 26;377(6609):960-966. doi: 10.1126/science.abp8337. Epub 2022 Jul 26. PMID: 35881005; PMCID: PMC9348752.

20:  Mueller B.  W.H.O. Accuses China of Withholding Data on Pandemic’s Origins.  New York Times March 17, 2023.

21:  Cohen J. Anywhere but here. Science. 2022 Aug 19;377(6608):805-809. doi: 10.1126/science.ade4235. Epub 2022 Aug 18. PMID: 35981032.

22:  Cohen J.  Chinese researchers release genomic data that could help clarify origin of COVID-19 pandemic.  Science 2023 March 29; doi:10.1126/science.adi0330.


Supplementary 1:

The director of the FBI came out in the media today (02/28/2023) and reiterated that the FBI has concluded the virus most likely originated as a lab leak but provided no additional data. As far as I know at this point the FBI and DOE data has not been released to the public.

Supplementary 2:

How is science ignored?  I realize after reading the post it contains historical information but nothing explicit about how science is ignored.  Here is the short list:

1:  Science is a process of serial approximations to reality or more to the point - an empirically acceptable model of reality.  Politics, journalism, and entertainment clearly are not. As a result the scientifically informed realize this is often series of hypothetical steps and missteps until a widely agreed upon model is accepted in the scientific community.  That contrasts sharply with a long series of provocative headlines and opinion pieces.  

2:  Science deals with probability statements - politics, journalism, and entertainment exists largely on the plane of dichotomous thinking.

3:  The probabilities on the probability statements can be adjusted in either direction.  As is the case in the Dr. Worobey references above - his probability of a "lab leak or nefarious activity" hypothesis was adjusted drastically downward over time as the probability of a wild origin was adjusted upward to the point where it became most likely.  This adjustment of probabilities is often seen as a "mistake" or "lie" by the nonscientific community. Within the scientific community it can be difficult to change your mind.  Neither of those considerations invalidates the process. 

4:  There are still scientific standards that acknowledge expertise and peer review. Although peer review is criticized by authors it has resulted in conventions that probably limit grand pronouncements like a newspaper headline.  The evidence should be in the 'limitations' section of any scientific paper.  In the postmodern world expertise is seen as relative by those in many nonscientific endeavors - to the point that anyone who can Google is considered an expert. This is also the predominate social media method of operation. 

5:  The legal/political model of ascertaining the truth or reality is highly flawed - and the evidence is obvious in studies of racial profiling, unjustified violent encounters with law enforcement, wrongful convictions, unequal treatment based on economic considerations, fallible eyewitness testimony, and highly flawed interrogations. Focusing only on coronavirus - the interrogations of Dr. Fauci by Sen. Paul is an additional example. And yet - this is the process that is going to be used by the government to decide on the origins of the virus.  Unless the DOE or the FBI have concrete scientific proof - it will be an exercise in rhetoric.

6:  If not science what? Typical analyses presented in the media can occur at several levels that cut science out of the mix. Anytime you hear an analysis by a group of journalists, politicians, regulators, administrators or consultants who lack the requisite expertise to analyze the problem take a close look at that final product. Ask yourself if there is anyone with scientific expertise who should have looked at it.  Be very skeptical of analyses that are not disclosed because they are proprietary or classified.


Supplementary 3 (Updates):

Update 03/02/2023:  As expected the COVID origins appearance of controversy was still whipping up the media today.  TMZ continued with their fractured analysis – continuing to focus on the FBI and DOE reports as a game changer and not mentioning at all what the evolutionary virologist Michael Worobey told them yesterday.  They played a brief John Stewart tape and suggest that he was now “vindicated” for suggesting early in the pandemic that this was probably a lab leak. Harvey Levin pointed out that Stewart was not crowing about being correct in the brief clip that they played and how could he? How can a guy who knows nothing about epidemiology or pandemic viruses and has no information about what transpired in Wuhan suggest there was a lab leak?  The excerpt that I saw had Stewart talking about the need to have both sides represented.  TMZ did touch on the most important aspect of this debate and that was rhetoric and how President Trump’s racist polarizing rhetoric led to conflation of the viral origin hypothesis with racism and that created significant backlash from the left. But we are still dealing with a non-scientific argument and ignoring Dr. Worobey. Harvey Levin seems stuck on these events as primarily a free speech issue.  To me that is obviously not a problem given the degree of bullshit and demagoguery that occurred around this issue.  There was probably no more “free speech” exercised at any other time in the history of the country. Watching TMZ the last two days just illustrates that they can avoid science as rigorously as anyone else – even after talking to a top scientist in the field. As some level the free speech argument just becomes a rationalization.

New York Times political columnist Jonathan Chait wrote a piece in the Intelligencer entitled “The Surprisingly Contrarian Case Against Lying About Science”.  He claims the DOE analysis has weight because there is a division there that is supposed to assess bioweapons threats. To me that just deepens the nonscience of it all. From a rhetorical standpoint we have gone from an appeal to emotion to an appeal to authority.  He goes on to analyze the rhetoric starting with the need to shift blame away from the Trump administration and their “mishandling of the epidemic.”  He is the first journalist I have seen who writes about how China unleashing the virus on their own people (one suggestion) is absurd.  I would add even considering the coronavirus as a bioweapon is equally absurd. In his analysis of Peter Hotez Tweets he gets it wrong.  Dr. Hotez characterizes the antiscience aggression of certain elements of the media and Congress as: “The best defense is a good offense”.  Chait’s response is:

 “I’m neither a professor, a doctor, nor a Ph.D., but I know enough to state confidently that the ethos of the scientific method is not “the best defense is a good offense.”

What about the ethos of journalism and politics? I am confident that is what Hotez is referring to.  He ultimately makes the argument that the left is not skilled enough to parse the anti-science rhetoric of the right and as a result lump legitimate scientific discussion with anti-science crankery and this is not a good thing. He concludes that ideology cannot be used to settle scientific debate. Some good points and some bad points. I will add it is pretty obvious to anyone who knows a thing about science that real scientific debates cannot be settled in the media and every scientist I know has had bad experiences with the media because they are trying to tell the story they want to tell.  My classic example was television interviews that I was asked to give around the Christmas holiday when I was a young psychiatrist. I knew the reporter was trying to sell the story that there were more suicides at Christmas and no matter what I said there would be that suggestion. I finally just told them – no more interviews. After all – in this case what is the more provocative headline ‘COVID is a bioweapon leaked or intentionally released’ or ‘COVID is a coronavirus that jumped from animal populations to humans like all human coronaviruses before it – including the 4 normally circulating coronaviruses that are considered common cold viruses.”  Rhetoric is a very strong component here and if the press wanted to really be useful, they might point out that on a timeline basis.  The arguments are largely rhetorical rather than scientific and factual.  All the press would have to say about the science is that it is not settled and digress a little into how scientific decisions are made. But I have never seen that happen.     

Update 03/03/2023:  The following document reviews some of the history of the controversy and points out that there really is no definitive proof of the viral origins at this point.  In the last few paragraphs the scientists who see zoonoses/spillover as the most plausible scenario are looking for falsifying data but have not found it.

Robertson L.  Still No Determination on COVID-19 Origin.  FactCheck.org 03/02/2023: https://www.factcheck.org/2023/03/scicheck-still-no-determination-on-covid-19-origin/

Update 03/06/2023:  TMZ was at it again today.  They put up a weekend poll on the origins of COVID and posted 2 possibilities -  wet market or lab leak.  The vote went like this:

wet market - 12%

lab leak - 88%

Harvey Levin's analysis was that this showed censoring the lab leak hypothesis at the outset was the problem.  This analysis is incorrect at two levels. First, there are endless headlines from 2021 where Republicans like Senator Rand Paul accused Dr. Fauci of lying about gain-of-function and labs leaks.  The demonized Dr. Fauci about this to the point that he started getting threats and needed protection for himself and his family. The same sequence of events happened to many public health officials who became objects of right wing scorn.  Secondly - I don't know what you expect when you are hyping unscientific proclamations about lab leak for the past week. Let's not pretend the media is a disinterested party here. TMZ chose the story about "censorship" when there was none and chose to suggest that was a better explanation for why two government agencies were suggesting a lab leak over the expert they interviewed last week. Just another clear example of the title of this post. 


Supplementary 4:

House Committee on Oversight - COVID origins:

Here is the web site - not the current references to Fox News and the New York Post - both obviously the farthest information from science:

https://oversight.house.gov/landing/covid-origins/


Graphics Credit:

Eduardo Colon, MD photo is much appreciated.

 

Monday, February 20, 2023

The arbitrary and often absurd rhetorical attacks on psychiatry

 


I drew the above graphic (click on it to enlarge) to highlight a few things about popular psychiatric criticism, but mainly that it is absurd.  I have commented on antipsychiatry rhetoric many times in the past and how it has a predictable pattern.  But this goes beyond antipsychiatry to include critics in the press, authors selling books (or being paid for lectures or appearances), and even critics in the field. I thought it might be useful to try to crowd as much of this rhetoric into one diagram as possible for easy reference.

Why is rhetoric so important?  Rhetoric is all about winning an argument.  The strategies are all well documented and you can read about them and the common fallacious arguments in any standard rhetoric or logic text.  My goal is not to teach rhetoric.  For the purpose of this post, I want the reader to understand that there is more rhetoric leveled at psychiatry than any other medical specialty. There is always a lot of speculation about why that might be – but nobody ever seems to come out and say the most obvious reasons – gaining political advantage or financial renumeration. There is also dead silence on the questions of facts and expertise - since practically all of the literature out there including much of the rhetoric advanced by psychiatrists is an overreach in terms of psychiatric knowledge and expertise.  When absurd rhetoric about psychiatry makes the New York Times or even prominent medical journals it is simply accepted as a fact. There is no marketplace of ideas approach or even a single alternating viewpoint. Some of the statements in the graphic are taken directly out of newspaper articles and they are absurd. 

I happen to believe that the best critiques of the field come from people who are experts and usually do not deteriorate into ad hominem attacks against the field or other experts in the field. I was trained by many of those experts who consistently demonstrated that a lot of thought and work goes into becoming a psychiatrist and practicing psychiatry. I have known that for 35 years and continue to impressed by psychiatrists from around the world who contact me every day.     

I sought feedback from psychiatrists through several venues about absurd psychiatric criticism, by showing them a partially completed table and asking for suggestions.  One suggestion was making a grid to evaluate plausible, implausible, and unproveable. I do not think that is the best way to analyze these remarks. There seems to be a lot of confusion about rhetoric versus philosophy and a tendency to engage in lengthy philosophical analysis and discourse. It turns out that a lot of what passes for philosophical critique of psychiatry is really rhetoric.  That rhetoric generally hinges on controlling the premise and arguing from there. For example – the statement that the DSM is a “blueprint for living” is taken directly out of a New York Times article where the author – a philosophy professor was critiquing the 2015 release of the DSM-5 on that basis. Never mind that no psychiatrist ever made that claim or even had that fantasy – there it was in the paper written like the truth. A reading of the first 25 pages of the manual would dispel that notion but it is clear nobody ever seems to do that. 

I seriously considered modifying the diagram based on a division proposed by Ron Pies, MD (1).  That would have involved dividing the area of the graph into a zone of “legitimate criticisms focused on problematic areas in psychiatry” versus “fallacious and baseless attacks ... aimed at delegitimizing and ultimately destroying psychiatry.”  As I attempted to draw that graph – I realized that I could not include any of the current statements in a legitimate criticism zone.  In order to do that I will need to find an equivalent amount of legitimate criticism and include it in a new graph.

This rhetoric has much in common with misinformation, except it has been around for decades. It is not an invention of the Internet or social media. An important aspect of rhetoric is that since it does not depend on facts it can be continuously repeated. That is the difference between the truth and facts versus rhetoric. The classic modern-day example is the Big Lie of the last Presidential campaign. Former President Trump stated innumerable times that the election was stolen by election fraud and at one point suggested that there was enough proof that it allowed the Constitution to be suspended. All that rhetoric despite no independent corroboration by any judiciary or election officials from his own party.  Major news services began reporting his claim as a lie.  Recent news reports revealed that the stars of the news outlet that Trump was most closely affiliated with - did not believe the election was stolen. Many of the statements leveled at psychiatry in the table are equivalent to the Big Lie.

Rhetoric typically dies very hard and that is why it is an integral part of political strategy. A current popular strategy is to use the term woke as a more pejorative description of politically correct. It creates an emotional response in people “You may be politically correct but I am not.”  The term is used frequently to describe many things including the teaching of Critical Race Theory (CRT) in public schools. Repetition alone has many Americans believe that CRT is being taught in public schools and that is something that they should actively resist. The fact is – CRT is not taught in public schools and yet the effect of the rhetoric has been enough to leave many people outraged and susceptible to political manipulation. The rhetoric itself is difficult to correct by a long explanation about CRT.  That approach will not win any arguments. The best approach is to characterize it for what it is at the outset – absurd rhetoric that is not reality based. But there is a good chance that will also not have much impact.

When I talk with psychiatrists about the problem of not responding to rhetoric – I typically encounter either blank stares, the rejoinder that “there might be a grain of truth there”, or  the suggestion that we should just ignore it and it will go away. Physicians in general seem to be clueless about the effect of politics and rhetoric on medicine and psychiatrists are no exception.  When you are trained in science and medicine, there seems to be an assumption that the scientific method and rational discourse will carry the day.  That may be why we were all shocked when the American people seemed to be responding in an ideological way to public health advice during the pandemic and they were so easily affected by misinformation. 

Rhetoric in science predates the pandemic by at least a century.  It has been suggested that Charles Darwin used natural selection as a metaphor for domestic animal breeding (1) in order to convince the predominately religious people and scientists of the day.  He had to argue the position that unpleasant natural states were intermediate steps leading to a more advanced organic state.  Without that convincing argument Darwin’s theory may not have received such widespread acceptance in the scientific community. It is useful to keep in mind that just presenting the facts is not necessarily enough to win an argument especially in the post truth environment that exists in the US today.

The “grain of truth” rhetoric is typically used to classify, generalize, and stereotype and may be more difficult to decipher than straightforward ad hominem attacks. A typical “grain of truth” argument in the graphic concerns pharmaceutical money being paid to psychiatrists and other physicians. Some psychiatrists are employed by pharmaceutical companies to conduct clinical trials and other business, some provide educational lectures, and more are passive recipients of free continuing medical education courses.  All of this activity is reported to a database where anyone can search how much reimbursement is occurring. From this activity it is typical to hear that psychiatrists are on the pay roll of, get kickbacks from, or are brainwashed by Big Pharma and KOLs (Key Opinion Leaders).  The reality is most psychiatrists have no financial conflict of interest and they are not free to prescribe new expensive medications because those prescriptions are controlled by for-profit PBMs (pharmacy benefit managers). Further – the entire issue was highlighted by a No Free Lunch movement that provided essentially rhetorical information about conflict of interest and how it affected prescription patterns.  Those arguments have a very weak empirical basis. 

What about just ignoring this rhetoric? Ignoring it has clearly not been a successful strategy.  Any quantitative look at antipsychiatry rhetoric and literature would clearly show that it has increased significantly over the past 20 years – to the point that papers written from this standpoint are now included in psychiatric journals and you can make money doing it.  Recent cultural phenomena including the Big Lie rhetoric of the last Presidential election, the partial recognition of climate change (despite firsthand experience with increasingly severe weather most do not believe it is due to human activity), and the multilayered problematic response to the coronavirus pandemic sends a clear signal that rhetoric must be responded to and not ignored. 

The American public has been fed a steady diet of absurd criticisms about psychiatry for decades. If you do not believe that – study the table and compare it to what you see in the papers and across the Internet.  And never take anything you read about psychiatry at face value.

 

George Dawson, MD, DFAPA


Supplementary 1:  As noted in the above post I am interested in graphing legitimate psychiatric criticism in the same format used in the above graphic. If you have critiques and references - feel free to post them here.  I have some favorites from Kendler, Ghaemi, and others. 

 

References:

1:  Pies R.  Four dogmas of antipsychiatry.  Psychiatric Times May 5, 2022:  https://www.psychiatrictimes.com/view/four-dogmas-of-antipsychiatry

2:  Herrick JA. The History and Theory of Rhetoric. 7th ed. New York, NY: Taylor and Francis, 2021: 221-223.  – I highly recommend this book on the historical and current importance of rhetoric. A lot of what passes for philosophical criticism of psychiatry is really rhetoric.

Saturday, February 18, 2023

Cosmopolitanism...

 


“I am not an Athenian or a Greek, but a citizen of the world.” – Socrates

 

I have always considered myself to be a citizen of the world but I don’t know why.  I was born and raised in an isolated place on the northern margins of the United States.  The overriding ethos was “mind your own business”.  I don’t know if that just fit my personality well or if my personality was molded to fit that rule but I was and am very good at it.  Despite that trait my exposure to people from other cultures and ethnicities through sports, school, the Peace Corps, and work went very well largely because I saw them as people with the same day to day problems that I had. Everybody’s trajectory through the world is unique and common at the same time. We all grow up in families and at some point, have families of our own. We all strive for continuity over time.  We get up in the morning, go to work, and expect to come home to the safety and support of our families at night. We all know that despite our efforts – disagreement, illness, accidents, disability, and death are major obstacles that we are going to encounter along the way.  There is no way around them.  It is universal human experience.

I had that idea about people in my neighborhood and people I read about from all over the world. It made sense when I heard from the leaders of the protest movements in the 1960s and 1970s.  It made sense when I heard Muhammad Ali talking about why he objected to the war in Vietnam. It makes perfect sense when I hear from people protesting about gun violence and women’s reproductive rights in the United States. In every case, these protests are about people who are not minding their own business and who are not mindful about the challenges that we all face. Why would you want to perpetrate an unnecessary war, take away women’s rights, and make gun violence a norm when people are just trying to make it home every night and survive?  In my lifetime, the United States has been involved in three unnecessary wars – 2 in Iraq and one in Afghanistan.  The one in Afghanistan was the longest and third most expensive war in the history of the country.  That expense minimizes the total cost of lives lost, disability, and infrastructure destroyed in these countries.

And yet everywhere currently – the world is in a crisis. The multiple crises are not precipitated by average folks like you and me but by a small number who seem intent on inflicting their will on the rest of us. I like the term megalomaniac.  It has nothing to so with psychiatry – but it connotes a person obsessed with their own power. When that exists, it is rare to not see the megalomaniac exercise that power often with horrific results.  The context that the power is exercised is also critical.  Autocrats and dictators who have absolute control of the military are probably the worst-case examples and history is full of them.  On the current world stage – Putin is probably the clearest example. The estimate of his net worth from various sources is anywhere from $1.7 to $200B.  At a time when most people are working toward retirement, he launched as assault on Ukraine based on the fictitious claim that it had to be “denazified”.  He is systematically destroying the infrastructure and killing people. He has also alluded to using nuclear weapons, based on further exaggerations of NATO being a threat to Russia.  At this point he is the clearest example of a leader out of control.  He is holding the world hostage in order to get control of Ukraine.  This strategy benefits only Putin and not the Russian people.

The most recent crisis that prompted me to complete this piece was the balloon over US airspace that originated from the People’s Republic of China (PRC). The timing coincided with a scheduled visit to China by Secretary of State Anthony Blinken. The visit was cancelled because of the balloon. As I type this the United States has added six PRC businesses to an Entity list to restrict them from buying US technology.  That decision was made based on inspection of the retrieved wreckage after the balloon was shot down by a US fighter jet over the Atlantic.  The United States also claims that US spy plane flybys confirmed that this was a surveillance balloon capable of eavesdropping on communications at US nuclear installations.  When I first heard about his development I thought the obvious concern would also be the dispersal of some kind of weapon at high altitude.  At any rate, it is a clear violation of US air space by a hostile government, despite denials by the PRC and their failure to communicate directly about this incident over a hotline between Washington and Beijing.

What does all of this mean for cosmopolitanism?  It leads to an obvious level of analysis that nobody ever seem to comment on. Is the average person in Russia, the PRC, or the US involved in all of these decisions?  Are they cheering their governments on? Are they keeping scorecards on who is winning?  I have no reason to believe that they are. At some level people around the world realize that their counterparts in other countries are facing the same challenges that they are and just trying to make it through the day.  At that level of analysis – all of these actions by their governments are detached form that simple reality. I some cases, so detached that nuclear war is being threatened. Nuclear war is really a euphemism for the end of civilization as we know it. Even a limited number of nuclear explosions can put enough debris into the atmosphere to destroy the crop growing environment and cause mass starvation. What citizen of the world wants that?

That disconnect between people and the governments who are supposed to represent them endangers the entire planet and it is unnecessary. There are very few places where this disconnect is not evident, but in some cases it is obvious. Iran comes to mind.  The Iranian government is clearly not sensitive to the day-to-day concerns of its people especially women, but at the same time is actively exporting weapons and terrorism across the globe. It illustrates a qualitative difference in governments that directly impacts cosmopolitanism captured in this quote (1):

"Only a state which understands its role as a governmental mechanism, rather than as having claims to particular truths, is likely to be able to play the enabling role that cosmopolitanism needs."

There are clearly many governments across the world that see themselves as much more that a “governmental mechanism” and instead insist that people under their rule live a certain way. Theocracies work out of the assumption that a certain religion is superior.  Autocracies do the same for a particular ideology.  In both cases large segments of their population can be suppressed, persecuted, or in extreme cases killed for non-adherence to these doctrines. There are many obvious historical and ongoing examples.

Reviewing some of the literature on cosmopolitanism it is typically criticized for being too idealistic and impractical. How can large numbers of people practically adhere humanistic principles when they are fractionated by governments and in many cases oppressive governments opposed to humanism? Some authors write about socioeconomic status of cosmopolitans – seeing the very wealthy classes as being the most likely cosmopolitans while others see refugees as having that status of necessity. Critical features that are not mentioned are humanism and empathy. Both need to be emphasized at an international level to attempt to move the threshold for more appropriate international behavior in the right direction.  Citizens of the world recognize that their counterparts around the world have the same problems and the same goals every day. They hopefully have some input into the mechanism of government in their geographic locations, but that is obviously not universal.   

One of my favorite modern philosophers Massimo Pigliucci (2) examined the issue of cosmopolitanism from the standpoint of tension between altruism and selfishness.  He suggests that this may be a false dichotomy.  Pigliucci is an expert in Stoic philosophy and the developments that group added to cosmopolitanism.  He explains that the Stoics as intelligent social beings had an expanded concern for humanity and thought that free people flourish in a cooperative society, therefore caring for others assures that you will also flourish. 

This is an excellent individual philosophy that may not translate well at the international level.  Part of the problem seems to be that entire nations do not operate on cosmopolitanism – at least not predominately.  There are certainly elements like international assistance in the event of natural disasters and catastrophes where it may occur.  But countries are more likely to operate out of a vaguely defined self-interest. That self-interest may lead to the vilification of average people in other countries rather than understanding that we all share similar struggles and problems in living. In some cases that vilification may extend to factions in the country of interest for not supporting government propaganda and aggression.

A recent review of the current situation in Russia by Hill and Stent (3) is illustrative. They describe the 23-year reign of Vladimir Putin in Russia and how his absolute power is basically unchecked.  The clearest evidence is prosecuting a war against Ukraine based on his fantasies about what Russia should be and making mistakes that would have led to his removal in any country where there was personal accountability. In addition to the ruthless attacks on Ukraine and its people – he is equally ruthless on the home front. The authors describe deserters from the army being murdered and the videos of those murders released.  He has assassinated businessmen who do not support the war against Ukraine.  He has sent poorly trained and equipped inmates from Russian prisons to the front lines to fight. He has basically inflicted a tremendous amount of suffering on both the Russian and Ukrainian people. And yet at this point he continues to maintain absolute control over the country.

Many countries in the world today are run by similar autocrats.  Autocrats have also been a part of human history and the amount of suffering they have caused is beyond biblical proportions. Why does that cycle continue to repeat itself?  I think a lot of it has to do with the human tendency to simplify issues by tribalism. There is significant anthropological study showing that very early humans have a tendency to get into all out wars at the tribal level and then successively higher levels of organization. That suggests that it is easier to mobilize for a violent conflict than to think about or conduct negotiations. It also implies that there is very little thought given to the fact that the purported enemy is facing the same uncertainties and problems as the aggressors. Wartime rhetoric suggests that the enemy is the cause of the problem.

What are the potential solutions?  If cosmopolitanism is a tough sell – it can potentially guide solutions. The first necessary step is to make all the people of the world aware of the process. Education is a first step.  If you are a citizen of the world, you must be aware of the similarities of all people and how they differ from governments. There must be a sense of empathy for fellow citizens across the globe. That must be true for people of different regions within the same nation.  The only way to be a global citizen is to be see yourself as like everyone else in your geographic location as a first step.   A second step is to notice how politics attempts to affect that basic inclusiveness. Politicians everywhere thrive on pointing out the differences between people, suggesting that they are irreconcilable, and then proposing a plan for winning against the marginalized group. Recent events suggest that this process is very common in democracies including the United States where we witnessed an insurrection against the government and a significant increase in hate crimes against ethnic groups as a direct result of extremist rhetoric from a specific political party and their members. Cosmopolitanism cannot get off the ground in those conditions, but there is a chance that exposure to those principles may harden the population against demagoguery.

Cosmopolitanism after all is a very humanistic approach to relationships. That runs counter to recent human history where the focus has been on episodic warfare and violent confrontations. It would seem to set the baseline conditions for peace and peace is not a common word these days.  It only comes up when the direst of conditions exist and lately with the threat of nuclear weapons from the Kremlin. Peace and cosmopolitanism, need to occupy a much higher position on individual and collective agendas.

 

George Dawson, MD, DFAPA

 

References:

1:  Kendall G, Woodward I, Skrbis Z. The sociology of cosmopolitanism: Globalization, identity, culture and government. Springer; 2009 Apr 28.

2:  Massimo Pigliucci. When I Help You, I Also Help Myself: On Being a Cosmopolitan.  November 17, 2017.   https://ordinaryphilosophy.com/2017/11/17/when-i-help-you-i-also-help-myself-on-being-a-cosmopolitan-by-massimo-pigliucci/

3:  Hill F, Stent A.  The Kremlin’s Grand Delusions What the War in Ukraine Has Revealed About Putin’s Regime.  Foreign Affairs February 15, 2023.


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