Personal pharmaceutical factory

Meet the anarchists who make their own medicines

Meet the Anarchists Making Their Own Medicine (Daniel Oberhaus, Motherboard).
Translation: Vyacheslav Golovanov, Habr For links, see the original or translation of the article.

The Vinegar Collective of Four Thieves is a network of anarchists relying on technology and challenging the giants of the pharmaceutical industry with the help of self–made medicines.

I first met Michael Lofer when he was throwing thousands of dollars worth of drugs into the audience of the HOPE (Hackers on Planet Earth) hacker conference, held every two years in New York.

"Has anyone here experienced anaphylactic shock without having access to epinephrine?" Lofer asked the audience. Several hands were raised, and Lofer threw to one of the people who raised his hand an EpiPen made at home [a ballpoint pen-like device for self-injection of adrenaline / approx. perev."This is one of the first devices we made," he said. "Use it wisely."

After gloating a little about how Martin Shkreli from the tribe of pharmaceutical giants raised the prices of the drug daraprim, necessary for people suffering from HIV, from $13 to $750, Lofer became serious. "Two years have passed, but despite everything that has happened, the cost of the drug daraprim has not changed," he said. He reached into his pocket and took out a handful of white pills. "I think we need to distribute some more," Lofer said, and threw daraprim into the audience.

With a shaved head, a dark beard and an eternal camouflage jacket, Lofer does not look like a person from whom you would want to ask for medical advice – but that's the point. Having founded the "Vinegar Collective of Four Thieves" [Four Thieves Vinegar], a voluntary network of anarchists and hackers developing technologies for self-production of medicines, Lofer has spent the last ten years liberating vital medicines from the huge corporations that own them. Lofer has no medical education, and he is the first to declare that he is not a doctor. From the point of view of legislators, it would be more suitable for mathematical calculations on nuclear weapons than for treating patients. But Lofer never let rules and regulations get in his way.

I met Lofer in a bar, across the street from the hall where HOPE was held, after his speech on the topic of making medicines with his own hands. He met with his comrades in the "four thieves", who had flown from all over the country to this conference to reveal the new medical technologies they were developing. Lofer began the celebration with a toast: "Let's drink to the dead, to children with cancer and AIDS," Lofer said, raising a glass of bourbon, and quoting hip–hop artist Felipe Andres Cornel, better known under the pseudonym Immortal Technique. "There is a cure, and you probably could have been saved."

In the last ten years, the US Food and Drug Administration (FDA), billionaire directors of pharmaceutical companies, doctors and chemists from the most prestigious universities in the USA have crossed the path. Lofer and his comrades do not stop infuriating influential people, because the "four thieves" serve as living proof that effective medicines can be developed within a small budget.

In a pharmacy [USA], a couple of syringes with Mylan adrenaline can cost you $600, a generic can cost you $300, but the ongoing shortage practically guarantees that you will not find them, even if you can afford them. In response to this, the "four thieves" published on their website instructions for self-manufacturing a syringe with a drug that will cost you $30, and it can be made from freely sold components, and then recharged for only $3. Shkreli brought the cost of a vital drug for HIV-infected people, daraprim, to $750 per piece. Then the "four thieves" developed a freely distributed chemical laboratory that allows anyone to produce their own daraprim for only 25 cents apiece.

The volume of the pharmaceutical industry in the United States is estimated at $446 billion, and its borders are zealously guarded by agencies like the FDA and the Drug Enforcement Administration (DEA). By freely distributing diagrams of medical devices and instructions for the manufacture of medicines, a group of anarchists and hackers threatens to shake the foundations of one of the most regulated and profitable industries in the world. And they have only just begun to act.

Free medicines

"Four thieves claim to have successfully manufactured five different types of medicines, and all of them are made using MicroLab. This device should simulate an expensive device that can be found in chemical laboratories, while costing a small percentage of their cost, and using available materials sold in stores. In the case of MicroLab, the reaction chamber consists of a glass jar placed inside a larger jar with a 3D-printed lid, the drawings of which are available on the Internet. Several plastic hoses and a thermistor measuring the temperature are connected to the lid – liquid circulates through the tubes through this device, contributing to chemical reactions necessary for the production of various medicines. The whole process is automated using a small computer that costs no more than $30.

To date, the "four thieves" have used this device to obtain drugs such as: naloxone, an antidote for opioid overdoses, primarily heroin (known as Narcan); daraprim, a drug that fights infections in people with HIV; Cabotegravir, a preventive drug to combat HIV that needs to be taken four times once a year; mifepristone and misoprostol are two compounds necessary for pharmaceutical abortions.

Michael Lofer demonstrates MicroLab at the 11th HOPE Conference in 2016

Considering the new candidates to the US Supreme Court from the current administration, the anarchist collective feels the need to hurry up with perfecting their medicines for abortions. They fear that the federal government will soon allow individual states to allow or prohibit legal abortions, and residents of some of them will not have the opportunity to have an abortion. This was the motivation for Tim Hailers (Louisville), a former sonar specialist from the US Navy, to join the "four thieves" last February.

"Kentucky is a very conservative state, and I think there is a real possibility that we will become the first state where abortion is completely banned," Heilers told me, "so I think it's very important to give people the opportunity to produce their own mifepristone as needed."

Although the "four thieves" managed to get five medicines, only the instructions for daraprim are available for download from the site so far. This, in particular, is due to the very different complexity of obtaining different molecules. Naloxone is particularly difficult, since this antidote uses the same precursors as opioids themselves for opioid overdoses. Their sale is controlled by the government, and only approved laboratories can purchase them, and then in small doses. To get around this problem, Lofer and his colleagues took a seemingly counterintuitive approach: they make medicine from poison.

Although they cannot legally purchase naloxone precursors, Lofer guessed that it was quite easy to buy opiates themselves. Having bought oxycodone (aka oxycontin) on the street, members of the community were able to carry out several chemical reactions, extract the necessary precursors from it, and use them to produce naloxone.

"Some clever drug dealers in the 90s discovered that it was possible to conduct a one-step reaction with oxycontin and get oxymorphone, a substance six times stronger," Lofer said. – And then you can make naloxone from oxymorphone in one step. It's pretty simple – and here you are already making a medicine out of poison."

Such unorthodox approaches to health are very common in the process of hacking pharmaceutical giants, and their purpose is to help people at any cost.

For example, there is the drug cabotegravir, a preventive drug that has been proven to prevent the spread of HIV by sharing needles in macaques. Unlike other preventive medications that need to be taken daily, cabotegravir can be taken four times a year, and it will protect you from HIV. And although the first clinical trials of the drug were extremely promising, the "four thieves" were tired of waiting for this drug to be approved for widespread use. Currently, the drug is undergoing the third phase of FDA trials, that is, it is being clinically tested on a large number of people. In addition, if we take into account the cost of other preventive medicines, cabotegravir is likely to be sold at an exorbitant price. For example, a month's supply of a similar drug Truvada, which must be taken daily, will cost you $ 2,000. Therefore, a group of hackers figured out how to make it themselves.

Cabotegravir is still undergoing preclinical trials, but this did not stop the "four thieves" from trying to transfer the preventive drug to those who may need it. The group continues to experiment with the synthesis of its own version of the drug, and some of its members have already begun to purchase the commercially available preventive drug tenofovir, mix it with a buffer, and supply it to heroin sellers who can offer it together with their product as an "additional service" for customers. For customers who decide to use this service, "heroin will have a side effect," Lofer said. "You won't get HIV with him."

The first prototype of MicroLab is tubes, a bicycle nipple and a glass jar that came to hand.

The "vinegar collective of four thieves" is obviously walking on the edge when it comes to the legality of their actions. And although Lofer has turned the overthrow of the medical industry into a kind of art, his mission to liberate medicine remains under constant threat of prosecution by law enforcement. When a pharmaceutical company makes a new drug, they also have a patent for a molecule that makes it effective. Nevertheless, Lofer and his colleagues are able to reproduce these molecules, since they are described in detail in patents, and often in scientific journals. Only the right technology is needed.

Since the "four thieves" do not sell or distribute the drugs they make, technically their actions are not illegal from the point of view of the FDA, although the agency has issued an open warning about their amateur activities. Shortly after the release of the $30 epinephrine syringe, the FDA issued a press warning stating that "the use of unapproved prescription drugs for personal purposes carries a potential danger," but did not mention the "four thieves" by name. Ironically, a few months earlier, the FDA issued a warning to Pfizer, which did not investigate hundreds of complaints about the failures of their syringes with adrenaline, some of which ended fatally. In May, the FDA issued another warning declaring a chronic shortage of these syringes.

As for the DEA, none of the medicines produced by the team falls under the definition of "controlled substances", so possession of them can be punished at most according to the law on prescription drugs. And a person suffers from a disease and he has a prescription for a cure for it, he should have no problems if he independently produces this medicine. The "Four Thieves", in fact, simply release information about the production of certain medicines at home and develop free tools for this. If someone decides to make medicines for themselves according to their prescriptions, it will be his personal business, but the "four thieves" do not pretend that they release information "only for educational purposes."

"People who support intellectual property laws keep calling it theft," Lofer told me. – If we take this as an axiom, then by the same logic, withholding information about medicines that can save lives should be called murder. From a moral point of view, it is necessary to steal to prevent murder."

"So, yes, we encourage people to break the law," Lofer added. – If you are terminally ill, and you are denied a medicine that can save you – will you choose to break the law and survive, or remain a respectable corpse?"

Doctors without prescriptions

The catalyst for the creation of the society was Lofer's trip to El Salvador in 2008, when he was still a student. Having visited a rural clinic as one of the delegates of the mission documenting human rights violations in the country, he learned that contraceptives had already run out in it three months ago. When the clinic contacted the central hospital in San Salvador, she was informed that other clinics have this problem. Lofer said he was amazed that hospitals could not provide people with access to contraceptives, a relatively easy–to-manufacture drug that has existed for more than half a century. He thought that if drug dealers could use clandestine laboratories to produce drugs, then a similar approach could be used to produce life-saving medicines.

Lofer organized the community shortly after returning from Central America, but announced its existence publicly only in 2016 at the HOPE conference. During the first performance, Lofer demonstrated a homemade syringe with adrenaline for $30, distributed a self-made daraprim among the audience, showed an early prototype of MicroLab, and called Martin Shkreli from the stage (he did not answer). At the beginning of the activity of the "four thieves", Lofer worked mostly by himself. Now, having come out of the underground, the group has grown a lot, although Lofer says that it is impossible to find out the exact number of members – people come and go, and share as much knowledge as they can.

Michael Lofer and a homemade syringe with adrenaline for $40

All people in the community have a technical education, but no one has a medical one. Lofer, for example, studied nuclear physics, and directs the mathematics program at Menlo College in Silicon Valley. The results of the diverse technical experience of the members of the society speak for themselves. Now it already has independent teams in biology, chemistry, data analysis, programming and equipment, the degree of involvement in which depends on the specific project.

The "Four Thieves" do not sell anything, but the group has two key "products". The first is open circuits of equipment, such as a syringe or a MicroLab synthesizer, which can be made from commercially available or 3D–printed components. The second is instructions on using this equipment for the production of medicines, which includes everything from using MicroLab for the simplest reactions to ways to get chemical precursors.

"I believe that it is simply necessary to provide easy access to information on how to make medicines on their own for everyone who has at least a small interest in this," Lofer told me. – The goal of the group is to make sure that people can do all this on their own. The idea is that anyone can download the instructions, read the list of materials, order them, read the assembly and programming instructions, download the code, order the precursors, and produce the medicine."

All the instruments of the group were developed without any funding – all the necessary funds come from the pockets of the group members. So far, the drugs they have produced have not killed anyone yet. However, some experts warn against taking self-made medicines if they have not passed the approval procedure.

Harm reduction

Eric von Hippel, an economist at MIT who studies "open innovation," is enthusiastic about the prospect of homemade medicines, but under certain conditions. He spoke about a pilot program in the Netherlands studying the independent production of medicines made to order for specific people as a good example of safe homemade production. These medicines are manufactured in hospitals by experts in medicine. Von Hippel believes that it is dangerous for patients to take medications made by them themselves.

"If you don't conduct chemical reactions with precisely sustained parameters, then you can easily get dangerous by–products together with the desired drug," von Hippel told me by e-mail. – Careful control of reaction conditions is hardly possible to carry out in such homemade reactors as MicroLab, offered freely by a team of hackers."

His colleague, Harold Demonaco, who works at MIT, agrees with him. Demonaco suggested that a more rational approach to the voiced problems would be an option in which patients would work with pharmacies that independently produce mixtures. They prepare drugs specifically for specific clients, and Demonaco says that they are able to synthesize the same drugs that the "four thieves" produced for little money, but with "appropriate security measures."

"If the system does not have foolproof protection and it is not able to evaluate the final product, then the user is in danger from a large list of unpleasant things," Demonaco wrote to me by e-mail. "The widespread use of devices from the Four Thieves will open a new category for the Darwin Prize."

Von Hippel and Demonaco agreed that for the safe use of medicines by patients, it is absolutely necessary to purify homemade medicines and conduct quality tests. Von Hippel suggested that scientists with experience in medical chemistry would be needed to solve these problems with homemade medicines.

"Michael Lofer's actions seem to me to be a valuable option for social activism, pointing the way to a promising future," said von Hippel. "But it seems to me that before homemade medical products become safe, it is necessary to work out issues with medical science and equipment much better."

The "Four Thieves" in a sense reproduce on a small scale what many hospitals are already doing. In the face of rising drug prices and shortages, many hospitals have started to produce their own medicines on the spot, in order to save money. The difference, however, is that these hospitals often have access to sophisticated laboratories and experienced staff, which significantly reduces the risk that something will go wrong.

The "Four Thieves" do not naively refer to the risks associated with the dissemination of instructions that allow other people to make medicines themselves. There is always a chance that someone will follow the instructions incorrectly and accidentally produce a toxic substance. However, there are ways to reduce the likelihood of such an event, and one of the most important contributions of "thieves" to homemade medicine is the priority of harm reduction in the research and development process.

There are several ways to produce a particular molecule, and some synthesis paths turn out to be easier, or give more room for deviations than others. Therefore, the "four thieves" seek to discover synthesis pathways that reduce the risk of synthesis of toxic substances to a minimum level. At the very beginning of the community's work, they were helped in this by the Chematica startup, which collected data on 250 years of research on synthesis in organic chemistry into a database, and developed software that uses this data to predict and create new ways to synthesize the necessary molecules. With such a database and software, the "four thieves" were able to create simple and safe synthesis methods, the result of which are life-saving drugs.

This scheme worked fine until Chematica was bought by Merck, an international pharmaceutical giant, last year. After the sale, the "four thieves" lost access to the software, and, more importantly, to the database. Lofer told me that their data research team had created an open-source version of the Chematica software, and had even assembled a small database of organic compounds for verification. Compared to the software from Chematica, their program looks rough, but Lofer said that it works quite well. However, to improve it, it is necessary to collect more data, which now belongs to Merck.

But, as every hacker knows, data sometimes "falls off the truck" – this is a polite way to say that the database from Chematica was posted on a password-protected site on the "dark Internet". During a presentation at the HOPE conference, Lofer asked the audience to help with cracking the password and releasing this data to the world. Getting access to data from Chematica via synthesis paths would open the doors to new versions of homemade drugs, but until then this situation will develop very slowly.

The Future of homemade medicines

The most expensive drug on the market is called "Glibera" and is used to treat lysosomal acid lipase deficiency, or Wolman's disease, a rare hereditary disease that affects only 7,000 people worldwide. The disease prevents the normal breakdown of fats, which leads to abdominal pain, acute pancreatitis, enlarged liver and kidneys, and the accumulation of fat deposits under the skin. The drug "Gliber" helps with these symptoms and is critically important for maintaining the quality of life of patients. The only problem is that this medicine will cost each patient $1.2 million a year – if they find it at all. In 2017, UniQure, the company that produces the drug, stopped selling it in Europe due to extremely low demand. This means that approximately 1,200 Europeans suffering from the disease will be very unlucky with treatment.

Approximately the same situation is developing with other rare diseases, which, by definition, concern less than 200,000 people in the United States. If there is a cure for such a disease, its cost is usually too high. If the company does not see a large enough demand for products, it will remove it from the market. Therefore, for many rare diseases, a medicine or an emollient may exist, but it will still be too expensive for patients, or not profitable enough to sell it.

In the future, Lofer wants the "four thieves" to concentrate on the production of medicines for rare diseases, so that people suffering from them will not be left without medicines. However, such drugs have their own unique problems.

For example, Lofer said that many medicines for rare diseases are made from biological material, for example, from fungi. Lofer said that the "four thieves" are working on creating a BioTorrent website that will distribute organic materials for the production of rare medicines. BioTorrent will work as a regular file sharing resource, like The Pirate Bay, but instead of downloading music and movies, people will be able to download instructions for synthesizing homemade medicines and share organic materials with each other. Since biological cells are capable of reproducing themselves, one user will simply need to grow enough cells for himself, and then send some cells to another, who will repeat this scheme – just like people give each other files on torrents.

The question then will be how to send biomaterial to each other cheaply and safely. To do this, the "four thieves" are exploring options with books and CD covers as a medium for biological precursors. Mycelium is something like the "roots" of many fungi, feeding on cellulose, which is easy to get from the pages of a book. That's why Lofer and his colleagues started injecting mycelium into books; it feeds on pages and grows. CDs resemble Petri dishes, and if scratched properly, they can be used as a medium for the growth of bacteria and other biological precursors. The advantage of this approach is that with the help of the BioTorrent website, it will be possible to send these cells using a cheaper tariff for parcels containing books and CDs, and at the same time avoid attention from law enforcement.

In the meantime, the "four thieves" are mainly engaged in improving their MicroLab and synthesizing new drugs. Recently, the group has started producing its own printed circuit boards for MicroLab, which will make it even easier to assemble the device at home. Lofer said he plans to distribute these fees as early as next month. At the same time, the group is working on perfecting the synthesis of Solvadi, a one–time drug that can cure hepatitis C. This medicine has been on the market for almost five years, but its cost of $84,000 makes it inaccessible to many in need. If the "four thieves" succeed, hepatitis C will soon be a thing of the past for everyone, regardless of their income.

At a time when many Americans lack medical care, Lofer's ideas seem as intuitive as they are radical. His work is based on the idea that too many critical decisions concerning healthcare have been given to individuals who care more about their profits than the health of customers. For Lofer, the case of the "four thieves" concerns not only medicines, but also the right to free dissemination of information and personal independence. From his point of view, there cannot be one without the other.

"Doing science is a human right," Lofer said. – It is from this right that all other rights flow. "You should have the right to do whatever you want with your body and think the way you want."

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