After 1,000 Years, Astronomers Still Unlocking Secrets of the Crab Nebula

By Korey Haynes | September 18, 2018 6:00 pm
nasa the crab nebula was spotted first in 1,054 A.D.

Skywatchers have been enjoyed views of the Crab Nebula for nearly 1,000 years. (Credit: NASA, ESA, J. Hester, A. Loll (ASU))

In late spring in the year 1054, a strange light appeared in the sky in what we would now call the constellation Taurus the Bull. It was a new star, where no star had been before. It grew quickly brighter, until by July it outshone everything except the moon. Over the next two years it faded away, becoming a star of normal brightness and eventually disappearing again entirely.

Astronomers in China and Japan recorded its arrival, and other observers around the world surely noticed it as well. But it was the Dark Ages in Europe, from which we have relatively few written records. Added to that, scholars both there and in the Middle East were more interested in the reliable and seasonable patterns of the incorruptible heavens, and less so in the unpredictable appearances of comets and guest stars. It’s also possible, and this should shock no one, that it was clouded over and rainy in England during the time the star shone most brightly.

But even for the most observant, the light that shone so brightly for almost two years was forgotten after hundreds more passed by without its reappearance. Its memory survived only in written records, and no one paid it much attention.

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CATEGORIZED UNDER: Space & Physics, Top Posts

The First Earthlings Around the Moon Were Two Soviet Tortoises

By Eric Betz | September 18, 2018 5:00 pm
zond 5 turtles tortoises survive first trip around the moon

Russia’s Zond 5 spacecraft carried two steppe tortoises on the first successful flight around the moon. The tortoises lived through their splash down in the Indian Ocean and were returned safely to Moscow, proving life could survive the trip around the moon. (Credit: S.P. Korolev RSC Energia/Courtesy of NASA)

Anders. Borman. Lovell. The names of the first three humans to journey around the moon will echo throughout eternity. But these brave Apollo 8 astronauts were actually not the first earthlings to complete the voyage. Two tortoises beat NASA to the moon by a matter of months.

Fifty years ago today, on September 18, 1968, the Soviet Union’s Zond 5 spacecraft circled the moon, ferrying the first living creatures known to have orbited another world. On board were two Russian steppe tortoises along with some worms, flies and seeds.

“It really was one of those last hurrahs for the Soviet spaceflight program because it was one of the last times they were able to preempt the Americans in any real way,” says Cathy Lewis, the international space program curator for the Smithsonian’s National Air and Space Museum.
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CATEGORIZED UNDER: Space & Physics, Top Posts
MORE ABOUT: moon, space exploration

Top 10 Secrets About Stress and Health

By Nathaniel Scharping | September 18, 2018 4:28 pm
panic button

(Credit: Studiostoks/Shutterstock)

It’s no secret that stress is bad for your health.

Everybody knows that “life stress events” — things like loss of a job, death of a loved one and getting divorced (or married) raise the risk of getting sick.

All sorts of other life events also generate stress, with possible negative health effects ranging from catching a cold to major depression to a fatal heart attack.

Of course, knowing about the link between stress and sickness just gives you something else to worry about, adding even more stress. If you value your health, perhaps you should stop reading now.

On second thought, don’t. Much of the lore about stressful events impairing health is certainly true, but some research is reassuring. There are some secrets about the stress-disease connection that aren’t all bad.

If you’ve read the psychological, psychiatric and medical scientific literature over the last several decades, you might already be aware of these “secrets.” If not, they’ve been nicely summarized in a paper to appear in the next issue of Annual Review of Psychology, in which Sheldon Cohen, Michael L.M. Murphy and Aric A. Prather analyze (in no particular order) what they call the “Ten surprising facts about stressful life events and disease risk.”

10. Experts disagree about what counts as stressful.

Nobody disputes that certain events inflict severe psychological (and physiological) stress. Death of a spouse, getting diagnosed with a terminal illness and (ahem) separation of children from parents are indisputably “major stressful life events.” But no clear rules have been established to define what features place an event in that category (which makes stress research complicated, with often ambiguous results).

Some researchers hold that stress magnitude hinges on how much “adaptation” is required to cope with it (which is why marriage can be considered especially stressful). A second theory gauges stressfulness as the amount of threat or harm an event poses. Some experts view stress as a mismatch between demands and resources. (If you have the resources — say, money — to address and control a demanding situation, it’s less stressful; if your boss expects you to complete a three-person project all by yourself under an impossible deadline, you’re stressed.) A fourth view regards “interruption of goals” as the prime feature of a life stress event; diabolically, one of the goals most commonly interrupted is the goal to be psychologically well.

These theories about stress-event criteria aren’t mutually exclusive, of course. “There is obvious overlap among these approaches,” Cohen and colleagues write. On the whole, though, they suggest the “threat or harm” perspective is the most commonly accepted.

life stresses

Examples of recent stressful life events (major and minor) psychologists may ask about to gauge a person’s stress level. These include everything from the death of a spouse to taking on a mortgage to getting a speeding ticket. Life events commonly included on stress questionnaires may be objectively bad or good, major or minor. They include the death of a spouse, divorce, the loss of a job — or even a big achievement. Some stress checklists focus more on traumatic events, such as assaults; others ask about events that in the last year have brought major or minor changes to everyday life, requiring adaptation or readjustments, even if they are seemingly beneficial (getting a promotion). Some important events related to illness are those that affect social status, self-esteem, identity and physical well-being. Not all are equal in effect, and there’s much variation in how people respond. (Credit: American Institute of Stress/Knowable Magazine)

9. Stress can affect a long list of diseases.

Depression and heart disease are commonly associated with stressful events, but stress’s influence extends to other health problems as well. Many, perhaps even most, diseases can be linked to life stress in some way. Stress can boost anxiety, mess with your hormones and discourage healthy practices such as exercising and eating well. At the same time stress can instigate bad behaviors such as smoking and drinking. All these responses can have negative impacts on important organs (brain, heart, liver), possibly resulting in multiple health problems either by triggering the onset or accelerating the progression of a disease. Stress events can reduce resistance to infections, and even cancer may be linked to stress. But the evidence on cancer is less clear. Stress might influence the development of cancer, but the strongest research shows that a more likely effect of stress is reducing cancer survival rates rather than initiating cancer onset.

8. Just being stressed doesn’t mean you’ll get sick.

There’s no doubt that trauma and stressful events can harm your health. But not always. “On the whole,” Cohen and colleagues write, “most people who experience stressful events do not get sick.” Experiments exposing stressed and nonstressed people to a common cold virus found that more of the stressed people caught the cold than those in the nonstressed group, but nevertheless half the members of the stressed group remained healthy. Even depression is not an inevitable effect of major life stress; some people are more resilient than others. Positive self-image and sense of control are signs of resilience; negative attitude and excessive rumination tip the scales toward depression.

7. Stressful events do not strike at random.

Apart from the relatively rare natural disasters, fatal accidents and a few other nasty exceptions, stressful events are not equal-opportunity assailants. Your personal traits and situation and the circumstances in which you live make you more or less at risk for life stress. Neighborhoods with low socioeconomic status are sites of higher-than-average levels of stressful events, and people with low personal socioeconomic status have more risk of encountering violence, death of a child and divorce. Even personality can boost your stress risk (neurotic, unconscientious and disagreeable people are more likely to get divorced, for some reason). One study found that “individuals characterized by negative attributional style” (i.e., jerks) encounter more “interpersonal conflicts,” raising the risk of stressful events. Furthermore, one stressful event — such as loss of a job — can lead to others (such as loss of income, moving or divorce).

Evidence is strong that stressful events make a disease you already have worse.

6. Disease might come before the stress.

While some evidence supports the notion that stress can initiate various diseases, this may not be the case in truly healthy people. “Rather, events may influence risk for disease by either suppressing the body’s ability to fight invading pathogens or exacerbating the progression of ongoing premorbid processes,” Cohen and colleagues write. What looks like a disease triggered by stress “may actually be stressor-triggered progression of previously unidentified disease.” So in some cases stress might not be responsible for the disease itself, just for making a previously unnoticed disease worse.

5. Some stressful events are more powerful than others.

The magnitude of a stressful event’s impact depends a lot on the nature of the stress. Most damaging, research indicates, are “experiences that threaten an individual’s sense of competence or status,” striking at a person’s “core identity.” Loss of status, losing a job and interpersonal conflict with spouses or close friends can all exacerbate health problems, from raising the risk of depression to worsening high blood pressure and reducing resistance to respiratory infection.

4. Chronic stress is worse than acute stress, usually.

It’s not necessarily obvious that chronic, long-lasting or recurrent stress is worse than one-shot stress events. It may be possible to adapt to ongoing stress — once you’re used to it, maybe it won’t bother you so much (or harm your health). On the other hand, ongoing stress may be worse for health because it’s always there, ready to attack whenever your body is vulnerable for some other reason. Overall, chronic stress is probably worse, as it may have a persistent detrimental effect on the body’s disease-fighting immune system. Acute stress, like single traumatic events, may trigger a dramatic worsening of an existing condition, such as heart disease. In that case, a sufficiently powerful stress event can induce a fatal heart attack.

3. Many stress events are worse than fewer, maybe.

Effects from stressful events may add up over time; simple checklists of how many stressful events a person has experienced over the past year show that experiencing more events predicts worse health. But it’s too complicated to say exactly why that is, or even if it is really generally true. (The checklist method of gathering data might be faulty.) In fact, if a single event is strong enough to increase health risk substantially, additional events don’t necessarily increase that risk further. For that matter, it isn’t clear how events should be counted; a divorce followed by changing residences and reduced income might count as one event or three, Cohen and colleagues point out. And it may not be the number of events but rather the number of “life domains” in which you’re experiencing stress that’s more important. (Job, home life, medical issues and financial issues all represent different domains in which stress may occur.)

Stress and sickness

One study looked at how people’s self-reported experiences of stress influenced their ability to fend off exposure to a common cold virus called rhinovirus. Those reporting more stress events were more likely to develop a biologically verified cold, but infection was not inevitable, even for the stressed-out: About half of those with stress did not get sick. (Credit: S. Cohen et al./Health Psychology 1998/Knowable Magazine)

2. The effect of stress events depends on where you are in life.

Just as some events are stressful, so are some nonevents — things that don’t happen when they’re supposed to in a typical course of life. People generally expect to graduate from school (high school or maybe college), get a job, get married, have kids and then retire. Failure to graduate, inability to get a job or rejection of marriage proposals can all be very stressful during the time of life when success at those things is expected. It may also be that different times of life are more susceptible than others to the ill effects of stress. Trauma in childhood, for instance, has been linked to higher risk of chronic diseases much later in life. Such trauma may induce long-lasting biological changes that contribute to disease in later years. In addition, “adversity during childhood may set an individual on a trajectory to being exposed to more stressors over the life course,” Cohen and coauthors write.

1. Stress doesn’t affect men and women equally.

Men and women respond differently to stress, both in their behavior and their physiological response. And women are apparently exposed more frequently to stressful experiences than men are. Partly that may be because “men tend to only report stressful events that occur directly to them” while women consider themselves stressed also when the actual event happens to someone close to them. Men and women may also differ in their vulnerability to stress-induced illness. Women seem more prone to stress-related depression, for instance.

Toll of Stress on Disease

All these “secrets” sketch a still incomplete picture of the stress-illness connection. Some things are clear: Evidence is strong that stressful events make a disease you already have worse, but the research is iffy about whether stress can make you sick to begin with. There are clues about how stressful events exacerbate disease — by altering your biology, your mood and your behavior. Chronic, ongoing stress (like working for a psychopath boss) generates a more general susceptibility to the kinds of physiological and emotional changes that promote disease, while acute immediate stressful events can be effective triggers for turning underlying conditions like cardiovascular disease into heart attacks.

Still many questions about the stress-disease relationship remain unanswered. Experts don’t even know exactly why stressful events are stressful. And evidence is meager on whether particular types of stress are especially likely to promote specific diseases. Much remains to be learned about how a stress event’s effects vary with your stage in life.

Nailing down those details remains a major research challenge. It’s not easy for researchers to answer all these questions, because the obvious experiments would be somewhat unethical. You’d have to give one big group of people a bad job with a bad boss and then make sure bad things happened to them all the time, while rigging conditions for another group to enjoy stress-free luxury. It would be kind of like The Truman Show, only with manipulating enough characters to get statistical significance.

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Sign up for the newsletter.

Knowable Magazine | Annual Reviews

CATEGORIZED UNDER: Health & Medicine

What Is CBD Oil and Why Do People Take It?

By Troy Farah | September 17, 2018 4:32 pm
cbd oil

CBD oil. (Credit: ELRoi/Shutterstock)

One of the most controversial drugs in America can’t even get you high. Derived from marijuana, CBD, or cannabidiol, could help treat a range of medical conditions, early research suggests — but its Schedule I status has made it hard to study, leaving researchers and patients in the dark.

Although it’s usually found as an oil, CBD can be infused into snacks and drinks, or come in transdermal patches, vaporizers, suppositories, and concentrates or “dabs.” It can be made synthetically, but it’s much easier to just harvest CBD from a plant like hemp or Cannabis sativa, using either ethanol or CO2 extraction. Read More

CATEGORIZED UNDER: Health & Medicine

Ancient Pets Got Proper Burials

By Bridget Alex | September 17, 2018 3:39 pm
dog burial

A dog buried at the site of Pad’ Kalasnikova in Siberia. This dog was buried in a crouched or sitting position. (Credit: Losey RJ, Garvie-Lok S, Leonard JA, Katzenberg MA, Germonpre´ M, et al. (2013) Burying Dogs in Ancient Cis-Baikal, Siberia: Temporal Trends and Relationships with Human Diet and Subsistence Practices. PLoS ONE 8(5): e63740. doi:10.1371/journal.pone.0063740)

As a kid, when my pet turtle died we had a funeral — of course — and buried him in the backyard. When the family dog passed, his remains were cremated and placed in an urn on the mantle. In today’s society, mortuary rites for animals are so common, Yelp has reviews of pet cemeteries (5 stars for Animal Aftercare. 4.5 for Pet Haven).

While online ratings are new, concern for the animal afterlife is not a modern fad.

“People were doing this thousands and thousands of years ago… it’s a long, long standing practice,” says archaeologist Robert Losey.

Archaeologists have unearthed ancient pet burials dating as far back as 14,000 years, from the dawn of animal domestication. Although interred animals are relatively rare (when considering the full archaeological record of all human societies), they occur in at least some cultures and time periods on every continent except Antarctica.

It’s fairly easy for archaeologists to identify a burial: Filled-in pits have loose, jumbled sediment, while surrounding earth is more compact and layered. Also, complete skeletons in proper alignment indicate burials; otherwise the bones would be scattered and fragmented.

The real challenge is to understand the motivations behind these burials. Ancient people may have interred animals for the same reasons we do today: because they were beloved pets, members of the family worthy of memorial. Alternatively, animals could have been sacrificed as part of a larger ritual or just buried to get rid of rotting carcasses.

Here’s how archaeologists have made cases for putative pet cemeteries.

Dogs Buried Human-style

dog burial

A canine burial at Todakta I Just below the dog were the cranium, mandible and lower leg bones of a calf. (Credit: Losey RJ, Garvie-Lok S, Leonard JA, Katzenberg MA, Germonpre´ M, et al.)

Man’s best friend was also man’s first buried pet. During the Paleolithic, or Stone Age, hunter-gatherers domesticated wolves into dogs. Although the specific time and place (or places) this happened is disputed, by 14,000 years ago a canine, shown to be a domesticated dog by anatomical features and ancient DNA, was interred at the site of Bonn-Oberkassel, Germany.  The approximately 6-month-old pup was buried with a middle aged man, twenty-something woman and grave goods including a bone hairpin, elk sculpture and the penis bone of a bear. Across the Atlantic, over 200 dog burials more than 3,000 years old have been discovered in North America. The oldest are three dogs found in shallow pits at the Koster family farm in Illinois, dating to 8,500 years ago.

Deliberate burial of special dogs was particularly common between 7,000-8,000 years ago around Lake Baikal in eastern Russia. During this period forager people began burying their dead in cemeteries, and gave the same treatment to some canines.

“It’s my hypothesis that people really saw those particular dogs as being spiritually the same as themselves. That they were an animal with a soul, an animal with an afterlife,” says Losey, a professor at the University of Alberta, Canada who researches ancient human-dog relationships.

The evidence to support his claim: First, dogs were buried amongst humans in designated areas that seem to have been cemeteries. According to Losey, people would have had to “travel with the dog’s body and take it to those locations. It’s not just putting it in a hole right next to where you’re living.” In some cases earlier human burials were disturbed to make way for more recently deceased canines.

Next, the dogs likely died of natural causes. Some are old, and they don’t exhibit cut marks or other indicators of sacrifice. Finally, these animals were laid to rest with the same items buried with people, such as a spoon and a deer tooth necklace. “We see people wearing essentially the exact same necklace in human graves in that same area… They literally seem to be treating that dog just like a human,” Losey says.

Resting by the Red Sea

Another convincing case comes from the port town of Berenike on the shores of the Red Sea, in southern Egypt. Between 75-150 A.D. people living there buried animals in a specific area on the outskirts of town, which, according to a 2016 study, was a cemetery of house pets.

A selection of cat burials from a cemetery at Berenike in Egypt. (Credit: M. Osypinska)

A selection of cat burials from a cemetery at Berenike in Egypt. (Credit: M. Osypinska)

In ancient Egypt, animals were commonly sacrificed and mummified to accompany people to the grave. But the Berenike animals were treated differently. They were not mummified or placed in human tombs. Rather, they were buried in a cemetery, which has yielded nearly 100 complete animals including 86 domestic cats, 9 dogs and 4 monkeys. A few wore iron collars and two graves were double burials, containing both a cat and kitten.

The largest pet cemetery or not a pet cemetery

The jury’s out on the largest concentration of ancient animals: The site of Ashkelon on Israel’s Mediterranean coast contains somewhere between 500 to 1500 dogs buried over the course of a century, beginning about 2,500 years ago.

The exact count is unclear because many skeletons were jumbled and incomplete, and others may have been eroded into the sea. But even the lower estimates indicate “an extraordinary number of burials,” says Paula Wapnish-Hesse, an archaeologist who studied the remains.

When Persian and early Greek cultures inhabited the city, dead canines of all ages were buried in shallow pits under streets and living quarters. Aside from being lain on their sides with tails tucked between their legs, the dogs showed no signs of funerary treatment. “There were never any grave goods, never any markers, never anything to indicate to us these burials were special outside of the burials themselves,” Wapnish-Hesse says.

The dogs were mostly puppies and old individuals — what you would expect from death by natural causes. There’s no evidence they were intentionally killed, at least by methods that leave marks on bones. Based on the shape and size of the skeletons, Wapnish-Hesse believes they were free roaming street mutts, rather than kept pets. And she does not consider the burials a cemetery per se, because they are found throughout a neighborhood, rather than in a separate area.

So perhaps the dogs were not pets, and graves did not constitute a cemetery. The question, though, remains, why were they buried in such abundance?

Other researchers have suggested the dogs were interred as part of a religious cult or after a catastrophe, like an epidemic, but Wapnish-Hesse does not find these explanations convincing. After more than three decades researching these dogs, she says, “We’ve never answered the question of why they were burying them.”

Some cases remain a mystery.

CATEGORIZED UNDER: Living World
MORE ABOUT: animals, archaeology

How Dance Brings the Mysteries of the Universe to Life

By Paul M. Sutter | September 14, 2018 3:36 pm
Cosmology is the story of the fundamental particles, forces, and energies that shape and govern our universe. And that story is one of rhythm and motion. (Credit: Paul M. Sutter/Youtube)

Cosmology is the story of the fundamental particles, forces, and energies that shape and govern our universe. And that story is one of rhythm and motion. (Credit: Paul M. Sutter/Youtube)

For millennia, cosmological and religious systems of thought were intertwined—and usually indistinguishable. European artwork of, say, the arrangements of planets and stars often went hand-in-hand with theological guides, and not a little bit of moralizing. But then Copernicus, Brahe, Kepler, and Galileo came along, and this connection fell apart. The result is a modern cosmological sense that is properly scientific, rooted in data and mathematics—but relatively inaccessible to non-experts. Read More

CATEGORIZED UNDER: Space & Physics
MORE ABOUT: cosmology

How Galveston Survived The Deadliest Hurricane in American History

By Daniel Pendick | September 13, 2018 5:30 pm
hurricane galveston texas deadliest natural disaster U.S. history collage

(Credit: Extreme Weather/Kellie Jaeger)

The citizens of Galveston, Texas, had achieved unprecedented economic prosperity. The city, built on a shallow, sandy island 2 miles (1.2 kilometers) offshore, had become the state’s leading center of trade, exporting some 1.7 million bales of cotton annually. At the turn of the century, the city stood in the doorway to an even more prosperous future.

This all changed September 8, 1900, when an unusually high tide and long, rolling sea swells gave way to a massive landfalling hurricane. During the night, the storm destroyed some 3,600 buildings and killed at least 6,000 residents out of a total population of about 38,000. Some estimates put the death toll as high as 10,000. The storm remains the most deadly natural disaster in U.S. history.

Even after a century of retelling, the tale of the great Galveston hurricane still chills us with the scale of its devastation and the sudden, anonymous loss of life. Today, 10 miles (16 km) of massive concrete seawall stands between the city of Galveston and the sea, reminding all behind it of the fantastically destructive potential of tropical storms.

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CATEGORIZED UNDER: Environment, Top Posts
MORE ABOUT: natural disasters

In the Face of High Costs, DIYers Hope to Brew Their Own Insulin

biomanufacturing

Miniature biomanufacturing kits like this prototype could revolutionize the pharmaceutical industry. (Credit: Amino Labs, CC BY-ND)

Soon after Federick Banting discovered that insulin could be used to treat diabetes in 1921, he sold the patent to the University of Toronto for about a dollar. Banting received the Nobel prize because his discovery meant a life-saving drug could become widely available. Nearly a century later, an American with diabetes can pay as much as US$400 per month for insulin, driving some uninsured patients to desperate and dangerous measures. Clearly, something went wrong.

Our lab studies biosecurity, so when we heard that a group of do-it-yourself biologists was working to solve the insulin affordability problem by figuring out how to manufacture insulin patent-free, we got to know them. After digging into the insulin affordability issue, we argue that what’s keeping insulin expensive is not patents – it’s regulations. By operating in a regulatory blind spot, DIYers could upset the status quo for drug production.

Patents don’t make insulin expensive

Discovering and developing drugs is expensive. Patents help drug companies recoup the costs from their investments by granting them a monopoly for a limited time. Once the patent expires, competing companies can begin producing generics: off-brand versions of a patented drug. This healthy competition drives prices down.

So why, with the original patent long-expired, is there still no affordable generic insulin?

The insulin for purchase today is not the same insulin used to treat diabetic patients nearly 100 years ago. That insulin came primarily from animals. Today, insulin is brewed up by microbes that have been genetically engineered with the gene for human insulin.

Insulin pumps are one of the newer ways to administer the drug to diabetic patients. (Credit: Click and Photo/Shutterstock)

Insulin pumps are one of the newer ways to administer the drug to diabetic patients. (Credit: Click and Photo/Shutterstock)

And insulin is seldom injected with an old-fashioned syringe and needle anymore. Now there are insulin pens, pumps, test strips and other devices that improve the quality of life for diabetic patients. Pharmaceutical companies have also modified the chemical formula to produce faster-acting or longer-lasting insulins.

With each of these inventions came a new patent.

But the benefits of these “improved” insulins are debatable, and there’s nothing preventing competing companies from selling older, long off-patent versions of insulin. So what’s the holdup?

Regulations keep insulin expensive

Insulin is a biologic drug, which means it’s produced by a living organism, not a chemical reaction. This process, called biomanufacturing, is more inconsistent than chemical synthesis of non-biologic drugs like aspirin.

Making reliable biologic drugs is a little like winemaking. Even though the winemaker carefully follows a well-established process, minute differences will affect the final product. It’s always wine, but some vintages are better than others and tasting the wine is the only way to evaluate the final product.

So if a new company wants to make insulin, that insulin has to be tested on patients in expensive clinical trials. Bringing a biologic drug to market can cost as much as $250 million. No company can afford that lump if it can’t file for a patent to recoup the investments.

 

insulin

Could big pharma eventually be cut out of the process by home brewers cooking up their own medications? (Credit: Sanofi Pasteur, CC BY-NC-ND)

That’s why there’s only one “generic” insulin available so far. It’s made by a company that was already a major player in the insulin market, and it’s only 15 percent cheaper than the patented version. By comparison, most non-biologic generic drugs cost 80 percent less than the original.

Obviously, regulations are important for keeping insulin safe, but at what cost? Ten percent of people living with diabetes in the U.S. are uninsured, and there are nearly 10,000 crowdfunding campaigns related to insulin on the site GoFundMe alone. Stories about diabetic patients ending up hospitalized or worse because they tried to ration their insulin are all-too common.

Democratizing Insulin Production

Some people are taking matters into their own hands, tinkering to meet their medical needs. In 2015, patients and hobby scientists launched an initiative known as the Open Insulin Project.

As in winemaking, the specific know-how required for insulin production is a guarded secret. The goal of the Open Insulin Project is to figure out a patent-free method and release the information, so that competing companies can manufacture “generic” insulin.

Given the cost of regulatory approval, it is more likely that the project could enable patients to “home brew” their own diabetic treatments. There is currently no structure for regulating drugs that are not produced commercially. One report estimates that as many as 2,000 patients have already reverse engineered their own insulin pumps and electronic monitoring systems. The insulin itself could be next.

Is it possible to make biologic drugs like insulin more affordable without compromising safety? One suggestion that has been gaining steam is to scale down biomanufacturing. Right now, biologic medicines like insulin are cooked up in giant batches. Ensuring that those batches are consistent and free of contamination is a major challenge.

Think about the meat department in your grocery store. Many big-box stores stock hamburger that was ground in a central processing plant and then distributed. If an E. coli outbreak occurs in the plant, it’s going to spread to all of the stores downstream, potentially infecting hundreds or thousands of people.

insulin

Industrial-scale production – whether of hamburger or drugs – makes it harder to zero in on the source of problems when they occur. (Credit: David Tadevosian/Shutterstock.com)

The meat is also exposed to more potential contamination events through storage and transport. And, if contaminated meat is identified in one store, it won’t be immediately clear whether or not all the others are safe.

Now, consider a small local butcher who grinds meat in-house. Any safety risk is going to be isolated to the customers of that one store and the source will be obvious.

Similarly, producing medications in smaller batches reduces the potential impact of any one safety event. Pharmacy compounding provides an example. In compounding, drugs are specially mixed or produced for a very small number of patients. Compounded medications are not subject to clinical trials.

If insulin were made in smaller batches, manufacturers might be able to forego clinical trials and use simpler and less expensive tests to confirm that each batch of insulin produced is safe and comparable to previously approved insulins. It would be like using chemical tests to identify important flavor compounds in two vintages of wine instead of organizing taste tests. This model could also apply to other expensive biologic drugs such as those that treat cancer, HIV and rheumatoid arthritis.

The technology necessary for small-batch insulin production already exists. Future research could help automate and streamline small batch medicine production in order to minimize safety risks.

The Future of Medicine

The pharmaceutical industry is ripe for disruption. In the coming decades, drugs might be produced in very different settings. Hospitals have already begun plans to make their own medicines. DIY biologists could provide patients with the knowledge needed to produce for themselves the drugs their lives depend on.

As the industry and regulatory agencies gain more experience with biologic drugs, it is also possible regulations will ease up, lowering the cost of approval. This would enable the emergence of small-scale drug manufacturers that could provide off-brand drugs at a lower cost.

One thing is certain, the future of medicine will not be “business as usual.” Biomanufacturing technologies will continue to evolve. These changes could enable decentralized production of life-saving drugs. How the regulatory system and pharmaceutical industry will adjust to that future is yet to be determined.The Conversation

 

Jenna E. Gallegos, Postdoctoral Researcher in Chemical and Biological Engineering, Colorado State University and Jean Peccoud, Professor, Abell Chair in Synthetic Biology, Colorado State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

CATEGORIZED UNDER: Health & Medicine, Technology

A Simple Blood Test Could Tell You the Time Inside Your Body

By Rosemary Braun, Northwestern University | September 12, 2018 2:40 pm
Circadian Rhythm

(Credit: BlurryMe/Shutterstock)

In life, timing is everything.

Your body’s internal clock – the circadian rhythm – regulates an enormous variety of processes: when you sleep and wake, when you’re hungry, when you’re most productive. Given its palpable effect on so much of our lives, it’s not surprising that it has an enormous impact on our health as well. Researchers have linked circadian health to the risk of diabetes, cardiovascular disease and neurodegeneration. It’s also known that the timing of meals and medicines can influence how they’re metabolized.

The ability to measure one’s internal clock is vital to improving health and personalizing medicine. It could be used to predict who is at risk for disease and track recovery from injuries. It can also be used to time the delivery of chemotherapy and blood pressure and other drugs so that they have the optimum effect at lower doses, minimizing the risk of side effects.

However, reading one’s internal clock precisely enough remains a major challenge in sleep and circadian health. The current approach requires taking hourly samples of blood melatonin – the hormone that controls sleep – during day and night, which is expensive and extremely burdensome for the patient. This makes it impossible to incorporate into routine clinical evaluations.

My colleagues and I wanted to obtain precise measurements of internal time without the need for burdensome serial sampling. I’m a computational biologist with a passion for using mathematical and computational algorithms to make sense of complex data. My collaborators, Phyllis Zee and Ravi Allada, are world-renowned experts in sleep medicine and circadian biology. Working together, we designed a simple blood test to read a person’s internal clock.

Listening to the Music of Cells

The circadian rhythm is present in every single cell of your body, guided by the central clock that resides in the suprachiasmatic nucleus region of the brain. Like the secondary clocks in an old factory, these so-called “peripheral” clocks are synchronized to the master clock in your brain, but also tick forward on their owneven in petri dishes!

Your cells keep time through a network of core clock genes that interact in a feedback loop: When one gene turns on, its activity causes another molecule to turn it back down, and this competition results in an ebb and flow of gene activation within a 24-hour cycle. These genes in turn regulate the activity of other genes, which also oscillate over the course of the day. This mechanism of periodic gene activation orchestrates biological processes across cells and tissues, allowing them to take place in synchrony at specific times of day.

The circadian rhythm orchestrates many biological processes, including digestion, immune function and blood pressure, all of which rise and fall at specific times of day. Misregulation of the circadian rhythm can have adverse effects on metabolism, cognitive function and cardiovascular health. (Credsit: Yassine Mrabet, CC BY-SA)

The circadian rhythm orchestrates many biological processes, including digestion, immune function and blood pressure, all of which rise and fall at specific times of day. Misregulation of the circadian rhythm can have adverse effects on metabolism, cognitive function and cardiovascular health. (Credit: Yassine Mrabet, CC BY-SA)

The discovery of the core clock genes is so fundamental to our understanding of how biological functions are orchestrated that it was recognized by the Nobel Committee last year. Jeffrey C. Hall, Michael Rosbash and Michael W. Young together won the 2017 Nobel Prize in Physiology or Medicine “for their discoveries of molecular mechanisms controlling the circadian rhythm.” Other researchers have noted that as many as 40 percent of all other genes respond to the circadian rhythm, changing their activity over the course of the day as well.

This gave us an idea: Perhaps we could use the activity levels of a set of genes in the blood to deduce a person’s internal time – the time your body thinks it is, regardless of what the clock on the wall says. Many of us have had the experience of feeling “out of sync” with our environments – of feeling like it’s 5:00 a.m. even though our alarm insists it’s already 7:00. That can be a result of our activities being out of sync with our internal clock – the clock on the wall isn’t always a good indication of what time it is for you personally. Knowing what a profound impact one’s internal clock can have on biology and health, we were inspired to try to gauge gene activity to measure the precise internal time in an individual’s body. We developed TimeSignature: a sophisticated computational algorithm that could measure a person’s internal clock from gene expression using two simple blood draws.

Designing A Robust Test

To achieve our goals, TimeSignature had to be easy (measuring a minimal number of genes in just a couple blood draws), highly accurate and – most importantly – robust. That is, it should provide just as accurate a measure of your intrinsic physiological time regardless of whether you’d gotten a good night’s sleep, recently returned from an overseas vacation or were up all night with a new baby. And it needed to work not just in our labs but in labs across the country and around the world.

To develop the gene signature biomarker, we collected tens of thousands of measurements every two hours from a group of healthy adult volunteers. These measurements indicated how active each gene was in the blood of each person during the course of the day. We also used published data from three other studies that had collected similar measurements. We then developed a new machine learning algorithm, called TimeSignature, that could computationally search through this data to pull out a small set of biomarkers that would reveal the time of day. A set of 41 genes was identified as being the best markers.

Surprisingly, not all the TimeSignature genes are part of the known “core clock” circuit – many of them are genes for other biological functions, such as your immune system, that are driven by the clock to fluctuate over the day. This underscores how important circadian control is – its effect on other biological processes is so strong that we can use those processes to monitor the clock!

Many genes peak in activity at different times of day. This set of 41 genes, each shown as a different color, shows a robust wave of circadian expression. By monitoring the level of each gene relative to the others, the TimeSignature algorithm learns to ‘read’ your body’s internal clock. (Credit: Rosemary Braun)

Many genes peak in activity at different times of day. This set of 41 genes, each shown as a different color, shows a robust wave of circadian expression. By monitoring the level of each gene relative to the others, the TimeSignature algorithm learns to ‘read’ your body’s internal clock. (Credit: Rosemary Braun)

Using data from a small subset of the patients from one of the public studies, we trained the TimeSignature machine to predict the time of day based on the activity of those 41 genes. (Data from the other patients was kept separate for testing our method.) Based on the training data, TimeSignature was able to “learn” how different patterns of gene activity correlate with different times of day. Having learned those patterns, TimeSignature can then analyze the activity of these genes in combination to work out the time that your body thinks it is. For example, although it might be 7:00 a.m. outside, the gene activity in your blood might correspond to the 5:00 a.m. pattern, indicating that it’s still 5:00 a.m. in your body.

We then tested our TimeSignature algorithm by applying it to the remaining data, and demonstrated that it was highly accurate: We were able to deduce a person’s internal time to within 1.5 hours. We also demonstrated our algorithm works on data collected in different labs around the world, suggesting it could be easily adopted. We were also able to demonstrate that our TimeSignature test could detect a person’s intrinsic circadian rhythm with high accuracy, even if they were sleep-deprived or jet-lagged.

Harmonizing Health

By making circadian rhythms easy to measure, TimeSignature opens up a wide range of possibilities for integrating time into personalized medicine. Although the importance of circadian rhythms to health has been noted, we have really only scratched the surface when it comes to understanding how they work. With TimeSignature, researchers can now easily include highly accurate measures of internal time in their studies, incorporating this vital measurement using just two simple blood draws. TimeSignature enables scientists to investigate how the physiological clock impacts the risk of various diseases, the efficacy of new drugs, the best times to study or exercise and more.

Of course, there’s still a lot of work to be done. While we know that circadian misalignment is a risk factor for disease, we don’t yet know how much misalignment is bad for you. TimeSignature enables further research to quantify the precise relationships between circadian rhythms and disease. By comparing the TimeSignatures of people with and without disease, we can investigate how a disrupted clock correlates with disease and predict who is at risk.

Down the road, we envision that TimeSignature will make its way into your doctor’s office, where your circadian health could be monitored just as quickly, easily and accurately as a cholesterol test. Many drugs, for example, have optimal times for dosing, but the best time for you to take your blood pressure medicine or chemotherapy may differ from somebody else.

Previously there was no clinically feasible way to measure this, but TimeSignature makes it possible for your doctor to do a simple blood test, analyze the activity of 41 genes and recommend the time that would give you the most effective benefits. We also know that circadian misalignment – when your body’s clock is out of sync with the external time – is a treatable risk factor for cognitive decline; with TimeSignature, we could predict who is at risk, and potentially intervene to align their clocks.The Conversation

 

Rosemary Braun, Assistant Professor of Biostatistics, Preventive Medicine and Engineering Sciences and Applied Mathematics, Northwestern University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

CATEGORIZED UNDER: Health & Medicine
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Pigeon Poop And Strange Static: How We Proved The Big Bang

By Korey Haynes | September 11, 2018 3:00 pm
big bang cosmos explosion creation

Our universe was born in the Big Bang. But confirmation of this incredible theory came as a surprise to its discoverers. (Credit: Astronomy/Roen Kelly)

Sometimes scientific discoveries are made in world-class laboratories, when brilliant scientists come together to prove a wonderful idea true with fresh experiments. And sometimes, the secrets of the universe are hidden under a pile of pigeon poop.

And so it happened that the first observation of the crackle of nascent energy left over from the Big Bang was not some long-sought holy grail of science. Instead, it was an annoying bit of static mistaken for bird droppings. Such is the lofty origin of the Cosmic Microwave Background energy, the Big Bang’s still-reverberating echo. Read More

CATEGORIZED UNDER: Space & Physics, Top Posts
MORE ABOUT: cosmology
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