A Flu Virus That Killed Millions In 1918 Has Now Been Recreated


Wikimedia Commons

Spanish flu

Scientists have recreated a nearly exact replicate of the deadly flu virus that killed an estimated 50 million in the 1918 Spanish flu pandemic.

But don’t worry, they say it’s totally safe.

Researchers at the University of Wisconsin-Madison reverse engineered an influenza virus from a similar one found in birds, combining several strains to create one that is nearly identical to the one that caused the 1918 outbreak. They then mutated the genes to make it airborne, and to study how it spreads between animals.

“Our research indicates the risks inherent in circulating avian influenza viruses,” Yoshihiro Kawaoka, the scientist who led the research team, told VICE News. “Continued surveillance of avian influenza viruses — and not only viruses that we know pose risks for humans, such as H5N1 and H7N9 influenza viruses, and attention to pandemic preparedness measures is important.”

According to the statement summarizing the project published this week, the “analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future.”

In other words, a common avian flu virus that has been circulating in wild ducks is pretty much the exact same one that infected humans a century ago. And now is in a lab.

The research was funded by the National Institute of Health as a way to find out more about similar virus’ and their transmissibility from animals to humans. It was done in a lab that complied with full safety and security regulations, said Carole Heilman, director of the Division of Microbiology and Infectious Diseases, at National Institute of Allergy and Infectious Diseases (NIAD), a division of NIH.

“It was an question of risk versus benefit,” Heilman told VICE News. “We determined that the risk benefit ratio was adequate if we had this type of safety regulations.”

But many scientists disagree and have condemned research that recreates virus’ such this, stating that if released accidentally, a virus could spread to humans and cause a pandemic. Marc Lipsitch, an epidemiologist at Harvard, has criticized research such as Kawaoka’s as unnecessarily risky.

“There is a quantifiable possibility that these novel pathogens could be accidentally or deliberately released. Exacerbating the immunological vulnerability of human populations to PPPs is the potential for rapid global dissemination via ever-increasing human mobility,” Lipsitch said in a paper about experiments with transmissible virus’. “The dangers are not just hypothetical.”

Lipsitch points out that many of the H1N1 flu outbreaks that have occurred between 1977 and 2009 were a result of a lab accident.

Kawaoka disagrees, saying, “We maintain that it is better to know as much as possible about the risk posed by these viruses so we may be able to identify the risk when viruses with pandemic potential emerge, and have effective countermeasures on-hand or ready for development.”

This article originally appeared at VICE News. Check them out on YouTube, Facebook, and Instagram. Copyright 2014. Follow VICE News on Twitter.

GM Mosquitos Could Eradicate Wild Populations By Only Producing Male Offspring


photo credit: James D. Gathany/CDC

Over 200 million people are infected by malaria each year, and the majority of the 627,000 deaths per year are children younger than five. The disease is carried by mosquitos who act as vectors for the parasite. It’s only transmitted to humans by female mosquitoes, as they’re the only ones who bite. A team of researchers led by Andrea Crisanti of the Imperial College London managed to genetically modify mosquitos to produce 95% male offspring, eliminating mosquito populations along with the risk of malaria. The results of the study were published in Nature Communications.

In most species of mosquito, the females need a blood meal in order to acquire the nutrients to create viable eggs. When she does, she can lay about 200 eggs at a time in water, and up to 3,000 eggs over the course of her lifetime. About half of those offspring will be daughters, many of whom will live long enough to produce that amount of offspring also. For humans living near mosquitos carrying the parasite that causes malaria, those numbers of female mosquitos present a very real threat.

But what if the numbers could be skewed so that the sex ratio favors males, who are harmless to humans? This is exactly what Crisanti’s team set out to do with Anopheles gambiae, a species of mosquito endemic to sub-Saharan Africa, where 95% of malaria deaths occur. The researchers modified the males with the enzyme I-Ppol, which excises the X chromosome during spermatogenesis. This renders sperm that would produce daughters to be non-functional, while the sperm that will create male offspring are unaffected. As a result, about 95% of the resulting offspring are male.

Next, modified males were introduced to five caged wild-type populations. As the males mated with the females, they passed along the same mutation until it dominated the population. For four of the five populations, it took only six generations for the mosquitos to die out due to a lack of females.

“What is most promising about our results is that they are self-sustaining,” co-author Nikolai Windbichler said in a press release. “Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us.”

This study was the first to successfully manipulate mosquito sex ratios, and it was done in a big way. The researchers hope that this information will be used to develop genetic mutations to be used in the wild, bringing large populations of mosquitos to their knees.

“The research is still in its early days, but I am really hopeful that this new approach could ultimately lead to a cheap and effective way to eliminate malaria from entire regions,” added lead author Roberto Galizi. “Our goal is to enable people to live freely without the threat of this deadly disease.”

Of course, while eradicating the mosquitos would be fantastic for eliminating the threat of malaria, what other affects would it have? Wouldn’t there be harsh consequences for the ecosystem? After all, mosquitos have been on the planet for about 100 million years and represent 3,500 species. As it turns out, mosquitos wouldn’t really be missed if they were to disappear. While mosquitos can act as pollinators as well as a food source for other animals, their absence would be merely a temporary setback before another species filled the niche. Of course, there is a gamble in assuming the replacement organism would be harmless.

“Malaria is debilitating and often fatal and we need to find new ways of tackling it. We think our innovative approach is a huge step forward. For the very first time, we have been able to inhibit the production of female offspring in the laboratory and this provides a new means to eliminate the disease,” Crisanti explained.

Each year, sub-Saharan Africa loses about $12 billion in economic productivity due to malarial infections. Considering developed areas in these countries have per capita incomes of about US$1500, this would have very real implications for the quality of life for people in those areas. Eliminating that disease would also allow doctors and hospitals to address other health concerns, and the environment would likely benefit from not having to use insecticides.

 

REFERENCE:

Galizi, R. et al. 2014. ‘A synthetic sex ratio distortion system for the control of the human malaria mosquito’. Nature Communications, 10 June 2014.

Hand Transplantations and Bionic Prostheses


Recently I attended an international medical student congress, Medical Student Journal Club – Pro et Contra, which took place on 23. and 24. May 2014 in Ljubljana, Slovenia.

It was a great congress, with a lot of interesting debates preesented by great speakers.

Myself, I have also registred as an active speaker, together with a colleague of mine, Barbara Šijaković. We debated on topic “Reconstructive surgery should focus on development of cadaver body parts transplantation rather than bionic prosthesis implantation“.

Below is a transcript of our debate.

And just for elaboration, the whole keynote was actually made with only videos tu support theses.


Reconstructive surgery should focus on development of cadaver body parts transplantation rather than bionic prosthesis implantation

Luka: Hello, it’s me up here again. So, I thought I could start with an old Marx brothers joke. No wonder it looks like the same room, because it is the same room. Ok, it doesnt go…

Well, since it’s Saturday afternoon and this is the last debate of this congress, we’ll try to be as interesting and short as possible. My name is Luka, on my left a college of mine, Barbara, and, already introduced, our mentor, Nina Suvorov, MD.

Before we actually start with the debate, let us ask you a question. Imagine you’ve lost your hand sometime in the past and now you are presented with two options. Either hand transplantation or bionic prosthesis. Which would you, right now, choose. Would you go for hand transplantation, or would you rather go with a bionic prosthesis. How many of you would choose hand transplantation? And how many bionic prosthesis? Interesting; 60% for bionics and 40% for transplantation. We’ll keep that number in mind.

Barbara: Now, before we begin, let’s clear the terms. Luka, could you tell us what a reconstructive transplant is?

Luka: Thank you, Barbara. A reconstructive transplant, or also called a composite tissue allograft, is an operation that involves transplantation of bone, tissue, muscle and blood vessels. According to WHO “transplantation is the transfer or rather engraftment of human cells, tissues or organs from a donor to a recipient with the aim of restoring function(s) in the body. And in cases when transplantation is performed between different species, e.g. animal to human, it is named xenotransplantation.

Now, Barbara, would you care to briefly explain what a bionic prosthesis is and how it works?

Barbara: Bionic creativity engineering is basically implementation of biological systems in the developing modern technology. Bionic hand isn’t just the hook. It mimics the real human hand. In some cases bionic hand even superposes human hand, as we shall see later.

There are different bionic prostheses, today I’ll talk about i-Limb Ultra, the one most advanced for now.

Here is how it looks: we can see power button here, the digits are motorized. It’s made out of plastic, titanium and silicone.

And just some mechanical properties…

This is a myoelectric prosthesis, which means it uses electrical sensors to detect contractions in the selected muscles of the residual limb. These contractions are than translated into movement of the bionic hand by a specific algorithms.

Luka: Ok, so which is better? Let’s start with transplantations of the hand. We will focus mainly on the hand, since leg prosthetics are nearly perfect, but with hand it’s different. You have many small and fine movements that are incorporated in every day’s life and you simply cannot function without a hand.

Just some short history for the beginning. The first hand transplant was actually performed in Ecuador in 1964, but the patient suffered from transplant rejection after only two weeks. Then, there was basically a long period of nothing. Up until January 1999. The first successful hand transplantation. Now, you should notice, we are talking about transplantation, not about replantation. The first successful replantation was performed in Shanghai, China, in January 1963.

So, in January 1999 the first person (a baseball player) underwent an operation. This kind of operation is probably one of the longest there is. It takes approximately 12 to 16 hours. In comparison, a typical heart transplant takes 6 to 8 hours and a liver transplant, 8 to 12 hours.

Hand transplantation is an extremely complex procedure, but may not be as difficult as a hand replantation in that a replantation usually involves crushed or mangled bones, tendons, and ligaments.

Barbara: Would you care to elaborate on how this is done? Read more…

Pithovirus: 30,000-year-old giant virus ‘comes back to life’


A new virus called Pithovirus sibericum has been isolated from 30,000 year old Siberian permafrost. It is the oldest DNA virus of eukaryotes ever isolated, showing that viruses can retain infectivity in nature for very long periods of time.

Pithovirus was isolated by inoculating cultures of the amoeba Acanthamoeba castellani with samples taken in the year 2000 from 30 meters below the surface of a late Pleistocene sediment in the Kolyma lowland region. This amoeba had been previously used to propagate other giant viruses, such as Mimivirus and Pandoravirus. Light microscopy of the cultures revealed the presence of ovoid particles which were subsequently shown by electron microscopy to resemble those of Pandoravirus. Pithovirus particles are flask-shaped and slightly larger than Pandoravirus – 1.5 microns long, 500 nm in diameter, encased by a 60 nm thick membrane. One end of the virus particle appears to be sealed with what the authors call a cork (photo). This feature, along with the shape of the virus particle,  inspired the authors to name the new isolate Pithovirus, from the Greek word pithos which refers to the amphora given to Pandora. The name therefore refers both to the morphology of the virus particle and its similarity to Pandoravirus.

Although the Pithovirus particle is larger than Pandoravirus, the viral genome – which is a double-stranded molecule of DNA – is smaller, a ‘mere 610,033 base pairs’, to use the authors’ words (the Pandoravirus genome is 2.8 million base pairs in length). There are other viruses with genomes of this size packed into much smaller particles – so why is the Pithovirus particle so large? Might it have recently lost a good deal of its genome and the particle size has not yet caught up? One theory of the origin of viruses is that they originated from cells and then lost genes on their way to becoming parasitic.

We now know of viruses from two different families that have similar morphology: an amphora-like shape, an apex, and a thick electron-dense tegument covered by a lipid membrane enclosing an internal compartment. This finding should not be surprising: similar viral architectures are known to span families. The icosahedral architecture for building a particle, for example, can be found in highly diverse viral families. The question is how many viruses are built with the pithovirus/pandoravirus structure. Prof. Racaniello’s guess would be many, and they could contain either DNA genomes. We just need to look for them, a process, as the authors say that ‘will remain a challenging and serendipitous process’.

Despite the physical similarity with Pandoravirus, the Pithovirus genome sequence reveals that it is barely related to that virus, but more closely resembles members of the Marseillviridae, Megaviridae, and Iridoviridae. These families all contain large icosahedral viruses with DNA genomes.  Only 32% of the 467 predicted Pithovirus proteins have homologs in protein databases (this number was 61% for Mimivirus and 16% for Pandoravirus). In contrast to other giant DNA viruses, the genome of Pithovirus does not encode any component of the protein synthesis machinery. However the viral genome does encode the complete machinery needed to produce mRNAs. These proteins are present in the purified Pithovirus particle. Pithovirus therefore undergoes its entire replication cycle in the cytoplasm, much like other large DNA viruses such as poxviruses.

Pithovirus is an amazing virus that hints about the yet undiscovered viral diversity that awaits discovery. Its preservation in a permafrost layer suggests that these regions might harbor a vast array of infectious organisms that could be released as these regions thaw or are subjected to exploration for mineral and oil recovery. A detailed analysis of the microbes present in these regions is clearly needed, both by the culture technique used in this paper and by metagenomic analysis, to assess whether any constitute a threat to animals.

The above story is reprinted from materials provided by Virology blog: About Viruses and Viral Disease.

Nanomotors Steered Inside Living Human Cells For the First Time


A group of researchers from Penn State have pushed the realm of possibilities for nanotechnology further as they have successfully steered a nanomotor inside of a human cell. This is the first time this feat has been accomplished. The team of chemists, biologist, and engineers was led by Tom Mallouk and has been published in Angewandte Chemie International Edition.

photo credit: Mallouk Lab/ Penn State

Nanomotors have been studied in vitro more more than a decade now. The hope is that eventually, they could be used inside of human cells for biomedical research. This nanotechnology could revolutionize drug delivery and even perform surgery in order to increase quality of life in the least invasive way possible. The earliest models were nonfunctional in biological fluid due to their fuel source. A huge breakthrough came later when the nanomotors were able to be powered externally via acoustic waves. The nanomotors used inside the human cells for the latest study were controlled by the ultrasonic waves as well as magnets.

The researchers used HeLa cells, derived from a long-lived line of cervical cancer cells, to study the nanomotors. Getting past the cell membrane was easy, as the cells ingested the nanomotors themselves. Once inside, the ultrasound was turned on and the nanomotors began to spin and move around the cell. If the signal was turned up even higher, the nanomotor can spin like a propeller, chopping up the organelles inside the cell. They were even able to puncture the cell membrane, finishing off the death sentence. Used at low powers, the nanomotor was able to move around the cell without causing any damage.

The addition of magnets gave an important advantage: steering. The motors are also able to be controlled individually, allowing the operator to take a much more targeted approach to killing diseased cells.

Ultimately, the researchers hope that one day the rocket-shaped gold nanorods will be able to move in an out of the cells without causing damage. The individual units could communicate with one another to target disease in the body, maximizing the efficacy of the treatment or even making the correct diagnosis. Working toward the goal of creating such advanced nanotechnology will not only push the boundaries of nanoengineering, but will increase our understanding of chemical and biological processes at the cellular level as well.

“The assembly of a rotating HeLa cell/gold rod aggregate at an acoustic nodal line in the xy plane. The video was taken under 500X overall magnification except for 00:23 – 00:32 and 01:16 – 01:42, where a 200X overall magnification was used.” Credit: Mallouk Lab, Penn State

“Very active gold nanorods internalized inside HeLa cells in an acoustic field. A demonstration of very active gold nanorods internalized inside HeLa cells in an acoustic field. This video was taken under 1000X magnification in the bright field, with most of the incoming light blocked at the aperture.” Credit: Mallouk Lab, Penn State

 

The above story is reprinted from materials provided by I F* Love Science.

Can ‘Robotic’ Pills Replace Injections?


The adage “Take two aspirin and call me in the morning” is destined for a futuristic makeover. Doctors may just as easily recommend swallowing sophisticated gadgets instead.

That is the hope of prolific inventor Mir Imran, who has created a robotic pill to replace injectable drugs for chronic conditions such as diabetes. The gadget, in preclinical studies and backed by Google Inc.’s venture-capital unit, consists of an ingestible polymer and tiny hollow needles made of sugar that are designed to safely deliver drugs to the small intestine.

Such a pill would have seemed unthinkable years ago. But advancements in technology and scientific research have recently led to two federally approved robotic pills.

The Food and Drug Administration earlier this month cleared the PillCam, a pill-sized camera from Given Imaging Ltd. that photographs human insides in a hunt for colon polyps. Another company, Proteus Digital Health Inc., received clearance a year and a half ago to put ingestible sensors inside pills to help patients and doctors determine how many they have taken.

Mr. Imran’s pill hasn’t yet been tested in humans, so it is probably still at least a year away from even seeking federal approval. It also would require substantial financing to manufacture millions of pills. But if it is successful, the gadget has the potential to disrupt a multibillion-dollar market for injectable drugs and make life easier for millions of sufferers of conditions such as diabetes and rheumatoid arthritis.

Mr. Imran is a safer bet than most entrepreneurs. The Indian-born founder of the research lab and business incubator InCube Labs in Silicon Valley has founded more than 20 medical-device startups, a dozen of which have been acquired by companies such as Medtronic Inc. He owns over 300 patents and helped develop the first implantable cardioverter defibrillator to correct irregular heartbeats.

Rani Therapeutics, the startup formed at InCube Labs to commercialize the robot pill, last year raised funds from Google Ventures and angel-investment fund VentureHealth.

Blake Byers, the Google Ventures general partner who spearheaded the investment, says Mr. Imran may be achieving one of the “holy grails” for biotechnology by figuring out how to deliver protein-based drugs such as basal insulin to the body without the use of a syringe.

“This investment is not exactly in our wheelhouse, but we’re open to people who can change our minds,” Mr. Byers said. “This one really stood out as a huge clinical need; $110 billion is spent in the U.S. every year on biologics, all of them injectable.”

Drugs used to treat a variety of chronic conditions, including diabetes, rheumatoid arthritis, osteoporosis and multiple sclerosis, can’t be delivered in pill form because stomach acids break down the proteins.

Mr. Imran’s idea is an “autonomic robotic delivery system” that can stay intact in the stomach and small intestine long enough to deliver enough of the drug. The body’s natural digestive processes activate the pill to perform a series of functions even without any electronics.

As the pH level, or acidity, builds up in the intestine, the outer layer of the polymer pill casing dissolves, exposing a tiny valve inside the device that separates two chemicals, citric acid and sodium bicarbonate.

When the valve becomes exposed, the chemicals mix together to create carbon dioxide. This acts as an energy source, gently inflating a balloon-like structure that is outfitted with needles made of sugar and preloaded with drugs.

The needles push into the intestinal wall, which has no pain receptors. Once lodged there, they detach from the gadget and slowly dissolve, while the balloon and polymer casing pass from the body.

In numerous attempts over the past 40 years to make insulin and other drugs available in pill form, pharmaceutical companies have been able to create coatings so tough that pills can reach the small intestine. But once there, they are attacked by enzymes, which has compromised the pills and prevented significant amounts of the drug from reaching the patient.

In preclinical studies, Rani Therapeutics has shown that its robotic pill can boost drug absorption at least as high as syringes can, Mr. Imran said.

“I am guardedly optimistic, and I say guardedly because there is still a lot of work left to do,” said Elliott Sigal, who several months ago retired from drug maker Bristol-Myers Squibb Co. His 16-year run at the drug maker included top posts in drug discovery and development and a nearly 10-year tenure as the head of research and development.

“Rani’s engineering-based approach to this is very innovative,” said Mr. Sigal, who doesn’t have a financial stake in the business. “He is getting results that I have not seen before. It hasn’t been tried in human patients yet, and things do sometimes fail at that level. But if the [trials] data continues, there will be a great deal of pharma interest.”

Mr. Imran said pharmaceutical companies, which would license the technology for use with their own drugs, have already expressed interest. He declined to give further details.

Rani Therapeutics will spend another year testing the robot pill, he said, in the hope that it will have definitive clinical data in 2015.

If the data back up his claim about the pill, it could not only help millions of patients ditch their syringes and stick-pens, but it could remove another barrier for a range of early-stage treatments that currently have no safe avenue into the body, said Google Ventures’ Mr. Byers.

Here is also a short video: Can ‘Robotic’ Pills Replace Injections?

The above story is reprinted from materials provided by The Wall Street Journal.

3D Model of Child’s Heart Helps Surgeons Save Life


A 14-month-old boy in need of life-saving heart surgery is the beneficiary of a collaboration among University of Louisville engineers, physicians and Kosair Children’s Hospital.

Roland Lian Cung Bawi of Owensboro was born with four congenital heart defects and his doctors were looking for greater insights into his condition prior to a Feb. 10 operation.

Philip Dydynski, chief of radiology at Kosair Children’s Hospital, recently had toured the Rapid Prototyping Center at the University of Louisville’s J.B. Speed School of Engineering and became impressed with the 3D printing capabilities available there.

He asked the center’s operations manager, Tim Gornet, if a 3D model of the child’s heart could be constructed using a template created by images from a CT scan to allow doctors to better plan and prepare for his surgery. No problem, Gornet said.

The result of the Rapid Prototyping Center’s work was a model heart 1.5 times the size of the child’s. It was built in three pieces using a flexible filament and required about 20 machine hours – and only about $600 — to make, Gornet said.

Once the model was built, Erle Austin III, cardiothoracic surgeon with University of Louisville Physicians, was able to develop a surgical plan and complete the heart repair with only one operation.

“I found the model to be a game changer in planning to do surgery on a complex congenital heart defect,” he said.

Roland was released from Kosair Children’s Hospital Feb. 14 and returned Feb. 21 for checkups with his doctors. His prognosis is good.

That’s good news for Gornet, whose work at the Rapid Prototyping Center routinely benefits manufacturers and heavy industry. Helping surgeons save a life was new territory for him.

“Knowing we can make somebody’s life better is exciting,” he said.

Here is also a short video:  UofL Engineers Construct 3D Heart Model

The above story is reprinted from materials provided by University of Louisville Today.