When viruses help us

 kw: book reviews, nonfiction, science, virology, bacteriophages, antibiotic resistance, medicine

These barely-living creatures look to me like a balloon attached to a hypodermic syringe. They are T2 bacteriophages injecting DNA into E. coli bacteria. The common term for a bacteriophage, a virus that infects bacteria, is "phage", which means "eater". They eat bacteria.

The phage's DNA is packed into the "balloon", a protein capsule, so tightly that the pressure inside is more than 300 psi. No wonder that, once the "syringe" pierces the cell wall of the bacterium, the DNA erupts into the cellular interior. There, "shepherd" proteins that accompany it help it integrate with the cell's DNA and begin to make great numbers of copies of the phage. Once all supplies within the cell are exhausted, lytic enzymes cause the cell to rupture, releasing thousands of new phages.

To learn of phages and the breadth of their usefulness, I read The Good Virus: The Amazing Story and Forgotten Promise of the Phage by Tom Ireland. The book has two strong themes: that phages save lives in an almost miraculous way; and that political and scientific blindness have hindered the study of phages in the "free world", primarily because they were primarily developed as a therapeutic tool in the Georgian SSR and Soviet Russia. By the time scientists in the West learned of their antibacterial use, the cultural trend was "Better dead than Red."

The first viruses discovered were phages. Doctors noticed that sometimes the bacterial "lawn" growing in a Petri dish would develop "plaques"—clear, circular holes—but that nothing could be seen under the microscope, just bits of broken bacteria. Later, by filtering the liquid mix from the clear spots through a very fine porcelain filter, a "something" could be produced that killed bacteria. The term "filterable virus" was coined. Only later, when the electron microscope was invented, were phages seen and given their name.

Bacterial cells are so different from the cells of animals that phages cannot infect us. While there are 600 or so human pathogenic viruses, there are tens to hundreds of thousands of known phages (so far), many millions of phages known only from DNA screening of water and soil, and from billions to perhaps more than a trillion varieties of phages in existence worldwide. I way "varieties" because the biological understanding of "species" doesn't really fit the way viruses, and phages in particular, evolve and reproduce.

Step a little closer to home. It is rather tricky to count the cells in a human body. About 80% of "our" cells are red blood cells, so when you hear a number like 30 trillion, realize that about 24 trillion are RBC's, and the other six trillion are nucleated cells (RBC's don't have a nucleus). We have a microbiome, mainly in our gut but also across our skin, that numbers 60-100 trillion bacterial cells. Bacteria are so small that this amazing number of cells weighs, in total, a few pounds, or a kilogram or two. How about viruses? They are in the air we breathe so of course we contain some. Just counting the phages that have been found preying on bacteria within and on us, the number is about ten phage particles per bacterial cell, or roughly a quadrillion. Phages are so tiny that a quadrillion of them totals about 1/30th of a gram.

After phages were discovered more than a century ago, they were found to have antibacterial properties that could be used to cure infections. Before the discovery of effective and economical antibiotics such as Penicillin, phages were the only cure.

Side note: no medicine is perfect. Whether antibiotic or phage therapy, the dose doesn't destroy 100% of the invading bacteria. Rather, bacterial numbers are reduced to the point that our immune system has time to kill every single bacterium that remains, and then we are fully well. We need at least a minimally functioning immune system to overcome an infection, no matter what medicines we may use.

An early practitioner and proponent of phage therapy, Felix D'Herelle, called phages a "third arm of the immune system". The classical arms of the immune system ("arm" in this case meaning "weapon system") are innate immunity and adaptive immunity. The first is immediate, the second requires cellular learning, but also confers longer-lasting immunity. More recently I have read that our microbiome can be considered a preventive arm of immunity, because the good bacteria in us prevent pathogens from getting a foothold and causing disease. Thus I would call phages either a part of this third arm, or a fourth arm, destroying many pathogens once they "land".

A long section of the book tells of the Eliava Institute in Georgia (European Georgia), in Tblisi, a focus of "medical vacations" by people with multi-drug-resistant bacterial infections. For decades Eliava was the only place where a patient could have a sample taken, a phage therapy either found in the "archives" at Eliava or developed from searching in dirty water (!), and, hopefully before dying, being treated and their life saved.

Later chapters tell us of an increasing number of phage therapy centers arising. Parallel to them, recent excitement about the possibilities of phages has led to some businesses developing ways to create custom phages from scratch. This is based on work done with the ΦX174 phage: This virus was the first organism to have its DNA completely sequenced, in 1977; and a slightly simplified phage based upon it was synthesized in 2012. It was first isolated in 1935 from sewer water in Paris. That makes sense, because it infects E. coli, the famous "poop germ".

ΦX174 is one of the smallest viruses. It doesn't have the syringe like the "T" phages and some others. It is just a tiny balloon containing the DNA for 11 genes. The capsule has 12 spikes that allow it to attach to a bacterial cell.

Phages, with their simplified genomes, were first-line tools in the early days of the genetic revolution, even before the structure of DNA was discovered in 1951 by Crick and Watson. They remain useful for genetic studies.

One reason for producing synthetic phages is that the capsules of certain ones, without the DNA content, can penetrate the brain-blood barrier. If the content of such a capsule is a chemotherapy drug, and the spikes are created to attach to cancer cells, extremely targeted therapy becomes possible, in the brain or elsewhere.

That is just one use for phages that we find in the last couple of chapters of The Good Virus. The author also discusses fears of "gray goo", because viruses are actually nanotechnological machines. If a nanotech machine has the directive, "reproduce at all costs", can it spread throughout the biosphere, turning all plants, animals, and everything into a mass of nothing but themselves? Considering that nature has already developed exactly such machines, but that they are engaged in an eternal "arms race" with bacteria—which quickly learn to fight back—we realize that no gray goo scenario is imminent.

One more note: not all phages are wholly beneficial to us. This lovely image from Science Photo Library shows A45 phages attacking Streptococcus pyogenes cells. These phages carry genes that induce the cells to release fever-inducing chemicals, which cause strep throat. If the Strep that naturally exists in you is healthy, there's no problem. When the bacteria get sick, though, so do you!

An even worse case of "sick bacteria causing sick people" results when this filamentous phage known as CTXφ infects Vibrio cholerae: the deadly waterborne disease cholera. No doubt, other such cases abound.

Nonetheless, the usefulness of the great majority of bacteriophages is so great that the author optimistically hopes that they will provide a very beneficial path toward treating infections that our antibiotics are increasingly unable to cope with.

By the way, images and articles regarding phages and E. coli seem to outnumber the rest, not because that's the most common, but because E. coli are used for so many kinds of genetic studies that they dominate the literature.

Spider activity subsiding

 kw: blogs, blogging, spider scanning

First thing in the morning, what do I see?
No more spiders looking at me.

After several weeks of hot action, things have settled down:

Singapore has been the heavy hitter, but represents only about half of the activity. There's no telling how much of this went through VPN's. I wonder how long things will remain "normal", or perhaps, just ordinary, at 50-100 views per day, or a few thousand per month. To me, that is satisfactory.

OPUS 500

 kw: art generation, ai art, simulated intelligence, milestones

I have been learning how to use art generation programs since November 2022. That is just a little more than two years. Initially DALL•E2 was all that was available. I used it until it went out of service a year later in favor of DALL•E3, which powers the Bing Image Creator. In the first few days using DALL•E2, with lots of experimentation, I produced two images that still please me a lot. One is a still-life "painting" in the style of Cezanne, the other is a "painting" of mountains in the style of the Hudson River School of painters:

Note the color blocks at lower right. That is DALL•E2's "signature". Pictures by DALL•E2 were 1024×1024, and to make them bigger one could Outpaint. I did that a lot. Eventually I began to make images that would be useful as screen wallpaper. I would prepare a large image and then crop it to 1920×1080, or a larger size with a 16×9 aspect ratio, and sign it in one of the lower corners with my name plus "/ Dall-E2", to give credit to both myself and my "commissioned artist".

At the very beginning I also tried out MidJourney and Stable Diffusion, but I wasn't too thrilled by the available toolsets, and SD required Discord, which I don't like to use.

Fast forward a couple of years. Over time I learned of other art generators:

• PlaygroundAI - I used it for 2-3 weeks during January 2024, but soon came across Playground, which may be related but had a better credit and subscription structure.
• Playground - I loved the Canvas mode, which also had Outpainting. It was taken out of service in November 2024, the company having decided to concentrate on graphic arts rather than fine art.
• I had been using Bard in Chrome as an alternative to ChatGPT. When its name was changed to Gemini, it was announced that it could generate art also. At first it would make four images at a time, but then it dropped three and now it only makes one per prompt, and it is always square, but 2048×2048. I've used it since February 2024.
• I found Leonardo AI in August 2024 and I've been using it since then. After a few months of using the free service, I bought a passel of credits.
• DreamStudio showed up the most recently, in November 2024. After a couple of months testing the free service, I bought some credits.
• Lastly, also in November 2024, I found Google Labs' ImageFX, which is free, but they don't keep history. Download what you want to keep right away or it'll vanish. It has some interesting features that I like, but not the rich feature set of DS or Leo AI.

My current "stable" of artists is DALL•E3, DreamStudio, Gemini, ImageFX, and Leonardo AI. All of these except Gemini can make images with various aspect ratios, although in the case of DALL•E3 the only alternative to square is "Resize to 4:3" which is actually nearly 16:9 (1792×1024), and it is a fresh image, similar to the one you "resized", but not a direct expansion of it. 

Recently I checked the folders that contain my "wallpaper" images, and found there were nearly 500. I had decided to try a different kind of image, similar to a piece of art we have that is embroidery on a floral theme. I wrote a few prompts and tried them out with the various art generators. I concluded that Leonardo AI and DALL•E3 worked with these prompts the best. At first I wanted a depiction of one artwork in a horizontal format, but none of the programs offered pictures that filled a 16×9 frame, or nearly so. Leonardo AI prepared a couple of images that featured two pieces side-by-side on a wall, so I began to concentrate on that. This is the prompt that produced the pictures of lilies:

Two pictures, finely detailed embroidery, of lily flowers of various colors and foliage within a pale green mat and dark green frame, mounted next to one another on a white wall

The upper image is of peonies, with a similar prompt but without "various colors". I also wanted an image with different flowers in each frame, and tried a prompt that said something like "peonies" first and "roses" next, but I kept getting peonies everywhere. Then I tried "roses" followed by "peonies", and still got only peonies! It seems that in existing art, peonies are a much more common theme for embroidery than roses. So I wrote a prompt that only mentioned roses, and got some images showing two pieces of art with roses. As I went along I produced wallpaper images from the ones I liked best.

I noticed at this point that I had 499 wallpaper files. I fired up Gimp (a Photoshop "cousin"), copied roses from one image with all roses and pasted them into one with all peonies, to produce my 500th wallpaper:

PS: I know that "opus" mainly refers to musical works, but I have seen it used for other creative products also.

Grin and bear down

 kw: book reviews, nonfiction, science, teeth, odontology, paleontology, biology

It is easier to get the bite force of an alligator than a human. With a large alligator, it may be more dangerous, but the process is simple: restrain the beast, tap the tip of its nose so it will open its mouth, and stick the measuring tool in between the teeth at the back of the mouth. The measuring tool is typically a steel rod fitted with one or two force plates that can survive a few tons of force. When the gator feels the intruding rod it will bite as hard as it can, even though one or more teeth might be knocked out or broken.

Humans are more cooperative than alligators. However, a human will never bite with full force, particularly when his or her teeth meet the instrument. We have a protective reflex that snaps our jaw back open when we bite on something harder than the average bit of gristle. Very few people can bite hard enough to crack open a hazelnut, for example. We are all strong enough to do so, but the reflex prevents it. Why can an alligator (or a shark) bite hard enough to break teeth, but we cannot?

It isn't for lack of strength. As adults, if we break a tooth, it stays broken. Without the help of a dentist to fit a denture or insert an implant (both quite costly), we have lost that tooth forever. But an alligator's teeth are replaced when any break. Even more so the teeth of sharks. So it makes sense that humans have a reflex that protects our teeth, but sharks and alligator's don't need that reflex.

This is just one subject covered in a very entertaining way in Bite: An Incisive History of Teeth, from Hagfish to Humans by Bill Schutt. The first section of the book consists of eight chapters that deal with various specialized kinds of teeth. The subject of bite force is found in chapter eight, where we find that a 17-foot crocodile can exert 3,700 pounds (~1,700 kg), and that regardless which of the four kinds of crocodilians were studied, bite force was based almost totally on size (the four "crocs" are alligators, crocodiles, caimans, and gharials). For example, even though the mouth of an alligator is twice as wide as the mouth of a crocodile of equal length, the length of their jaws is very nearly the same, and the bite force is the same.

Compared to the peg-shaped teeth of these reptiles, a human molar is rather complex, as this dentist's sign shows. The strong, curved roots of the molar hold it firmly in the jaw. This is why, whenever someone needs to have a molar removed, the dentist schedules a double-length appointment, and these days takes great care to inject enough Novocain or Lidocaine, because the tooth will probably need to be broken in half to get it out, and removing each section requires a great deal of force. I've noticed that dentists tend to be built like weightlifters, and it makes sense!

Human teeth are not particularly sharp. Our pet cat's teeth are much sharper than mine. But perhaps the sharpest teeth belong to vampire bats, the subject of the first chapter. The incisors of a vampire bat are so sharp that the bat can slice off a bit of skin, really a shallow scrape, without disturbing the sleep of the victim. The typical location of the bite is a toe or ear or other easy-to-reach extremity—certainly not the neck! The shallow wound will ooze blood, which the bat laps up. Along with this understanding, we learn how the mythology of vampires and of bats had to be gradually swept aside so scientists could learn how these tiny mammals really live.

A side note on the subject of Chapter 2, the candiru fish of Brazil. Contrary to rumors, these slender catfish don't swim into you while you are peeing in the river. They are about half an inch in diameter, and won't fit. The author was able to track down just one apparently verified account of a man who had this happen, but "apparently verified" turned out to be not really verifiable.

Other kinds of specialized teeth include fangs, both the large canines of baboons and the venom-bearing fangs of certain snakes and lizards such as the Gila monster. They include tusks, which are teeth that project out of the mouth or skull. And we learn why the teeth of horses continue to grow with age: Grass is so abrasive it wears down the crowns of the teeth, so new material has to be grown continually, or no horse would live more than a few years.

Does every animal have teeth? Or at least, all the animals big enough for us to notice? Apparently the earliest vertebrates had no teeth, and no jaws. Hagfish have a weird Y-shaped sort-of-tongue with two patches of toothlike scrapers. They eat from a fallen fish or whale by gripping a bit of flesh with the Y, then tying themselves into a knot that they slip forward until they can pry against the flesh and tear out the piece, which they just swallow. Some frogs and toads are toothless, and turtles have a beak of keratin rather than teeth. Of course birds have a beak also, and the proverb "scarce as hens' teeth" is apt. Certain experiments show that the genes for making teeth are present in birds, but are inactive. The dinosaur ancestors of birds probably all, or nearly all, had teeth.

While the toothed whales—porpoises, orcas, and sperm whales—have many teeth, the other major group of whales instead have baleen or "whalebone", a filtering organ, and no teeth. The echidna, or spiny anteater, and other anteaters, have no teeth, swallowing their prey whole; their main "utensil" is the tongue.

Cephalopod mollusks (octopus, squid, cuttlefish, etc.) have beaks similar to a parrot's beak, made also of keratin. Contrary to this fanciful image of Jack Sparrow about to enter the gullet of a Kraken, or mythical giant squid, squids don't have any teeth. The beak of a giant squid is about the size of a fist; the exposed portion that actually bites is just 2-3 inches across (5-7 cm).

The last section of the book is all about human teeth, and the things people do and have done with them. You may have heard that George Washington had wooden teeth. He lost most of his teeth rather early, probably because of mercury poisoning due to medical practices of the time. His dentures contained teeth of porcelain and of human origin. When dentists of the era extracted teeth, they kept them to be fitted into dentures. Certain cultures drilled holes into the front of incisors to put jewels or other ornaments in. That's a rather painful way to show status! 

As someone who has a bunch of fillings, and now a few crowns, I know the rigors and discomfort, and sometimes the pain, of dental work. The author tells of research that may one day allow us to re-grow lost teeth. It would be a slow process, but a few months of careful chewing while the new tooth grows into place would be no worse than a few months of careful chewing while the titanium root of an implant becomes firmly incorporated into the jaw, until the titanium-and-ceramic crown can be attached. And it may cost a lot less.

Appreciate the teeth you have. Take care of them. Perhaps some folks alive today will live to see the re-growth of lost teeth. Until then, love your dentists; they really try to cause minimal pain while doing maximum good!

In French spider is araignée

 kw: blogs, blogging, spider scanning

I logged in to Blogger to begin a post and saw that there has been a lot of activity. In the recent past, when spiders aren't active, the total number of views has been around 700, with half of that from the US. For the past week, however:

I think that the roughly equal spread of ~14,000 views between France, the US and Singapore reflects VPN usage, probably by several entities. Getting such large numbers, for a blog with less than 3,000 posts, doesn't make sense otherwise. However, at this point I can do no more than marvel at it.