Featured

A Moldy Cantaloupe & The Dawn of Penicillin

by bodyhorrors Antibiotics & Drugs, Bacteria, History, Military •

For something that grows so carelessly and freely on our fruits and breads, mass producing the white mold and its hidden wonder drug penicillin was devilishly difficult. After Alexander Fleming’s accidental discovery of a bacteria-killing mold contaminating his cultures of Staphylococcus aureus, it languished as a laboratory parlor trick until World War II and the desperate need for treatments to fight bacterial infections became quickly apparent (1).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048009/

An image of Alexander Fleming’s original culture of penicillium mold. In his 1929 paper, it is described as a “photograph of a culture-plate showing the dissolution of staphylococcal colonies”. Image: A Fleming. Click for source.

British researchers in the late 1930s had been able to isolate the penicillin compound and prove demonstrably that it could be used to treat deadly infections but the matter of transforming the spores from kitchen pests to medicinal powerhouses still remained. In 1941, struggling under the relentless blitz of their cities and factories, Britain turned to the United States to develop methods of the industrial manufacturing of penicillin (2).

It would be another fluke – the discovery of a moldy cantaloupe - that would yield a particular strain of mold that could produce prodigious amounts of this “magic bullet” antibiotic. Factories with the expert know-how on man-handling yeast and fungi into yielding their strange fruits - alcohol distilleries and mushroom factories – were then tasked with the production of penicillin (2). Watch the video below to catch a glimpse of the very beginnings of what would ultimately become a behemoth pharmaceutical industry.

I love this video and all of its unspoken implications. The manufacturing of mankind’s very first antibiotic. The dynamism of an industry on the verge of changing death itself. Women in lab coats, Rosie the Riveter lab gals, toiling away in the molasses and mushroom factories to stop their young men from dying from sepsis (and to help cure those pesky gonorrhea infections!). Watching this video and swayed by the brimming optimism of its narrator, I thought, “By golly, with penicillin we CAN win this war!” And we did – penicillin radically changed the outlook of the war for the Allies, while Germany’s pharmaceutical companies scrambled, frantically trying to find the one strain of mold that would produce penicillin in its required quantities.

We won the war against the fascists but we’ve largely lost the war on microbes. This video will make you fall in love with the once mighty power of antibiotics but our Pyrrhic victory has now brought the battle to hospitals and antibiotic-resistant bacteria have turned against us again. Penicillin is now only effective for a chump change of bacteria and we are swiftly running out of our very best options. Enjoy this video and reflect on our short-lived golden age of antibiotics.

Resources

You can read Alexander Fleming’s paper on his oddball discovery, “On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ” published in 1929 in the British Journal of Experimental Pathology, here.

Absolutely fantastic: Fleming’s “germ paintings” using pigmented bacteria.

An ancient Sudanese tribe may have been guzzling penicillin in their beer, the antibiotic a by-product of the fermentation process. Sign this girl up!

Kulturkampf: The German Quest for Penicillin details the history of Germany’s efforts to steal/secure Fleming’s strain of mold and the penicillin arms race with the US and Britain.

References

(1) A Fleming (1929) On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ. Br J Exp Pathol; 10(3): 226–236

(2) J Stafford (December 4, 1943) More Penicillin Coming. Science News-Letters. 44(23): 362-4

&NA;, . (1930). Antibacterial Action in Cultures of Penicillium, With Special Reference to Their Use in Isolation of Bacillus Influenzas The American Journal of the Medical Sciences, 180 (3) DOI: 10.1097/00000441-193009000-00056

Featured

A Season of Hemorrhagic Fevers

by bodyhorrors Bloodborne Pathogens, Cooking & Cuisine, Geography, Occupations & Work, Viruses, Zoonotic Diseases •

Uganda and the Democratic Republic of Congo have been bedeviled by viral hemorrhagic fever outbreaks this year. Since the summer, Ebola and Marburg have appeared throughout the two verdant countries killing dozens of people.

An Ebola outbreak in western Uganda began in early July, another Ebola outbreak materialized in eastern DR Congo in August, and then Marburg made an appearance in south-western Uganda as well as in the capital Kampala in October. Last month, Uganda finally declared the country free of hemorrhagic fevers after three months of battling these seemingly omnipresent sanguinary viruses. And then Ebola appeared yet again in Luweero, a village located just 47 miles from the capital. It has been an incredibly psychologically and financially taxing period for the two countries.

(Confused on the timeline of events? I certainly was! But the WHO is here to help with a chronology of Ebola outbreaks here and Marburg outbreaks here.)

Ebola and Marburg hemorrhagic fevers outbreaks in Uganda and the Democratic Republic of Congo in 2012. Red crosses represent reported cases and the green amorphous shapes represent parks, forests and reserves as identified by Google Maps. Click to visit the map, zoom in and get additional info. © Google.

The thing to remember with viral hemorrhagic fevers is that they’re not toxic miasmas, diffusing through households and indiscriminately infecting innocents. They’re viruses. They spread through contact with infected bodily fluids, resulting in the transmission of viral particles and like any other infectious disease, there’s a method to the madness. True, they’re frightful illnesses and quite deadly, but there are clear epidemiological patterns and even cultural contexts to their arrival and spread in communities.

Take these viral hemorrhagic fever outbreaks, for example. Uganda and the DR Congo are incredibly rich and diverse in their ecology – the Congo Basin is one of the largest and densely forested regions in the world – and much of their economy depends upon safari tourism and gorilla trekking (1). The livelihood of their peoples is also greatly reliant on poaching and bushmeat; for many in the DR Congo, primates, ungulates, primates and rodents are often their only form of animal protein considering the prohibitive cost of raising or purchasing domesticated animals for food (1). It can be easier and kinder on limited finances just to go into the forests to get your dinner. Coincident with the diverse wildlife and the lush wilderness that flourishes in these countries are also viruses simmering away, undisturbed for the most part.

The recent outbreaks in Uganda and the DR Congo have some local officials pinpointing the origin of the these most recent outbreaks on infected bushmeat and contaminated fruit. The Ebola outbreak in August in the Dungu district in northern DR Congo began with a hunter who found and consumed the remains of an antelope, quickly fell ill and died (2). October’s Marburg outbreak in Kabale, Uganda is speculated to have occurred when villagers ventured into the wild to collect fruits that were contaminated by fruitbats, a known reservoir of the virus (3).

An isolation camp for infected patients and suspected cases during Uganda’s Ebola hemorrhagic fever outbreak this year. Image: The Lancet. Click for source.

There’s an unexpected upside to these grim epidemics as public fears of these deadly viral hemorrhagic fevers are keeping wildlife poachers and bushmeat hunters from venturing into the forests for profit and food. Park rangers in the DR Congo report that there has been demand for bushmeat has crashed with a concomitant rise in fear of contracting a fatal disease. Media Congo, an online newspaper covering the Congo, notes, “the fight against poaching of rare species that was once the sole preserve of NGOs and officials of the Congolese Institute for the Conservation of Nature (ICCN) has become the business of everyone” (4). Giant primates have been threatened for years by poachers and bushmeat hunters and though our closest ancestors are also at great risk of contracting and dying of Ebola and Marburg, for now they’re safe from those hunting them (5).

To figure out just where the outbreaks were occurring, I began playing around with a few maps to pinpoint the locations of reported villages in relation to nearby protected park, forests and game reserves. There’s limited information on the outbreaks – even from the WHO and Medecins Sans Frontiéres/Doctors Without Borders – on the exact origins of the many victims who have traveled to hospitals seeking care and then have died and these maps are the best I could do with the limited information available. The maps give a good idea of how geographically disparate the epidemics were, the proximity of the legion parks and reserves to reported outbreaks and how the two countries are just entirely covered in lush, green forest.

Resources

Ebola may be transmitted by respiratory means; the possibility of airborne transmission of this virus would go far in explaining how transmissible the virus is within households and hospitals.

“Protein from forest wildlife is crucial to rural food security and livelihoods across the tropics.” A great read on bushmeat in the two most densely forested and least populated places in the world.

The WHO’s Global Alert & Response monitors all global epidemics and public health emergencies. This is the current list of 2012 epidemics.

The gorilla population was devastated in 2002 and 2003 as outbreaks of the Zaire strain of Ebola killed nearly 5000 gorillas in northwestern DR Congo.

References

(1) R Nasi et al. (2011) Empty forests, empty stomachs? Bushmeat and livelihoods in the Congo and Amazon Basins. International Forestry Review 13(3):355-368

(2) Irin News Africa (August 23, 2012) DRC: Bushmeat blamed for Ebola outbreak. Irin News. Accessed here on November 20, 2012.

(3) E Biryabarema (October 23, 2012) Killer disease reaches Uganda capital, five dead. Reuters. Accessed here on November 20, 2012.

(4) J. Kikumi (October 26, 2012) Le virus d’Ebola chasse les braconniers. Media Congo [mediacongo.net]. Accessed here on November 20, 2012.

(5) M Bermejo et al. (2006) Ebola outbreak killed 5000 gorillas. Science. 314(5805):1564

Nasi, R., Taber, A., & Van Vliet, N. (2011). Empty forests, empty stomachs? Bushmeat and livelihoods in the Congo and Amazon Basins International Forestry Review, 13 (3), 355-368 DOI: 10.1505/146554811798293872

Featured

The Immunological Blitzkrieg That Is HIV Infection

by bodyhorrors Bloodborne Pathogens, Sex & Sexually Transmitted Diseases, Viruses •

It can be hard to comprehend the damage that pathogenic viruses and microbes can inflict on the human body, especially if you have scientists prattling on about cells, using multi-syllabic acronyms and tossing around – god forbid! – actual numbers. It’s helpful to have easily understood images to help put diseases into perspective, to understand that viruses like HIV have tangible and real effects. That’s why I’m so happy to have stumbled upon an incredible image from a 2004 paper that is a pictorial testament to the immunological blitzkrieg that is HIV infection.

A well-known hallmark of HIV infection is the loss of lymphocytic CD4+ T-cells, otherwise known as “helper T-cells”, that hunt and destroy invading bacteria, viruses and fungi. In this paper, the investigators were studying the underlying mechanisms that hasten the loss of these vital CD4+ T-cells from the gastrointestinal tract and the lymph nodes of HIV infected individuals.

Though we often think that the gastrointestinal tract has one job – to digest the meals that we organize our day around – it is, in fact, much more than just a digesting tube. The large intestine houses bacteria that produce vitamin K as well as a slew of water-soluble vitamins belonging to the B family, including folic acid, biotin and riboflavin. Serotonin factories in the stomach and small intestine, known as enterochromaffin cells, produce 90% of this vital neurotransmitter that modulates our emotions and moods, which might explain why a stomach bug can leave us emotionally depleted, why our stomach ”flutters” with anxiety or love or why we might get a certain “gut instinct” about future events.

The intestine also houses immune cells in groups known as Peyer’s patches that are sown along the tail-end of the GI tract known as the ileum, that abuts the large intestine. These cells lie in wait for that one moment when you go against your physician’s recommendations and chow down on a microbe-laced ceviche on your vacation south of the equator. They serve as the “immune sensors of the intestine” (1). The gut has so many immune cells housed in its crevices – including at least 70% of the body’s lymphocytes – that it is technically the body’s largest lymphoid organ (1)!

In short, our intestine is not only the heart and soul of our body, but it is also its immunological epicenter. Perhaps we should consider being a little kinder to this spectacular wonder-organ.

Representative endoscopic photographs of the terminal ileum in the small intestine of a healthy patient on the left and a HIV-infected patient on the right. Arrows point to Peyer’s patches, areas of lymphoid tissue housing CD4+ T-cells.

But back to this paper and this great image! On the left, we can see a snapshot of the ileum in a HIV-negative person. The endoscope – an expensive tube with a camera on its end exploring your nether regions – shows a rocky, Mars-like terrain in the ileum. This is healthy, all around A-plus stuff – those bumps scattered throughout are the Peyer’s patches filled with immunological cells.

On the right, we see an incredibly smooth, denuded ileum in a HIV-positive individual. There are no lymphocytic bumps to be seen and the researchers attest to the subject’s “almost complete absence of discernible lymphoid tissue” (2). In this patient, HIV has infected and destroyed many of the CD4+ cell clusters in the ileum. It’s a rather grim sight; the difference between this HIV-infected ileum and the healthy one is striking in its austerity.

Now, a few caveats. These two pictures could be the only suitable images that the researchers found in both of the participants, though they do state that they are representative of their findings in all of the studied participants. But it could be the case that there exists ileum in healthy people that looks very much like our desolate AIDS ileum above, just as there could be ileum in AIDS patients that resemble pebbly, healthy ileum. Or these images could be confounded by age – younger individuals have far more Peyer’s patches than older people – just another one of the innumerable upshots to getting old and wise (1). Or these pictures could represent just a momentary “snap shot” in time of a section of the gut whose immunological landscape is liable to change from week to week.

The researchers acknowledge that the images “could be considered anecdotal in isolation” but the endoscopic findings weren’t an aberration. They found that certain CD4+ T-cells, bearing the very receptor that HIV uses to infect these cell, were preferentially depleted from the gastrointestinal tract; the frequency of these particular T-cells in the GI tract were far lower relative to other T-cells, indicating that HIV is selectively infecting and killing these cells and resulting in a diminished population in the gut. This depletion was only found in the GI tract, not in the blood or in other lymph nodes.

Other studies have confirmed this gut-focused assassination by the HIV virus, finding that HIV delivers a devastating blow to the immune system by killing up to 60% of CD4+ T-cells within 2 to 4 weeks of infection, and that this depletion can last for up to five years even with the use of retroviral therapy (3). HIV is truly a wrecking-ball of a virus, systematically destroying cells and tissues beginning with the very organ that takes such good care of us, physically and emotionally - our gut.

Resources

“Two brains are better than one”. A great 2011 article from the New York Times on our “second brain”, the gut and its nervous system. Check out The Other Brain Also Deals With Many Woes.

Find out more about Peyer’s patches and their role in the intestine in this 2010 article, Peyer’s Patches: The Immune Sensors of the Intestine.

References

(1) C. Jung et al. (2010) Peyer’s Patches: The Immune Sensors of the Intestine. Int J Inflam. 2010: 823710.

(2) JM. Brenchley et al. (2004) CD4 T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract. J Exp Med. 200(6):749–759

(3) Evering TH et al (2012) Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection. PLoS Pathog. 8(2): e1002506.

Brenchley, J. (2004). CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract Journal of Experimental Medicine, 200 (6), 749-759 DOI: 10.1084/jem.20040874

Featured

The Sea Has Neither Sense Nor Pity: the Earliest Known Cases of AIDS in the Pre-AIDS Era

by bodyhorrors Bloodborne Pathogens, Emerging Diseases, Geography, History, Occupations & Work, Sex & Sexually Transmitted Diseases, Viruses •

This is the story of a sailor and a pirate, and the two different types of oceans that they traversed. There are seven on Earth but only one courses through man. This ocean contains no mysterious and pale sea creatures, bottomless depths or brightly-flashing predators, but it does brim with industrious cells, with dissolved carbon dioxide and occasionally with unwanted parasites.

In August of 1961, a Norwegian teenager sailed from a fjord in Oslo through the North Sea and the Atlantic Ocean to Douala, Cameroon, a port tucked under the outward slab that makes up West Africa. He was a freshly turned fifteen year old and was working as a kitchen hand on a Norwegian merchant vessel. From Cameroon, he and his crew on the Hoegh Aronde sailed northwesterly from port to port, docking at Nigeria, Ghana, Cote D’Ivoire, Liberia, Guinea and Senegal over a period of 10 months before returning to his homeland (1).

The route of the Norwegian sailor’s initial trip abroad on the Hoegh Aronde, from Oslo, Norway to Doula, Cameroon from August 1961 to May 1962. Image: Edward Hooper, 1997 (See References). Click for source.

It was an exotic start to what would be a short but wide-ranging career as a sailor – over a period of four years, he would call at ports in Asia, Europe, Canada and throughout the Caribbean. Though he would never find himself in West Africa again, he would always carry a souvenir of his visit to this incredibly diverse and ecologically rich niche of the world.

His journeys were lonesome, solitary. In Cameroon the sailor unburdened himself of his loneliness and slept with at least one woman, catching gonorrhea – this much is known. Perhaps it was the same woman or another that infected him with an unfamiliar virus simmering away in West Africa just waiting to travel foreign oceans and lands. A viral hitchhiker with a proclivity for the horizon, a pirate if you will. This virus, a certain strain of HIV included in the rare outlier group O that is genetically and immunologically distinct from the main group M that is plaguing the world today, a HIV group that native to West Africa and to Cameroon in particular but found itself in a Norwegian man who would travel the world.

When he returned to his homeland in 1965, he married and became a father to two children in a short two-year span. In spite of his exciting new role as husband and father, he often felt unwell and his family was plagued with strange illnesses. His muscles ached, a red rash covered his body and he found himself often besieged by respiratory ailments (2). In 1967, his wife became ill with fevers, an omnipresent yeast infection as well as the same respiratory infections that lurked in her husband. The next year, the sailor would see his youngest daughter developing unusual diseases not often seen in toddlers – arthritis, blood and bone infections, along with the same yeast and respiratory infections afflicting her family.

Despite his poor health, the sailor found himself crossing the sea again to Europe. From 1969 to 1973, he worked as a long-distance truck driver delivering cargo as he traversed Belgium, the Netherlands, France, Germany, Austria, Switzerland and Italy (1).

With his ailing family far away across the North Sea, the sailor would seek refuge again in Europe. His coworkers would later say that he slept with many women and prostitutes along his long and lonely lorry routes. Often beginning his route in Wesseling, Germany, he would deliver to Liége and Lyons in France, occasionally stopping in Reims between the two cities (1). Investigators in this part of France would later find cases of HIV group O in individuals that had died in the late 1970s and early 1980s but had never visited verdant Cameroon.

In 1974, the sailor fell deeply ill. He died two years later, at the age of 29, his body riddled by bizarre diseases and was followed quickly in death by his wife and his youngest daughter. Autopsies would find puzzling results – overwhelming systemic infections not often seen except in the severely immunocompromised. The pathologist conducting the autopsy would save the sailor’s lymph node, liver, kidney and lung, the mother’s leg muscle and the daughter’s lymph node, spleen and liver and, years later, the family’s serum samples would test positive for HIV antibodies. This unfortunate family, to this day unidentified, represent the first recorded cluster of confirmed HIV/AIDS infections in the pre-AIDS era, before the AIDS pandemic sparked in the late 1970s and early 1980s. The sailor’s daughter is the earliest known case of pediatric AIDS (3).

“The sea has neither sense nor pity,” wrote Anton Chekov in his short story “Gusev”. Blood churns, dark liquids pumped through the valves by the stalwart heart, all the while feeding our bodies oxygen. A corrosive virus pirates the sea, hijacking cells and visiting the ports of our body, our brain, muscles, spleen and liver. Why infect that one person, at that moment in time? There is no meaning or sense to it. The tides rise, the tides fall. The earth spins, blood spills. A ship makes its port on schedule, becomes lost or is brought to the bottom of the sea. A man dies from an infection caught 15 years earlier in a distant port, a salty partner that he introduced to his family. There is no meaning, little salvation and only grief.

Resources

If you’d like to read the “Gusev” story by Chekhov, you can do so here.

Shortly after the researchers’ work into the Norwegian AIDS cluster, researchers from Tulane discovered evidence that a St. Louis teenager, Robert Rayford, was infected and died of AIDS in 1969. His case is troubling – a 15 year old succumbing to an infection that typically takes year before progression to AIDS and death. Some sources claim he was a gay prostitute while others say that he was sexually abused as a child. Whichever may be tragic alternative it is, the fact remains that this boy had never traveled outside of St. Louis, someone had infected him and that AIDS was most certainly circulating in a limited fashion in the United States before the 1970s. Read more about him in this 1988 New York Times article.

A few months back, I created a playlist of hip hop and R&B artists singing about the HIV/AIDS crisis and admonishing safe sex to their listeners. Check out the playlist and accompanying article “Let’s Talk About Sex: Hip Hop on HIV” here.

References

1) Hooper E. (1997) Sailors and star-bursts, and the arrival of HIV. BMJ. 315(7123): 1689-91

2) Lindboe CF et al. (1986) Autopsy findings in three family members with a presumably acquired immunodeficiency syndrome of unknown etiology. Acta Pathol Microbiol Immunol Scand A. 94(2):117-23

3) Frøland, SS et al. (1988) HIV-1 infection in Norwegian Family before 1970. Lancet. 1(8598): 1344-5

Frøland SS, Jenum P, Lindboe CF, Wefring KW, Linnestad PJ, & Böhmer T (1988). HIV-1 infection in Norwegian family before 1970. Lancet, 1 (8598), 1344-5 PMID: 2897596