Immunotherapy, the hottest field in cancer research, seeks to supercharge the body’s natural defenses against deadly tumors. Two different approaches are driving the buzz, and one of them got a big boost in August when the Food and Drug Administration approved a “living drug” to treat acute lymphoblastic leukemia (ALL) in children and young adults who’ve stopped responding to chemotherapy. The product, dubbed tisagenlecleucel (pronounced tis-a-gen-LEK-loo-sell), is the first gene therapy of any kind to be approved in the United States.
More specifically, tisagenlecleucel is a type of chimeric antigen receptor T cell (CAR-T) therapy, a technique pioneered by immunologist Carl June and colleagues at the University of Pennsylvania. First, an inactivated form of HIV, the virus that causes AIDS, is packed with snippets of custom-designed DNA. Next, T cells — the immune system’s foot soldiers — are harvested from the patient’s blood and infected with the virus, which rewrites their genetic code to recognize and destroy cancer cells. Once the engineered T cells have multiplied, they’re infused into the patient, where they go to war.
Like the other leading-edge immunotherapy technique — a class of drugs known as checkpoint inhibitors — CAR-T has shown unparalleled potency against cancers that once meant almost certain death. In clinical trials that June’s team initially launched in 2010, over 80 percent of children with recalcitrant ALL went into remission. The therapy was also effective for several other types of blood cancer. “It was really extraordinary,” says David Porter, director of Penn’s blood and bone marrow transplant program. “These were patients for whom nothing else had worked.”
The pharma giant Novartis, which agreed to fund further research in exchange for ownership of the results, will bring tisagenlecleucel to market under the trade name Kymriah. In October, the FDA approved a second CAR-T therapy, axicabtagene ciloleucel (developed by Kite Pharma and dubbed Yescarta), for patients with relapsed or refractory non-Hodgkin lymphoma. Rival companies are racing to develop similar products.
CAR-T has its hazards. Many patients develop severe whole-body inflammation that can last for days. (Trials of another CAR-T therapy, by Juno Therapeutics, were halted in 2016 after five patients died from brain swelling.) But if the one-time procedure is successful, they’re spared the months or years of side effects that often accompany chemotherapy. The treatment can also eliminate the need for a bone marrow transplant, which carries a far greater risk of death.
Researchers are now testing CAR-T therapies against other cancers, including pancreatic and the deadly brain cancer glioblastoma. They’re trying combinations of CAR-T with other treatments, and working to make the technique safe enough to use as an early stage therapy rather than a last resort. “We’re at a tipping point,” says June. “Someday, our current ways of treating cancer will be looked on as barbaric.”
A Functioning Fake Womb
In a potential breakthrough for human babies born prematurely, scientists announced this year they’d successfully removed lamb fetuses from their mother’s wombs and raised them into healthy sheep. Their survival comes thanks to an artificial placenta — called a BioBag — created by researchers at the Children’s Hospital of Philadelphia.
The fake womb consists of a clear plastic bag filled with electrolytes. The lamb’s umbilical cord pulls in nutrients, and its heart pumps blood through an external oxygenator. The success caps a decades-long effort toward a working artificial placenta.
The BioBag could improve human infant mortality rates and lower the chances of a premature baby developing lung problems or cognitive disorders. But there are still challenges to scaling the device for human babies, which are much smaller than lambs. The scientists are also refining the electrolyte mix and studying how to connect human umbilical cords. They expect human trials in three to five years.
Are Airplanes Really a Microbial Playground?
(credit: Matej Kastelic/Shutterstock)
Crying babies, chronic snorers — they’re the usual targets of our displeasure when we fly. But, the real villains of the sky might be germs.
Flyers are packed into a cramped metal tube for hours on end where movement is limited. It seems like a microbe’s playground. But research on the topic is a bit inconclusive, despite worrying cases involving SARS and an aggressive type of influenza. Studies suggest that caution is warranted, but researchers have so far had trouble saying exactly how air travel affects disease transmission. At the moment, public health guidelines state that anyone within two rows of an infected individual could be at risk, although other studies suggest otherwise.
Fly the Germy Skies?
Most recently, a team of researchers from Emory University and the Georgia Institute of Technology—funded by Boeing—conducted their own boots-on-the-plane study of infectious disease transmission aboard commercial aircraft. On 10 flights from Atlanta to the West Coast and back, they took swabbed samples of various surfaces and recorded how often passengers and crew members moved around. Pairing the data with models of air movement and microbe dispersion gave them an idea of just how far a potential pathogen might travel.
Their findings, published Monday in the Proceedings of the National Academy of Sciences, indicate that a sick neighbor is certainly something to worry about when flying. Those within a row of a sick person and within two seats to either side had an 80 percent chance of getting sick in their model, which used a fairly high assumed rate of transmission. The risk of infection drops off sharply after that, though. Those more than a few seats away had little to worry about. That’s even closer than the two row-minimum suggested by public health agencies.
A sick crew member, however, posed a little more danger. They move around the cabin more and have more contact with passengers, so the risk of transmission increases. Just one sick flight attendant infected almost five people on average in the researcher’s model. That’s a big number, but it does make some assumptions, the biggest of which is that sick crew members even come in to work. It’s more likely that they would just stay home.
Back Down to Earth
There are difficulties in modeling disease transmission rates on such a small scale like this, and this particular study wasn’t very big. They looked at just ten flights and the longest was only a bit over five hours. International flights can go for fifteen hours or longer, and involve much more movement on the part of passengers, something that could increase the risk of infection.
Their model also only looked at microbes that could be carried by droplets, which don’t travel very far. Viruses spread by smaller aerosol particles could circulate much longer and farther. This includes diseases like tuberculosis and measles. Air travel also involves extended periods of contact with other passengers at boarding gates, security checkpoints and elsewhere, and this could affect rates of transmission as well.
It’s also worth pointing out that we encounter similarly confined, crowded spaces during the course of our daily lives. Buses, movie theaters, workplaces and more pose the same sort of risks, though the authors don’t provide any measure of comparison here. Airplanes, do, however, travel long distances very quickly, something that can turn a local epidemic into a pandemic within days. That hasn’t happened yet, though scattered cases involving SARS and Ebola, among other diseases, have stoked worry.
Ultimately, a review of the scientific literature on the topic found moderate evidence that airplane cabins helped to spread influenza. This latest study doesn’t really change that, though it does reveal the danger that an infected crew member poses.
So, for flight attendants — and for all of us, really — if you’re sick, just stay home.
This Optical Illusion Could Help to Diagnose Autism
(Credit: Turi et al., eLife, 7:e32399, 2018)
You probably see a cylinder when you look at the illusion above. But how our brains translate two intersecting sheets of moving dots into a 3D image reveals telling differences in visual perception that could perhaps help diagnose autism spectrum disorder.
It’s been shown that people with autism are better at picking out the details of complex images, at the cost of understanding what all those details mean when put together. This can mean seeing the trees, but not the forest, or the strokes of a paintbrush but not the subject of a painting. It’s a trait that’s supported by years of research, but it can be difficult to assess exactly how an individual perceives an image just by asking them questions. The cylinder illusion, applied here by a group of researchers from Italy and Australia, offers a more reliable way of telling what a subject is seeing.
Grow and Shrink
It comes down to the pupils. Our pupils are responsive to light, but they also widen and constrict in response to the notion of brightness or darkness, even if light levels remains the same. Here, the white dots are perceived as brighter, and the black dots as darker, and our pupils respond accordingly. It’s a way for the researchers to tell what parts of the illusion study participants are focusing on. They published their findings in March in the journal eLife.
The illusion itself relies on our brain’s assumptions of how a rotating cylinder behaves. The dots cross over each other just as marks on a transparent cylinder would, they even slow down at the edges to give the impression of curvature. The two colors give imply depth, though a closer look reveals that neither actually seems to be in front — some white dots cross over black dots, and some black over white. It allows us to reverse the cylinder’s apparent direction by focusing on one color over the other. Importantly for the researchers, the illusion is composed of both discrete details in the form of the dots, and a holistic image, in the form of the cylinder. Having both allows them to see which component their study participants favor.
They asked 50 adults, none of whom had autism, to watch the illusion, and while they were doing so, the researchers were watching them — their pupils at least. They wanted to see whether their pupils changed size rapidly throughout the experiment or stayed the same. If they changed size, it indicated that the participants were switching focus back and forth between the white and the black dots — i.e. they were focused on the details of the images. If their pupils stayed about the same, they were likely focused on both at once, meaning they saw the image as a whole. Crucially, both methods of perception produce the same cylinder illusion. But how they do so differs.
Before taking the test, the subjects all took the autism spectrum quotient, a self-reported questionnaire that measures various behaviors associated with autism. Higher scores indicate more correlation with autistic traits. When they paired scores on the test with measurements of pupil dilation and contraction, they saw that they were clearly related. Those whose pupils changed with greater frequency also reported more autistic traits. It was another validation of the theory that those with autism tend to focus on specific details as opposed to entire images.
Remember, none of the subjects had been formally diagnosed with autism, and none of their scores on the test indicated that they should be. In fact, the mean value of the test scores was about average. But, autism is a spectrum, and we all lie on it somewhere. Even in nominally average individuals, a tendency toward autistic traits was associated with a propensity to focus on details over holistic images. It adds further evidence that autism alters how we process visual information, and hints that it extends beyond those diagnosed with the disorder. The researchers say measuring changes in pupil size could potentially serve as another means of diagnosing autism.
The results are still a bit preliminary, so it’s too soon to draw definite conclusions based on their work. The surveys were all self-reported, for one thing, which can skew results a bit. And the study involved participants without autism, meaning that we’d need to see similar work in those with autism spectrum disorder to back up their findings.
But, with more research, the authors think their research could be used to perform assessments of those with autism who are non-verbal, which can happen in children. It would give doctors and teachers a way to get information from those who may not be able to communicate it themselves.
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