A team of biohackers is on a David-versus-Goliath mission to make insulin affordable to an increasing number of diabetics.
- Diabetes is the seventh-leading cause of death in America.
- About 463 million people (including 34 million Americans) are diabetic.
- The cost of insulin continues to surge, so the Open Insulin Project is fighting back by replicating medical-grade insulin that can be made at a lab in your neighborhood.
The Biohackers Making Insulin 98% Cheaper www.youtube.com
The sticker price for a vial of insulin has increased more than 3000 percent over the last 60 years, making it cost-prohibitive for the world's 463 million diabetics. While type 2 diabetics often manage symptoms through lifestyle changes, type 1 diabetics must inject insulin or risk death.
Merely three companies control 90 percent of the world's insulin — and they raise the price in chorus, year after year. To fight this trend, the Open Insulin Foundation is developing the first practical, small-scale, community-centered solution for insulin production. Once they replicate medical-grade insulin, they are going to share the recipe with the public for free.
Insulin and type 1 vs. type 2 diabetes
Since insulin was first discovered at the University of Toronto in 1921, it has become one of the planet's most important medications. Normally, insulin — a peptide hormone that regulates the metabolism of carbohydrates, fats, and protein — is synthesized by beta cells in the pancreas. When blood glucose levels are high, insulin is released, which encourages body cells to absorb glucose, lowering its level in the blood.
This process can go awry for a variety of reasons, including an abundance of sugar-rich foods, genetics, and a general lack of movement in our lives.
There are two different types of diabetes. Type 1 diabetics have an autoimmune condition that prevents them from producing their own insulin. Thus, type 1 diabetics must inject insulin in order to survive.
Type 2 diabetics have some resistance to insulin's effects. Their bodies overproduce insulin in an attempt to maintain proper blood glucose levels. (Eventually, the pancreatic cells that produce insulin can burn out.) Roughly 90 percent of the world's 463 million diabetics suffer from type 2 diabetes. While they often can manage their insulin levels through healthier nutrition and exercise, many type 2 diabetics need prescription insulin as time goes on.
The greatest danger of not receiving an insulin injection is diabetic ketoacidosis (DKA), in which the bloodstream becomes extremely acidic and the diabetic is rendered dehydrated. Symptoms of DKA include vomiting, hyperventilation, coma, and death.
As of 2018, 34.2 million Americans had diabetes, with 1.6 million suffering from type 1 diabetes. Every year, 1.5 million more Americans are diagnosed with diabetes, resulting in an overall cost of $327 billion to the economy. ($237 billion is attributable to direct medical costs, and $90 billion is attributable to reduced productivity.) Currently, about 7.4 million Americans are taking insulin as a form of treatment for diabetes.
How is insulin made? And why is it so expensive?
Insulin is made using the tools of modern biotechnology. A gene for insulin is inserted into a microbe, such as E. coli or yeast. The host becomes a bio-factory, cranking out large amounts of insulin, which is then collected and purified before being bottled for sale.
The original patent on insulin was sold by its creators for $3 to the University of Toronto because they believed it was essential medicine that should not be monetized. But times have changed. The big three insulin manufacturers (Eli Lilly, Novo Nordisk, and Sanofi) have 90 percent market share. While a vial of insulin costs them roughly $5 to manufacture, each vial is sold for $180 to $400.
Though the original patent expired long ago, pharmaceutical companies implement a practice in which a successful medicine is slightly tweaked in order to make it better. Each tweak earns them a new patent. Additionally, while generic insulin exists and can cost as low as $6 (as in Spain), the big three insulin manufacturers exploit the mind-bogglingly complicated American health insurance system to maximize revenue. This leaves the uninsured or under-insured left paying exorbitant rates out of pocket.
Science writer Dana G. Smith explains:
"[Dr. Mariana] Socal says that the rebate money is split between the insurance providers and benefits managers, and patients see none of the savings. If you're uninsured, you pay the list price, not the lower net price. If you are insured but have a deductible, you have to buy the drug at the list price before your insurance company will kick in. And even with full insurance coverage, the co-payment for the drug is still a percentage of the higher list price, not the cheaper net price."
According to the American Diabetes Association, a quarter of insulin patients are now self-rationing their medication in order to cut down expenses. This is dangerous.
Photo: Prostock-studio / Adobe Stock
Open Insulin Foundation
The non-profit Open Insulin Foundation began in 2015 in Oakland, California with $16,000 in crowdfunding. Over the past six years, the lab has grown with the goal of providing diabetics with life-saving insulin at an affordable cost.
Type 1 diabetic Anthony Di Franco is the founder of Open Insulin. His goal is to make insulin production open-source and decentralized. Di Franco was inspired to found the organization after experiencing a temporary lapse in insurance coverage in which he had to pay $2400 per month for insulin supplies. At the time, that dwarfed the $1600 per month he received as a graduate school stipend.
Open Insulin hopes to design a "recipe" that other small labs all over the country can follow to produce insulin for diabetics living in the area. Once the recipe is perfected, the team will purify the protein and test it on Di Franco, who has agreed to become the project's guinea pig. (There are no FDA regulations against testing drugs that you produce yourself.) As Di Franco says of the project, "It's not like a new drug where you don't really know what it does. This is a drug that we already know what it does, and we just have to see if we made it correctly."
If Di Franco's test run is a success, he will release the recipe online and hope that hospitals and clinics take advantage of it to produce low-cost insulin for their patients.
Stay in touch with Derek on Twitter. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Plan S is starting to take hold, but the cost is merely shifting even more to the researchers.
- Launched in 2018, cOAlition S is trying to make all of the world's state-backed scientific papers open-access.
- Prestigious publishers like Springer Nature and Elsevier have now adopted a Plan S option for researchers.
- While more studies will be available to read for free, some of the expense is being passed back to authors, which could limit research in the future.
In 2018 cOAlition S launched an ambitious program: to make all of the world's state-backed scientific papers open-access. Their agenda, Plan S—the S stands for "shock"—is backed by over a dozen European research agencies and funders.
While the group has fallen short of achieving their stated agenda by 2021, they're certainly making strides. Just this week, 160 Elsevier journals, including renowned publications by Cell Press, are registered as "Plan S aligned Transformative Journals." This could be a good move by Elsevier, which has been severely criticized in the past for price gouging practices—although critics cite increased researcher fees as a cause for alarm.
Unlike the 10-year-old Sci-Hub, which houses over 85 million research papers and regularly changes URLs to avoid the legal ramifications of providing access to paywalled studies, cOAlition S is changing the journal system from within. Their 10 principles call for greater autonomy for researchers conducting scientific studies and having publication fees covered by universities, not researchers. The latter could prove pivotal, as publication budgets are often no match for journal fees.
In just three years, cOAlition S has gained the support of the World Health Organization, the European Commission, and research institutions and agencies in China, Sweden, France, Jordan, and the United States, including the Gates Foundation and Howard Hughes Medical Institute. While many journals initially opposed this agenda, a few have come around. Bureaucratic red tape and inflated prices have hamstrung science for decades. Plan S is not a perfect solution, but it's the closest we've seen.
Science's associate news editor Jeffrey Brainard breaks down how open access works for authors. Publishing studies is an essential part of a researcher's career, bringing with it the potential for career advancement, tenure, peer respect, and, occasionally, popular renown. But it comes at a cost.
Golden open access is one model used by journals such as The Lancet Golden Health, which charges researchers up to $5,000 to make their studies open access. Nature publications now clock in at up to $11,600 and Cell charges $9,900, though the median fee for journals is $2,600.
Pay-to-play doesn't only exist in music. The more respect a journal carries, the higher the fee.
When Springer Nature, publisher of the reputable Nature journals, announced it was adopting a Plan S option last month, the editorial team announced the $11,600 fee was mandatory for anyone requesting their articles be made open-access, regardless of their financial status. These journals are notoriously expensive: submitting an article for consideration costs roughly $2,700 with no guarantee of publication. One journal, Nature Physics, rejects 90 percent of submissions.
cOAlition S executive director Johan Rooryck expressed happiness that Springer Nature is now offering an open-access model but stated "that doesn't mean we have signed a blank check and are willing to pay any price for the articles appearing in those journals."
Springer Nature has also adopted a model more in alignment with Spotify: universities and research institutions pay a single fee to publish their authors. Some publishers offer a hybrid approach: some articles are free while others live behind a paywall. There are also embargo models, where authors can offer their papers to the public free of charge after a six-month or year-long waiting period.
The cost to publish remains prohibitive for some researchers, with certain journal prices for one article exceeding annual budgets. This has forced many researchers to confront an existential question: publish behind a paywall and wither in obscurity, or pay up and hope enough people read (and cite) your work.
While inflated journal prices have plagued the scientific community, Brainard notes that a purely open-access model could place even more of a burden on researchers.
"A complete shift to open access could lead publishers to boost publishing fees even further, to try to make up for lost subscription revenues[...] Although just over 30% of all papers published in 2019 were paid open access, subscriptions still accounted for more than 90% of publishers' revenues that year."
cOAlition S is advocating for increased transparency to push back on price gouging. Just as researchers must disclose funding and conflicts of interest, "Plan S requires publishers to disclose to funders the basis for their prices, including the cost of services such as proofreading, copy editing, and organizing peer review."
Although Brainard briefly mentions an increase in the number of non-researchers and institutions—laypeople—reading open-access journals, this topic is relevant to this conversation. America is suffering from a longstanding dearth of public science information, evidenced in the anti-vax fervor that's growing in volume (if not in numbers) since the introduction of the COVID-19 vaccines.
Access to scientific studies won't solve all of our woes. But lack of transparency is a major reason why so many citizens have grown suspicious of pharmaceutical companies and public health agencies. An ability to read studies without having to pay exorbitant prices (to the layperson) would be an important step in public health and science education.
Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
There has been a dramatic increase in abuse and misuse.
- Benzodiazepine usage has increased in 2020 due to the pandemic.
- The FDA is requiring new label warnings due to increased abuse and misuse of benzos.
- Drugs like Valium and Xanax are approved for short-term use only, yet many are on them for years and even decades.
There have been many troubling consequences of the pandemic: massive rates of unemployment, government gridlock over whether to provide further stimulus, an inability to see family members or travel, over 213,000 deaths in America, and increasing rates of anxiety and depression.
Early into quarantine rates of alcohol consumption also rose—unsurprising, given how much more time people were spending at home. Living alone was one factor, yet so was living with a partner who regularly drinks. In an interesting analysis, one European agency found decreased usage of stimulants like cocaine and MDMA in wastewater, which matches self-reported claims. Without late-night parties, people began tranquilizing instead of getting hyped up.
Speaking of tranquilization, rates of benzodiazepine (such as Valium and Xanax) use are also increasing in both the U.S. and UK. While antidepressants and anti-anxiety medications are only approved for short-term use, the uptick in prescription rates, as well as illicit use, is troubling. With no sanctioned tapering protocols available, the potential for long-term abuse—and chronic side effects—means we're in dangerous territory with drugs that we really know little about.
This news comes on the heels of an FDA announcement that benzodiazepine manufacturers will be required to update label packaging to reflect the potential for abuse and addiction. This includes brand names like Xanax, Klonopin, Librium, Valium, and Ativan.
Benzodiazepine Dependence and Withdrawal - How To Avoid This
Since the early '50s, tranquilizer and sedative abuse has been a common yet under-discussed phenomenon in American society. The first blockbuster drug was Miltown. In 1955, meprobamate, a derivative of the short-acting mephenesin, was brought to market. Discovered by Czechoslovakian pharmacologist Frank Berger while developing a penicillin preservative, he noticed mephenesin calmed rats without knocking them out. In 1950, Berger moved from the UK to Cranbury, New Jersey where he developed meprobamate alongside chemist Bernard John Ludwig. By 1957, a billion pills of this drug, now called Miltown, were being produced.
Then the fire went out. In the sixties, Miltown was reclassified as a sedative. The manufacturers were sued for monopolizing the tranquilizer market. Doctors eventually recognized the risks outweighed the benefits. Miltown addicts flooded treatment centers. Instead of understanding the risks tranquilizers pose, pharmaceutical manufacturers simply shifted focus to other drugs, such as benzodiazepines, antipsychotics, SSRIs, and SNRIs.
Every decade, more problems arise with these pills. While short-term efficacy is clinically proven (especially when coupled with psychotherapy), underlying risks have long been known and little discussed. As Dr. Harshal Kirane, medical director of Wellbridge Addiction Treatment and Research, recently said after the FDA announcement,
"Benzodiazepines will not be the next big epidemic. They have been a 'silent' epidemic for decades, intensifying consequences from the current opioid epidemic."
The FDA's decision is based on growing evidence that benzos are prescribed more frequently and for longer durations than they're approved for. This has led to increasing cases of abuse and misuse.
Credit: Tomas Nevesely / Shutterstock
As journalist Robert Whitaker told Big Think earlier this year, drug approval regulations are looser than many assume. Drug manufacturers, which often sponsor clinical trials for their own drugs, only have to show efficacy over placebo—how much efficacy doesn't matter. If a company doesn't like the result, they can throw out the data and never report it. Then there's chronic use.
"We also don't measure long-term exposure. If you look at Xanax, it doesn't show any efficacy after about four weeks. If you're taking it on a daily basis, you really should get off it. But all sorts of people have been on it for two years, three years, five years, 10 years. We don't have a mechanism for assessing what happens to people on these drugs for that amount of time."
In fact, the original Xanax trial was for 14 weeks. At the end, the drug was under-performing the placebo. Instead of submitting that data, the company only reported the four-week data. As of 2017, Xanax was the 21st most-prescribed drug in the country, with nearly 26 million prescriptions written, even though it only shows efficacy for about a month.
Psychiatrist Bechoy Abdelmalak explains the road to addiction:
"When you start taking these drugs, the response is very positive so it becomes hard for patients to discontinue them. So patients often take them for many years and, with chronic use, the risk of side effects increases, especially in the elderly."
Overall, roughly 92 million prescriptions for benzodiazepines were dispensed in America in 2019, with an estimated 50 percent of patients taking them for two months or longer (according to 2018 data).
A label warning is a step in the right direction, but given the increasing amounts of mental health troubles in 2020, we need more protections. The only winner right now is the $17 billion antidepressant industry and the burgeoning anti-anxiety market. That money is made on our suffering. From the looks of it, these drugs are creating more problems than they're solving, and we're all paying the price.
Stay in touch with Derek on Twitter and Facebook. His new book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
We owe a lot to vaccines and the scientists that develop them. But we've only just touched the surface of what vaccines can do.
- "Vaccines are the best thing science has ever given us," says Larry Brilliant, founding president and acting chairman of Skoll Global Threats. From smallpox, to Ebola, to polio, scientists have successful fought viruses and saved millions of lives. So what's next?
- As Covaxx (formerly United Neuroscience) cofounder Lou Reese explains in this video, the issue with vaccines is that they don't work against "non-external threats." This is a problem, especially now when internal threats (things that cause cancers, Alzheimer's, diabetes, and other chronic illnesses) are killing people more than external threats like viruses.
- The future of vaccine tech, which scientists are already working toward today, is developing safe vaccines to eradicate these destructive internal agents without harming our bodies in the process.
The U.S., China, and Russia are in a "vaccine race" that treats a global challenge like a winner-take-all game.
The board game "Pandemic" tasks players with stopping deadly diseases as they spread across the world. But what separates "Pandemic" from its winner-take-all peers is that it's a collaborative endeavor. Players either pull together to stamp out their microscopic foes, or they all lose.
Commentators have naturally drawn comparisons between the game and the COVID era it has become emblematic of, and those parallels have become more fitting lately. On September 21, the World Health Organization (WHO) announced that 156 countries had joined the COVAX Facility, a worldwide collaboration to develop a vaccine and distribute it strategically and equitably.
But as any "Pandemic" fan will tell you, there are always those players: the ones who cut ties with the others, who play to be the most powerful, who reinterpret the goal as domination in a zero-sum game of their own devising. Unfortunately for WHO and its allies, three big global players have refused to play cooperatively: China, Russia, and the United States.
All for one (vaccine)
Launched this April, the Access to COVID-19 Tools (ACT) Accelerator brought together a panoply of governments, scientists, businesses, and global health organizations with the goal of accelerating the development, production, and distribution of an efficacious COVID-19 vaccine. The "vaccines pillar" of this initiative is the COVAX Facility.
COVAX is coordinated by the WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), and Gavi, the Vaccine Alliance. The program maintains a diverse portfolio of COVID-10 vaccines, monitoring each to identify promising candidates. It has also partnered with manufacturers to ease investment risks and serves as a purchasing pool for self-financing countries, while offering fundraising efforts to poorer ones.
"[G]overnments from every continent have chosen to work together, not only to secure vaccines for their own populations, but also to help ensure that vaccines are available to the most vulnerable everywhere," Seth Berkley, CEO of Gavi, said in a release. "With the commitments we're announcing today for the COVAX Facility, as well as the historic partnership we are forging with industry, we now stand a far better chance of ending the acute phase of this pandemic once safe, effective vaccines become available."
In an interview with Vox, Berkley noted that the ACT Accelerator is the largest global collaboration since the Paris Climate Agreement. He added, "This type of solidarity is critical because otherwise what you're going to end up with is just a constant reintroduction of infections and the inability to go back to normal."
As of Monday, 64 higher-income countries and 92 low- and middle-income countries—representing nearly two-thirds of the world's population—have signed commitments to COVAX. Thirty-eight more are expected to sign soon.
COVAX's goal is to have 2 billion doses by the end of 2021. Experts estimate this amount will cover high-risk and vulnerable people, as well as healthcare workers, worldwide. Participating nations must cover those populations before administering vaccines according to national priorities. As part of the agreement, countries agree to support equal access to the vaccine once it becomes available, a move aimed at preventing hoarding and price gouging.
Currently, CEPI is supporting nine candidate vaccines, of which eight are in clinical trials.
Why has the U.S. backed out?
The United States is gambling that its bilateral deals with various pharmaceutical companies will win the "vaccine race." This U.S.-only initiative, named (sigh) Operation Warp Speed, has already spent approximately $10 billion and is pushing to deliver 300 million doses by January 2021. Many experts worry this speedy push through the regulatory path could result in premature and dangerous approvals.
China and Russia have likewise bet on their own high-priced ponies. Russia is touting an unvetted vaccine nicknamed (double sigh) "Sputnik V." This vaccine has only concluded phase 1 and 2 trials with a small number of participants, yet Russia claims to have already received international requests. Meanwhile, China has administered tens of thousands of doses of a vaccine before completing phase 3 clinical trials.
An additional barrier to the United States' participation: COVAX is a WHO-led initiative. Earlier this year, President Donald Trump admonished the WHO as a corrupt organization and claimed it assisted China in covering up the coronavirus outbreak and its severity. Though he presented no evidence for the accusation, Trump has used it as the basis for his threat to cut ties with, and funding for, the agency.
"The United States will continue to engage our international partners to ensure we defeat this virus, but we will not be constrained by multilateral organizations influenced by the corrupt World Health Organization and China," said Judd Deere, a spokesman for the White House, said in a statement.
He added, "This president will spare no expense to ensure that any new vaccine maintains our own FDA's gold standard for safety and efficacy, is thoroughly tested, and saves lives."
By shirking COVAX, these countries hope to gain peerless access to a vaccine. Each could secure large numbers of doses for its citizens while also reaping the political boons to follow. In the United States, President Trump has pinned his re-election bid on a timely vaccine, while Chinese officials seem posed to use a vaccine to repair diplomatic ties.
But the loss of such rich economies will prove a blow to COVAX and the ACT Accelerator. Vaccines are notoriously expensive and risky to develop; the costs to manufacture doses at scale will be immense. WHO Director-General Tedros Adhanom Ghebreyesus stated the ACT Accelerator would cost roughly $30 billion, and the final bill for the tools to combat novel coronavirus would be at least $100 billion. But that's a pittance compared to the $10 trillion already spent on the pandemic so far.
"COVID-19 is an unprecedented global crisis that demands an unprecedented global response," Tedros said. "Vaccine nationalism will only perpetuate the disease and prolong the global recovery. Working together through the COVAX Facility is not charity, it's in every country's own best interests to control the pandemic and accelerate the global economic recovery."
The winner won't necessarily take all
By COVAX's count, there are 170 COVID-19 vaccines in development. None have been approved, few have reached phase 3, and most will fail to exit clinical trials. While one or two may be ready by year's end, they probably won't be a corona-cure-all. They will likely be similar to flu vaccines, reducing the contraction risk and the severity of symptoms.
"We all recognize that flu vaccine, in a year when it's efficacious, you have what, 50% protection? And in a year when it's poor you have 30% or less than that—and still we use that," Marie-Paule Kieny, WHO assistant director-general of Health Systems and Innovation, told Stat.
That means any country to pass the approval finish line won't necessarily win it all. After approval, it will still take a global effort to manufacture and distribute doses. Without blanketed protection, even countries with a high inoculation rate will risk reintroduction of the virus from those still struggling to contain it.
As any player of "Pandemic" will tell you, when a player decides to go it alone, they don't just make the game more difficult. They diminish the trust and cooperation for many games to come.