The Doctor is Out, Pt 2. THE BUGS ARE BACK IN TOWN

The previous post glossed over the history of magic bullets, their inherent limitations and the way they have distorted the practice of medicine. In an unexpected plot twist, it now appears that due to over-reliance on magic bullets to treat the non-communicable diseases, while allowing public nutrition and therefore health to decline, the original antimicrobial bullets are being blunted.

At the same time, the bugs are taking advantage of our malnourished and enfeebled status to fight back.

We’ve been firing Paul Ehrlich’s magic bullets at them since 1910 (1), and resistance is growing; antimicrobial resistance (AMR) has become a global and increasing public health threat (2). In 2019, 1.27 million deaths were directly attributed to AMR, with another 3.7 million associated deaths (3).

A startling one in six laboratory-confirmed bacterial infections are now resistant to antibiotic treatments (4). You’ve got to ask yourself one question: ‘Do I feel lucky?’ (5).

Over-prescription, inappropriate use, counterfeiting and mis-directed public demand got us here, counter-productive regulations and under-investment made it worse. Pasteur, Koch, Ehrlich, Domagk and Fleming would turn in their graves if they knew how their legacy had been squandered. Hippocrates would be horrified by the Gadarene rush towards specificity which started with zauberkugels, grew the pharma industry into the golem it is today and led, indirectly, to the sickening of the world.

I wonder how he would have felt about today’s Hippocratic Oath Keepers.

First do no harm started off as a relatively simple idea, but things change. In an age when patients often present with multiple conditions, and diagnostic paranoia, costs and the fear of possible litigation colour every medical decision, ‘Primum non nocere’ morphed into ‘minimize foreseeable harm and aim for the best risk/benefit ratio while staying within budget and out of the law courts’.

The equation started to become more complex when the model of specificity, so tuned to the demands of infectology and the 19th century, was grafted onto the world of non-communicable disease during the second half of the 20th century.

Due to a series of negative dietary changes, chronic non-communicable diseases had been increasing since the mid-‘50s (ie 6). This prepared a market for the pharmaceutical block-busters (drugs with over $1 billion in annual sales) which arrived shortly thereafter. The H2 blocker Tagamet was launched in 1976, and by 1986 aggressive marketing had pushed this magic bullet over the magical 1-billion-dollar threshold.

If there was a lead magician it was James Whyte Black, the monochromatic and charmingly humble Scottish pharmacologist who won the Nobel Prize in Physiology and Medicine in 1988. A lock and key man whose thinking was profoundly influenced by Paul Ehrlich’s receptor theory and his work on arsenicals, Black and his team discovered the H2 receptor and cimetidine, the first clinically useful H2 blocker, in the early ‘70’s. (He had also discovered, a decade earlier, the beta receptor blocker propranolol.)

By focussing on identifying locks and then designing keys to fit, he was named the father of rational drug design. Given the way he operated (7), I think this is entirely correct. From a public health perspective, however, and through no fault of his own, I submit that it was mis-directed.

Black’s research, which promised a set of new ultra-specific tools to fight disease, changed the financial landscape. Funding flowed to Big Pharma and thence to the medical schools, by now churning out pill millers who truly believed that better health could only be achieved through (synthetic) chemistry. They still prevail today. By 2022, the number of blockbusters had increased to 152 (8). Tagamet and propranolol moved on via Prozac and Lipitor to Eliquis and Keytruda, the Scylla and Charybdis de nos jours.

Sales are increasingly healthy because increasingly, the market is not. Public health went into a long and not-so-slow decline as doctors turned further to drugs, we turned further away from whole foods, and the numbers of chronically poisoned people with non-communicable diseases continued to rise (ie 7, 8). More and more folks therefore need polypharmacy, especially – but not exclusively – the elderly (9, 10).

Which brings us to the latest turn of the screw.

Recent research shows that polypharmacy itself increases antimicrobial resistance (12, 13). Culprits include the anti-inflammatory analgesics ibuprofen, acetaminophen and diclofenac, the diuretic furosemide, James Black’s beta blockbuster propranolol, and the lipid-lowering drug gemfibrozil. These drugs are widely used to treat chronic inflammation, hypertension and hyperlipidemia respectively, conditions mostly caused by the industrial diet.

This drug-induced increase in AMR is happening against a deteriorating backdrop, a triple blow to our health caused by the industrial diet which has reached its toxic apotheosis and become the leading cause of disease world-wide (14).

By definition it causes widespread dysnutrition (15-17); and this, combined with a metropolitan lifestyle which reduces contact with immune-modulating commensals (18) and damages the host microbiota (19), reduces herd immunity (16-19). More of us become vulnerable to infection, and at the same time more of us suffer from diet-related disease which necessitates taking drugs which make bacteria more likely to become resistant. It is a most vicious circle.

Drug companies respond by pushing ever-more aggressive vaccination schedules.

In the 1950’s I was vaccinated against polio, smallpox and TB, caught mumps, measles and chickenpox, and survived. When the US paediatric program was harmonised in 1995 it contained 9 vaccines (20), by 2025 it had expanded to 16 (21). Children are less healthy today than they were in 1995, their resistance to infection is lower (2, 18, 23) and in terms of chronic illness they are certainly less healthy than in 1935 (24-27). Their growing load of vaccine adjuvants may factor into this.

The big reduction in many infectious diseases, which took place prior to the introduction of vaccine schedules, is generally attributed to improved sanitation and living conditions (26, 27). Unsurprisingly, our bought and paid-for K street politicians side with the vaccine vendors. We are harmed, tithed and then harmed again, as in the Covid catastrophe.

Numbers of sick and maimed continue to rise in a sequence of king tides; among my contemporaries, only a very few (28, 29) remain drug and pain-free. The failure of the medical profession to look up from their prescription pads, comprehend the failure of the pharma model and consider the obvious alternatives, will be regarded by future generations as criminal negligence or at best, well-meaning myopia.

This is one hot mess, and we need to stop it, but it would be highly irresponsible to simply jam on the brakes. Half or more of all adults are physically or psychologically dependent on one or more prescription drugs (30-32), and cannot just say no. Nor can their doctors. They require careful weaning.

This slow withdrawal can only be achieved with pharmaconutritional support, and is best initiated at the earliest opportunity. The chances of achieving pharmaceutical independence depend inversely on the time since diagnosis, and the degree of accumulated tissue damage. Considerable improvement, however, may be achieved even in later cases.

Dum spiro, spero.

References:

1. https://drpaulclayton.eu/blog/the-doctor-is-out/
2. https://drpaulclayton.eu/blog/magic-bullets-vs-the-smart-bomb/
3. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022 Feb 12;399(10325):629-655. 
4. W.H.O. Global antibiotic resistance surveillance report 2025. https://www.who.int/publications/i/item/9789240116337
5. Eastwood, C. Dirty Harry, 1971
6. Deaths from Infectious, Parasitic and Non-Communicable Diseases. Division of Vital Statistics, National Centre for Health Sciences, Report 1963
7. McGregor A. James Whyte Black. 14 June 1924-22 March 2010. Br J Pharmacol. 2010 Jul;160 Suppl 1(Suppl 1):S3-4.
8. https://www.living.tech/articles/worlds-bestselling-drugs-addicted-broken-us-healthcare#:~:text=World’s%20Bestselling%20Drugs%20Addicted%20to,by%20Emilian%20Danaila%20from%20Pixabay.
9. The US Burden of Disease Collaborators. The state of US health, 1990-2016 burden of diseases, injuries, and risk factors among US states. JAMA. 2018;319:1444-1472.
10. GBD 2023 Disease and Injury and Risk Factor Collaborators. Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025 Oct 18;406(10513):1873-1922.
11. Wang X, Liu K, Shirai K, Tang C, Hu Y, Wang Y, Hao Y, Dong JY. Prevalence and trends of polypharmacy in U.S. adults, 1999-2018. Glob Health Res Policy. 2023 Jul 12;8(1):25.
12. Wang Y, Lu J, Zhang S, Li J, Mao L, Yuan Z, Bond PL, Guo J. Non-antibiotic pharmaceuticals promote the transmission of multidrug resistance plasmids through intra- and intergenera conjugation. ISME J. 2021 Sep;15(9):2493-2508.
13. Chen H, Sapula SA, Turnidge J, Venter H. The effect of commonly used non-antibiotic medications on antimicrobial resistance development in Escherichia coli. NPJ Antimicrob Resist. 2025 Aug 25;3(1):73.
14. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 May 11;393(10184):1958-1972. doi: 10.1016/S0140-6736(19)30041-8. 
15. Clemente-Suárez VJ, Beltrán-Velasco AI, Redondo-Flórez L, Martín-Rodríguez A, Tornero-Aguilera JF. Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients. 2023 Jun 14;15(12):2749.
16. Christ A, Lauterbach M, Latz E. Western Diet and the Immune System: An Inflammatory Connection. Immunity 51(5), November 2019, 794-811
17. Morales F, Montserrat-de la Paz S, Leon MJ, Rivero-Pino F. Effects of Malnutrition on the Immune System and Infection and the Role of Nutritional Strategies Regarding Improvements in Children’s Health Status: A Literature Review. Nutrients. 2023 Dec 19;16(1):1.
18. https://drpaulclayton.eu/blog/the-bug-is-a-feature-pt-4-good-fences-make-good-neighbors/
19. Shelly A, Gupta P, Ahuja R, Srichandan S, Meena J, Majumdar T. Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases. Viruses. 2020 Oct 10;12(10):1150.
20. The Development of the Immunization Schedule, History of Vaccines. https://historyofvaccines.org/getting-vaccinated/vaccines-children/development-immunization-schedule
21. Vaccines by Age. CDC Vaccines & Immunizations. https://www.cdc.gov/vaccines/by-age/index.html
22. https://drpaulclayton.eu/blog/innately-trained/
23. National Survey of Children’s Health. NSCH 2018–19: Number of Current or Lifelong Health Conditions, Nationwide, Age in 3 Groups. Accessed February 24, 2021. childhealthdata.org
24. The national health survey 1935-1936: significance, scope and method of a nation-wide family canvass of sickness in relation to its social and economic setting, preliminary reports. Generated by the United States Division of Public Health Methods, Washington 1938
25. Cumming HS. “Chronic Disease as a Public Health Problem,” Milbank Memorial Fund Quarterly 14, no. 2 (1936): 125–131, 127.
26. Guyer B, Freedman MA, Strobino DM, Sondik EJ. Annual summary of vital statistics: trends in the health of Americans during the 20th century. Pediatrics. 2000 Dec;106(6):1307-17. 
27. Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA. 1999 Jan 6;281(1):61-6.
28. Barat I, Andreasen F, Damsgaard EM. The consumption of drugs by 75-year-old individuals living in their own homes. Eur J Clin Pharmacol. 2000 Sep;56(6-7):501-9. 
29. Cohen RA, Mykyta L. Prescription Medication Use, Coverage, and Nonadherence Among Adults Age 65 and Older: United States, 2021-2022. Natl Health Stat Report. 2024 Sep 5;(209):10.15620/cdc/160016.
30. https://civicscience.com/a-growing-number-of-americans-report-taking-prescription-medications-daily/#:~:text=Prescription%20medications%20used%20to%20treat,tightened%20due%20to%20inflationary%20prices.
31. https://yougov.co.uk/society/articles/40279-yougov-big-survey-drugs-britons-taking-prescription
32. Zhang F, Mamtani R, Scott FI, Goldberg DS, Haynes K, Lewis JD. Increasing use of prescription drugs in the United Kingdom. Pharmacoepidemiol Drug Saf. 2016 Jun;25(6):628-36.