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New type of dual-acting antibiotic shows promise
A new antibiotic hits germs with a two pronged attack.
- Antibiotic resistance is a big problem, but not many new drugs are currently under development.
- A recent discovery may give us a new antibiotic that is effective against a wide range of germs, including those resistant to other drugs.
- The new drug's mechanism also appears to signal the immune system, helping to amplify its response.
Antibiotic resistance is a major problem, but one that seems to bother academics and specialists more than it worries members of the general public. Years of intemperate and often outright irresponsible antibiotic usage has given many formally treatable diseases more chances to evolve immunity to first-line drugs. In some cases, terrible diseases are increasingly resistant to a wide variety of medications.
These bacteria have evolved various techniques for surviving exposure to antibiotics, including growing stronger cell walls to keep drugs out, producing enzymes that neutralize them, and even little pumps that remove them when they do get in.
This is concerning, as not only are these diseases challenging to treat, but research into new antibiotics is limited. There aren't that many new drugs in development. However, a new study published in Nature suggests that a new line of synthetic drugs might be able to rev up the immune system and attack bacteria in a powerful new way.
The delicate art of carpet bombing bacteria
The trick with finding any antibiotic is to identify a substance that can damage bacterial cells without also harming the cells of the animal they are making sick. This is a relatively simple concept, but a difficult problem to get around.
Researchers at the Wistar Institute dealt with it by selecting something unique to bacteria, which was important in their functioning to focus on, and then finding chemicals that would disrupt it. They chose a metabolic pathway, known as the non-mevalonate pathway, which is used to create molecules necessary for the bacteria cell to survive. They then selected an enzyme in this pathway, the IspH enzyme, to target specifically.
Using computer models, the researchers screened several million existing compounds and substances to determine which ones would bind to IspH and then began experiments with the most promising candidates. A new, synthetic IspH inhibitor was created as a result of this.
How it works
The molecules that IspH helps to make are required in bacteria for respiration and repairing the cell wall. When this new antibiotic attaches to them and keeps them from doing their job, the cell either dies because it can't breathe or keep its insides in, or it stays alive but is unable to function normally. Both of these methods are commonly seen in other antibiotics. By either killing off the germs or slowing them down, they give the immune system time to step up and keep the infection under control.
The antibiotic was also found to amplify the response of the immune system. In tests involving mice, Gamma Delta T-cells, an important part of the immune system, activated at higher rates, often leading to better outcomes. This effect appears to be caused by the disruption to the bacteria; their impaired function caused them to signal themselves to the immune system.
This gives the new drug a dual function, which is hypothesized to not only make it quite effective but also may help prevent bacteria from developing resistance to it. It is thought that bacteria being hit from both directions are less likely to mutate responses to both.
IspH is a common enzyme in bacteria. Unlike some antibiotics, which are effective only against a narrow range of similar germs, this one may prove effective against a wide variety of microbes includes ones that are resistant to other drugs.
The researchers are, justly, proud of their discovery. Farokh Dotiwala, the study's lead author, suggested the finding may be more than just the discovery of a new drug in a press release:
"We believe this innovative DAIA strategy may represent a potential landmark in the world's fight against AMR, creating a synergy between the direct killing ability of antibiotics and the natural power of the immune system."
So, I presume I can get this tomorrow?
Not quite. This was an initial study conducted in mice, various kinds of plasma, and in test tubes.
While the results were promising, it will take some time before further studies are conducted and the drug becomes widely available. Additionally, while the study suggests the new drugs may be more effective against certain kinds of bacteria than existing antibiotics, exactly how well it works in humans remains to be seen.
Beyond that, if it is used as a front line drug or as a last resort is still to be determined. Future circumstances, dictated by what diseases we'll face, will likely answer that question.
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How would the ability to genetically customize children change society? Sci-fi author Eugene Clark explores the future on our horizon in Volume I of the "Genetic Pressure" series.
- A new sci-fi book series called "Genetic Pressure" explores the scientific and moral implications of a world with a burgeoning designer baby industry.
- It's currently illegal to implant genetically edited human embryos in most nations, but designer babies may someday become widespread.
- While gene-editing technology could help humans eliminate genetic diseases, some in the scientific community fear it may also usher in a new era of eugenics.
Tribalism and discrimination<p>One question the "Genetic Pressure" series explores: What would tribalism and discrimination look like in a world with designer babies? As designer babies grow up, they could be noticeably different from other people, potentially being smarter, more attractive and healthier. This could breed resentment between the groups—as it does in the series.</p><p>"[Designer babies] slowly find that 'everyone else,' and even their own parents, becomes less and less tolerable," author Eugene Clark told Big Think. "Meanwhile, everyone else slowly feels threatened by the designer babies."</p><p>For example, one character in the series who was born a designer baby faces discrimination and harassment from "normal people"—they call her "soulless" and say she was "made in a factory," a "consumer product." </p><p>Would such divisions emerge in the real world? The answer may depend on who's able to afford designer baby services. If it's only the ultra-wealthy, then it's easy to imagine how being a designer baby could be seen by society as a kind of hyper-privilege, which designer babies would have to reckon with. </p><p>Even if people from all socioeconomic backgrounds can someday afford designer babies, people born designer babies may struggle with tough existential questions: Can they ever take full credit for things they achieve, or were they born with an unfair advantage? To what extent should they spend their lives helping the less fortunate? </p>
Sexuality dilemmas<p>Sexuality presents another set of thorny questions. If a designer baby industry someday allows people to optimize humans for attractiveness, designer babies could grow up to find themselves surrounded by ultra-attractive people. That may not sound like a big problem.</p><p>But consider that, if designer babies someday become the standard way to have children, there'd necessarily be a years-long gap in which only some people are having designer babies. Meanwhile, the rest of society would be having children the old-fashioned way. So, in terms of attractiveness, society could see increasingly apparent disparities in physical appearances between the two groups. "Normal people" could begin to seem increasingly ugly.</p><p>But ultra-attractive people who were born designer babies could face problems, too. One could be the loss of body image. </p><p>When designer babies grow up in the "Genetic Pressure" series, men look like all the other men, and women look like all the other women. This homogeneity of physical appearance occurs because parents of designer babies start following trends, all choosing similar traits for their children: tall, athletic build, olive skin, etc. </p><p>Sure, facial traits remain relatively unique, but everyone's more or less equally attractive. And this causes strange changes to sexual preferences.</p><p>"In a society of sexual equals, they start looking for other differentiators," he said, noting that violet-colored eyes become a rare trait that genetically engineered humans find especially attractive in the series.</p><p>But what about sexual relationships between genetically engineered humans and "normal" people? In the "Genetic Pressure" series, many "normal" people want to have kids with (or at least have sex with) genetically engineered humans. But a minority of engineered humans oppose breeding with "normal" people, and this leads to an ideology that considers engineered humans to be racially supreme. </p>
Regulating designer babies<p>On a policy level, there are many open questions about how governments might legislate a world with designer babies. But it's not totally new territory, considering the West's dark history of eugenics experiments.</p><p>In the 20th century, the U.S. conducted multiple eugenics programs, including immigration restrictions based on genetic inferiority and forced sterilizations. In 1927, for example, the Supreme Court ruled that forcibly sterilizing the mentally handicapped didn't violate the Constitution. Supreme Court Justice Oliver Wendall Holmes wrote, "… three generations of imbeciles are enough." </p><p>After the Holocaust, eugenics programs became increasingly taboo and regulated in the U.S. (though some states continued forced sterilizations <a href="https://www.uvm.edu/~lkaelber/eugenics/" target="_blank">into the 1970s</a>). In recent years, some policymakers and scientists have expressed concerns about how gene-editing technologies could reanimate the eugenics nightmares of the 20th century. </p><p>Currently, the U.S. doesn't explicitly ban human germline genetic editing on the federal level, but a combination of laws effectively render it <a href="https://academic.oup.com/jlb/advance-article/doi/10.1093/jlb/lsaa006/5841599#204481018" target="_blank" rel="noopener noreferrer">illegal to implant a genetically modified embryo</a>. Part of the reason is that scientists still aren't sure of the unintended consequences of new gene-editing technologies. </p><p>But there are also concerns that these technologies could usher in a new era of eugenics. After all, the function of a designer baby industry, like the one in the "Genetic Pressure" series, wouldn't necessarily be limited to eliminating genetic diseases; it could also work to increase the occurrence of "desirable" traits. </p><p>If the industry did that, it'd effectively signal that the <em>opposites of those traits are undesirable. </em>As the International Bioethics Committee <a href="https://academic.oup.com/jlb/advance-article/doi/10.1093/jlb/lsaa006/5841599#204481018" target="_blank" rel="noopener noreferrer">wrote</a>, this would "jeopardize the inherent and therefore equal dignity of all human beings and renew eugenics, disguised as the fulfillment of the wish for a better, improved life."</p><p><em>"Genetic Pressure Volume I: Baby Steps"</em><em> by Eugene Clark is <a href="http://bigth.ink/38VhJn3" target="_blank">available now.</a></em></p>
It's hard to stop looking back and forth between these faces and the busts they came from.
- A quarantine project gone wild produces the possibly realistic faces of ancient Roman rulers.
- A designer worked with a machine learning app to produce the images.
- It's impossible to know if they're accurate, but they sure look plausible.
How the Roman emperors got faced<a href="https://payload.cargocollective.com/1/6/201108/14127595/2K-ENGLISH-24x36-Educational_v8_WATERMARKED_2000.jpg" ><img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQ2NDk2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyOTUzMzIxMX0.OwHMrgKu4pzu0eCsmOUjybdkTcSlJpL_uWDCF2djRfc/img.jpg?width=980" id="775ca" class="rm-shortcode" data-rm-shortcode-id="436000b6976931b8320313478c624c82" data-rm-shortcode-name="rebelmouse-image" alt="lineup of emperor faces" data-width="1440" data-height="963" /></a>
Credit: Daniel Voshart<p>Voshart's imaginings began with an AI/neural-net program called <a href="https://www.artbreeder.com" target="_blank">Artbreeder</a>. The freemium online app intelligently generates new images from existing ones and can combine multiple images into…well, who knows. It's addictive — people have so far used it to generate nearly 72.7 million images, says the site — and it's easy to see how Voshart fell down the rabbit hole.</p><p>The Roman emperor project began with Voshart feeding Artbreeder images of 800 busts. Obviously, not all busts have weathered the centuries equally. Voshart told <a href="https://www.livescience.com/ai-roman-emperor-portraits.html" target="_blank" rel="noopener noreferrer">Live Science</a>, "There is a rule of thumb in computer programming called 'garbage in garbage out,' and it applies to Artbreeder. A well-lit, well-sculpted bust with little damage and standard face features is going to be quite easy to get a result." Fortunately, there were multiple busts for some of the emperors, and different angles of busts captured in different photographs.</p><p>For the renderings Artbreeder produced, each face required some 15-16 hours of additional input from Voshart, who was left to deduce/guess such details as hair and skin coloring, though in many cases, an individual's features suggested likely pigmentations. Voshart was also aided by written descriptions of some of the rulers.</p><p>There's no way to know for sure how frequently Voshart's guesses hit their marks. It is obviously the case, though, that his interpretations look incredibly plausible when you compare one of his emperors to the sculpture(s) from which it was derived.</p><p>For an in-depth description of Voshart's process, check out his posts on <a href="https://medium.com/@voshart/photoreal-roman-emperor-project-236be7f06c8f" target="_blank">Medium</a> or on his <a href="https://voshart.com/ROMAN-EMPEROR-PROJECT" target="_blank" rel="noopener noreferrer">website</a>.</p><p>It's fascinating to feel like you're face-to-face with these ancient and sometimes notorious figures. Here are two examples, along with some of what we think we know about the men behind the faces.</p>
Caligula<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQ2NDk4Mi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY3MzQ1NTE5NX0.LiTmhPQlygl9Fa9lxay8PFPCSqShv4ELxbBRFkOW_qM/img.jpg?width=980" id="7bae0" class="rm-shortcode" data-rm-shortcode-id="ce795c554490fe0a36a8714b86f55b16" data-rm-shortcode-name="rebelmouse-image" data-width="992" data-height="558" />
One of numerous sculptures of Caligula, left
Nero<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQ2NTAwMC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1NTQ2ODU0NX0.AgYuQZzRQCanqehSI5UeakpxU8fwLagMc_POH7xB3-M/img.jpg?width=980" id="a8825" class="rm-shortcode" data-rm-shortcode-id="9e0593d79c591c97af4bd70f3423885e" data-rm-shortcode-name="rebelmouse-image" data-width="992" data-height="558" />
One of numerous sculptures of Nero, left
Scientists use new methods to discover what's inside drug containers used by ancient Mayan people.
- Archaeologists used new methods to identify contents of Mayan drug containers.
- They were able to discover a non-tobacco plant that was mixed in by the smoking Mayans.
- The approach promises to open up new frontiers in the knowledge of substances ancient people consumed.
PARME staff archaeologists excavating a burial site at the Tamanache site, Mérida, Yucatan.
To understand ourselves and our place in the universe, "we should have humility but also self-respect," Frank Wilczek writes in a new book.