They’re about the size of a computer memory stick, yet they could represent the greatest potential for non-animal-based scientific advancement in history. They’re called “organs-on-chips”—and they just might change the way researchers model diseases, develop drugs and approach personalized medicine. And in the process, they’ll save the lives of countless animals.
Chances are, you’ve heard about organs-on-chips—at least in passing. These tiny devices have been getting a lot of attention lately, both in the media and within the scientific community. But what are they, exactly?
Organs-on-chips are specially-constructed systems that are designed to replicate the structure and function of human organs. Each “organ” contains transparent channels lined with living human cells. Multiple cell types can be incorporated into these devices to better mimic the complex microenvironments of human organs. The cells can be grown in such a way that enables them to change shape and respond to physical cues in ways that are not possible with traditional cell-based mod.
Variations of these chips have already been developed and continue to be optimized. Among them are models of the human lung, liver, kidney, gut, bone, brain and heart, among others.
The first organ-on-a-chip to be developed was the lung-on-a-chip, which has lung and blood vessel cells grown on opposite sides of a flexible, porous platform that can expand and contract like a breathing lung. This model has been used to study chronic obstructive pulmonary disease, asthma, cancer and even the effects of smoking on bronchial cells.
There’s a lot of excitement about organs-on-chips because they offer the potential of making drug development and toxicology testing faster and cheaper, in addition to being more accurate and more relevant to the human body.
And importantly, many believe that these devices have the potential to drastically reduce—even replace—the need for animal testing in many areas of research.
Researchers who developed the first organs-on-chips did so, in large part, to overcome limitations of the current drug development pipeline. Drugs that make it to human clinical trials are often unsuccessful because the animal models they are tested in do not accurately predict how the drugs will work in people. An estimated 30 percent of drugs that show promise in preclinical animal models fail in human clinical trials because they are toxic to humans. An additional 60 percent of drugs fail because of lack of efficacy. This wastes time, resources and countless animal lives.
The fact that 90 percent or more of these drugs that worked in animals subsequently failed in humans meant there was an urgent need to develop a human-relevant alternative to facilitate drug development and advance personalized medicine. Organ-on-a-chip technology is one response to this need, and it has been developing rapidly over the past several years.
Here are some of the exciting advancements that have been made recently.
Regulatory agencies, including the Food and Drug Administration (FDA), are very interested in the organ-on-a-chip devices. Last year, the FDA announced a multi-year research and development agreement with Emulate, a company that makes organs-on-chips, to use the devices in food safety testing. The FDA will begin conducting tests with liver-on-a-chip devices to determine whether they can serve as effective models for studying the effects of potential hazards in food and dietary supplements.
The FDA is also interested in how individual organs process cosmetics and dietary supplements and may carry out testing of additional organ chips, including kidney, lung and intestine models. This marks the first time that a U.S. regulatory agency has actively pursued the use of organs-on-chips as animal testing alternatives.
Organs-on-chips are also revolutionizing the field of personalized medicine, which uses a patient’s unique genetic background and medical history to develop therapies and treatments that directly address the unique biology of each individual.
Earlier this year, Emulate and Cedars-Sinai Medical Center in Los Angeles announced that they are collaborating to begin a revolutionary Patient-on-a-Chip program. In this program, cells from patients will be incorporated into organ-on-a-chip devices to generate models that allow for the most effective, patient-specific treatments to be identified. This approach has tremendous potential for improving patient health.
Even Big Pharma sees the potential for organs-on-chips, with multiple pharmaceutical companies now incorporating these cutting-edge devices into their research and development pipelines.
Recently, Emulate also announced partnerships with Takeda Pharmaceuticalbased in Japan and Roche, a Swiss-based company. The companies plan to use organ chips to generate human-relevant data that they believe will better predict the safety and efficacy of drug candidates.
But the potential of organs-on-chips doesn’t end with individual organs. Because they are modular devices, it’s possible to link individual organs-on-chips together to create a human-relevant, multi-organ model system. In fact, the goal of the Human-on-a-Chip project, which represents a collaboration between the Food and Drug Administration (FDA), the Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health, is to generate a miniature 3-D model which includes 10 different human mini-organs linked together to form a physiological system, which would be more likely to mimic the activities and biological processes of the human body.
A team led by Dr. Linda Griffith, a biological engineering professor at Massachusetts Institute of Technology, has recently reported that they successfully reached this milestone, after linking together 10 organ-on-a-chip systems for an entire month. Such a human-relevant model would be invaluable for drug testing, as researchers could screen for toxicity of drugs in various organs and could detect side effects of drugs. These innovative models are proving to be not only better science, but more humane, sparing the lives of so many research animals.
Because of the value organs-on-chips have in helping to reduce, and potentially replace animal use, the National Anti-Vivisection Society (NAVS) has prioritized support for the development of these models as part of its overarching mission to end the exploitation of animals used in science.
Through its affiliate, the International Foundation for Ethical Research, NAVS has, for more than 30 years, funded early career researchers with an interest in developing alternatives to animal experiments. And in recent years, NAVS has provided critical funding for projects investigating the use of organs-on-chips to study cancer cell growth and invasion, as well for the development of a gut-on-a-chip microdevice to study human intestinal inflammation—studies that are commonly performed in animal models.
Of course, only time will tell if reality will live up to all the hype. However, there’s a great deal of optimism among scientists and animal advocates that organs-on-chips will function as intended: That they will produce data that is reproducible, accurate and reliable—and that they will ultimately replace the use of animals in many areas of scientific research.
For the first time, scientists have identified the existence of a new DNA structure never before seen in living cells.
The discovery of what’s described as a ‘twisted knot’ of DNA in living cells confirms our complex genetic code is crafted with more intricate symmetry than just the double helix structure everybody associates with DNA – and the forms these molecular variants take affect how our biology functions.
“When most of us think of DNA, we think of the double helix,” says antibody therapeutics researcher Daniel Christ from the Garvan Institute of Medical Research in Australia.
“This new research reminds us that totally different DNA structures exist – and could well be important for our cells.”
The new DNA component the team identified is called the intercalated motif (i-motif) structure, which was first discovered by researchers in the 1990s, but up until now had only ever been witnessed in vitro, not in living cells.
Now, thanks to Christ’s team, we know the i-motif occurs naturally in human cells, meaning the structure’s significance to cell biology – which has previously been called into question, given it had only been demonstrated in the lab – demands new attention from researchers.
If your only familiarity with DNA shapes is the dual helical spirals made famous by Watson and Crick, the configuration of the intercalated motif could come as a surprise.
“The i-motif is a four-stranded ‘knot’ of DNA,” explains genomicist Marcel Dinger, who co-led the research.
“In the knot structure, C [cytosine] letters on the same strand of DNA bind to each other – so this is very different from a double helix, where ‘letters’ on opposite strands recognise each other, and where Cs bind to Gs [guanines].”
According to Garvan’s Mahdi Zeraati, the first author of the new study, the i-motif is only one of a number of DNA structures that don’t take the double helix form – including A-DNA, Z-DNA, triplex DNA and Cruciform DNA – and which could also exist in our cells.
Another kind of DNA structure, called G-quadruplex (G4) DNA, was first visualised by researchers in human cells in 2013, who made use of an engineered antibody to reveal the G4 within cells.
In the new study, Zeraati and fellow researchers employed the same kind of technique, developing an antibody fragment (called iMab) that could specifically recognise and bind to i-motifs.
In doing so, it highlighted their location in the cell with an immunofluorescent glow.
“What excited us most is that we could see the green spots – the i-motifs – appearing and disappearing over time, so we know that they are forming, dissolving and forming again,” says Zeraati.
While there’s still a lot to learn about how the i-motif structure functions, the findings indicate that transient i-motifs generally form late in a cell’s ‘life cycle’ – specifically called the late G1 phase, when DNA is being actively ‘read’.
“We think the coming and going of the i-motifs is a clue to what they do,” says Zeraati.
“It seems likely that they are there to help switch genes on or off, and to affect whether a gene is actively read or not.”
Now that we definitively know this new form of DNA exists in cells, it’ll give researchers a mandate to figure out just what these structures are doing inside our bodies.
As Zeraati explains, the answers could be really important – not just for the i-motif, but for A-DNA, Z-DNA, triplex DNA, and cruciform DNA too.
“These alternative DNA conformations might be important for proteins in the cell to recognise their cognate DNA sequence and exert their regulatory functions,” Zeraati explained to ScienceAlert.
“Therefore, the formation of these structures might be of utmost importance for the cell to function normally. And, any aberration in these structures might have pathological consequences.”
The findings are reported in Nature Chemistry.
Fertilization is possible in any way on earth but what will be the result of Space in the microgravity. Now NASA decides to investigate the sperms in the space to unveiled its ability to fertilize an egg.
NASA is now preparing to deliver the frozen sperm cells off to the International Space Station to investigate them in the Zero Gravity. The American Space Agency has decided to execute this plan with the SpaceX Falcon 9 as a Micro-11 mission.
According to the statement released by NASA human and bull sperms are the two chosen type of sperms cells that were planned to send to space. As per the previous experiments with the sperm of Sea Urchin, the movement of the sperm towards the fertilized egg seems quicker in the microgravity but fusion became slow and results in a failed fertilization.
The bull sperms also expected to show the similar changes in the movement in that type of gravity and hence the bull’s will help the scientists to alter the movement of human sperms in the zero gravity by calculating the movement of bull sperms.
They also stated that either the results may be positive or negative the astronauts will pack back those results with preservatives added to the earth. It is still an unknown thing that how the zero gravity helps human reproduction and how the duration of spaceflight will affect the human reproduction. This mission will serve as the first step towards the understanding the human reproductive system in microgravity condition.
Previously in 1979, the Russian space agency sent a couple of rats to the space to understand the reproduction capability in the space condition. But that try ended up in no baby rats while returning back.
However, this mission is considered as a dangerous by the scientists where the microgravity effect on estrogen level is still under studies and whether the reproduction in space and conception of human life in space is still unknown.
Cuteness comes in many forms,
And seen on every day.
If you want to see something cute,
Open your eyes and filter out the gray.
Too many of us are cuteness blind,
And see only shades of gray.
We allow ourselves to become too busy,
And leave no room for play.
When you allow happier shades to come through,
And you start to look for the cute.
You’ll realize all you have been missing,
As cute should never be put on mute.
To see a life with so much cuteness,
Is to see a life through the eyes of your heart.
And our heart is full of love and kindness,
It would be like seeing only the good parts.-Kindra Simmons