Scientists unveil a giant leap for anti-aging

Researchers have discovered a protein complex in humans that helps protect cells from DNA damage.
The finding could be helpful for astronauts in space, who are at greater risk of DNA damage from cosmic radiation. Credit: David Sinclair, Harvard Medical School

UNSW researchers have made a discovery that could lead to a revolutionary drug that actually reverses ageing, improves DNA repair and could even help NASA get its astronauts to Mars.

In a paper published in Science today, the team identifies a critical step in the molecular process that allows cells to repair damaged DNA.

Their experiments in mice suggest a treatment is possible for DNA damage from ageing and radiation. It is so promising it has attracted the attention of NASA, which believes the treatment can help its Mars mission.

While our cells have an innate capability to repair DNA damage—which happens every time we go out into the sun, for example - their ability to do this declines as we age.

The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair.

Treating mice with a NAD+ precursor, or "booster," called NMN improved their cells' ability to repair DNA damage caused by radiation exposure or old age.

"The cells of the old mice were indistinguishable from the young mice, after just one week of treatment," said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School Boston.

Human trials of NMN therapy will begin within six months.

"This is the closest we are to a safe and effective anti-ageing drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair, who maintains a lab at UNSW in Sydney.

What it means for astronauts, childhood cancer survivors, and the rest of us:

The work has excited NASA, which is considering the challenge of keeping its astronauts healthy during a four-year mission to Mars.

Even on short missions, astronauts experience accelerated ageing from cosmic radiation, suffering from 

• muscle weakness, 
• memory loss and 
• other symptoms 

when they return. On a trip to Mars, the situation would be far worse: five per cent of the astronauts' cells would die and their chances of cancer would approach 100 per cent.

Professor Sinclair and his UNSW colleague Dr Lindsay Wu were winners in NASA's iTech competition in December last year.

"We came in with a solution for a biological problem and it won the competition out of 300 entries," Dr Wu says.

Professor David Sinclair and his UNSW team. Credit: Britta Campion

Cosmic radiation is not only an issue for astronauts. We're all exposed to it aboard aircraft, with a London-Singapore-Melbourne flight roughly equivalent in radiation to a chest x-ray.

In theory, the same treatment could mitigate any effects of DNA damage for frequent flyers.The other group that could benefit from this work is survivors of childhood cancers.

Dr Wu says 96 per cent of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, Type 2 diabetes, Alzheimer's disease, and cancers unrelated to the original cancer.

"All of this adds up to the fact they have accelerated ageing, which is devastating," he says.

"It would be great to do something about that, and we believe we can with this molecule."

An anti-ageing pill could be on the horizon:

For the past four years, Professor Sinclair and Dr Wu have been working on making NMN into a drug substance with their companies MetroBiotech NSW and MetroBiotech International.

The human trials will begin this year at Brigham and Women's Hospital, in Boston.

The findings on NAD+ and NMN add momentum to the exciting work the UNSW Laboratory for Ageing Research has done over the past four years.

They've been looking at the interplay of a number of proteins and molecules and their roles in the ageing process.

They had already established that NAD+ could be useful for treating various diseases of ageing, female infertility and also treating side effects of chemotherapy.

In 2003, Professor Sinclair made a link between the anti-ageing enzyme SIRT1 and resveratrol, a naturally occurring molecule found in tiny quantities in red wine.

"While resveratrol activates SIRT1 alone, NAD+ boosters activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity," he says.

Explore further: Anti-ageing drug breakthrough

More information: "A conserved NAD+ binding pocket that regulates protein-protein interactions during aging," Science, science.sciencemag.org/cgi/doi/10.1126/science.aad8242

Journal reference: Science

Provided by: University of New South Wales

ORIGINAL: MedicalXpress

March 23, 2017

Squishy Clockwork Biobot Could Dose You With Drugs From the Inside

Photo: Sau Yin Chin. Soft and 3D-printed micromachines can be implanted in the body to deliver doses of a chemo drug.

When Swiss watchmakers invented the Geneva drive, a two-geared mechanism that produces precise ticks forward, they probably never imagined that bioengineers would one day craft a 15-millimeter version out of squishy hydrogel. But then, they weren’t trying to make a biocompatible micromachine that could be implanted in the body to deliver doses of drugs.

This strange new biobot comes from the lab of Samuel Sia, a professor of biomedical engineering at Columbia University, in New York City. It uses neither battery nor wires, and can be controlled from outside the body to deliver a dose on command. It’s a gadget well suited for this new era of personalized medicine, Sia tells IEEE Spectrum. “Doctors want to see how the patient is doing and then modify the therapy accordingly,” he says.

He has already tested the gizmo in lab mice with bone cancer, with exciting results that were published today in the journal Science Robotics. More on that experiment later.

Photos: Sau Yin Chin The researchers constructed their Geneva device layer by layer, in a process that took about 30 minutes.

Sia’s team first had to invent a type of 3D printing to fabricate their tiny Geneva drive and several other soft micromachines. They came up with a fabricator that lays down layers of a hydrogel to produce rubbery solid shapes. While human hands are required to put the pieces together, Sia says those assembly steps could be automated. And it’s pretty quick, as is: The whole process of printing and assembling one Geneva drive takes less than 30 minutes. Today’s typical 3D printers would take several hours to construct a similar device, Sia says, and most can’t handle soft materials like hydrogel.

Here’s the part that runs like clockwork! The squishy Geneva drive clicks forward when an external magnet moves a simple gear, which is just a rubbery piece with embedded iron nanoparticles (the black curved piece in the video below). With each click, one of six chambers lines up with a hole and a dose of medicine flows out. In the video, a magnet (the silver disk) keeps the device running continuously to demonstrate the mechanism, but in clinical use, a doctor could apply a magnet only when a dose is required.

You may be wondering: Could someone’s implanted micromachine be triggered accidentally by an external magnet or by a malicious person with fiendish magnetic powers? In other words, is the X-Men’s Magneto a risk factor? “Somebody walking by with a magnet won’t trigger it, but there are some cases where it’s not ideal,” Sia says. His lab is working on other ways to wirelessly drive the mechanism, including an ultrasound technique.

The hardest part of the design process was getting the material right, Sia says. Very flexible and soft materials are compatible with the body’s soft innards, unlike rigid silicon or metal devices. “But if your material is collapsing like jello, it’s hard to make robots out of it,” he says. “It has to be stiff enough to work like a tiny implantable machine.”

Image: Sau Yin Chin The pieces of the Geneva device were each printed in soft hydrogel.

The next step was in vivo.
Sia’s team wanted to see if their devices would work inside the body, with all the complications of chemistry and anatomy. Some mice with bone cancer received implanted devices that were loaded up with a chemo drug; other mice received typical chemotherapy, which floods the whole body with a toxic drug. When the team compared the effects of the device’s localized and periodic delivery of the drug to those of the typical treatment, the results were impressive. The bionic mice’s tumors grew slower, more tumor cells died off, and fewer cells elsewhere in the body suffered peripheral damage.

Photos: Sau Yin Chin Fluorescent imaging shows a chemo-delivering device inside a lab mouse.

The clinical possibilities seem obvious—oncologists could deliver more targeted and concentrated doses of powerful chemo drugs, and Sia imagines other uses, like regulating the release of hormones. But the drug delivery device is really just a proof of concept, he says. He’s not rushing out to form a startup: “We have to do the cost-benefit analysis to see if this is really a commercializable device,” he says.

He is bullish, however, on the medical potential of tiny squishy robots in general. Soft and mobile little bots could one day act as internal repair crews, doing a doctor’s work from the inside. (For more on this, check out IEEE Spectrum’s article on medical microbots.) Sia says his fabrication platform is capable of turning out a wide variety of devices. “I’m confident that we’ll find something useful,” he says.

Sia won’t say exactly what types of devices his lab is now experimenting with, except to say that they’re looking at implanted devices that move. Here’s my guess: It’s a tiny squishy micromachine that resembles a cuckoo clock.

ORIGINAL: IEEE Spectrum
By Eliza Strickland
4 Jan 2017

Scientists Built a Biological Computer Inside a Cell

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MIT engineers have developed biological computational circuits capable of both remembering and responding to sequential input data.

The group's work, which is described in this week's issue of Science, represents a critical step in the progression of synthetic biology with the integration of DNA-based memory, in particular, pointing the way toward building large computational systems from biological components—computing devices that are living cells—and, ultimately, programming complex biological functions.

More specifically, Nathaniel Roquet and colleagues at MIT's Synthetic Biology Group were able to implement within a living cell what's known as a state machine: an abstract mathematical model describing computation as a list of of distinct internal states paired with an associated list of operations (or machine inputs) required to transition from state to state. So: a new state is always the result of an old state taken in combination with new inputs (history matters). State machines happen to describe a very large number of different things, from natural language processing algorithms to neurological systems to something as simple as a vending machine.

In a living cell, DNA is the natural candidate for storing state information. After all, that's what DNA does: store information. What Roquet and co. have created is a framework for chemically manipulating DNA such that states are encoded in DNA sequences. As a storage mechanism, this allows for both conveniently reading out a given state via genetic sequencing and also regulating gene expression via state transitions. In other words, the states can be linked to cellular behavior. The DNA serves as the memory for the state machine. The rest is in how, specifically, the DNA is manipulated and what effect that has on cellular behavior.

This could mean integrating biological state machines into tumor models, where they may be used to genetically surveil the activation of genes that may cause cancer

In their experiments, Roquet and co. programmed E. coli cells to react to several substances commonly used in biological laboratory experiments, including an analogue of the antibiotic tetracycline, a sugar called arabinose, and a chemical called DAPG that helps plants protect their roots from pathogens. The cells could be reprogrammed to other inputs as needed, however.

The actual cell behavior being programmed by the researchers was the expression of genes coding for the production of different fluorescent proteins representing different colors. With three different inputs they were able to produce 16 different combinations of colors.

"Synthetic state machines that record and respond to sequences of signaling and gene regulatory events within a cell could be transformative tools in the study and engineering of complex living systems," Roquet writes. In other words, by implementing a state machine (a computer) in a living cell, it's possible to use that state machine to surveil otherwise impossible-to-observe cellular happenings.

For example, progenitor cells (similar to stem cells) develop into differentiated cell types with specific functions thanks to transcription factors, proteins that help regulate gene expression in cells. Transcription factors have allowed researchers to program both progenitor cells to become certain specific types of functional cells—and also to do the opposite, programming functional cells to behave as undifferentiated cells. However, much about the process remains mysterious. A state machine that could record the DNA transitions resulting from TF activation could go a long way toward not only understanding these processes, but manipulating them as well. 

The circuits in the biological state machine are dependent on enzymes called recombinases. These enzymes are activated by various inputs into a cell, such as chemical signals, and act to tweak that cell's DNA. But the tweak that actually occurs depends on the orientation of two DNA sequences known as recognition sites. The important thing is that the effect of changing any two recognition sites (the resulting cellular behavior) depends on how other recognition sites have been altered previously. Hence, memory.

There's really no shortage of potential applications here. The example Roquet gives is in integrating biological state machines into tumor models, where they may be used to genetically surveil the activation of oncogenes (genes that may cause cancer) and deactivation of tumor suppression mechanisms in individual cells.

"This idea that we can record and respond to not just combinations of biological events but also their orders opens up a lot of potential applications," Roquet offers in a statement. "A lot is known about what factors regulate differentiation of specific cell types or lead to the progression of certain diseases, but not much is known about the temporal organization of those factors. That's one of the areas we hope to dive into with our device."

Computers have become "alive," but perhaps not in the way that many of us anticipated. A unicellular organism itself won't ever be packing much computational horsepower, but considered as a building block, the potential is pretty wild.

ORIGINAL: Vice

by MICHAEL BYRNE EDITOR 
July 21, 2016

'Universal cancer vaccine’ breakthrough claimed by experts

Researchers have found a way to persuade the body's immune system to attack tumours – and it is largely free from side effects

The vaccine prompted the body to make killer T-cells designed to attack cancer cells like the one above Rex Features

Scientists have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumours as if they were a virus, experts have said.

Writing in Nature, an international team of researchers described how they had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease.

The patients' immune systems responded by producing "killer" T-cells designed to attack cancer.

The vaccine was also found to be effective in fighting “aggressively growing” tumours in mice, according to researchers, who were led by Professor Ugur Sahin from Johannes Gutenberg University in Germany.

“[Such] vaccines are fast and inexpensive to produce, and virtually any tumour antigen [a protein attacked by the immune system] can be encoded by RNA," they wrote

“Thus, the nanoparticulate RNA immunotherapy approach introduced here may be regarded as a universally applicable novel vaccine class for cancer immunotherapy.”

The paper said the three patients were given low doses of the vaccine and the aim of the trial was not to test how well the vaccine worked. While the patients' immune systems seemed to react, there was no evidence that their cancers went away as a result.

Cancer breakthrough revealed

In one patient, a suspected tumour on a lymph node got smaller after they were given the vaccine. Another patient, whose tumours had been surgically removed, was cancer-free seven months after vaccination.

The third patient had eight tumours that had spread from the initial skin cancer into their lungs. These tumours remained “clinically stable” after they were given the vaccine, the paper said.

The vaccine, which used a number of different pieces of RNA, activated dendritic cells that select targets for the body's immune system to attack. This was followed by a strong response from the "killer" T-cells that normally deal with infections.

Cancer immunotherapy is currently causing significant excitement in the medical community.

It is already being used to treat some cancers with a number of patients still in remission more than 10 years after treatment.

While traditional cancer treatment for testicular and other forms of the disease can lead to a complete cure, lung cancer, melanoma, and some brain and neck cancers have proved difficult to treat.

Being able to inject an effective treatment into a patient’s bloodstream would be a significant step forward. The vaccine also produced limited flu-like side-effects in contrast to the extreme sickness caused by chemotherapy.

Professor Alan Melcher, of the Institute of Cancer Research, said: “Immunotherapy for cancer is a rapidly evolving and exciting field. This new study, in mice and a small number of patients, shows that an immune response against the antigens within a cancer can be triggered by a new type of cancer vaccine.

“Although the research is very interesting, it is still some way away from being of proven benefit to patients.

“In particular, there is uncertainty around whether the therapeutic benefit seen in the mice by targeting a small number of antigens will also apply to humans, and the practical challenge of manufacturing nanoparticles for widespread clinical application.”

Dr Helen Rippon, chief executive of Worldwide Cancer Research, said “We know the immune system has great potential to be manipulated and reactivated to fight cancer cells, that’s why we’ve been funding research into this for 15 years.

“These are exciting and novel results, showing the promise of an RNA nanoparticle vaccine to do just that.”

She described the immune response in the three patients as “positive” and noted that advanced skin cancer was “a notoriously difficult cancer to treat”.

“However, more research is needed in a larger number of people with different cancer types and over longer periods of time before we could say we have discovered a ‘universal cancer vaccine’. But this research is a very positive step forwards towards this global goal,” she said.

ORIGINAL: The Independent

By Ian Johnston Science Correspondent 

Genetically engineered algae kills 90% of cancer cells without harming healthy ones

Diatom algae genetically engineered to destroy cancer cells
Derek Keats/Flickr

Algae has been genetically engineered to kill cancer cells without harming healthy cells. The algae nanoparticles, created by scientists in Australia, were found to kill 90% of cancer cells in cultured human cells. The algae was also successful at killing cancer in mice with tumours.

Nico Voelcker, from the University of South Australia, worked with researchers from Dresden in Germany to engineer diatom algae and loaded it with chemotherapeutic drugs. Publishing their study in the journal Nature Communications, the team also found that when they injected the nanoparticles into mice, tumours regressed.

Diatom algae is a type of tiny, unicellular, photosynthesising algae. It measures just four to six micrometres in diameter and is enclosed within a porous skeleton made of silica. Because chemotherapeutic drugs are often toxic to healthy tissue, the researchers were able to hide the drugs inside the algae.

Researchers genetically engineered the algae to produce an antibody-binding protein on the surface of their shells. In turn, the antibody binds only to molecules found on cancer cells, meaning it could deliver drugs to the target cells.

Voelcker explained: "By genetically engineering diatom algae - tiny, unicellular, photosynthesising algae with a skeleton made of nanoporous silica, we are able to produce an antibody-binding protein on the surface of their shells. Anti-cancer chemotherapeutic drugs are often toxic to normal tissues.

"To minimise the off-target toxicity, the drugs can be hidden inside the antibody-coated nanoparticles. The antibody binds only to molecules found on cancer cells, thus delivering the toxic drug specifically to the target cells.

The report authors sate: "These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites."

As algae mostly only needs water and light to grow, the team believes the technique could reduce the cost and waste of nanoparticle manufacturing and has huge potential for future cancer treatments. "Although it is still early days, this novel drug delivery system based on a biotechnologically tailored, renewable material holds a lot of potential for the therapy of solid tumours including currently untreatable brain tumours," Voelcker said.Genetically engineered diatom biosilica (green) containing liposome-encapsulated drug molecules (yellow) can be targeted to lymphocyte cells in suspension (purple) by functionalizing the biosilica surface with cell specific antibodies. Liposome-encapsulated drug molecules are released from the biosilica carrier in the immediate vicinity of the target cells (inset).Marc Cirera.

ORIGINAL: International Business Times

By Hannah Osborne

November 10, 2015 

Brazilian Wasp Venom Kills Cancer Cells, But Not Healthy Cells

photo credit: Wasp close up. Attila Fodemesi/Shutterstock.

Wasps get their fair share of bad press. They have painful stingers, and they're not as useful (or cute) to us as bees. However, their time to step in the spotlight may be just around the corner: Their venom has been shown to attack cancer cells while leaving healthy cells alone.

The cancer-targeting toxin in the wasp is called MP1 (Polybia-MP1) and until now, how it selectively eliminates cancer cells was unknown. According to new research, it exploits the atypical arrangement of fats, or lipids, in cancer cell membranes. Their abnormal distribution creates weak points where the toxin can interact with the lipids, which ultimately pokes gaping holes in the membrane. These are sufficiently large for essential molecules to start leaking out, like proteins, which the cell cannot function without.

The wasp responsible for producing this toxin is the Polybia paulista. The toxin has so far been tested on model membranes and examined using a broad range of imaging techniques. You can see the team's research results in the Biophysical Journal.

The wasp, Polybia paulista, which produces the venom containing MP1. Professor Mario Palma/Sao Paulo State University.

"Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs," said Paul Beales from the University of Leeds and co-author of the study. "This could be useful in developing new combination therapies, where multiple drugs are used simultaneously to treat a cancer by attacking different parts of the cancer cells at the same time."

In healthy cell membranes, the inner layer (facing the inside of the cell) is packed with phospholipids, including PS (phosphatidylserine) and PE (phosphatidylethanolamine). However, in cancer cells, PS and PE are located on the outer layer of the cell membrane, facing the opposite way. 

To test the different effects of PS and PE's presence on a cell, the scientists examined how the MP1 interacted with model membranes infused with PE and/or PS. The presence of each phospholipid had a destructive effect on the cells. PS increased the chance of MP1 binding to the membrane by a factor of seven to eight. The presence of PE inflated the size of the holes created by the MP1 by a factor 20 to 30.

"Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells," said João Ruggiero Neto from São Paulo State University and co-author of the study. "The dramatic enhancement of the permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising."

The next stage for this research is to adjust the amino acid sequence of MP1 to see what gives it its selective properties, and to try and refine them. "Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine," Beales says. "As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that."

ORIGINAL: IFLScience

by Caroline Reid

September 2, 2015

Google Won The Internet. Now It Wants to Cure Diseases

Click to Open Overlay Gallery RAFE SWAN/GETTY IMAGES

WHEN GOOGLE CO-FOUNDER Larry Page dropped his now-famous blog post revealing that Google was reorganizing itself as Alphabet, one of the most striking things was what he chose to highlight as the kind of work these newly independent non-Google companies would be pursuing.

“The companies that are pretty far afield of our main Internet products [are] contained in Alphabet instead,” Page wrote in the blog post announcing Alphabet’s existence. “Good examples are our health efforts: Life Sciences (that works on the glucose-sensing contact lens), and Calico (focused on longevity).”

Google has long dabbled in medicine, but Page’s announcement signaled that he wants biomedical research to be more than just a side project for his newly christened company. Behind the scenes, efforts were already well under way to transform Google into a place that was serious about life sciences.

Under Alphabet, life sciences will become its own independent division, though it doesn’t have an official name just yet. (The company says to expect more news soon.) But a few hints suggest the life sciences group had been operating fairly independently already. Last month, CFO Ruth Porat singled out life sciences during a quarterly earnings call as one of the areas Google sees as “longer-term sources of revenue.” To get there, the company has been quietly recruiting top scientific talent, from immunologists to neurologists to nanoparticle engineers.

“Google Life Sciences is focused on shifting health care from a reactive, undifferentiated approach to a proactive, targeted approach,” reads one of the company’s recent job listings. Biomedical researchers at Google will work to transform the “detection, prevention, management and even our basic understanding of disease,” the company says. In other words, just like everything else it does, the company once known as Google intends to train its outsized ambition on fixing the most basic problems afflicting human health.

Building An Infrastructure

For the past two years, Google’s life science efforts have been headed up by Andrew Conrad, previously the chief scientific officer at LabCorp and the co-founder of the National Genetics Institute. He leads more than 150 scientists who come from fields as wide-ranging as astrophysics, theoretical math, and oncology. “Our central thesis was that there’s clearly something amiss in Western medicine,” Conrad told Steven Levy of Backchannel back in October.

Sam Gambhir, a professor of radiology, bioengineering, and materials science at Stanford University who has collaborated with Conrad since before Google Life Sciences was a formal division within Google X, says the division isn’t just playing around. Gambhir says projects on which he’s partnered with Google’s life sciences team include the use of nanotechnology to improve diagnostics as well as devices to continuously monitor biomarkers.

“They’re systematically building an infrastructure to tackle things in-house as well as collaborate with multiple universities,” Gambhir tells WIRED. “It’s a very serious effort, and it seems to have always been supported from the very top of the company.”

Tackling Chronic Disease

One of the longest-standing efforts has been a project to develop new ways of diagnosing and treating diabetes. Last year Google unveiled a smart contact lens diabetics can use to read blood sugar levels through the tears in their eyes. Pharmaceutical giant Novartis announced that it would license the smart lens tech from Google, and the two companies are exploring other uses for the tech. Just this month, Google announced it was partnering with Dexcom, a glucose-monitoring company, to focus on making a continuous glucose monitor that’s cheaper, more convenient than current solutions, and disposable, the company said.

Google is also diving deep into genomics. Gambhir says a committee of scientists from Google, Duke University, and Stanford University have been meeting multiple times a week for about a year now to work on the design of what Google has called its Baseline Study, a project that will ultimately collect anonymous genetic information from 10,000 people to create a “baseline” picture of what a healthy human being looks like on a molecular level. Gambhir, a collaborator on the project, says Baseline is intended to be a “longitudinal study on human health to understand the transition from health to disease.”

Other work on the molecular level include a cancer-detecting pill that pairs with a wristband, all part of what Google called its “nanoparticle platform.” Part of getting the wearable to work correctly included understanding how light passed through skin, which led Conrad and his team to make artificial human skin. Life Sciences is looking at other chronic diseases, too. In January, Conrad told Bloomberg that the team planned to partner with multiple sclerosis drugmaker Biogen to study environmental and biological contributors to the disease’s progression.

Ageless Problems

Last September, Google bought Lift Labs, maker of Liftware—a high-tech spoon designed to help people with neurodegenerative tremors eat. But Google wouldn’t be Google (er, Alphabet wouldn’t be Alphabet) if it was just concerned with addressing the symptoms of disease. Aging itself is another problem it hopes to disrupt. Calico, which is organizationally separate from the life sciences group, aims to maximize the human lifespan by preventing aging. The life sciences division, meanwhile, is focused on staving off diseases that could interfere with Calico’s goal. Neither of those efforts seems very closely tied to Google’s original business model of targeting ads to users based on Internet searches. Now that life sciences have become independent under Alphabet, it looks like they don’t have to be.

ORIGINAL: Wired

08.19.15 

Here's how we're fighting cancer in a completely new way

Image: Juan Gaertner/Shutterstock.com

Why chemo could be a thing of the past.

This article was written by Mark Cragg from the University of Southampton, and was originally published by The Conversation.

We’re beginning to treat cancer in a whole new way. Rather than killing cancer cells directly with chemo or radiotherapy, the latest treatments are designed to promote the body’s natural immune control over the disease. So-called immunotherapy works to stimulate the body’s own immune system to destroy the cancer. It is not a new concept and was first described more than a century ago, but for the first time it is beginning to deliver long-lasting responses, which some are daring to call cures.

Behind these advances has been a more sophisticated understanding of the relationship between the immune system and cancer, particularly how the cancer is seen as a danger by the body and can disguise itself from immune attack.

The most promising immunotherapies are antibody drugs, which target key switches on immune cells and fall into two main classes:

• checkpoint blockers such as ipilimumab and nivolumab, which remove the cancer’s ability to switch off the immune system, and 
• immunostimulators such as anti-CD40 and anti-4-1BB, which promote active immune responses from the body.

Immunotherapy advantages

There are several key reasons why weaponising the immune system in this way shows such promise in the fight against cancer.

1. First, the immune system is mobile. Its ability to patrol the whole body means it is able to recognise cancer cells wherever they are. And cancer’s ability to spread is frequently the cause of recurrence following other treatments.
2. Second, the immune system is self-amplifying. It is able to increase its response as required to tackle large, advanced cancers. This property means that it will sometimes work better the more cancer is present, responding to a larger immune stimulation.
3. Third, the immune system can evolve and adapt to changes in the cancer. Cancers are genetically unstable, meaning that they can change and 'escape' from conventional treatments. This situation is exactly what the immune system has evolved to cope with in its battle with pathogens. So as the tumour changes, the immune system can also change in parallel, keeping the cancer cells locked down.
4. Fourth, the immune system can recognise an almost limitless number of target molecules on the cancer. This ability to recognise so many targets at once makes it much more difficult for rare variant cancer cells to escape out of immune control by changing their appearance. It also broadens the types of cancer that may be susceptible to immunotherapy.
5. Finally, the immune system has memory. We see this with infectious diseases, with protection against a second round of infection from a particular germ. This is what provides us with life-long protection from some diseases after catching them as children or receiving vaccinations. For cancer, this means that the immune system can be 'immunised' to the cancer cells and detect and delete them if they try to grow back. Most cancer treatments only work while they are being given: an immune response can last a lifetime.

These five features of immunotherapy combine to deliver major benefits, including the ability to deliver durable, perhaps life-long responses, tantamount to cures, even in advanced, previously fatal cancers.

Future challenges

The challenge now is to understand why some people, and some cancers, respond much better to these therapies than others and how to increase the proportion of people who experience good responses. Data reported only last month shows that combining immunotherapy treatments by giving two checkpoint-blocking antibodies at the same time extends the number of patients with effective and lasting responses. Unfortunately, it also increases the unwanted side effects from immune attack on some of the body’s normal tissues.

While the results from the recent clinical trials are incredibly promising, it is clear that we are just at the beginning of our journey to understand the immune system and harness its power to destroy cancer. We already know that the complex interplay between

• the genetic make-up of the tumour, 
• the status of someone’s immune system, and 
• the interaction between the two will sculpt the immune response in different ways.

How, then, to best boost the immune system? We recognise that large multidisciplinary teams – comprising clinicians, immunologists, molecular biologists, geneticists and others – with concentrated resources are required. In Southampton, this will coalesce around a new purpose-built Centre for Cancer Immunology, which will open in 2017 with the aim of bringing the right people together and providing cutting edge facilities.

With the development of such centres, our understanding of the immune system in health and disease will continue the rapid expansion of immunotherapy, leading to many new opportunities for treatment. Soon these will become more specific, effective and safe – leading us into a new era of cancer treatment.


Mark Cragg is Professor of Experimental Cancer Research at University of Southampton.

This article was originally published on The Conversation. Read the original article.


ORIGINAL: Science Alert

MARK CRAGG, THE CONVERSATION
23 JUN 2015

Scientists Have Discovered That Bees Can Detect Cancer And This Designer Is Taking It A Step Further

Scientists have discovered that honey bees, Apis mellifera, have an extraordinary talent. Using their superior sense of smell, even more sensitive than that of a dog, bees can be trained to detect specific chemical odors. Those odors include biomarkers associated with lung, skin, and pancreatic cancer, as well as tuberculosis.

A Portuguese designer, Susan Soares, took that knowledge and developed a device that can utilize trained bees to detect serious diseases.

Bees are simply placed in the glass chamber and the patient simply exhales into it. The bees fly into a smaller, secondary chamber if they detect any cancer.

Bees don’t always live terribly long lives, but this method is still effective because bees can be trained in just 10 minutes by using Pavolv’s reflex, which connects certain odors with a food reward.

When bees are exposed to that odor, they are fed sugar and water as a reward. Once taught, the bees remember for the entirety of their six-week-long lives.

Early diagnosis is key for treating these deadly diseases, and fortunately, bees can help. Just one more reason to do everything we can to save the bees.

ORIGINAL: Higher Perspectives

March 25, 2015

Ido Bachelet DNA nanobots summary with a couple of extra videos

In a brief talk, Bachelet said DNA nanobots will soon be tried in a critically ill leukemia patient. The patient, who has been given roughly six months to live, will receive an injection of DNA nanobots designed to interact with and destroy leukemia cells—while causing virtually zero collateral damage in healthy tissue.

According to Bachelet, his team have successfully tested their method in cell cultures and animals and written two papers on the subject, one in Science and one in Nature.

Contemporary cancer therapies involving invasive surgery and blasts of drugs can be as painful and damaging to the body as the disease itself. If Bachelet's approach proves successful in humans, and is backed by more research in the coming years, the team’s work could signal a transformational moment in cancer treatment.

If this treatment works this will be a medical breakthrough and can be used for many other diseases by delivering drugs more effectively without causing side effects.

2012 Video with answers from George Church, Ido Bachelet and Shawn Douglas on the medical DNA double helix clamshell nanobucket nanobot

George Church indicates the smart DNA nanobot has applications beyond nanomedicine. Applications where there is any need for programmable and targeted release or interaction at the cellular or near molecular scale.

2014 Geek Time Presentation from Ido Bachelet

At the British Friends of Bar-Ilan University's event in Otto Uomo October 2014 Professor Ido Bachelet announced the beginning of the human treatment with nanomedicine. He indicates DNA nanobots can currently identify cells in humans with 12 different types of cancer tumors.

A human patient with late stage leukemia will be given DNA nanobot treatment. Without the DNA nanobot treatment the patient would be expected to die in the summer of 2015. Based upon animal trials they expect to remove the cancer within one month.

Within 1 or 2 years they hope to have spinal cord repair working in animals and then shortly thereafter in humans. This is working in tissue cultures. 

Previously Ido Bachelet and Shawn Douglas have published work on DNA nanobots in the journal Nature and other respected science publications.

One Trillion 50 nanometer nanobots in a syringe will be injected into people to perform cellular surgery.

The DNA nanobots have been tuned to not cause an immune response.

They have been adjusted for different kinds of medical procedures. Procedures can be quick or ones that last many days.

Medicine or treatment released based upon molecular sensing - Only targeted cells are treated

Ido's daughter has a leg disease which requires frequent surgery. He is hoping his DNA nanobots will make the type of surgery she needs relatively trivial - a simple injection at a doctor's office.

We can control powerful drugs that were already developed

Effective drugs that were withdrawn from the market for excessive toxicity can be combined with DNA nanobots for effective delivery. The tiny molecular computers of the DNA nanobots can provide molecular selective control for powerful medicines that were already developed.

Using DNA origami and molecular programming, they are reality. These nanobots can seek and kill cancer cells, mimic social insect behaviors, carry out logical operators like a computer in a living animal, and they can be controlled from an Xbox. Ido Bachelet from the bio-design lab at Bar Ilan University explains this technology and how it will change medicine in the near future.

Ido Bachelet earned his Ph.D. from the Hebrew University in Jerusalem, and was a postdoctoral fellow at M.I.T. and Harvard University. He is currently an assistant professor in the Faculty of Life Sciences and the Nano-Center at Bar Ilan University, Israel, the founder of several biotech companies, and a composer of music for piano and molecules.

Researchers have injected various kinds of DNA nanobots into cockroaches. Because the nanobots are labelled with fluorescent markers, the researchers can follow them and analyse how different robot combinations affect where substances are delivered. The team says the accuracy of delivery and control of the nanobots is equivalent to a computer system.

• This is the development of the vision of nanomedicine. 
• This is the realization of the power of DNA nanotechnology. 
• This is programmable dna nanotechnology.

The DNA nanotechnology cannot perform atomically precise chemistry (yet), but having control of the DNA combined with advanced synthetic biology and control of proteins and nanoparticles is clearly developing into very interesting capabilities.

"This is the first time that biological therapy has been able to match how a computer processor works," says co-author Ido Bachelet of the Institute of Nanotechnology and Advanced Materials at Bar Ilan University.

The team says it should be possible to scale up the computing power in the cockroach to that of an 8-bit computer, equivalent to a Commodore 64 or Atari 800 from the 1980s. Goni-Moreno agrees that this is feasible. "The mechanism seems easy to scale up so the complexity of the computations will soon become higher," he says.

An obvious benefit of this technology would be cancer treatments, because these must be cell-specific and current treatments are not well-targeted. But a treatment like this in mammals must overcome the immune response triggered when a foreign object enters the body.

Bachelet is confident that the team can enhance the robots' stability so that they can survive in mammals. "There is no reason why preliminary trials on humans can't start within five years," he says

Biological systems are collections of discrete molecular objects that move around and collide with each other. Cells carry out elaborate processes by precisely controlling these collisions, but developing artificial machines that can interface with and control such interactions remains a significant challenge. DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems, logic circuits and robotics. The molecule also interfaces naturally with living systems, and different forms of DNA-based biocomputing have already been demonstrated. Here, we show that DNA origami can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof of principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT and a half adder). Following an ex vivo prototyping phase, we successfully used the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets their cells.

Nature Nanotechnology - Universal computing by DNA origami robots in a living animal

44 pages of supplemental information

Ido Bachelet's moonshot to use nanorobotics for surgery has the potential to change lives globally. But who is the man behind the moonshot?

Ido graduated from the Hebrew University of Jerusalem with a PhD in pharmacology and experimental therapeutics. Afterwards he did two postdocs; one in engineering at MIT and one in synthetic biology in the lab of George Church at the Wyss Institute at Harvard. 

Now, his group at Bar-Ilan University designs and studies diverse technologies inspired by nature.

• They will deliver enzymes that break down cells via programmable nanoparticles.
• Delivering insulin to tell cells to grow and regenerate tissue at the desired location.
• Surgery would be performed by putting the programmable nanoparticles into saline and injecting them into the body to seek out remove bad cells and grow new cells and perform other medical work.

Research group website is here. 

Nanoparticles with computational logic has already been done

Load an ensemble of drugs into many particles for programmed release based on situation that is found in the body

Author: brian wang on 3/15/2015

ORIGINAL: Next Big Future
brian wang
3/15/2015