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.

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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.

Security Guards at U.S. Nuclear Weapons Base Used LSD

Nuclear weapons are an existential threat to humanity, as even one of the strong ones going off could cause a dangerous nuclear winter. Also, while it’s not necessarily a problem that people are experimenting with hallucinogens, it should clearly not be at a nuclear weapons facility. The Doomsday Clock — measuring the risk of widespread human catastrophe by nuclear weapons — is already at its most dire reading in over half a century.

There are a lot of safe and responsible places people have found over the years to ingest hallucinogens in order to experience their pleasures  and explore the challenges their potent properties can present, but it’s a judgement statement to declare that a U.S. military base which houses some of the world’s most powerful atomic weapons would qualify as such a place.

Nevertheless, the Associated Press reports Thursday that U.S. service members charged with guarding U.S. nuclear weapons at a “highly secure” military facility in Wyoming “bought, distributed and used the hallucinogen LSD and other mind-altering illegal drugs as part of a ring that operated undetected for months.”

Those accused of involvement in the drug ring were “from the 90th Missile Wing, which operates one-third of the 400 Minuteman 3 missiles that stand ‘on alert’ 24/7 in underground silos scattered across the northern Great Plains.”

When military investigators broke up the ring, one airmen reportedly fled the country. “Although this sounds like something from a movie, it isn’t,” said Capt. Charles Grimsley, the lead prosecutor of one of several courts martial the resulted from the case.

The AP story is based on internal military documents the news agency obtained and is just the latest example of frightening cracks in the way the U.S. military manages and protects its vast nuclear arsenal.

While the reporting notes that none of those court martialed were charged with being under the influence while “on duty,” the transcripts from the files show one soldier admitting he “felt paranoia, panic” for hours after dropping acid and at one point said he “didn’t know if I was going to die that night or not.” Another soldier confessed, “I absolutely just loved altering my mind.”

As the story hit the AP wire, this was a common sentiment on social media: “Nuclear weapons and LSD seem a bad combination, but that’s just my opinion.”

Saving a Few Hundred Billion Dollars a Year on Prescription Drugs in America

Cost savings of a few thousand dollars per household that are eminently possible — if Big Pharma can be defeated or at least constrained much more. The main basic problem is the patent monopolies that allow pharmaceutical companies to charge exorbitant prices, and a main solution is to use direct public funding as a more efficient process at producing innovation.

Broadly speaking, a prescription drug in the United States goes through three main stages of development: On the front end, researchers make a scientific breakthrough in their labs, discovering the building blocks of a new drug. Then it goes through the second stage, which includes the often-costly process of clinical research and trials. Last, once the FDA has reviewed and approved it, the drug goes on the mass market, sold at drugstores and doctor’s offices.

The United States is already involved in the earliest stages of drug development. It’s the top funder of basic science research in this country through the National Institutes of Health, which has an annual budget of $37 billion, more than what the federal government pays for Head Start and Pell Grants combined. Most agree that this is money well spent: Every one of the 210 new drugs approved between 2006 and 2010 trace their origins back to government funding.

The government is also involved in the third stage, as a top purchaser of medicines. Through Medicare, Medicaid, the Department of Veterans Affairs, and other programs, the federal government pays for $300 billion worth of prescription drugs each year.

Where the system runs into trouble is in the middle of the process, when the government hands over a glittering prize: the multi-decade patents that give private companies a monopoly on life-essential products. Through a mechanism established by the Bayh-Dole Act of 1980, private companies are allowed to claim patents on promising compounds discovered with government funding–and that means exclusive rights to manufacture and sell the resulting drug for a period of 20 years and often longer.

This isn’t just an outdated model; it’s also deeply inefficient. Companies can price medicines at hundreds of times what it costs to make them (it’s how a hepatitis C medicine could cost $1,000 for each pill that is manufactured for a few dollars), and with the government providing a guaranteed market for the drugs, companies like Gilead and Pfizer have had years where their reported profit margins exceeded a staggering 40 percent. All of the Big Pharma companies average between 15 and 20 percent profit each year. Most Fortune 500 companies are happy to claim half of that. There is “absolutely no reason why the taxpayer should be forced to subsidize a private monopoly and have to pay twice: first for the research and development and then through monopoly prices,” Senator Russell Long insisted when Bayh-Dole was passed in 1980.

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If the United States were to move towards a NASA system, the federal government would have to find up to $75 billion in its budget to replace what private industry spends on R&D. But that’s not an insurmountable obstacle. There should be plenty of money available. Baker and other economists calculate that a NASA for drug development, which would eliminate patents and the price markups for prescription drugs that come with them, would save Americans hundreds of billions of dollars every year thanks to drugs being generic-level cheap from day one. The savings to government spending alone would be more than enough to pay for every penny of the $75 billion that the private pharma industry claims it spends on R&D–and replace it with research that is more widely shared and targeted more at public health than at quarterly profits. In this alternate universe, scientists and labs could switch their focus away from developing yet another iteration of an erectile dysfunction drug towards tackling challenges like tuberculosis.

 

Creating Medicines With Less Side Effects Through a New Chemical Dividing Process

Overall, medications today have way too many harmful side effects, and so this breakthrough technological process should be helpful in reducing them. It also has the potential to “produce better medical and agricultural products, including medicines, food ingredients, dietary supplements and pesticides.”

Chemical compounds are made up of molecules. The most important molecules in biology are chiral molecules. “Chiral,” the Greek word for “hand,” describes molecules that look almost exactly alike and contain the same number of atoms but are mirror images of one another — meaning some are “left-handed” and others are “right-handed.” This different “handedness” is crucial and yields different biological effects.

Understanding chiral differences was made painfully clear by the drug thalidomide. Marketed to pregnant women in the 1950’s and 1960’s to ease morning sickness, thalidomide worked well under a microscope. However, thalidomide is a chiral drug -its “right” chiral molecule provides nausea relief while the “left” molecule causes horrible deformities in babies. Since the drug company producing Thalidomide did not separate out the right and left molecules, Thalidomide had disastrous results for the children of women who took this medication.

Though a crucial step for drug safety, the separation of chiral molecules into their right- and left- handed components is an expensive process and demands a tailor-made approach for each type of molecule. Now, however, following a decade of collaborative research, Paltiel and Naaman have discovered a uniform, generic method that will enable pharmaceutical and chemical manufactures to easily and cheaply separate right from left chiral molecules.

Their method relies on magnets. Chiral molecules interact with a magnetic substrate and line up according to the direction of their handedness — “left” molecules interact better with one pole of the magnet, and “right” molecules with the other one. This technology will allow chemical manufacturers to keep the “good” molecules and to discard the “bad” ones that cause harmful or unwanted side effects.

“Our finding has great practical importance,” shared Prof. Naaman. “It will usher in an era of better, safer drugs, and more environmentally-friendly pesticides.”

While popular drugs, such as Ritalin and Cipramil, are sold in their chirally-pure (i.e., separated) forms, many generic medications are not. Currently only 13% of chiral drugs are separated even though the FDA recommends that all chiral drugs be separated. Further, in the field of agrochemicals, chirally-pure pesticides and fertilizers require smaller doses and cause less environmental contamination than their unseparated counterparts.

The Amazing Treatment for Drug Addiction (Medication-Assisted Treatment) Too Rarely Used

Drug addictions need to be treated as health problems instead of as crimes, and in any case, it’d be valuable to direct more resources towards helping people with addictions. That could be rather than using the resources on a senseless or harmful pursuit such as building even more nuclear weapons systems that threaten to cause disasters.

The death toll from the opioids epidemic continues to soar – nearly 64,000 people died in 2016 alone.

Scientists are working to find creative tools to fight it, and President Donald Trump has called the overdose crisis a public health emergency. But he has not yet outlined any targeted solutions aside from calling for drug dealers to be given the death penalty.

A growing cadre of health professionals say we already have a science-backed treatment that works. It’s called medication-assisted treatment, or MAT, and it involves administering FDA-approved medications that help curb cravings and reduce the excruciating symptoms of withdrawal.

“Medications are an effective treatment for opioid addiction,” Kelly J. Clark, president of the American Society of Addiction Medicine, told Business Insider.

The problem is that very few people can get those medications.

Only about half of private-sector treatment programs for opioid use disorder currently offer access to MAT, and of those that offer it, only one third of patients actually receive the medication, according to a study published in the Journal of Addiction Medicine.

There are many reasons for this lack of access to medication. Some stem from a misconception about how the treatments – which can include buprenorphine, methadone, or naltrexone – work.

The stigma surrounding drug use and addiction plays a role, too. Still other issues include federal and state laws that restrict the availability of the medications.

“It’s more of an implementation problem than a basic science problem,” Clark said, “because we know what works.”

Medications do not ‘substitute one drug for another’

In someone with opioid use disorder, using the drugs is often not a pleasurable experience, but rather a practice that has become a necessary fact of life. Being without the drugs leads to painful symptoms that can include severe nausea, shaking, diarrhoea, and depression.

The need to use is simultaneously a physical and emotional compulsion – the lines between those kinds of pain are blurred.

One of the main misconceptions about medication-assisted treatment is that medications simply replace the drugs that hooked users – leading to more highs and fuelling a pattern of repeated use.

But that view is outdated and ill-informed, experts say. Instead, the drugs work by staunching cravings and reducing or preventing withdrawal and relapse.

Buprenorphine and methadone help suppress cravings, while naltrexone blocks the euphoric and sedative effects of opioids so users don’t experience a high.

“People ask me all the time, ‘well, aren’t they just substituting one drug for another?’ The answer is no. These are evidence-based treatments and they work,” Patrice A. Harris, the former president of the American Medical Association and a board certified psychiatrist, told Business Insider.

Several large studies suggest that as access to MAT rises, drug overdose deaths fall.

A study of heroin overdose deaths in Baltimore between 1995 and 2009 published in the American Journal of Public Health, for example, found a link between the increasing availability of methadone and buprenorphine and a roughly 50 percent decrease in the number of fatal overdoses.

“These treatments are life saving and they work,” Sarah Wakeman, the medical director of the substance use disorder initiative at Massachusetts General Hospital and an assistant professor at Harvard, told Business Insider.

From jail to court to rehab, medication-assisted treatment is hard to find

Despite the evidence demonstrating MAT’s effectiveness, it is surprisingly difficult to obtain.

One of the hardest-to-access forms of medication for recovery is methadone. In the US, the medication can only be accessed in specialised clinics; because of the way the treatment works, people on MAT must come to a facility to be injected daily.

But those facilities typically have negative reputations because of policies that restrict them to locations considered seedy or run-down.

And patients who come for treatment often have to push past active drug users – a big trigger for someone with substance use disorder – on their way to and from the clinic.

“You can access heroin pretty easily, yet we make it really hard to get a treatment that’s life-saving and allows you to live healthily,” Wakeman said.

On Friday, the US Food and Drug Adminstration issued a new set of guidelines aimed at underlining the important role MAT should play treating opioid use disorder.

“Unfortunately, far too few people who suffer from opioid use disorder are offered an adequate chance for treatment that uses safe and effective medications,”commissioner Scott Gottlieb said.

Other countries take a very different approach to medication-assisted treatment that makes the treatments easier to obtain. In Canada, for example, methadone is distributed in pharmacies.

Rehabilitation facilities and courts in the US often don’t offer medication-assisted treatment either. Instead, most operate on an abstinence-based model, in which patients must detox and then are offered counseling.

They’re encouraged to attend 12-step meetings like Narcotics Anonymous, which remains opposed to MAT despite the growing body of evidence behind it.

Patents and Copyrights as Plutocratic Tariffs That are Relics of the Medieval Guild System

A useful analysis rarely seen in the debate.

Many pundits have attacked Trump’s focus on steel and manufacturing because they argue, we should be more concerned about protecting US corporations’ patents and copyrights overseas. This doesn’t make sense.

At the most basic level, stronger and longer patent and copyright protection means that people in other countries have to pay more money. These government-granted monopolies often allow companies to raise the price of the protected items by a factor of 10 or even a 100. In this way, they are equivalent to tariffs of several thousand percent.

Just to be clear, this is not a point that can be honestly disputed by economists. If a government barrier raises the price of a good, it doesn’t matter whether we call that barrier a “tariff” or a “patent,” the impact on the market is the same.

This means if Pfizer’s patent protection on a drug allows it to raise the price it charges for a drug in China or some other developing country by a factor of 10 over the free market price, it is equivalent to imposing a tariff of 1000 percent on the drug. The difference is that instead of the tariff revenue going to the government, it goes back to Pfizer as higher profits.

It’s obvious that higher profits for Pfizer are good for its shareholders and top executives, but why should the rest of us be happy about people in developing countries paying more money to Pfizer for its drugs? Many of us care more about poor people being able to get drugs than Pfizer’s profits.

The story gets even worse. The more money that Pfizer and other US companies collect overseas for their patents and copyrights, the less these people have to spend on other goods and services. In effect, because Pfizer can charge more for its drugs, people in China and other countries have less money to spend on US-made cars and planes. How is this good for most of the people in the United States?

The pushers of stronger and longer patent and copyright protection will undoubtedly claim that higher profits will provide more incentive for research and creative work. This is true, but what are the numbers? If Pfizer gets another $1 billion in profit will they invest one percent of it in research?

That would be an increase, but that means the world would be spending $1 billion in higher drug prices to get an additional $10 million in research. That’s not a very good deal. And, even this research could be largely wasted on developing copycat drugs that are intended to gain a portion of a competitor’s patent earnings by duplicating a successful drug. Again, that could be good for Pfizer, but it is not especially helpful for the rest of us who want to see research focused on developing treatments for conditions where there is not already an effective drug.

To be clear, we do need a mechanism for financing research and creative work, but there is little reason to believe that patent and copyright monopolies are the most effective tool. These are relics of the Medieval guild system. We can do better in the 21st century.