Mankind has known for a hundred years that there are two basic mechanisms by which you get sick - you can be infected by bacteria or you can be infected by viruses. Bacteria are living cells which reproduce themselves; most bacteria multiply by splitting in half every few hours. Unless they're in an environment where something eats them, bacteria multiply until there's no more food at which point they starve to death.
Along the way, unfortunately, deadly bacteria generate waste chemicals which poison humans, so we die of the infection long before the bacteria eat all the food available from our bodies. The bacteria die eventually once they've eaten whatever's left of our corpses after we die, but that's cold comfort to a person dying of infection.
Viruses are far simpler than bacteria. Some scientists argue that viruses aren't really alive because they can't reproduce themselves. Viruses multiply by sneaking through the membrane around a cell and taking over the mechanism by which the cell makes copies of itself, like hijacking a factory. Instead of making another cell, the cell makes many copies of the virus, falls apart, and dies.
Like bacteria, unless something destroys the viruses, they'll multiply until all the cells are gone then starve to death. Along the way, they destroy enough of your cells that you die. The viruses die when all your cells die because they need living cells to reproduce, but knowing that isn't much comfort when you're dying.
When penicillin came on the market shortly after WW II, it was literally a miracle drug - it killed harmful bacteria, cured infections, and saved many lives. Unfortunately, doctors overused it.
Bacteria reproduce every few hours and go through many generations while you're fighting a disease. Any bacteria that survive pass on their resistance by natural selection. Eventually, bacteria were able to defend themselves against penicillin and it didn't work very well any more.
Drug companies developed and sold as many different antibiotics as they could. Eventually, bacteria became resistant to the point that we have MRSA, a potentially fatal strain of bacteria that resists almost all antibiotics. Some experts predict that we'll soon find ourselves back in pre-penicillin days as resistant bacteria spread further and further.
There is another way, however. In "Viruses Stop Antibiotic Resistant Bacteria," Science News reports:
Nearly a century ago, biologists discovered viruses that prey upon bacteria. When penicillin and other antibiotics emerged a few decades later, however, physicians largely abandoned their efforts to use these bacteriophages, or phages, to thwart infectious diseases.
There were sound reasons why drug companies concentrated on artificially-manufactured antibiotics as opposed to phages:
Antibiotic compounds could be patented; naturally-occurring phages could not. Any competitor could grow FDA-approved phages from a sample and sell them without restriction.
Many antibiotics were "broad spectrum" in that they killed many different kinds of bacteria. Once an antibiotic was patented and passed the FDA approval process, it could be used against many different infections which increased the market.
No patient wants to take broad-spectrum viruses which can infect many different kinds of cells, that would be like becoming infected with H1N1 in order to cure a cold. The only medically-useful phages kill one or two kinds of bacteria.
This makes it a lot harder to make money selling phages because there's no point in giving a patient a phage which doesn't destroy the specific bacteria that's causing the infection. Doctors have to culture the infection, determine precisely which phage kills it, and give the patient that phage and only that phage.
On the other hand, because phages are so specific, they have certain advantages. They don't kill off the good bacteria you need to digest food, for example. Also, phages die out when the bacteria are gone as opposed to antibiotics which some researchers claim hang around in your tissue and keep killing off the good bacteria you need to digest food.
As more bacteria develop resistance to antibiotics, there's renewed interest in phages (SN: 6/3/00, p. 358: http://www.sciencenews.org/20000603/fob5.asp). Scientists now report that these viruses can prevent mice from dying after being infected with an antibiotic-resistant bacterium.
Popular Science reports on one of the very few American doctors who're using phages:
How to heal an infection that defies antibiotics? Another infection. Doctors in Eastern Europe have used lab-grown viruses to safely cure millions of wounds. So why can't we do the same here?
The article discussed Roy Brillon who nearly died from an infection which antibiotics couldn't touch. After a great deal of research, his doctor suggested that they try phages:
Even U.S. drug companies sold them until the early 1940s, when penicillin came along and proved easier to use, generally more effective and, in the end, more lucrative than phages. The viruses might not help, he [the doctor] admitted, but if they didn't hurt, what was the harm in trying? [emphasis added]
Brillon didn't need much convincing. The Food and Drug Administration was another story. Since 1963, the agency has mandated a strict approval process for all medications sold in America. Phage therapy has yet to be subjected to it, so Wolcott had to petition his state regulatory board to allow him to administer it only to people who had exhausted all other options. Then, because you can't find phages in U.S. pharmacies, he had to trek all the way to the former Soviet republic of Georgia to get it. There it's sold over the counter like eyedrops. He bought, for $2 each, three clear glass bottles, each filled with a liquid containing hundreds of types of phages.
The phage mixtures the drug stores sold were effective against the most common types of infectious bacteria. The sellers could not guarantee that these mixtures would cure a patient who had a rare infection, but patients found these mixtures effective against common infections so it was at least worth a try. In Mr. Brillon's case, the infection that had defeated every tool known to modern Western science was healed in three weeks for $6 plus travel costs.
Having cured Brillon, Dr. Wolcott reasoned, the same therapy might work for the estimated 100,000 American who die each year due to resistant infections. Problem: The fact that the phages to cure a major infection sold for $6 means that there's not enough profit in phages for any American firm to go through the approval process.
The researchers at the George Eliava Research Institute in the Republic of Georgia who've used phages sinde 1923 to cure literally millions of patients have found that as bacteria change to resist phages, the phages change right along with them. The fact that phages can be expected to change during a clinical trial means that the FDA's method of approving medicine won't work - there's no guarantee that the phages will be the same at the end of the study as at the beginning.
Nobody can say how a phage might mutate when exposed to different bacteria. This makes bureaucrats nervous. The fact that phages are safe enough to sell over the counter in faraway Georgia cuts no ice with the FDA, of course.
What's worse, any given infection may be caused by many different strains of bacteria. In difficult cases, the Institute cultures bacteria from the wound and mixes up a custom cocktail containing hundreds of phages from their library of thousands. It can take several weeks to tune the mixture to attack all the bacteria and cure the patient, but it's better than dying and cheaper than intensive care.
The FDA has not only ruled that phages can't really fit into their clinical trial process, they've also ruled that each individual combination has to be tested the same way. This is utterly impractical; custom mixes of phages are essentially out of reach to save your life unless you personally travel to the Institute.
The irony is that phages are in commercial use in the United States. The FDA says that when they're sprayed on lunch meat to kill harmful bacteria, they're a food additive which is OK. When you use phages to save a dying patient, they're a drug, which is against the law.
Some researchers argue that the regulatory hurdles combined with phages' tendency to mutate along with the bacteria they eat makes them too risky. The millions of people who've been cured by phage-based therapy would beg to differ, but the fact that phages have cured millions of infections in real, live patients is irrelevant to the FDA:
It's clear that unless the FDA is willing to consider revised approval guidelines, phage therapy in the U.S. will remain in a holding pattern indefinitely.
Today's FDA has enough power over medical treatment to be hazardous to your health. Obamacare will make matters worse by giving government agencies yet more power.
On the bright side, the more people who're killed because they're not allowed to try cures that work in other countries, the less we'll spend on Social Security payments.
What does Chinese history have to teach America that Joe Biden doesn't know?
Maybe, possibly, there'd be a way to do an end-run using pharmacists; I seem to recall reading somewhere that since times of yore, pharmacists have the right to make their own mixes?
Yes I know the supreme court would tell the state that it was wrong... which is when the state informs the supreme court that it was not granted exclusive right to interpret the Constitution and believes that the supreme court is in error on the matter.
Although things being as they are, the Fed would just produce a bale of cash to shovel out to the states, minus any state that involved itself in such a lawsuit, and then said state would prance right back into position like the trained dog they've all become.
And the Constitution... What an annoyance! Who will finally free us from it so that the Fed can rule as it was meant to?
Germs eyed to make foods safer
Adding viruses to foods doesn't sound appetizing, much less healthy. But it's a stratagem being explored to knock some of the more virulent food poisoning bacteria out of the U.S. food supply. Scientists described data supporting the tactic July 18 at the Institute of Food Technologists' annual meeting in Chicago.
http://www.sciencenews.org/view/generic/id/61270/title/Germs_eyed_to_make_foods_safer
Every year, some 76 million food poisoning cases occur throughout the United States. Most people suffer major distress but recover fine. Roughly 375,000 Americans do become hospitalized, however, and roughly 5,000 die. Since bacteria play a major role in provoking these gut wrenching illnesses - remember the E.coli O157:H7 outbreak affecting spinach four years ago - the food industry is looking for new ammo to protect its products and reputation.
A whole session of the IFT meeting was devoted to mushrooming interest in bacteriophages - viruses that quash bacteria. Phages are very discriminating. Each seeks out a particular bacterial species and largely ignores the rest.
These viruses also eschew larger beings, like plants, fish, birds and mammals. Indeed, it's this exquisite selectivity that makes them so appealing to food scientists. Find the right phage, and it will knock out the food poisoner of concern. And nothing else.
Some phages have already been granted federal approval for use on foods; approval for others is still pending, noted Lawrence Goodridge of Colorado State University in Fort Collins.
He described experiments that showed spraying cattle a few hours prior to slaughter could reduce by roughly 90 percent the pathogens present on the hide of those animals over the next 90 minutes. (In these tests, the bacteria had been added in known amounts prior to treatment.) University of Florida experiments on tomatoes suffering from a blight in the field due to a test inoculation with Xanthomonas not only slowed the spread of lesions to other plants, Goodridge said, but also improved crop yields by preventing vigor-robbing low-level disease.
Encouraging but no panacea
The Food and Drug Administration has approved phages for use in foods - but only against Listeria monocytogenes, notes food microbiologist Ipek Goktepe of North Carolina Agricultural and Technical State University in Greensboro. And these products find use primarily on meat and deli products, she added. But that's not bad, since Listeria is one of the most common food-poisoning agents. And a particularly recalcitrant one since it happily grows at refrigerated temperatures.
Goktepe reported new data showing that Listeria phages aren't uniformly effective in protecting every contaminated food to which they're applied. Food producers would like to see at least a "4 log" reduction in bacteria - that is, a reduction to one ten-thousandth of the starting population of bugs. In some of Goktepe's tests, she may see a three log reduction or less.
One recent success: An E. coli phage that targets O157:H7 strains killed a huge share of these bacterial cells that had been growing on loose lettuce and spinach leaves. When the phages were applied in a moist mist, Goktepe says, "We achieved a 3 to 7 log reduction - and that's a lot. We were not expecting that," she says. "Usually a 4 log reduction is considered very significant."
She cautions that the big bacterial drop occurred under fairly ideal conditions, such as at 3 °C, a good refrigerator's temperature. Raise the leafy greens' temperature to 10 °C (about 50 °F) and the phage delivered only a 2 to 5 log drop in E. coli numbers.
Some phages prey on Salmonella. But to date, Goktepe says, most phage studies haven't yielded much success in quashing populations of these bacteria. So viral protection from this major pathogen remains a challenge. This, as in many instances, may reflect trouble matching the right virus to the bacterium. Select the wrong phage and the virus will die of hunger as the food-poisoning agent prospers.
Such observations suggest, Goktepe says, that because farmers or food manufacturers are unlikely to be able to predict which strain of bacterium stands poised to afflict their crops or product, effective treatment may require the development of viral cocktails containing many phages. Indeed, her lab is actually interested in developing a supercocktail mixed from phages specific to a medley of pathogens - from E. coli to Salmonella.
Science News again:
http://www.sciencenews.org/view/generic/id/350573/title/Viruses_and_mucus_team_up_to_ward_off_bacteria
The last thing most people would want in their bodies is mucus laden with viruses. But a new study suggests that viruses called bacteriophages, or phages, grab onto mucus and then infect and kill invasive bacteria. The finding, reported May 20 in the Proceedings of the National Academy of Sciences by Forest Rohwer of San Diego State University and colleagues, could mean that some viruses partner with animals and humans to stave off bacterial infections and control the composition of friendly microbes in the body.
Bacteriophages are viruses that break open bacteria, killing them. Researchers have studied bacteriophages for decades, and some disease therapies take advantage of the viruses’ bacteria-slaying abilities, says microbiologist Frederic Bushman of the University of Pennsylvania medical school. But the study provides what Bushman says is a revelation that should have been obvious; phage may be a natural part of the immune system. “It’s new in a way that is sort of common-sensey,” he says.
Previously, researchers thought of mucus mainly as a physical barrier to keep invading organisms from entering the body. The slimy substance made by our noses, intestines and other organs also fights invaders with antimicrobial molecules. Some researchers had found bacteriophages stuck in mucus, but they figured that the mucus had stopped or slowed the viruses. No one realized that the viruses are part of the body’s defense, says study coauthor Jeremy Barr, who works in Rohwer’s lab. “This is a natural use of phage therapy that has probably been around since mucosal surfaces evolved,” Barr says.
Rohwer, who studies corals, had noticed that phages tend to concentrate in mucus. To find out why, the researchers collected mucus from human gums, sea anemones, fish, corals and mouse intestines. Mucus layers had more phages and fewer bacteria than the surrounding environment, suggesting that the viruses helped to limit the number of bacteria allowed into the mucus.
Phages are coated in proteins that latch onto sugars called glycans, anchoring the viruses in the mucus, the team discovered. From there the phages can ambush encroaching bacteria.
So far, the researchers have demonstrated that mucus and phages can work together to protect cells in a dish. The next step, Bushman says, would be determining what happens inside an organism, an experiment the researchers are already planning.
The NYT is beginning to understand that clincal trials aren't as useful as we had thought.
http://www.nytimes.com/2013/07/14/opinion/sunday/do-clinical-trials-work.html?nl=todaysheadlines&emc=edit_th_20130714
...
Indeed, even after some 400 completed clinical trials in various cancers, it’s not clear why Avastin works (or doesn’t work) in any single patient. “Despite looking at hundreds of potential predictive biomarkers, we do not currently have a way to predict who is most likely to respond to Avastin and who is not,” says a spokesperson for Genentech, a division of the Swiss pharmaceutical giant Roche, which makes the drug.
That we could be this uncertain about any medicine with $6 billion in annual global sales — and after 16 years of human trials involving tens of thousands of patients — is remarkable in itself. And yet this is the norm, not the exception. We are just as confused about a host of other long-tested therapies: neuroprotective drugs for stroke, erythropoiesis-stimulating agents for anemia, the antiviral drug Tamiflu — and, as recent headlines have shown, rosiglitazone (Avandia) for diabetes, a controversy that has now embroiled a related class of molecules. Which brings us to perhaps a more fundamental question, one that few people really want to ask: do clinical trials even work? Or are the diseases of individuals so particular that testing experimental medicines in broad groups is doomed to create more frustration than knowledge?
Researchers are coming to understand just how individualized human physiology and human pathology really are. On a genetic level, the tumors in one person with pancreatic cancer almost surely won’t be identical to those of any other. Even in a more widespread condition like high cholesterol, the variability between individuals can be great, meaning that any two patients may have starkly different reactions to a drug.
That’s one reason that, despite the rigorous monitoring of clinical trials, 16 novel medicines were withdrawn from the market from 2000 through 2010, a figure equal to 6 percent of the total approved during the period. The pharmacogenomics of each of us — the way our genes influence our response to drugs — is unique.
...
Scientists discover largest bacteria-eating virus. It blurs line between living and nonliving.
https://www.livescience.com/largest-bacteriophage-discovered.html
Huge bacteria-killing viruses lurk in ecosystems around the world from hot springs to freshwater lakes and rivers. Now, a group of researchers has discovered some of these so-called bacteriophages that are so large and so complex that they blur the line between living and nonliving, according to new findings.
Bacteriophages, or "phages" for short, are viruses that specifically infect bacteria. Phages and other viruses are not considered living organisms because they can't carry out biological processes without the help and cellular machinery of another organism.
That doesn't mean they are innocuous: Phages are major drivers of ecosystem change because they prey on populations of bacteria, alter their metabolism, spread antibiotic resistance and carry compounds that cause disease in animals and humans, according to the researchers in a new study, published Feb. 12 in the journal Nature.
To learn more about these sneaky invaders, the researchers searched through a DNA database that they created from samples they and their colleagues collected from nearly 30 different environments around the world, ranging from the guts of people and Alaskan moose to a South African bioreactor and a Tibetan hot spring, according to a statement.
From that DNA, they discovered 351 huge phages that had genomes four or more times larger than the average genome of phages. Among those was the largest phage found to date with a genome of 735,000 base pairs — the pairs of nucleotides that make up the rungs of the DNA molecule's "ladder" structure — or nearly 15 times larger than the average phage. (The human genome contains about 3 billion base pairs.)
These phages are "hybrids between what we think of as traditional viruses and traditional living organisms," such as bacteria and archaea, senior author Jill Banfield, a University of California, Berkeley, professor of Earth and planetary science and of environmental science, policy and management, said in the statement. This huge phages' genome is much larger than the genomes of many bacteria, according to the statement.
The authors found that many of the genes coded for proteins that are yet unknown to us. They found that the phages had a number of genes that are not typical of viruses but are typical of bacteria, according to the statement. Some of these genes are part of a system that bacteria use to fight viruses (and was later adapted by humans to edit genes, a technique called CRISPR-Cas9).
Scientists don't know for sure, but they think that once these phages inject their DNA into bacteria, the phages' own CRISPR system strengthens the CRISPR system of the bacteria. In that way, the combined CRISPR system could help to target other phages (getting rid of the competition).
What's more, they found that some of the phages had genes that coded for proteins necessary for the functioning of ribosomes — a cellular machine that translates genetic material into proteins (the proteins are the molecules that carry out DNA's instructions). These proteins aren't typically found in viruses, but they are found in bacteria and archaea, according to the statement.
Some of these newfound phages may also use the ribosomes in their bacteria host to make more copies of their own proteins, according to the statement.
"Typically, what separates life from nonlife is to have ribosomes and the ability to do translation; that is one of the major defining features that separate viruses and bacteria, nonlife and life," co-lead author Rohan Sachdeva, a research associate at UC Berkeley, said in the statement. "Some large phages have a lot of this translational machinery, so they are blurring the line a bit."