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Can Synthetic Biology Make Insulin Faster, Better and Cheaper?

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September 22, 2019

Have you seen these horrific headlines in recent months?

Another person has died from rationing insulin.”“Woman says her son couldn’t afford insulin — and now he’s dead.”“He lost his insurance and turned to a cheaper form of insulin. It was a fatal decision.”Rising insulin prices have become a dangerous norm for diabetics. Whether on Twitter, TV, or public radio, the insulin market has the world’s attention — and for all the wrong reasons.Insulin prices are not only skyrocketing (they increased by 99% from 2012 to 2016); lack of access is killing Americans. People with Type 1, Type 2, and even gestational diabetes need to take insulin to regulate their blood sugar levels. Insulin is the signal that tells our cells to take in glucose and convert it to energy. Without this molecule, glucose builds up in the bloodstream and can cause serious complications, including cardiovascular disease.We are at the precipice of a profound public health crisis. If insulin has been around for nearly fifty years, and production has become cheaper over time, how did we get here? And what can synthetic biology do about these circumstances?

Insulin

In the early 1900s, Frederick Banting and Charles Best, two scientists at the University of Toronto, found that insulin extracted from dogs’ pancreases could effectively regulate blood glucose levels. The discovery was earth-shattering, marking the first hope of a feasible treatment for diabetics.In 1923, Eli Lilly and Company created Iletin, a mass-produced version of insulin derived from the pancreas of pigs and cows. However, the animal-based molecule tended to cause allergic reactions in patients. By the late 1970s, Lilly could not keep up with increasing demand for insulin because of the inordinately large number of animals (56 million per year) that it required to do so.Then came Genentech in 1976, a start-up that developed a synthetic version of human insulin using new gene editing technology in bacteria. Genentech demonstrated that it was possible to produce human insulin in bacteria but needed to scale production for this approach to actually be effective in comparison to the established animal-based production methods. It was brought to market in 1983, marking the first-ever FDA-approved human therapeutic made using gene editing.Today, there are three companies that virtually rule the global insulin market: Eli Lilly and Company, Novo Nordisk, and Sanofi. While there have been gradual improvements in insulin production, they have been hindered by two bottlenecks: the technology is still monopolized through intellectual property loopholes, and old versions of the medicine have become “obsolete,” with other companies unwilling to manufacture generic versions. The drug-development supply chain is also incredibly convoluted and involves rebates to third-party pharmacy benefit managers. This recurring overhead kickback cost hikes up the price of development, even though the initial engineering happened decades ago. These three companies, therefore, have the power and “justification” to continually raise prices and strangle the market.

Although there may be no perfect solution for the insulin crisis, advances in synthetic biology — a field that aims to “rewire” living organisms to program them with new functions — may hold the key to ameliorating insulin pricing problems by reducing R&D bottlenecks, drastically increasing productivity and quality, and slashing manufacturing costs. While Genentech’s original, insulin leveraged what may now be considered an old school scientific technique, synthetic biology of today leverages a much broader and more powerful set of tools. Rather than just recombining DNA, it designs and produces entirely new systems and functions that can be implemented in organisms — a process overhaul that combines engineering with biology to improve the efficiency and quality of running experiments, creating lab-grown meat, developing therapeutics, and more. Here are three ways that synthetic biology is making drug development faster, better, and cheaper.Using machine learning and big data to take better shots on goal Computers are, perhaps, the world’s greatest biologists. From modeling the relationship between a drug’s structure and function to analyzing the impact of genetic mutations in DNA,  machine learning is enabling scientists to examine and act on data with an unprecedented level of precision.Currently, it costs about $4 billion and takes over 10 years to bring a new drug to market — and that’s assuming that the drug actually works. Fewer than 10% of drug discovery projects succeed. With machine learning, these odds are beginning to improve. Not only is there a higher number of “shots” on goal for potentially having good therapeutic, but the quality of those shots are that much better. This makes lab experiments that much more valuable: the baseline for testing and improvement is that much better and no longer focusing on filtering through noise. Pharmaceutical companies are increasingly wielding the power of machine learning — biotech giant GlaxoSmithKline entered a $43-million partnership in 2017 with AI company, Exscientia, to design molecules to attack 10 disease-related targets in about 25% of the time and at 25% of the cost of traditional drug discovery approaches.High-throughput sequencing, reading, and writing of DNA Researchers have risen above and beyond the challenge to wield the power of DNA — the fundamental building block of life, encoding all the instructions for an organism to function with just 4 letters (nucleotides “A,” “T,” “G,” and “C”).  George Church, a Professor at Harvard University known for his seminal works on genetic sequencing, writing, and recoding, says that our DNA reading and editing capabilities have grown exponentially over the last few years — even faster than the Moore’s Law curve that the silicon chip industry followed. Sequencing the first human genome took $2.7 billion and almost 15 years. The cost has dropped to about $1000 today — almost the same as a new iPhone — and the process takes just a few days . The better we understand and manipulate DNA, the greater our ability to harness the beauty of nature’s production pipeline embedded in all living things.

Funding synthetic biology

Price per base of DNA sequencing and synthesis

Companies like Twist Bioscience have led the charge in increasing quality and decreasing the cost of DNA synthesis from almost $100 to just 10 cents per letter, opening up a wide array of scientific doors by simply making synthetic biology that much more feasible.  Our ability to run high-throughput DNA experiments is the epitome of a positive feedback loop — technology facilitated by better computational methods that in turn allows us to gather more biological data and design better technology. Whether that’s using CRISPR-Cas9 to edit DNA to treat cancer, storing data in DNA, or the democratization of personal genetic testing kits, our ability to understand and engineer DNA is revolutionizing the drug development pipeline.From small molecules to proteins Most pharmaceuticals developed today are small molecules, drugs that are tiny enough to enter cells and initiate a desired therapeutic effect. These small-molecule therapeutics already constitute 90% of drugs on the market, but the pharmaceutical industry is beginning to shift instead towards protein engineering to develop therapeutics. While this class of medicines is much more difficult to manufacture (and therefore more expensive), advances in synthetic biology techniques, particularly improvements in the synthesis of DNA and machine learning, have facilitated an explosion in the field over the last few years. The investment is incredibly valuable, too, as protein-based drugs (particularly antibodies) allow for greater specificity in drugging targets.This is especially powerful for treating complex diseases like cancer and rheumatoid arthritis and developing next-generation insulin and developing drugs for relatively more rare diseases, such as lupus or allergic asthma, with a higher chance of success while still turning a profit.The drug development world is already rapidly changing for the better because of synthetic biology. From Ebola and influenza to cancer and HIV, access to therapeutics stands to keep improving due the decrease in cost and increase in quality and efficiency in the pharmaceutical world.As for insulin: synthetic biology has been able to make its mark even on a drug from the previous generation of biotech. New type 1 diabetes research from the J. Craig Venter Institute engineers bacterial cells that are already in our skin to produce insulin, potentially allowing patients to one day be their own mini-pharmaceutical company with a one-time investment for lifelong medication. If we continue to progress in the right direction, insulin prices may begin to restabilize. With the help of synthetic biology, the insulin crisis could become a lesson from the past — a demonstration of how cutting-edge science and equitable healthcare access can work in tandem to build a better tomorrow.Thanks to Aishani Aatresh for additional research and reporting in this article. Please note: I am the founder of SynBioBeta, the innovation network for the synthetic biology industry, and some of the companies that I write about are sponsors of the SynBioBeta conference (click here for a full list of sponsors).

Follow me on Twitter. Check out my website or some of my other work here.Originally published on Forbes https://www.forbes.com/sites/johncumbers/2019/09/21/can-synthetic-biology-make-insulin-faster-better-and-cheaper/

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