Some Drug Company Executives Criminally Charged in America’s Flawed Democracy

A major producer of opioids known as the Rochester Drug Cooperative has recently witnessed its executives criminally charged with illegally distributing controlled substances. With the prosecution of corporate criminals at a 20 year low in America, amidst a major wave of corporate crime — crime in the suites instead of crime in the streets — it is a notable development during the despair-ridden opioid crisis.

Much of this opioid crisis is attributable to the patent monopolies on prescription drugs, which enable American pharmaceutical companies to charge ridiculously high prices. A patent monopoly on a drug legally prevents competitors from producing or selling that drug, and the lack of governmental negotiation to rein in prices allows pharmaceutical companies to charge to a large extent whatever they want. Purdue Pharma would have had nowhere near as much incentive to market Oxycontin if it was sold at generic prices, but since they had a tremendous incentive, many communities have suffered as a result of the addictive drug.

The case of patent monopolies on prescription drugs such as Oxycontin is another example of the government using its power in a way that’s overall against the public interest. The government is not necessarily an evil or inefficient entity, as people sometimes believe or that propaganda might suggest. There is plenty of evidence that structured properly, the government can be a force for the common good — government-run programs such as Medicare and Social Security remain popular because they work well. The administrative overhead on Medicare is about 2 percent, while the administrative overhead on corporate health insurance is often 12 to 20 percent.

It is beneficial for much of the corporate sector if the public automatically despises the government and doesn’t pressure for public interest control of it. Unlike the corporate sector, where the boards of directors (those who run the corporations) are largely determined by top management, in a undemocratic process where one share of the corporation equates to one vote in the board of directors election, there is a built-in democratic process in the government. This built-in process of one person (rather than one share) and one vote may currently be quite dysfunctional, but it is a mechanism of democratic values nonetheless, and one of the things to be strengthened for an improved society.

About every year at least, the Bulletin of Atomic Scientists meets to discuss the most significant threats to human societies, and if necessary they adjust their famous Doomsday Clock. The Doomsday Clock measures the probability of major catastrophe by the minute hand’s closeness to midnight, and it is now 2 minutes to midnight, the closest it has ever been since 1953, when America and Russia detonated thermonuclear weapons. In 2019, the Bulletin of Atomic Scientists added a third major problem to climate change and the potential of nuclear war — the breakdown of and threats to democracy. This is significant because lively and functioning democracy offers perhaps the only way to solve many of the world’s most serious problems.

Activism that is deservedly popular (and therefore democracy-based, or majority supported) is very often how things change for the better, from worker’s rights to new government programs and movements producing a beneficial change in public consciousness. Instead of only examining problems, it’s necessary to remember that to achieve progress.

Using Chronoprinting to Cheaply Detect Food and Drug Impurities

The world has long needed this valuable sort of development to safeguard people’s health.

If we could tell authentic from counterfeit or adulterated drugs and foods just by looking at them, we could save money and lives every year, especially in the developing world, where the problem is worst. Unfortunately, the technologies that can detect what a sample is made of are expensive, energy-intensive, and largely unavailable in regions where they are needed most.

This may change with a simple new technique developed by engineers from the University of California, Riverside that can detect fake drugs from a video taken as the sample undergoes a disturbance.

If you’ve ever used online photo tools, you’ve probably seen how these tools use image analysis algorithms to categorize your photos. By distinguishing the different people in your photos, these algorithms make it easy to find all the photos of your daughter or your dad. Now, in the journal ACS Central Science, researchers report they have used these algorithms to solve a very different problem: identifying fake medicines and other potentially dangerous products.

Called “chronoprinting,” the technology requires only a few relatively inexpensive pieces of equipment and free software to accurately distinguish pure from inferior food and medicines.

The World Health Organization says that about 10 percent of all medicines in low- and middle-income countries are counterfeit, and food fraud is a global problem that costs consumers and industry billions of dollars per year. Fraudulent food and drugs waste money and jeopardize the health and lives of their consumers. But detecting fakes and frauds requires expensive equipment and highly trained experts.

William Grover, an assistant professor of bioengineering in UC Riverside’s Marlan and Rosemary Bourns College of Engineering, and Brittney McKenzie, a doctoral student in Grover’s lab, wondered if it would be possible to distinguish authentic from adulterated drugs and food by observing how they behave when disturbed by temperature changes or other causes. Two substances with identical compositions should respond the same way to a disturbance, and if two substances appear identical but respond differently, their composition must be different, they reasoned.

McKenzie designed a set of experiments to test this idea. She loaded samples of pure olive oil, one of the world’s most commonly adulterated foods, and cough syrup, which is often diluted or counterfeited in the developing world, into tiny channels on a microfluidic chip, and chilled it quickly in liquid nitrogen. A USB microscope camera filmed the samples reacting to the temperature change.

McKenzie and Grover wrote software that converts the video to a bitmap image. Because the image showed how the sample changed over time, the researchers called it a “chronoprint.”

The team then used image analysis algorithms to compare different chronoprints from the same substance. They found that each pure substance had a reliable chronoprint over multiple tests.

Next, they repeated the experiment with samples of olive oil that had been diluted with other oils and cough syrup diluted with water. The adulterated samples produced chronoprints that were different from the pure samples. The difference was so big, so obvious, and so consistent the researchers concluded that chronoprints and image analysis algorithms can reliably detect some types of food and drug fraud.

“The significant visual differences between the samples were both unexpected and exciting, and with them being consistent we knew this could be a useful way to identify a wide range of samples,” McKenzie said.

Grover said their technique creates a powerful new connection between chemistry and computer science.

“By basically converting a chemical sample to an image, we can take advantage of all the different image analysis algorithms that computer scientists have developed,” he said. “And as those algorithms get better, our ability to chemically identify a sample should get better, too.”

The researchers used liquids in their experiments but note the method could also be used on solid materials dissolved in water, and other types of disturbance, such as heat or a centrifuge, could be used for substances that don’t react well to freezing. The technique is easy to learn, making highly trained experts unnecessary. Chronoprinting requires hobbyist-grade equipment and software downloadable for free from Grover’s lab website, putting it well within reach of government agencies and labs with limited resources.

Video on how this chronoprinting works: https://youtu.be/qbyE68qD2Zo

Drug Price Gouging in Generics

General info on prescription drugs and generic drug price gouging.

Martin Shkreli managed to make himself a household name a few years back. His claim to fame stemmed from the decision by Turing Pharmaceuticals, a company he founded and controlled, to acquire the rights to produce Daraprim. He then raised the price of the drug by 5,000 percent.

This was very bad news for the people who were dependent on the drug. Daraprim is an anti-parasitic drug that is often taken by people with AIDS to keep them from getting opportunistic infections. People with AIDS who are being successfully treated with Daraprim are not going to want to experiment with alternatives.

Daraprim was already a 60-year-old drug at the time Turing acquired it and had long been available as a generic. This meant that other manufacturers could in principle come into the market and compete with Turing’s inflated price.

Shkreli made the bet that no other drug company would take advantage of this opportunity, because even for a generic drug, there are still substantial costs for entry. Since the market for Daraprim was small, a new entrant would be unlikely to recover these costs if Turing pushed the price back down somewhere near its original level. While Daraprim was his biggest “success,” Shkreli was trying this strategy with a number of other drugs before the Justice Department put him out of business with unrelated charges of securities fraud.

Shkreli’s days of price gouging in the generic drug world may be over, but he established a model that other ambitious entrepreneurs are likely to follow. Close to 40 percent of generic drugs have only a single manufacturer. This is partly a result of the failure of anti-trust policy to stem a wave of mergers in the industry. It is also a result of the fact that many drugs simply have very limited markets where it is difficult to support multiple producers.

Most generic producers have not tried to follow the Shkreli model and jack up prices of drugs that people need for their health or even their lives, but some have. The soaring price of insulin is one important example, EpiPen, the asthma injector, is another. Both involve well-known treatments that have long been used, but the limited number of suppliers has allowed for huge price increases in recent years.

This is the context for the public drug-manufacturing corporation being proposed in a bill by Senator Elizabeth Warren and Representative Jan Schakowsky. The idea is that the federal government should create manufacturing capacity (which could be privately licensed) that would allow it to quickly enter a market to compete with the next Martin Shkreli.

If a company tries to jack up its prices by an extraordinary amount, it would find itself soon competing with a government manufacturer that is selling the same drug for the cost of production, plus a normal profit. This is a great strategy, since simply the existence of this capacity should be sufficient to discourage the next Shkreli.

There will be little money in jacking up the price of a drug by 5,000 percent if it quickly results in the disappearance of their market. This should encourage the generic industry to keep its prices in line.

It is important to note a key difference between the generic industry and brand industry. The brand pharmaceutical companies, like Pfizer and Merck, could argue that they need high prices to pay for research. These companies hugely exaggerate their research costs and downplay the extent to which high profits just mean more money for shareholders, but they actually do research.

By contrast, the generic industry is not researching new drugs. They are manufacturing drugs that have been developed by others. In this sense they can be thought of like a company that manufacturers paper plates or shovels. They need a normal profit to stay in business, nothing more.

For this reason, the Warren-Schakowsky proposal is very much the right type of remedy for excessive prices in the generic drug industry. At the same time, we have to recognize that generic drugs are the smaller part of the problem with high drug prices.

Although generics account for almost 90 percent of prescriptions, they account for only a bit more than a quarter of spending on prescription drugs. The story of drugs costing tens or hundreds of thousands of dollars a year is almost entirely a story of brand drugs with high prices as a result of patent monopolies or related protections.

This will require a larger fix, likely along the same lines, with the government paying for research and allowing new drugs to be sold as generics. But the Warren-Schakowsky bill is a huge first step in bringing drug costs down and ensuring that people will not find themselves suddenly at the mercy of the next Martin Shkreli.

Hundreds of Supplements Tainted With Hidden Drugs

This is why people should use caution when taking supplements, and it also shows the risk of inadequate corporate oversight. Unlike pharmaceutical drugs, the American supplement industry is barely regulated at all.

The labels promise miracles: Fast Weight Loss! Eliminates Hunger! Burns Calories!

Now new research highlights how hundreds of brands of dietary supplements deliver so much kick from a modest blend of vitamins and herbs. The answer is many labels leave out one important ingredient: a hidden payload of pharmaceutical drugs and experimental chemicals.

A new analysis of 10 years of FDA records reveals that from 2007 to 2016, almost 750 dietary supplements were found to be contaminated with secret doses of totally unregulated drugs, including prescription medicines, banned and unapproved chemicals, and designer steroids.

Over 20 percent of these offending products contained more than one unapproved drug ingredient, and numerous contained a cocktail of clandestine chemicals – in two cases, as many as six unlisted ingredients.

For a US$35 billion industry patronised by about half of American adults, it’s possible this data could be just the tip of the iceberg, too.

“The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement,” researchers from the California Department of Food and Agriculture, Sacramento, explain in their paper.

Given that supplement use is associated with some 23, 000 ER visits and 2,000 hospitalisations in the US each year, it’s clear we’re looking at a big problem here, but what’s even more shocking than the brazen selling of these illicit additives is how tame and toothless the FDA’s official actions were.

Of 746 products identified as adulterated by the FDA, just 360 (48 percent) were subsequently recalled, leaving more than half of the contaminated supplements available for sale.

“The agency’s failure to aggressively use all available tools to remove pharmaceutically adulterated supplements from commerce leaves consumers’ health at risk,” writes general internist Pieter Cohen from Harvard Medical School in a commentary on the new research.

Many of the tainted supplements analysed in the study contained sildenafil (the active ingredient of Viagra) to boost their powers of sexual enhancement. Another erectile dysfunction drug, tadalafil, was also common.

Other chemicals included hidden antidepressants, a withdrawn weight loss drug called sibutramine, and undeclared anabolic steroids or steroid-like substances.

It’s been argued however that since almost 75 percent of the offending supplements were sold online or through international mail order, they don’t represent the ‘mainstream’ of the supplements industry.

“These come from dark corners of the internet,” president of the Natural Products Association, Daniel Fabricant, told the San Francisco Chronicle.

“They’re not what you get at your health food store.”

Still, given that none of these products are actually subjected to the same stringent tests reserved for pharmaceutical drugs, it’s possible any supplement could contain anything – which is why Cohen advises choosing products that only contain a single ingredient and avoiding products that purport to offer spurious, medical-sounding benefits.

Why? Because as this research shows, many supplements turn out to be medicine after all – only it’s an unknown drug, potentially a banned one, and there’s no way of measuring your dose.

“If the company is saying it works like Viagra or you’re going to gain muscle like you’re on steroids – that’s not a supplement. That’s a drug,” Fabricant says.

“Dietary supplements are meant to maintain health, not to take 30 minutes before sex.”

The findings are reported in JAMA Network Open.

Good Immunotherapy is Amazing at Treating Cancer — And It’s Unnecessarily Expensive

Drugs are cheap to produce — it’s things like unjust government-granted patent monopolies that allow pharmaceutical companies to charge exorbitant prices that make drugs expensive.

To quote economist Dean Baker’s latest October 2018 paper:

“Many items that sell at high prices as a result of patent or copyright protection would be free or nearly free in the absence of these government granted monopolies. Perhaps the most notable example is prescription drugs where we will spend over $420 billion in 2018 in the United States for drugs that would almost certainly cost less than $105 billion in a free market. The difference is $315 billion annually or 1.6 percent of GDP. If we add in software, medical equipment, pesticides, fertilizer, and other areas where these protections account for a large percentage of the cost, the gap between protected prices and free market prices likely approaches $1 trillion annually, a sum that is more than 60 percent of after-tax corporate profits.”

On to the article though.

Last week, researchers James Allison and Tasuku Honjo were awarded this year’s Nobel Prize in medicine for their work on cancer immunotherapies, heralded by the Nobel committee as “seminal discoveries” that “constitute a landmark in our fight against cancer.”

Immunotherapies like those developed on the basis of Allison and Honjo’s work are indeed an important step towards a whole new way to treat cancer, as well as a host of other chronic diseases. However, this Nobel award should remind us that these innovative therapies are out of reach for so many patients in the United States due to the exorbitant prices drug companies charge for them.

Just weeks before the Nobel announcement, oncologist Ezekiel Emmanuel wrote in a Wall Street Journal essay, “We Can’t Afford the Drugs That Could Cure Cancer,” that “a cure for cancer has become possible, even probable” with immunotherapies, but that our health system cannot afford their price tag. Just after the Nobel announcement, Vox reporter Julia Belluz reminded us that “the average cost of cancer drugs today is four times the median household income” (emphasis added).

Immunotherapies constitute a part of the class of drugs called biologics (as opposed to chemical pharmaceuticals) that have shown very promising results in treating many previously intractable conditions, such as multiple sclerosis, asthma, chronic pain, and Crohn’s disease, due to their ability to more precisely target individual diseased cells. Therefore it’s no surprise that currently most of the top 10 best-selling drugs worldwide are biologics.

[…]

If biologics really are the future of medicine, we must change the way prescription drugs are priced in the United States, or millions of patients will be left behind. One way to do that is to invest in public pharmaceuticals that can assure an adequate supply of and equitable access to essential medications.

AI System that Develops Drugs Developed

In a more sensible world, many more resources would be immediately put into this development to (benevolently) accelerate research into medicine. We would have more money for that if we didn’t allow pharmaceutical companies to charge ridiculous prices and then spend woefully inadequate amounts of their revenue on actual research.

An artificial-intelligence approach created at the University of North Carolina at Chapel Hill Eshelman School of Pharmacy can teach itself to design new drug molecules from scratch and has the potential to dramatically accelerate the design of new drug candidates.

The system is called Reinforcement Learning for Structural Evolution, known as ReLeaSE, and is an algorithm and computer program that comprises two neural networks which can be thought of as a teacher and a student. The teacher knows the syntax and linguistic rules behind the vocabulary of chemical structures for about 1.7 million known biologically active molecules. By working with the teacher, the student learns over time and becomes better at proposing molecules that are likely to be useful as new medicines.

Alexander Tropsha, Olexandr Isayev and Mariya Popova, all of the UNC Eshelman School of Pharmacy, are the creators of ReLeaSE. The University has applied for a patent for the technology, and the team published a proof-of-concept study in the journal Science Advances last week.

“If we compare this process to learning a language, then after the student learns the molecular alphabet and the rules of the language, they can create new ‘words,’ or molecules,” said Tropsha. “If the new molecule is realistic and has the desired effect, the teacher approves. If not, the teacher disapproves, forcing the student to avoid bad molecules and create good ones.”

ReLeaSE is a powerful innovation to virtual screening, the computational method widely used by the pharmaceutical industry to identify viable drug candidates. Virtual screening allows scientists to evaluate existing large chemical libraries, but the method only works for known chemicals. ReLeASE has the unique ability to create and evaluate new molecules.

“A scientist using virtual screening is like a customer ordering in a restaurant. What can be ordered is usually limited by the menu,” said Isayev. “We want to give scientists a grocery store and a personal chef who can create any dish they want.”

The team has used ReLeaSE to generate molecules with properties that they specified, such as desired bioactivity and safety profiles. The team used the ReLeaSE method to design molecules with customized physical properties, such as melting point and solubility in water, and to design new compounds with inhibitory activity against an enzyme that is associated with leukemia.

“The ability of the algorithm to design new, and therefore immediately patentable, chemical entities with specific biological activities and optimal safety profiles should be highly attractive to an industry that is constantly searching for new approaches to shorten the time it takes to bring a new drug candidate to clinical trials,” said Tropsha.

At least one of the creators of the AI system seems to have the wrong view of drug patents. Patents on “chemical entities” are definitely not what we need more of.

The U.S. spent $450 billion on prescription drugs in 2017, an amount that could have been about $380 billion less if there were no drug patent monopolies. With that $450 billion, the pharmaceutical industry spent around $70 billion in research and development — less money than they spent on stock buybacks that reward shareholders (and most people aren’t significant shareholders).

It would be sensible to get rid of drug patent monopolies that allow for ridiculous prices, and then simply have the government pay for the $70 billion in research directly. The difference would amount to a savings worth thousands of dollars per family, and it would mean better pharmaceutical research too.

Combining Antibiotics Changes How Effective They Are

The implications from this should be studied more in light of the major antibiotic resistance problem this century. Among other things, the research found that the compound vanillin (which gives vanilla its taste) combined with an antibiotic that has mostly stopped being used (spectinomycin) increased the effectiveness of the antibiotic.

The effectiveness of antibiotics can be altered by combining them with each other, non-antibiotic drugs or even with food additives. Depending on the bacterial species, some combinations stop antibiotics from working to their full potential whilst others begin to defeat antibiotic resistance, report EMBL researchers and collaborators in Nature on July 4.

In the first large-scale screening of its kind, scientists profiled almost 3000 drug combinations on three different disease-causing bacteria. The research was led by EMBL group leader Nassos Typas.

Overcoming antibiotic resistance

Overuse and misuse of antibiotics has led to widespread antibiotic resistance. Specific combinations of drugs can help in fighting multi-drug resistant bacterial infections, but they are largely unexplored and rarely used in clinics. That is why in the current paper, the team systematically studied the effect of antibiotics paired with each other, as well as with other drugs and food additives in different species.

Whilst many of the investigated drug combinations lessened the antibiotics’ effect, there were over 500 drug combinations which improved antibiotic outcome. A selection of these positive pairings was also tested in multi-drug resistant bacteria, isolated from infected hospital patients, and were found to improve antibiotic effects.

[…]

According to Nassos Typas, combinations of drugs that decrease the effect of antibiotics could also be beneficial to human health. “Antibiotics can lead to collateral damage and side effects because they target healthy bacteria as well. But the effects of these drug combinations are highly selective, and often only affect a few bacterial species. In the future, we could use drug combinations to selectively prevent the harmful effects of antibiotics on healthy bacteria. This would also decrease antibiotic resistance development, as healthy bacteria would not be put under pressure to evolve antibiotic resistance, which can later be transferred to dangerous bacteria.”

General principles

This research is the first large-scale screening of drug combinations across different bacterial species in the lab. The compounds used have already been approved for safe use in humans, but investigations in mice and clinical studies are still required to test the effectiveness of particular drug combinations in humans. In addition to identifying novel drug combinations, the size of this investigation allowed the scientists to understand some of the general principles behind drug-drug interactions. This will allow more rational selection of drug pairs in the future and may be broadly applicable to other therapeutic areas.