Thursday, June 11, 2020

Timely Secret Science Club Zoom Lecture

Tonight, while at work, I am logged into this month's Secret Science Club Zoom lecture featuring Muhammad H. Zaman of Boston University. While I miss the lovely people of the beautiful Bell House, I am currently basking in the rays of the setting sun behind the main building at my workplace.

This is going to be a bit of a liveblog. Dorian Devins just made a statement about the official SSC support for Black Lives Matter. I'm just going to say that racism is incompatible with science. PERIOD! Kudos to Dorian and Margaret for all they do.

Tonight's lecture is based on Dr Zaman's new book: Biography of Resistance: The Epic Battle Between People and Pathogens Dr Zaman began his talk by mentioning the role of systemic racism in the spread of illnesses. What can the history of antibiotic resistance tell us about future pandemics? Medical science took a fork in the road which led us to this place. Dr Zaman then shifted to the topic of the 1918 Flu, which was worldwide in scope, affecting such geographically separated individuals as Mustafa Kamal, Mohandas Ghandi, and T.S. Eliot all contracted the 1918 flu. Forty percent of the flu deaths occurred in India,

He then displayed the abstract of a paper co-written by Anthony Fauci concerning the role of bacterial pneumonia in influenza deaths. Patients who are intubated receive antibiotics, and antibiotic resistant secondary infections pose great danger to such patients.

Dr Zaman then discussed writing books in addition to research papers- books can broaden the conversation about scientific subjects. He wants to be able to discuss these subjects with neighbors, with his children's teachers, with his aunts and uncles. He also noted that books allow a holistic perspective of problems involving public health and policy.

Bacteria can be described as gram positive and gram negative according to how they react to a Gram stain developed by Hans Christian Gram, who studied pneumonia pathogens. Dr Zaman then noted that Louis Pasteur, while a titan of science, had stolen

Robert Koch formulated Koch's postulates of disease, but he also forced East Africans to take a medicine for sleeping sickness which turned out to be extremely dangerous. Dr Zaman stressed that even great scientists are humans with all of those flaws.

Dr Zaman noted that viruses can not only cause disease, but can be used to cure disease. British virologist Frederick William Twort discovered bacteriophages, viruses which harm bacteria. This research became popular with Stalin, so phage therapy was seen as 'Soviet', so the development of antibiotics was favored. Sulfa drugs were used to teat infections, but bacteria started to become less effective. Then Alexander Fleming discovered penicillin. Mary Barber was a British doctor who noted that penicillin resistance was evolving in bacteria, so new antibiotics had to be developed, such as methicillin.

There are so many different bacteria strains which produce antibiotics to provide an adaptive advantage. Bacteria have been 'waging war' since time immemorial. Dr Hazel Barton, a cave microbiologist, has been studying microbes from deep portions of the Lechuguilla cave in New Mexico. Bacteria have been competing, humans just 'put their thumbs on the scale'.

In another case, an isolated Yanomami group in Venezuela had been contacted by soldiers, and despite their isolation, fecal samples and non-invasive skin samples showed that they had resistant microbes.

There's a need to discuss overuse of antibiotics beyond talking of bad patients and bad doctors. One major factor in common outbreaks is global conflicts. In the first Gulf War, many US soldiers contracted a new, resistant bacterium, Acinetobacter baumannii. The bacterium still infects Iraqis. War kills doctors, destroys infrastructure, and contaminates soil, fostering bacterial resistance development. Similar outbreaks developed in Kabul, and Yemen is a potential source for a novel 'superbug'.

Large-scale agriculture also fosters antibiotic resistance. Citrus growers use antibiotics to affect fruit shape and color. Farm animals are given antibiotics, which get into milk and meat. Indiscriminate antibiotic use pushed by ill trained druggists is common throughout the world.

Dr Zaman posed a thought experiment: if you are a pharmaceutical executive, do you develop antibiotics which are taken for a few days or pharmaceuticals which need to be taken every day for a patient's life? Also if you develop a novel antibiotic, should it be kept 'in reserve'?
There's a 2% success rate for new antibiotics working, and most 'new' antibiotics are merely reworking old antibiotics. For gram positive bacteria, a new antibiotic hasn't been developed for thirty years, fifty years for gram negative bacteria.

Our system doesn't work because the private sector cannot sufficiently provide a public good.

The story of antibiotic resistance is a story of bad decisions, people doing things they shouldn't have done. The problem is solvable, though, if different sectors combine- public, business. People with chronic conditions are the ones most affected by resistant infections, in the United States, African-Americans are the most vulnerable. The barriers which prevent people from having decent lives must come down if we want a society in which everyone is healthy.

The lecture has now shifted into the Q&A phase. One question regarded the pace of resistance development in medicine vis-a-vis nature. The selective pressures in a lab are just more rapid in pace, so resistance evolves more quickly. Another question involved overuse of alcohol-based wipes in the current pandemic- we don't know the long-term impact because there are no good studies. They are probably less conducive to resistance than antibiotics, but they do kill beneficial bacteria as well. There could be serious concerns. What is the best thing we can do as patients to counter antibiotic resistance? Perhaps it involves forgoing immediate relief for long-term benefits. As patients and consumers, we should also push back on excessive antibiotic use in farm animals, particularly use to foster growth, rather than to treat infection. Can bacteria lose resistance to old antibiotics? Resistance is a cost to bacteria, they have to carry that gene. Antibiotics which are ineffective here in the US can still be effective in countries which have tighter controls on their use. Is humanity destined to lose the battle with bacterial resistance? Dr Zaman is an optimist. People are suffering, and socioeconomically disadvantaged people suffer the most, and our humanity is suffering. Some bastard in the audience asked: Would it be possible to use 'selective pressure' to foster bacteria which are less deleterious to human hosts? If that is done, everybody must buy in. Such bacteria would be more prone to antibiotic resistance, which is not hard to evolve. Bacteria have been around for four billion years, they are hard to 'outsmart' evolutionarily. Another question regarded the best way to combat outbreaks. Dr Zaman gave his top three: stop conflicts, which drive suffering, make sure that proper information is transmitted, and involve everyone in health decisions, not just medical professionals.

I'm going to hit 'publish' now, though the Q&A is still ongoing. Please, put your name on the Secret Science Club mailing list, because there is another lecture taking place next week.

Kudos to Dr Zaman, Dorian and Margaret for another great Secret Science Club presentation.

UPDATE: In response to a young listener, Dr Zaman stressed that the old model of a 'war on bacteria' has been discounted, and that beneficial bacteria play an important role in human health. Another good question involved a global outbreak of resistant C. difficile- while numbers have been going up, the transmission isn't as quick as a viral infection. Another question involved the danger of knocking out beneficial bacteria, which Dr Zaman noted can impact our immune systems, which are under constant pressure, upsetting the balance is bad. The follow up involved ways to restore bacterial symbionts after a course of antibiotics. Dr Zaman opined that it depends on what antibiotics are involved, but suggesting consulting a nutritionist for advice.

SECOND UPDATE: There was a question about how antibiotic resistance arises, and Dr Zaman indicated that bacteria have multiple strategies... they can evolve thicker walls, they can develop more effective efflux pumps to remove toxins, they can move genetic material to different areas to thwart antibiotics. He reiterated that bacteria have been around for billions of years, and have many survival strategems.

THIRD UPDATE: There was a question about reviving phage therapy making a comeback. Broad clinical trials are needed. We need to know how phages affect bacteria. Studies of viral mutations must be done to ensure safety. Phage therapy should supplement antibiotic and vaccine use to create a broad spectrum of therapeutic techniques.

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