The first data from clinical trials of Moderna’s mRNA-based seasonal flu vaccine, released by the company Friday morning, were underwhelming — a finding that shows gene-based vaccines might not be a fix for all the problems with vaccine development.
The overwhelming success of the mRNA COVID-19 vaccines, made by Moderna and Pfizer / BioNTech, supercharged interest in that strategy for developing shots. The shots inject people with tiny snippets of the gene for a virus, which the body builds and then uses to learn how to fight the virus.
Current flu shots contain inactivated copies of the influenza virus. mRNA vaccines are faster to design and produce because manufacturers don’t have to grow copies of the virus, which is why experts have for years seen them as the future of vaccines.
Moderna launched a clinical trial of an mRNA seasonal flu vaccine this summer, hoping to capture the same success as it did with its COVID-19 vaccine. Typically, seasonal flu shots are around 40 to 60 percent effective, and pharmaceutical companies want to make that better. Three other companies are also working on mRNA flu shots.
Moderna released its first results during an investor phone call and presented slides showing that the mRNA flu shots did generate antibodies — but the levels of those antibodies weren’t higher than those for other flu shots already on the market. They also had more side effects than existing shots.
The findings don’t necessarily mean that mRNA flu shots aren’t any better than what we have now. Because mRNA vaccines are faster to design and make, the shots don’t have to be developed as far in advance. Companies may not have to do as much guesswork around what strain of the flu to target them against each year because they can wait to make the shots until they see what strains are circulating.
And as far as efficacy goes, there’s still a lot more data to collect: Moderna is preparing to conduct larger trials that would test how well the shots actually keep people from getting sick in the real world (not just testing antibody levels)..
Still, this early data shows that the immune system is tricky and that mRNA vaccines probably aren’t an easy shortcut for stopping a virus as persistent as the flu. More studies will be needed to figure out if there is a specific benefit to using mRNA vaccines to fight the flu, wrote chemist and writer Derek Lowe in Science. But it’s not a sure thing.
We’ve been living in a COVID world for more than 18 months now. At the outset of the pandemic, government agencies and health authorities scrambled to inform people on how to identify symptoms of the virus.
But as the virus has evolved, it seems the most common symptoms have changed too.
Emerging data suggest people infected with the Delta variant — the variant behind most of Australia’s current cases and highly prevalent around the world — are experiencing symptoms different to those we commonly associated with COVID earlier in the pandemic.
Clear explanations about the pandemic from a network of research experts
We’re all different
Humans are dynamic. With our differences come different immune systems. This means the same virus can produce different signs and symptoms in different ways.
A sign is something that’s seen, such as a rash. A symptom is something that’s felt, like a sore throat.
The way a virus causes illness is dependent on two key factors:
viral factors include things like speed of replication, modes of transmission, and so on. Viral factors change as the virus evolves.
host factors are specific to the individual. Age, gender, medications, diet, exercise, health and stress can all affect host factors.
So when we talk about the signs and symptoms of a virus, we’re referring to what is most common. To ascertain this, we have to collect information from individual cases.
It’s important to note this data is not always easy to collect or analyse to ensure there’s no bias. For example, older people may have different symptoms to younger people, and collecting data from patients in a hospital may be different to patients at a GP clinic.
So what are the common signs and symptoms of the Delta variant?
Using a self-reporting system through a mobile app, data from the United Kingdom suggest the most common COVID symptoms may have changed from those we traditionally associated with the virus.
The reports don’t take into account which COVID variant participants are infected with. But given Delta is predominating in the UK at present, it’s a safe bet the symptoms we see here reflect the Delta variant.
While fever and cough have always been common COVID symptoms, and headache and sore throat have traditionally presented for some people, a runny nose was rarely reported in earlier data. Meanwhile, loss of smell, which was originally quite common, now ranks ninth.
There are a few reasons we could be seeing the symptoms evolving in this way. It may be because data were originally coming mainly from patients presenting to hospital who were therefore likely to be sicker. And given the higher rates of vaccination coverage in older age groups, younger people are now accounting for a greater proportion of COVID cases, and they tend to experience milder symptoms.
It could also be because of the evolution of the virus, and the different characteristics (viral factors) of the Delta variant. But why exactly symptoms could be changing remains uncertain.
While we still have more to learn about the Delta variant, this emerging data is important because it shows us that what we might think of as just a mild winter cold — a runny nose and a sore throat — could be a case of COVID-19.
This data highlight the power of public science. At the same time, we need to remember the results haven’t yet been fully analysed or stratified. That is, “host factors” such as age, gender, other illnesses, medications and so on haven’t been accounted for, as they would in a rigorous clinical trial.
And as is the case with all self-reported data, we have to acknowledge there may be some flaws in the results.
Does vaccination affect the symptoms?
Although new viral variants can compromise the effectiveness of vaccines, for Delta, the vaccines available in Australia (Pfizer and AstraZeneca) still appear to offer good protection against symptomatic COVID-19 after two doses.
Importantly, both vaccines have been shown to offer greater than 90% protection from severe disease requiring hospital treatment.
A recent “superspreader” event in New South Wales highlighted the importance of vaccination. Of 30 people who attended this birthday party, reports indicated none of the 24 people who became infected with the Delta variant had been vaccinated. The six vaccinated people at the party did not contract COVID-19.
In some cases infection may still possible after vaccination, but it’s highly likely the viral load will be lower and symptoms much milder than they would without vaccination.
We all have a role to play
Evidence indicating Delta is more infectious compared to the original SARS-CoV-2 and other variants of the virus is building.
It’s important to understand the environment is also changing. People have become more complacent with social distancing, seasons change, vaccination rates vary — all these factors affect the data.
But scientists are becoming more confident the Delta variant represents a more transmissible SARS-CoV-2 strain.
As we face another COVID battle in Australia we’re reminded the war against COVID is not over and we all have a role to play. Get tested if you have any symptoms, even if it’s “just a sniffle”. Get vaccinated as soon as you can and follow public health advice.
By: Lara Herrero Research Leader in Virology and Infectious Disease, Griffith University
While the alpha and beta genera are derived from the bat viral gene pool, the gamma and delta genera are derived from the avian and pig viral gene pools.
Recombination appears to be common among deltacoronaviruses.Recombination occurs frequently in the viral genome region that encodes the host receptor binding protein. Recombination between different viral lineages contributes to the emergence of new viruses capable of interspecies transmission and adaptation to new animal hosts.
Lau SKP, Wong EYM, Tsang CC, Ahmed SS, Au-Yeung RKH, Yuen KY, Wernery U, Woo PCY. Discovery and Sequence Analysis of Four Deltacoronaviruses from Birds in the Middle East Reveal Interspecies Jumping with Recombination as a Potential Mechanism for Avian-to-Avian and Avian-to-Mammalian Transmission. J Virol. 2018 Jul 17;92(15):e00265-18. doi: 10.1128/JVI.00265-18. Print 2018 Aug 1. PMID: 29769348
Part of Dennis Plenker’s daily job is growing cancer. And a variety of different ones, too. Depending on the day and the project, different tumors may burgeon in the petri dishes stocked in the Cold Spring Harbor Laboratory where Plenker works as a research investigator. They might be aggressive breast cancers.
They might be glioblastomas, one of the deadliest brain tumors that rob patients of their ability to speak or read as they crowd out normal cells. Or they might be pancreatic cancers, the fast and vicious slayers that can overtake a healthy person within weeks or even days.
These tiny tumor chunks are transparent and bland—they look like little droplets of hair gel that accidentally plopped into a plastic dish and took hold. But their unassuming appearance is deceptive. If they were still in the human bodies they came from, they would be sucking up nutrients, rapidly growing and dodging the immune system defenses.
But in Plenker’s hands—or rather in the CSHL’s unique facility—these notorious killers don’t kill anyone. Instead, scientists let them grow to devise the most potent ways to kill them. These tumor chunks are called organoids. They are three-dimensional assemblages of malignant growths used to study cancer behavior and vulnerability to chemotherapy and the so-called “targeted drugs”—the next generation therapies.
Scientists used to study tumors at a single-cell level, but because tumors grow as cell clusters in the body, it proved to be inefficient. The three-dimensional structures make a difference. For example, chemo might destroy the tumor’s outer cell layer, but the inner ones can develop resistance, so where single cells may die, a 3D mass will bounce back. Organoids can provide a window into these little-known mechanisms of drug resistance.
They can reveal how normal tissues turn malignant and where the cellular machinery goes off-track to allow that to happen. As their name suggests, organoids are scientists’ windows into organs, whether healthy or stricken with disease. You need to know your enemy to beat it, Plenker says, and cancer organoids offer that opportunity.
Taken from patients currently undergoing cancer treatments, these tumor chunks will reveal their weaknesses so scientists can find the cancers’ Achilles’ heel and devise personalized treatments. “Organoids are essentially patients in a dish,” Plenker says. Only unlike real patients, the organoids can be subjected to all sorts of harsh experiments to zero in on the precise chemo cocktails that destroy them in the best possible way.
And they will likely provide a more realistic scenario than drug tests in mice or rats, as animal models aren’t perfect proxies for humans.
These notorious killers don’t kill anyone. Instead, scientists devise the most potent ways to kill them.
The way that cancer proliferates in the body is hard to reproduce in the lab. Stem-cell research made it possible. After scientists spent a decade understanding how various cells multiply and differentiate into other cell types based on molecular cues and nourishment, they were able to make cells grow and fuse into tissues.
To stick together like bricks in a nicely laid wall, cells need a biological scaffold that scientists call an extracellular matrix or ECM, which in the body is made from collagen and other materials. Today, the same collagen scaffolds can be mimicked with a gooey substance called Matrigel—and then seeded with specific cells, which take root and begin to multiply.
Some tissue types were easy to grow—Columbia University scientists grew viable bones as early as 2010.1 Others, like kidney cells, were trickier. They would grow into immature tissues incapable of performing their job of cleaning and filtering blood. It took scientists time to realize that these cells wanted more than scaffolding and food—they needed to “feel at home,” or be in their natural habitat. Kidney cells needed the feeling of liquid being washed over them, the Harvard University group found, when they first managed to grow functioning kidney tissue in 2018.2
Cancers have their own growth requirements. In the body, they manage to co-opt the organism’s resources, but keeping them happy in a dish means catering to their dietary preferences. Different cancers need different types of molecular chow—growth factors, hormones, oxygen and pH levels, and other nutrients. Pancreatic adenocarcinoma thrives in low-oxygen conditions with poor nutrients.3 Glioblastomas feed on fatty acids.4 These nutrients are delivered to organoids via a specific solution called growth medium, which the lab personnel regularly doles out into the dishes.
Plenker is charged with keeping this murderous menagerie alive and well. He is the one who designs the cancers’ dietary menu, a specific protocol for each type. And while his official title is facility manager and research investigator who works closely with David Tuveson, director of the CSHL’s Cancer Center, he is essentially a cancer custodian, a curator of a unique collection that aims to change the paradigm of cancer treatment.
Plenker’s research area is pancreatic cancer—one of the most notorious killers known. Often diagnosed late and resistant to treatment, it is essentially a death sentence—only 8 to 10 percent of patients remain alive five years after diagnosis. The chemo drugs used to treat it haven’t changed in 40 years, Plenker says. In the past decade, physicians tried combining multiple drugs together with relative success. Identifying winning combos can save lives, or at least prolong them—and that’s what the organoids will help clinicians do better.
In a groundbreaking clinical trial called PASS-01 (for Pancreatic Adenocarcinoma Signature Stratification for Treatment), Plenker’s team collaborates with other American and Canadian colleagues to identify the most effective chemo cocktails and to understand the individual patients’ tumor behaviors, which would lead to more personalized treatments.5
Scientists know the same cancer types behave differently in different patients. Typically, all malignancies have the so-called “driver mutation”— the cancer’s main trigger caused by a mutated gene. But tumors also often have “passenger mutations” that happen in nearby genes. These additional mutated genes can generate various proteins, which may interfere with treatment.
Or not. Scientists call these mutated gene combinations tumor mutational signatures, which can vary from one patient to the next. With some cancers, doctors already know what mutations signatures they may have, but with pancreatic cancer they don’t have good tale-telling signs, or biomarkers. “There aren’t many biomarkers to help clinicians decide which chemo may be better for which patient,” explains oncologist Grainne O’Kane, who treats pancreatic cancer patients at the Princess Margaret Hospital in Toronto, Canada.
That’s the reason O’Kane participates in the PASS-01 trial—it will give doctors a better view into the exact specifics of their patients’ malignancies. As they take their patients’ biopsies, they are sending little cancer snippets to the CSHL to be grown into organoids, which will be subjected to chemo cocktails of various combinations to design more personalized regiments for them.
The hospital treats all patients with the so-called standard of care chemotherapy, which is more of a one-size-fits-all approach. Some patients will respond to it but others won’t, so the goal is to define the second line of chemo defense in a more personalized fashion. “That’s where the biopsies we send to Tuveson’s lab might be useful,” O’Kane says. “They can help us find something to benefit patients after the first line of chemo stopped working.”
Organoids are patients in a dish. Unlike real patients, organoids can be subjected to experiments.
Scientists can try all kinds of combos on the tumorous organoids, which they can’t do in living people. “You can treat 100 organoids with 100 different compounds and see which one works, or which compound does a good job and which ones don’t work at all,” Plenker says. That would also allow scientists to define the precise amount of chemo, so doctors wouldn’t have to over-treat patients with harsh drugs that create sickening side effects. Ultimately, organoids should take a lot of guesswork out of the process.
With about 150 patients’ adenocarcinomas already collected, the team hopes to come up with some answers. O’Kane says her team already has three patients for which they were able to design the more personalized second line of defense chemo, based on what their organoids revealed. They haven’t yet tried it, because the trial has only started recently, but this would be the next step.
“Being able to piece all this information together in real time as patients are moving through their therapies can really improve the outcomes,” O’Kane says. And while they may not be able to save all of those who graciously donated their biopsy snippets to science, it will help build better treatments in the future. “Even if we won’t be able to help these specific patients we’re hoping to use this info in the future clinical trials,” O’Kane says.
Organoids can also help understand how cancer develops. This is particularly true for breast cancers, says Camilla dos Santos, associate professor and a member of the CSHL Cancer Center. She studies the inner life of human mammary glands, more commonly referred to as breasts, and is also part of the cancer custodian crew. The hormonal changes that women go through during pregnancy subsequently modify breast cancer risk, sometimes lowering it and sometimes increasing—a complex interplay of the body’s chemicals.
“We know that women who get pregnant for the first time before they turn 25 years old, have a 30 percent decrease in breast cancer incidents later in life,” dos Santos says. “When they turn 60 or 70, 30 percent of them will not develop cancer.” On the contrary, those who are pregnant past 38 have a 30 to 50 percent increase in developing aggressive breast cancer types. Clearly, some molecular switches are involved, but they are very hard to study within the body. That’s where organoids can provide a window into the surreptitious process.
Using breast organoids, scientists can model the complex life of mammary glands at various stages of a woman’s life. And while most women wouldn’t want their breasts poked and pierced when they are pregnant or breastfeeding, many donate their tissues after breast reduction surgery or prophylactic mastectomy due to high-risk mutations like the BRCA gene.
That’s where organoids shine because scientists can not only grow them, but also give them the pregnancy hormonal cues, which will make cells generate milk, stop lactating, or do it again—and study the complex cellular interactions that take place in real life.
There’s a lot to study. At birth, mammary glands are similar in both genders—just little patches of the mammary epithelium tissue. But when puberty hits, the female glands fill up with the so-called mammary tree—a system of ducts for future milk production, which fully “blooms” in pregnancy.
“When a woman becomes pregnant, the duct tree expands, growing two types of cells—luminal and myoepithelial ones,” explains Zuzana Koledova, assistant professor of Masaryk University in Czech Republic who also uses organoids in her work. When the baby is born, the luminal cells, which line the inside of the ducts, produce the proteins that comprise milk.
The myoepithelial cells reside outside the ducts and work as muscles that squeeze the ducts to push milk out. Dos Santos likens this pregnancy mammary gland growth to the changes of the seasons. The images of sprouting ducts look like blossoming trees in the spring while later they shrivel like plants do in the fall.
The body governs these processes via the molecular machinery of hormones, which stimulate breast cells growth during pregnancy, and later cause them to die out. The two pregnancy-related hormones, prolactin and oxytocin, are responsible for milk production. Prolactin induces the luminal cells to make milk while oxytocin makes the myoepithelial cells contract. Once the baby is weaned, the levels of these hormones drop, causing cells to shrink back to their non-pregnant state.
With organoids scientists can observe these cellular dynamics at work. Koledova’s team had watched breast organoids secrete milk based on biological cues. They even recorded movies of cells pumping tiny milk droplets in the dish they were growing in. Using tiny snippets of donated breast tissue, the team grew the organoids inside the Matrigel matrix in the growth media and then added the two pregnancy hormones into the mix, explains Jakub Sumbal, a mammary gland researcher in Koledova’s group.
As they began to secret proteins that compose milk, the organoids, which looked like little domes inside the dish, changed from translucent to opaque. “At first, you can see through them, but then as they produce these proteins, they kind of darken,” Sumbal says. “And you can see them pushing out these little droplets.”
Cancer patients would no longer have to undergo chemotherapy by trial and error.
Dos Santos’s team, who also did similar work, outlined molecular changes that follow such dish-based hormonal cues in their recent study.6 In response to hormonal messages, cells produce proteins, which they display on their surfaces, like status symbols. During pregnancy the burgeoning cells prepping for milk production display the “proteins flags” that make them look important, attracting nourishment. When it’s time to die, they commit a cellular suicide.
They signal to the bypassing macrophages—immune system cleanup crew—to devour them. “They essentially say ‘come eat me!’ to the macrophages,” dos Santos says. “Because I’m no longer needed.”
The ability to mimic these processes in a dish, allows scientists to study the molecular switches that trigger breast cancer development—or minimize it. Scientists know that cancerous cells can hide from the immune system and even co-opt it into protecting themselves. They do it by displaying their own “do not eat me” protein flags on the surface and avoid destruction.
“Sometimes cancer cells can recruit specific types of immune cells to protect them,” dos Santos says. “They can not only say ‘do not eat me,’ but say ‘come hang out with me’ to the macrophages, and the macrophages will send suppressive signals to the B-cells or T-cells, the body defenders.” It is as if the cancer requests protection—a crew of guardians around it to defend against other cells that would otherwise wipe it out.
Scientists can’t telescope into the body to peek at these interactions, but they now can watch these stealth battles unfolding in a dish. “Right now we are looking at the proteins that are secreted by the organoids—the proteins that go on the surface of the organoids’ cells and what they would communicate to the immune system,” dos Santos says.
“Even when there’s no immune system surrounding them, they would still be doing that.” There’s a way to mimic the immune system, too. Scientists can add B-cells, T-cells, macrophages, and other players into the growth medium and watch the full-blown cellular warfare in action. “That’s the next step in our research,” dos Santos says.
Understanding what hormonal fluxes trigger breast cancer, and how it recruits other cells for safekeeping, can give scientists ideas for pharmaceutical intervention. “We can find drugs that pharmacologically turn off the switches that trigger cancer or interrupt its signaling for protection,” dos Santos says. “That opens novel ways to treat people.”
Can organoid research lead to a new standard of care for cancer patients? That’s the ultimate goal, researchers say. That’s why Plenker works at keeping his collection of cancer glops alive and well and thriving—he calls it a living biobank. And he keeps a stash in the cryogenic freezer, too.
He is also developing protocols that would allow commercial companies to grow organoids the same way chemical industries make reagents or mice suppliers grow rodents for research. A benefit of organoid experiments is they don’t involve animals at all.
Hospitals may one day start growing organoids from their patients’ biopsies to design and test personalized chemo cocktails for them. Once science crosses over to that reality, the entire treatment paradigm will change. Cancer patients won’t have to undergo chemotherapy by trial and error.
Instead their cancer organoids will be subjected to this process—knocked out by a gamut of drug combinations to find the winning one to use in the actual treatment. Plenker notes that once enough data is gathered about the tumors’ mutational signatures, scientists may create a database of tumor “mugshots” matching them to the chemo cocktails that beat them best.
And then just sequencing a biopsy sample would immediately inform oncologists what drug combo the patient needs. “We may be about 10 years away from that,” Plenker says, but for now there’s a lot more research to do. And a lot more cancers to grow.
Lina Zeldovich grew up in a family of Russian scientists, listening to bedtime stories about volcanoes, black holes, and intrepid explorers. She has written for The New York Times, Scientific American, Reader’s Digest, and Audubon Magazine, among other publications, and won four awards for covering the science of poop. Her book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, will be released in October 2021 by Chicago University Press. You can find her at LinaZeldovich.com and @LinaZeldovich.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.
These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.
Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy.
The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.
Johnson & Johnson will pay as much as $230 million to settle a lawsuit from New York state over its sale and marketing of opioid painkillers, New York Attorney General Letitia James announced Saturday, as state and local governments move to extract money from the pharmaceutical companies that developed the drugs to help combat an epidemic of addiction to them.
The settlement will remove Johnson & Johnson from a trial in a lawsuit brought by James against multiple pharmaceutical companies that’s set to start on Long Island next week.
Johnson & Johnson will pay as much as $230 million into a state-operated settlement fund to underwrite addiction recovery services, overdose prevention, training for healthcare providers and other opioid-related purposes.
James said Johnson & Johnson has agreed to stop selling opioids in the United States, but the company says it stopped selling prescription painkillers in the U.S. last year.
The settlement does not require Johnson & Johnson to admit any wrongdoing or liability, and the company called its marketing of painkillers “appropriate and responsible” in a Saturday morning statement.
Crucial Quote
“While no amount of money will ever compensate for the thousands who lost their lives or became addicted to opioids across our state or provide solace to the countless families torn apart by this crisis, these funds will be used to prevent any future devastation, James said in a statement.
Key Background
James sued Johnson & Johnson along with several other drugmakers in 2019, accusing the New Jersey-based pharmaceutical company of aggressively marketing its opioid painkillers to doctors and inaccurately downplaying the risk of addiction. The lawsuit tied the company to a nationwide opioid abuse epidemic fueled largely by the overuse of powerful, addictive prescription drugs. Several other state and local officials have weighed action against Johnson & Johnson, and the company said last year it’s open to paying $5 billion in settlements.
Tangent
When James’ court case against drugmakers starts next week, it will not include the suit’s best-known target: Oxycontin manufacturer Purdue Pharma. Saddled with a federal criminal probe and hundreds of lawsuits, Purdue is navigating bankruptcy proceedings, and the company and members of the Sackler family — the company’s billionaire owners — are offering to pay billionsof dollars in settlements and restructure Purdue as a public benefit company. This plan is controversial, with some politicians and advocates pushing back on a provision to make the Sackler family personally immune from future lawsuits.
I am a breaking news reporter at Forbes. I previously covered local news for the Boston Guardian, and I graduated from Tufts University in 2019. You can contact me at jwalsh@forbes.com.
The opioid epidemic, also referred to as the opioid crisis, is the phrase used to describe the overuse, misuse/abuse, and overdose deaths attributed either in part or in whole to the class of drugs opiates/opioids, and the significant medical, social, psychological, and economic consequences of both the medical and the non-medical or recreational use of these medications.
Opioids are a diverse class of moderate to strong painkillers, including oxycodone (commonly sold under the trade names OxyContin and Percocet), hydrocodone (Vicodin, Norco) and a very strong painkiller, fentanyl, which is synthesized to resemble other opiates such as opium-derived morphine and heroin. The potency and availability of these substances, despite the potential risk of addiction and overdose, have made them popular both as medical treatments and as recreational drugs.
Due to their sedative effects on the part of the brain which regulates breathing, the respiratory center of the medulla oblongata, opioids in high doses present the potential for respiratory depression and may cause respiratory failure and death. Opioids are highly effective for treating acute pain, but a debate rages over whether they are effective in treating chronic (long term) or high impact intractable pain, as the risks may outweigh the benefits.
Most deaths worldwide from opioids and prescription drugs are from sexually transmitted infections passed through shared needles – citation needed. This has led to a global initiative of needle exchange programs and research into the varying needle types carrying STIs. In Europe, prescription opioids account for three‐quarter of overdose deaths, which represent 3.5% of total deaths among 15-39-year-olds.
Some worry that the epidemic could become a worldwide pandemic if not curtailed.Prescription drug abuse among teenagers in Canada, Australia, and Europe were comparable to U.S. teenagers. In Lebanon and Saudi Arabia, and in parts of China, surveys found that one in ten students had used prescription painkillers for non-medical purposes. Similar high rates of non-medical use were found among the young throughout Europe, including Spain and the United Kingdom.
While many AI biotech companies are on journeys to discover new drug targets, Hong Kong-based Insilico Medicine is a step ahead. The startup not only scouts for new drug sites using its AI and deep learning platforms but also develops novel molecules to target them.
In February, the company announced the discovery of a new drug target for idiopathic pulmonary fibrosis, a disease in which air sacs of the lungs get scarred, leading to breathing difficulties. Using information about the site, it developed potential drug targets. The startup recently raised $255 million in series C funding, taking its total to $310 million. The round was led by private equity firm Warburg Pincus. Insilico will use the funds to start human clinical trials, initiate multiple new programs for novel and difficult targets, and further develop its AI and drug discovery capabilities.
The company has stiff competition in the industry of using AI to discover new drugs. The global AI in Drug Discovery market was valued at $230 million in 2021 and is projected to reach a market value of over $4 billion by 2031, according to a report from Vision Gain. The area has already minted at least one billionaire, Carl Hansen of AbCellera, and others have also gained attention from investors. Flagship Pioneering-backed Valo Health announced this month it’s going public via SPAC.
Investors said that Insilico’s AI technology and partnerships with leading pharmaceuticals attracted them to the startup, despite the crowded field. “Insilico fits strongly with our strategy of investing in the best-in-class innovators in the healthcare,” said Fred Hassan of Warburg Pincus, “Artificial Intelligence and Machine Learning is a powerful tool to revolutionize the drug discovery process and bring life-changing therapies to patients faster than ever before, he added.
CEO and founder Alex Zhavoronkov got his start in computer science, but his interest in research into slowing down aging drew him to the world of biotech. He received his Masters from Johns Hopkins and then got a PhD from Moscow State University, where his research focused on using machine learning to look at the physics of molecular interactions in biological systems.
The process for finding a preclinical target for idiopathic pulmonary fibrosis highlights Insilico’s approach. The company had initially found 20 new target sites to treat fibrosis. Then it used its machine learning processes to narrow those down to a specific target which is implicated in idiopathic pulmonary fibrosis. Then using its in-house tool, Chemistry42, it generated novel molecules to target the new site. The new preclinical drug candidate was found efficacious and safe in mice studies, the company said in a press release.
“Now we have successfully linked both biology and chemistry and nominated the preclinical candidate for a novel target, with the intention of taking it into human clinical trials, which is orders of magnitude more complex and more risky problem to solve,” Zhavoronkov added in a statement.
Treatments for this condition are a dire need. Patients with idiopathic pulmonary fibrosis develop respiratory failure as their blood doesn’t receive adequate oxygen. Most patients die within two to three years of developing the condition. If the company’s drug candidate proves out during clinical trials, it would be a major step forward both for these patients and the industry as a whole.
“To my knowledge this is the first case where AI identified a novel target and designed a preclinical candidate for a very broad disease indication,” Zhavoronkov said in a statement.
I am a New York based health and science reporter and a graduate from Columbia’s School of Journalism with a master’s in science and health reporting. I write on infectious diseases, global health, gene editing tools, intersection of public health and global warming. Previously, I worked as a health reporter in Mumbai, India, with the Hindustan Times, a daily newspaper where I extensively reported on drug resistant infections such as tuberculosis, leprosy and HIV. I also reported stories on medical malpractice, latest medical innovations and public health policies.
I have a master’s in biochemistry and a bachelor’s degree in zoology. My experience of working in a molecular and a cell biology laboratory helped me see science from researcher’s eye. In 2018 I won the EurekAlert! Fellowships for International Science Reporters. My Twitter account @aayushipratap
CEO Alex Zhavoronkov founded Insilico Medicine in 2014, as an alternative to animal testing for research and development programs in the pharmaceutical industry. By using artificial intelligence and deep-learning techniques, Insilico is able to analyze how a compound will affect cells and what drugs can be used to treat the cells in addition to possible side effects. Through its Pharma.AI division, the company provides machine learning services to different pharmaceutical, biotechnology, and skin care companies. Insilico is known for hiring mainly through hackathons such as their own MolHack online hackathon.
The company has multiple collaborations in the applications of next-generation artificial intelligence technologies such as the generative adversarial networks (GANs) and reinforcement learning to the generation of novel molecular structures with desired properties. In conjunction with Alan Aspuru-Guzik‘s group at Harvard, they have published a journal article about an improved GAN architecture for molecular generation which combines GANs, reinforcement learning, and a differentiable neural computer.
In 2017, Insilico was named one of the Top 5 AI companies by NVIDIA for its potential for social impact. Insilico has R&D resources in Belgium, Russia, and the UK and hires talent through hackathons and other local competitions. In 2017, Insilico had raised $8.26 million in funding from investors including Deep Knowledge Ventures, JHU A-Level Capital, Jim Mellon, and Juvenescence. In 2019 it raised another $37 million from Fidelity Investments, Eight Roads Ventures, Qiming Venture Partners, WuXi AppTec, Baidu, Sinovation, Lilly Asia Ventures, Pavilion Capital, BOLD Capital, and other investors.
The first data from clinical trials of Moderna’s mRNA-based seasonal flu vaccine, released by the company Friday morning, were underwhelming — a finding that shows gene-based vaccines might not be a fix for all the problems with vaccine development.
