Scientists are killing superbugs with viruses
Fighting fire with fire.
- CDC estimates say that 154 million antibiotic prescriptions are given out each year, 30 percent of which are unnecessary.
- The overuse of antibiotics have led to the rise of nigh-untreatable superbugs.
- Phage therapy offers a promising new way to overcome antibiotic resistance, but it also comes with its own risks and challenges.
In 1928, Alexander Fleming had just returned from vacation to his disorderly laboratory when he discovered he had made a mistake. He had been researching the bacteria Staphylococcus and had accidentally left one culture uncovered, exposing it to the environment of his laboratory and compromising the culture. The culture appeared to be covered in a fungus that had destroyed the bacterial colonies in its immediate proximity. Investigating further, he discovered the fungus had released what he initially called "mold juice."
Later, he would call this substance penicillin after the fungus's genus, Penicillium. This marked the start of the antibiotic era.
Bacteria had been the cause of many different forms of human suffering, so the discovery of a substance that could suddenly cure scarlet fever, meningitis, pneumonia, and other diseases was met with wild enthusiasm. Unfortunately, we became a little too enthusiastic.
We distributed penicillin and other antibiotics, such as tetracycline and erythromycin, to soldiers, sick civilians, livestock, and often to people who were sick with viruses or other conditions unrelated to bacteria. It was only in 1944 that we first uncovered strains of Mycobacterium tuberculosis that could resist antibiotics.
It took some time afterwards for the scientific community to fully accept that our overuse of antibiotics was "teaching" bacteria to defend against it. They were evolving to release chemicals that inactivated the antibiotic, learning to pump antibacterial chemicals outside of their cell walls, changing their structures, and developing a variety of other defense mechanisms.
Bacteria are simple, prolific, and therefore evolve quickly, and pretty soon medical texts began to issue this piece of advice: "The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them."
Addicted to antibiotics
Clumps of methicillin-resistant Staphylococcus aureus (MRSA) bacteria viewed under a scanning electron microscope.
But we still overuse antibiotics all the time. In fact, the CDC estimates that 154 million antibiotic prescriptions are issued each year, and a full 30 percent of those prescriptions are unnecessary. They're simply too useful not to deploy under the right conditions. Now, new superbugs are emerging that are completely or mostly resistant to antibiotic treatment, meaning many of the ills that once plagued humanity could return in force. What are we going to do about this?
Phage therapy: The new antibiotics?
There are a few methods that may help us contend with this new challenge, but one of the most promising fields of research is phage therapy. Bacteriophages (or just phages) are viruses that specifically target bacteria, though viruses as a whole target a variety of different cell types. Generally, viruses cause a great deal of trouble for people: they give you colds, the flu, chickenpox, herpes, and other diseases. Bacteriophages, too, can target the helpful bacteria that humans need to go on living a healthy life.
Phages look like creepy, cyborg spiders for the most part. The kind of phage we're interested in— lytic phages — land on the surface of a cell, bind to receptors on the its membrane, inject their own DNA or RNA, and hijack the cell's own machinery to make more of itself until the whole cell bursts. Then, the cycle repeats. Think of a much smaller version of the facehugger from the Alien franchise. Fortunately, some kinds of these killers specialize in assaulting the harmful bacteria that makes us sick.
The benefits of phage therapy
Phages attacking a bacterium. Image source: Wikimedia Commons
Phages only hunt the particular species of bacteria they can bind to, which makes them infinitely more targeted than antibiotics. An antibiotic kills indiscriminately, even killing the bacteria that may be strengthening the immune system, promoting gut health, or doing some other kind of important work for us. A phage that targets, say, Staphylococcus, will only kill Staphylococcus.
They also evolve, just as bacteria do. Phages may be able to develop new strategies of attack to overcome bacteria's new strategies of defense. In contrast, once a bacterium learns to defend itself against antibiotics, that antibiotic ceases to work. In the future, we may even be able to genetically modify phages to more effectively combat bacteria.
Just as antibiotics come with a downside, so too does the use of phages to treat bacterial infections. For one, phages can accidentally provide bacteria new genes and new capabilities. Essentially, some phages destroy their host cell (called lytic phages), while others insert themselves in the host cell's genome (called lysogenic phages), leaving the bacterium relatively unharmed but copying itself into all the genomes of that bacterium's offspring.
Because this second class of phages hijacks the bacteria's DNA, they can accidentally introduce new genes that code for undesirable properties, such as greater bacterial virulence. Laboratory studies have shown that these phages can take harmless bacteria and turn them pathogenic, causing diphtheria, cholera, and potentially other diseases. While we would avoid using lysogenic phages in practice, filtering them out would add to the cost and effort involved, and there's some concern that a phage that was lytic in the lab could become lysogenic in the body. And even lytic phages can accidentally pick up bits of its host bacteria DNA, spreading them to new bacteria with unpredictable effects.
There's also a logistical issue that arises from one of phage therapy's benefits: specificity. In order to treat an infection, there would need to be multiple strains of phages on hand to treat the multiple strains of bacteria in an infected patient — burn wounds, for instance, are often rife with a wide variety of infectious bacteria. To be ready for any kind of infection, large phage "banks" would need to be developed holding a variety of different phage strains. Due to the rapidly evolving nature of the microbial world, these banks would also need to be consistently updated to combat emerging local strains of bacteria.
But the biggest challenge may lie in regulation and marketing. Because phages can evolve so rapidly, going through a thorough vetting procedure for each new version of a phage-based treatment could paralyze the regulatory process. What's more, patent laws don't really have an answer for phage therapy, and it will be difficult for any company to make money off of them — no profit means no investment, and no investment means no research. And finally, phages are plain creepy: it's going to be difficult to persuade intractable parents that the best cure for their child is to inject them with viruses.
So, will we begin curing all our incurable diseases with cocktails of viruses? Probably not anytime soon. With enough time and research, the challenges listed above can likely be overcome, and even if they cannot be overcome entirely, certain limited applications will be (and already are) deployed. It may not be a one-size-fits-all solution to antibiotic resistance, but it's at least another arrow in our quiver.
Join Radiolab's Latif Nasser at 1pm ET on Monday as he chats with Malcolm Gladwell live on Big Think.
A vertical map might better represent a world dominated by China and determined by shipping routes across the iceless Arctic.
- Europe has dominated cartography for so long that its central place on the world map seems normal.
- However, as the economic centre of gravity shifts east and the climate warms up, tomorrow's map may be very different.
- Focusing on both China and Arctic shipping lanes, this vertical representation could be the world map of the future.
The world, but not as we know it<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMDU1Nzg1NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNTkwMjIyNn0.qmQfwUdjQka8JX6q4KGANagleiuucpWay5ytMenZxUU/img.jpg?width=980" id="b95e4" class="rm-shortcode" data-rm-shortcode-id="ac088ec55c0585a93a9a310faab9a4c7" data-rm-shortcode-name="rebelmouse-image" />
A Chinese 'vertical world map,' showing the world in a different perspective from the one we're used to.
Image: Prior Probability<p>Europe is tucked away in a corner, an appendage of Asia dwarfed by neighboring Africa. North America is stood on its head, facing the rest of the world from the top of the map — cut off from South America, which cuts a solitary figure at the bottom. Africa is justifiably huge, but equally eccentric. </p><p>The eye scouts elsewhere for a place to land: not the Indian Ocean, which dominates the middle of the map, but some terra firma. Antarctica and Australia are too small, mere stepping stones for the land mass of Asia. Ultimately our gaze is drawn toward China, the lynchpin of this unfamiliar world. </p><p>Managing to leave both poles intact, this "vertical" world map is about as far away as you can get from the classic Mercator projection – which slices up both, giving center stage to a puffed-up Europe. Perhaps this new map will become more familiar soon: It may do more justice to the world of the near future, dominated by China and determined by shipping routes across the iceless Arctic. <br></p>
China's 'ten-dash line'<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMDU1Nzg1Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1NTI4MzQyNn0.sBe0oFTif4Jef1vWh1kAnUylU_QMPXT5xQjm-5aA3sA/img.jpg?width=980" id="a3b81" class="rm-shortcode" data-rm-shortcode-id="80fc6e4f5c9c1c978f698be2c8de5484" data-rm-shortcode-name="rebelmouse-image" />
'China without any part left out': includes Taiwan and the islands and atolls in the South China Sea, surrounded by a ten-dash line
Image: Global Times<p>While there's no indication that this map represents the Chinese government's "official" worldview, it is no secret that China has a thing with maps – and more specifically, the country's representation on them. </p><p>In China, the country's current economic success is seen as a redress of the unequal treatment meted out by western superpowers in the 19th century. China's world dominance is a return to a more natural state of world affairs, many feel. Cartographic rectifications are a symbolically significant corollary of that sentiment.</p><p><a href="https://www.citylab.com/equity/2015/12/china-cracks-down-on-politcally-incorrect-maps/421032/" target="_blank">Fines are regularly imposed</a> on companies – domestic and foreign – that fail to represent China to the fullest extent of its external borders, disputed though they may be by others (e.g. India, Taiwan and any of the countries with claims overlapping China's in the South China Sea). But the People's Republic's cartographic obsession doesn't end at China's territory itself. It also includes the country's position on the world map. <br></p>
The Kingdom at the Middle of the World<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMDU1Nzg2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyOTkwODEzMX0.SGrAZBH6iJVggFYSaIahzv9GvfEh17y1SwUNINbVicQ/img.jpg?width=980" id="1774c" class="rm-shortcode" data-rm-shortcode-id="99790d80a909d17a948f7c5d463d7d98" data-rm-shortcode-name="rebelmouse-image" />
Early Japanese color copy of Ricci's world map
Image: public domain<p>China's name for itself is <em>Zhōngguó</em>, which means 'Central State' or 'Middle Kingdom', reflecting its ancient self-image as the civilized center (<em>Huá</em>) of the world, with wild tribes (<em>Yí</em>) at the edge. That view is not unique to China. Vietnam, for example, at certain times also styled itself as the "central state" (<em>Trung Quóc</em>) – considering the Chinese in turn as the uncouth outsiders.</p><p>It may be surprising to recall, but Europeans themselves once considered their own continent a relative backwater, viewing Jerusalem as the true center of the world. That changed with the Age of Discovery, which placed Europe at the center of an ever-expanding world. Maps reflected that worldview, and largely continue to do so. That's why today's standard world map still has Europe at its center – with China off toward the periphery on the map's right-hand side. </p><p>The most notable feature of the very first major modern world map produced in China, the <em>Kunyu Wanguo Quantu</em> (1602), is that it places China firmly at the center of the world. Produced for the Chinese emperor by Jesuit missionary Matteo Ricci, it was the first map ever to combine that perspective with modern western knowledge: it was the first Chinese map to show the Americas, for instance. </p><p>That representation may not have taken off elsewhere, but it will be instantly recognizable to Chinese students, as it's the standard format for world maps in China's schools today.<br></p>
America on its head<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMDU1Nzg2My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwMzQ5NTc0MH0.EqadI2Yp-2dPwi3VccFZelIDK4V9t0ZOfTfHjdB6wVw/img.jpg?width=980" id="97104" class="rm-shortcode" data-rm-shortcode-id="2b66e8de389b3d736bc28e019e445cd0" data-rm-shortcode-name="rebelmouse-image" />
Upside down you turn me: North America on its head, in Chinese characters
Image: Prior Probability<p>For those used to "classic" Eurocentric world maps, Europe's marginalization may come across as a bit of an upset. America's new position on the horizontal Chinese world map is less jarring: It merely moves from the left- to the right-hand side of the picture. But then there's this vertical world map, which deals a similar blow to the American land mass: divided in two and pushed to the upper and lower edges of the map.</p><p>Unfamiliar? Sure. Shocking? Perhaps. Wrong? Not really. First off, no world map is totally right, since it's mathematically impossible to transfer the surface of a three-dimensional object onto a flat surface without some distortion. And since the world is a globe, where you center that map is a matter of purely subjective choice.<br></p><p>Those choices have historical reasons. Mercator's map was not specifically designed to put an inflated Europe at the center of the world. That was just a side effect; its main purpose was to aid shipping: Straight lines on the map correspond to straight lines sailed on the seas.</p>
By 2050, a completely melted Arctic could enable the Transpolar Passage, shortening trade routes between Asia and Europe and boosting business for Alaskan ports like Nome and Dutch Harbor.
Image: The Maritime Executive<p>The vertical world map, showing the relative proximity of China (and the rest of Asia) to Europe and (even the East Coast of) North America, has a similarly maritime <em>raison d'être</em>, or it will have by mid-century. <a href="https://www.maritime-executive.com/editorials/the-arctic-shipping-route-no-one-s-talking-about" target="_blank" rel="noopener noreferrer">Experts project</a> that by 2050 (if not sooner), the Arctic will be sufficiently ice-free to enable the so-called Transpolar Passage, i.e. shipping straight across the North Pole. </p><p>That would shave more than three weeks off a traditional sea voyage between Europe and Asia, via the Suez Canal – and even be significantly faster than other northern alternatives like the Northwest Passage (via Canada) or the Northern Sea Route (hugging the Siberian coast). Since ships would not need to go through locks or pass over shallow waters, it would also remove current restrictions on tonnage per ship. <br></p><p>The only country seriously preparing for such a future: China. None of the other Arctic powers is giving the Transpolar route any strategic thought. On the other hand, China's Arctic Policy document, released in January 2018, already matter-of-factly refers to the Transpolar route as the 'Central Passage' – one of several 'Polar Silk Roads' that China seems to want to develop. And they already have the world map to go with it.</p>
The Labour Economics study suggests two potential reasons for the increase: corruption and increased capacity.
Cool hand rebuke<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyMTIyNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjY1NTYyOH0.0MCPKN3If94mYCNf3mMNrnTvJXjXN_bKLhgk9203EXk/img.jpg?width=917&coordinates=0%2C0%2C0%2C0&height=453" id="1627b" class="rm-shortcode" data-rm-shortcode-id="6d76421ba1ea0de4b09956b97e80c384" data-rm-shortcode-name="rebelmouse-image" />
A chart showing prison population rates (per 100,000 people) in 2018. The United States has the highest rate of incarceration in the world.
Who profits with for-profit prisons?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="97ac37e6c7f6f22ec130ea2d56871701"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/dB78NV2WpWc?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>The Labour Economics study suggests that privately-run prisons do convicts a few favors at the moment of sentencing. However, proponents of private prisons often point to other benefits when making their case. Specifically, they argue that private prisons reduce operating costs, stimulate innovation in the correctional system, and reduce recidivism—the rate at which released prisoners are rearrested and return to prison.</p><p>In regard to recidivism, the research is mixed. <a href="https://journals.sagepub.com/doi/abs/10.1177/0011128799045001002" target="_blank">One study</a> compared roughly 400 former prisoners from Florida, 200 released from private prisons and 200 from state-run facilities. It found the private-prison cohort maintained lower rates of recidivism. However, <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1745-9133.2005.00006.x" target="_blank" rel="noopener noreferrer">another Florida study</a> found no significant rate differences. And two other studies—one from <a href="https://journals.sagepub.com/doi/abs/10.1177/0011128799045001002" target="_blank" rel="noopener noreferrer">Oklahoma</a> and another out of <a href="https://journals.sagepub.com/doi/abs/10.1177/0734016813478823" target="_blank" rel="noopener noreferrer">Minnesota</a>, both comparing much larger cohorts than the first Florida study— found that prisoners leaving private prisons had a greater risk of recidivism.</p><p>The research is also inconclusive regarding cost savings. <a href="https://www.hamiltonproject.org/assets/files/economics_of_private_prisons.pdf" target="_blank" rel="noopener noreferrer">A Hamilton Project analysis</a> noted that such comparisons are difficult because private prisons, like all private companies, are not required to release operational details. In comparing what studies were available, the authors estimate the costs to be comparable and that "in practice the primary mechanism for cost saving in private prisons is lower salaries for correctional officers"—about $7,000 less than their public peers. They add that competition-driven innovation is lacking as the three largest firms control nearly the entire market.</p><p>"We aren't saying private prisons are bad," Galinato said. "But states need to be careful with them. If your state has previous and regular issues with corruption, I wouldn't be surprised to see laws being more skewed to give longer sentences, for example. If the goal is to reduce the number of incarcerated individuals, increasing the number of private prisons may not be the way to go."</p>
What exactly does "questions are the new answers" mean?
- Traditionally, intelligence has been viewed as having all the answers. When it comes to being innovative and forward-thinking, it turns out that being able to ask the right questions is an equally valuable skill.
- The difference between the right and wrong questions is not simply in the level of difficulty. In this video, geobiologist Hope Jahren, journalist Warren Berger, experimental philosopher Jonathon Keats, and investor Tim Ferriss discuss the power of creativity and the merit in asking naive and even "dumb" questions.
- "Very often the dumb question that is sitting right there that no one seems to be asking is the smartest question you can ask," Ferriss says, adding that "not only is it the smartest, most incisive, but if you want to ask it and you're reasonably smart, I guarantee you there are other people who want to ask it but are just embarrassed to do so."