Tag: virus

FDA nonsense

FDA commissioner Alexander M. Schmidt

In all of FDA’s history, I am unable to find a single instance where a congressional committee investigated the failure of FDA to approve a new drug. But, the times when hearings have been held to criticize our approval of new drugs have been so frequent that we aren’t able to count them. … The message to FDA staff could not be clearer.

2013-11-26: as usual, the FDA is up to no good.

At the same time that the NSA is secretly and illegally obtaining information about Americans the FDA is making it illegal for Americans to obtain information about themselves.

2014-08-05: the FDA could help by eliminating its onerous rules for diseases with 60% mortality rates. Won’t happen of course, it’s easier to bury lots of innocents than to overcome cover-your-ass (pretty much the reason for the FDA to exist). Or as the onion put it, the Ebola Vaccine is at least 50 white people away.
2016-07-15: Fluoride still not available

American dentists first started using similar silver-based treatments in the early 1900s. The FDA is literally over 100 years behind the times.It seems that the future of dental treatment has been here all along but a combination of dentists wanting to be surgeons, lost knowledge, and FDA cost and delay prevented it from being distributed

Silver diamine fluoride been used for decades in Japan, but it’s been available in the United States, under the brand name Advantage Arrest, for just ~1 year. Toddlers in low-income families sometimes have to wait 1 year for fillings in an operating room. Transporting and treating frail patients, assuming they can afford to see a dentist, can be difficult. But now some patients can be quickly treated where they live.
2020-04-17: Nutrition overregulation

1 reason why food intended for restaurants is not reallocated to supermarkets: Nutrition labeling also frequently doesn’t comply with Agriculture Department and FDA guidelines for consumer sales

2020-12-05: This is nonsense. “Delay to allay” won’t convince anyone, and meanwhile people are dying.

Dr. Fauci said the politicization of the pandemic in his own country had led regulators to move a little more cautiously than the British, to avoid losing public support. There is no plausible reason why this basic analysis cannot be done in 24 hours. The FDA and external scientists have a simple task: confirm or reject the review already conducted by the trial’s independent data safety monitoring board before FDA submission.

2021-02-07: The FDA is unable to make sense.

Think of centers of expertise like the CDC or the IGM Economists Panel as giant systems for disentangling corruption and power. Their job is to produce 1 or 2 people who can get in front of the population and say something which has some resemblance to reality, even though the entire rest of the economy and body politic is trying to corrupt them. They…actually do sort of okay. Anthony Fauci is neither Attila the Hun nor Trofim Lysenko. He’s a kind of bumbling careerist with a decent understanding of epidemiology and a heart that’s more or less in the right place. The whole scientific-technocratic complex is a machine which takes Moloch as input and manages – after spending billions of $ and the careers of 1000s of hard-working public servants – to produce Anthony Fauci as output. This should be astonishing, and we are insufficiently grateful.

2021-02-15: Why isn’t there a reciprocal approval with the EU?

I’ve long argued that if a drug or medical device is approved in another country with a Stringent Regulatory Authority it ought to be approved in the United States. But, of course, the argument is even stronger in the other direction. Drugs and devices approved in the United States ought to be approved elsewhere. Indeed, this is how much of the world actually works because most countries do not have capability to evaluate drugs and devices the way the FDA or the EMA does. Although it’s the way the world works, few will admit it because that would violate pretensions of regulatory nationalism. Moreover, keeping up with pretenses means transaction costs and unnecessary delays. Regulatory nationalism has added months to vaccine delivery and now threatens to put to waste millions of stockpiled doses.

2021-03-02: millions of people die of heart disease every year. there has been no progress in artificial hearts in 50 years due to.. wait for it.. FDA:

The FDA gave Abiomed permission to implant 60 more devices, but it was clear that the heart would need to be updated, and then approved all over again—a lengthy process for which no one had the fortitude. “Abiomed threw in the towel. They were, like, ‘This is too hard!’ ”

2021-03-16: What are FDA inspectors even doing?

Grocery store workers are working, meat packers are working, hell bars and restaurants are open in many parts of the country but FDA inspectors aren’t inspecting. It boggles the mind.

Let’s review. The FDA prevented private firms from offering SARS-Cov2 tests in the crucial early weeks of the pandemic, delayed the approval of vaccines, took weeks to arrange meetings to approve vaccines even as 1000s died daily, failed to approve the AstraZeneca vaccine, failed to quickly approve rapid antigen tests, and failed to perform inspections necessary to keep pharmaceutical supply lines open.

2021-04-14: the FDA is completely insane and is halting the distribution for the J&J vaccine due to very rare side effects. as before, there’s no consequences for acts of omission vs acts of commission. they’re much more worried about their “reputation” than actually saving lives, just like ethicists have been in this crisis. a disgrace.

As the Johnson & Johnson vaccine pauses in the United States, Philip Bump for The Washington Post offers a quick visualization that shows 100 vaccinations per second. A red one appears if there’s a side effect. But because the side effect is rare, currently at 1 in 1.1M, the red dot on the visualization likely never appears as you watch. The blue dots are potential lives saved if the J&J vaccine continues.

Prebiotic Chemistry

The RNA hypothesis is very popular but doesn’t explain how fragile RNA can survive in hostile environments.

Dr. Joyce has been studying the possible beginning of history by developing RNA molecules with the capacity for replication. RNA, a close cousin of DNA, almost certainly preceded it as the genetic molecule of living cells. Besides carrying information, RNA can also act as an enzyme to promote chemical reactions. Dr. Joyce has developed 2 RNA molecules that can promote each other’s synthesis from the 4 kinds of RNA nucleotides. “We finally have a molecule that’s immortal”

2016-02-21: Talk of RNA-like

Perhaps before biology arose, there was a preliminary stage of proto-life, in which chemical processes alone created a smorgasbord of RNAs or RNA-like molecules. “I think there were a lot of steps before you get to a self-replicating self-sustaining system”. In this scenario, a variety of RNA-like molecules could form spontaneously, helping the chemical pool to simultaneously invent many of the parts needed for life to emerge. Proto-life forms experimented with primitive molecular machinery, sharing their parts. The entire system worked like a giant community swap meet. Only once this system was established could a self-replicating RNA emerge.

2019-06-30: Viroids, survivors from the RNA World?

Because RNA can be a carrier of genetic information and a biocatalyst, there is a consensus that it emerged before DNA and proteins, which eventually assumed these roles and relegated RNA to intermediate functions. If such a scenario–the so-called RNA world–existed, we might hope to find its relics in our present world. The properties of viroids that make them candidates for being survivors of the RNA world include those expected for primitive RNA replicons: (a) small size imposed by error-prone replication, (b) high G + C content to increase replication fidelity, (c) circular structure for assuring complete replication without genomic tags, (d) structural periodicity for modular assembly into enlarged genomes, (e) lack of protein-coding ability consistent with a ribosome-free habitat, and (f) replication mediated in some by ribozymes, the fingerprint of the RNA world. With the advent of DNA and proteins, those protoviroids lost some abilities and became the plant parasites we now know.

2022-05-06: RNA “species”

Over 100s of hours of replication, 1 type of RNA evolved into 5 different molecular “species” or lineages of hosts and parasites that coexisted in harmony and cooperated to survive, like the beginning of a “molecular version of an ecosystem”. Their experiment, which confirmed previous theoretical findings, showed that molecules with the means to replicate could spontaneously develop complexity through Darwinian evolution. Some of these results confirmed the predictions of earlier experimental studies of how complexity can arise in viruses, bacteria and eukaryotes, as well as some theoretical work.
“Without parasites, this level of diversification is probably not possible”. Evolutionary pressures that parasites and their hosts place on each other lead both sides to split into new lineages.


2024-02-01: Obelisks

A new kind of viruslike entity that inhabits bacteria dwelling in the human mouth and gut. These “obelisks” have genomes seemingly composed of loops of RNA and sequences belonging to them have been found around the world. The Stanford search yielded 30k predicted RNA circles, each consisting of ~1000 bases and likely representing a distinct obelisk. They were unlikely to be bona fide viruses because RNA viruses typically have many more bases. But some of the obelisk sequences encoded proteins involved in RNA replication, making them more complex than standard viroids. Like viroids, however, obelisks don’t seem to encode proteins that make up a shell. Because obelisks contain genes that are unlike any discovered so far in other organisms, they “comprise a class of diverse RNAs that have colonized, and gone unnoticed in, human, and global microbiomes”

Cancer

Personalized Cancer Treatment

The team solved the problem of delivery of siRNAs into cells by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA’s negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.

2013-07-16: Cancer uses ancient genes

We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells. It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort. The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.

2014-05-17: Measles Virus as a Cancer Fighter. Remarkable: fighting one scourge with another.

2015-03-14: Cancer Cell Mutations

1 study of kidney cancers found that no 2 patients had exactly the same set of genetic mistakes; in fact, no 2 tumors within the same patient had the same mutations. Taking it one step further, 1 high-resolution DNA-sequencing study of breast cancer couldn’t find 2 cells within 1 tumor that were genetically identical

2015-08-26: Reprogramming cancer cells. Apply a large grain of salt to the claim, but the mechanism is still very interesting.

miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. Restoring normal miRNA levels in cancer cells can reverse that aberrant cell growth.

2015-09-23: Dark matter cancer? This is pretty much speculation, but interesting speculation.

We can thus speculate that the mirror micrometeorite, when interacting with the DNA molecules, can lead to multiple simultaneous mutations and cause disease

2016-03-07: Winning the Cancer War

Unfortunately, we’re still stuck in dogma. We continue to live in a world where the standard of cancer care is built on the naïve, almost arrogant, assumption that simply understanding the gene is the only important thing. Or that understanding 50 genes or even 500 genes will give us all the information to unlock the secrets of cancer cell metastasis. But our research is beginning to show that this is no longer the case. The bottom-line is that the biology of cancer is extraordinarily complex. It’s so complex that the output of the gene—specifically, the downstream networks of proteins within our bodies—is even more important than the gene itself.

2016-11-18: CRISPR for lung cancer

Scientists at Sichuan University have injected a person with aggressive lung cancer with cells modified using the gene-splicing technology in a bid to make the patient’s immune system more effective at combating cancer cells.

2017-11-08: Cancer survival

cancer death rates continue to fall across most cancer types. From 2010 to 2014, overall death rates decreased by 1.8%. 5-year survival rates for most common types of cancer have increased quite significantly in the past 30-40 years.

2018-08-02: Cancer progress

Official statistics say we are winning the War on Cancer. Cancer incidence rates, mortality rates, and 5-year-survival rates have generally been moving in the right direction over the past few decades.

More skeptical people offer an alternate narrative. Cancer incidence and mortality rates are increasing for some cancers. They are decreasing for others, but the credit goes to social factors like smoking cessation and not to medical advances. Survival rates are increasing only because cancers are getting detected earlier. Suppose a certain cancer is untreatable and will kill you in 10 years. If it’s always discovered after 7 years, 5-year-survival-rate will be 0%. If it’s always discovered after 2 years, 5-year-survival-rate will be 100%. Better screening can shift the % of cases discovered after 7 years vs. 2 years, and so shift the 5-year-survival rate, but the same number of people will be dying of cancer as ever.

This post tries to figure out which narrative is more accurate.

and another perspective:

Death rates from the disease in the US dropped in the 2016-2017 period by their largest recorded %. This is unequivocally good news, and is attributed to advances in treatment – specifically, the advent of immunotherapies and of various targeted agents for lung and skin cancer. It may come as a surprise to some, but these death rates have actually been falling since the early 1990s at ~1.5% a year, a good part of which can be attributed to the decline in smoking. But the 2016-2017 decline bumped up to 2.2%, which has never been seen before

2019-08-20: Cancer Speciation

Aggressive cancers can spread so fiercely that they seem less like tissues gone wrong and more like invasive parasites looking to consume and then break free of their host. If a wild theory recently floated in Biology Direct is correct, something like that might indeed happen on rare occasions: Cancers that learn how to roam between hosts may gradually evolve into their own multicellular species. Researchers are now scrutinizing a peculiar group of marine parasites called myxosporeans to see whether they might be the first known example.

2021-05-22: Starving Cancer

Scientists are unraveling the molecular pathways by which slashing calories or removing a dietary component can bolster the effects of drugs. In mice with cancer, the effects are oftentimes on the same order of magnitude as those from the drugs that we give patients. If those trials show the ketogenic diet helps curb tumor growth for 2 years longer than the PI3K inhibitor otherwise would, the diet could become the standard of care. “That will be what physicians will tell patients to do.”


2022-08-14: Tumors recruit the nervous system to help them spread.

“The nervous system controls everything in normal tissues—growth or atrophy, or anything else”. So there’s a reason to believe that the same is happening with malignancies. “Cancer tissue grows fast so it needs the support of the nervous system”. Moreover, scientists know that certain cancers have a particular predilection for nerves. “For example, breast and prostate tumors have a propensity to look for nerves and kind of invade and travel through those nerves. That suggests that there is synergy there.”

The observational knowledge suggests that a greater amount of nerves bunching up around a tumor signals grimmer prognosis. For example, when pathologists assess the severity of prostate cancer, the number of nerves that surround these tissues factors in. “The pathologist will score that, and if there’s a lot of nerves in the area, it usually means a worse, or a more urgent situation. To us, that seems like a blind spot or a missing link.”

2022-11-23: Cancer vaccines?

After several decades, therapeutic cancer vaccines now show signs of efficacy and potential to help patients resistant to other standard-of-care immunotherapies, but they have yet to realize their full potential and expand the oncologic armamentarium. Here, we classify cancer vaccines by what is known of the included antigens, which tumors express those antigens and where the antigens colocalize with antigen-presenting cells, thus delineating predefined vaccines (shared or personalized) and anonymous vaccines (ex vivo or in situ). To expedite clinical development, we highlight the need for accurate immune monitoring of early trials to acknowledge failures and advance the most promising vaccines.

Barcode of Life

Mitochondrial genes are inherited maternally. They are not scrambled by recombination, and mitochondrial variation offers rough clues about evolutionary history. Insect people were using the back end of a mitochondrial gene known as CO1 to help identify specimens, marine invertebrate people liked the front end, and vertebrate zoologists used a different mitochondrial gene altogether. Hebert’s idea was that, out of a hodgepodge of related techniques, he could build a simple, universal identification system — assuming, that is, the same small piece of mitochondrial DNA worked reliably for all the animals in the world. “We believe that a CO1 database can be developed within 20 years for 5-10m animal species on the planet for $1b”

2020-12-18: Genomic Encyclopedia

Researchers announced a significant advance. They have assembled the largest catalog of microbes to date, containing over 50k genomes from 18k different microbial species—12k of which have never been documented before. Their study expands the known tree of life by 45%. They also found 700k viruses and linked them to their bacterial and archeal hosts, further illuminating the vast interconnections in this unseen world.

“It’s a fucking incredible amount of data. There are only ~10K species of microbes that have been cultured and described formally, and yet there might be 1B species. That is why this study is so important.”

2021-08-06: The database currently holds 10m barcodes mapped to 330k species.
2022-07-15: Evolution isn’t a tree

“If the evolutionary history of the hoatzin conformed to processes we already understand well, then we’d probably have already figured out what it is most closely related to. The fact that we don’t know its nearest relative suggests that there were processes involved that we still do not understand.” The hoatzin could have more than 1 set of closest relatives— “an unsettling prospect in the context of existing classification and in the minds of many contemporary biologists.”

This strange-sounding state of affairs is not unique to the hoatzin; we see it in our own DNA. Human beings share their most recent common ancestor with chimpanzees and bonobos, but more than 10% of the human genome is actually more closely related to the gorilla genome. Another tiny fraction of the human genome also seems to be most closely shared with an even more distant relative: the orangutan. “This implies that there is no such thing as a unique evolutionary history of the human genome. Rather, it resembles a patchwork of individual regions following their own genealogy.”

Antibiotics

For all you antibacterial soap-using dummies.

Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.

The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.

2010-11-08: We are essentially back to an era with no antibiotics

This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.

2015-01-08: New Antibiotics Platform?

A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.

2015-02-24: Antibiotics market failure

we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?

2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.

Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel

So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant

2016-01-23: Antibiotics synthesis

Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?

2018-05-21: Phage Therapy

3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”

2019-11-04: CRISPR Antibiotics

An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.

In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.

As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.

2020-02-22: Antibiotics ML

So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.

2020-07-24: SCH-79797

Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance

2020-08-07: Maybe the non-profit route will work

If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.

2021-07-28: Biofilms are nasty

This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.

2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

2023-05-23: Odd that phage therapy only made progress in former soviet republics

“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.