Tag Archives: embryo

Artificial embryo without sperm or egg forms live fetus

For the very first time, scientists have made artificial embryos from scratch, without sperm or egg, and implanted them into female mice. The embryos developed into live fetuses, but these exhibited major malformations.

Left: a natural 7-day-and-a-half-old embryo implanted in a female mouse. Right artificial 7-day-and-a-half-old embryo implanted in a female mouse with major malformations.

The team at the University of Texas Southwestern Medical Center used extended pluripotent stem cells, which are cells that have the potential, like an embryo, to develop into any type of tissue in the body. These ‘master cells’ are able to form all three major types of cell groups (ectoderm, endoderm, and mesoderm). Unlike simple pluripotent stem cells, the ‘extended’ variety can develop into tissues that support the embryo, such as the placenta. Without this type of stem cells, embryos cannot develop and grow properly.

The researchers coaxed stem cells to form into all the cells required for the development of an embryo by bathing them into a solution made of nutrients, growth stimulants, and signaling molecules. The cells assembled into embryo-like structures, including placental tissue.

Next, the artificial embryos were implanted into the uteruses of female mice. Only 7% of the implants were successful but those embryos that did work actually started developing early fetal structures. There were major malformations, however, as the tissue structure and organization did not closely resemble that of a normal embryo.

Previously, other research groups had managed to grow artificial embryos but this was the first time that they were successfully implanted and developed placental cells.

In the future, the University of Texas researchers plan on refining their method in order to grow fetuses that are indistinguishable from normal ones. The goal is to replace real embryos and make artificial ones at scale. These embryo models could then be grown in dishes to study early mammalian development and accelerate drug development.

Some of the cells that the researchers used to grow into embryos originally came from the ear of a mouse. Theoretically, the same should be possible for human embryos, but why would we? Besides testing drugs, artificial embryos could be grown from the skin cells of an infertile person. Then, in the lab, these embryos could be studied in order to identify potential genetic defects that might cause infertility.

Even if such stem cell-derived embryos do not completely mimic normal embryo growth, there is still a lot we can learn about mammalian development. But, as is always the case with research that breaks the frontiers of what was once thought possible, our policies haven’t yet kept up with advances. There are serious ethical considerations to possibly making a person from a synthetic embryo. Although such a prospect is still science fiction, rapid developments such as the present study suggest that it is not impossible — and we better prepare.

The findings were reported in the journal Cell.

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

Scientists edit the first human embryos in the United States

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

A video shows the injection of gene-editing chemicals into a human egg near the moment of fertilization. The technique is designed to correct a genetic disorder from the father. Credit: MIT Tech Review.

A team at the Oregon Health and Science University (OHSU) in Portland performed the first ever gene editing on a human embryo carried out inside the borders of the US. The researchers reportedly used CRISPR to edit portions of the genome where there were defective genes. These defects are known to cause inherited diseases in one-cell embryos.

Further than anyone has taken gene editing in the US so far

CRISPR-Cas9, the technique employed by the Oregon scientists, was invented a decade ago and makes gene editing incredibly easier and cheaper. Essentially, CRISPR acts like a molecular scissor of sorts that can be used to cut and paste portions of DNA. In early 2013,  researchers reported for the first time that they had used the CRISPR–Cas9 system to slice the genome in human cells at sites of their choosing. By 2014, 600 research papers mentioned it and now, a quick Google Scholar search reveals over 30,000 articles mentioning CRISPR, signaling the technique is rapidly becoming a mainstream scientific tool.

Of course, it’s not all fun and games with CRISPR. Such a powerful tool that acts on the blueprint of life — the genome — needs to be used with the utmost responsibility. One example of a safety concern is that a researcher created a virus with CRISPR-Cas9 that gave mice human lung cancer. A small mistake could work on human lungs also.

Previously, in 2015, Chinese researchers caused a lot of stir after they edited human embryos to remove a gene involved in the blood disorder beta-thalassemia. Then, in 2016, another group from China, which is the leading nation in CRISPR research, did something similar only this time the DNA was modified such that the embryo would be resistant to infection with HIV. However, the two attempts involved embryos fertilized by two sperm during in vitro fertilization (IVF), making them unviable past a certain post in their development.

CRISPR has been likened to a molecular scissor that can precisely cut portions of DNA. Credit: Science Mag.

CRISPR has been likened to a molecular scissor that can precisely cut portions of DNA. Credit: Science Mag.

The first CRISPR human trial started in October 2016 at the West China Hospital in Chengdu. Researchers harvested cells from a patient suffering from lung cancer and removed a gene called PD-1 — which cancer cells use to “trick” the body into not attacking them. The trial is set to end in 2018, so we’re still waiting for the results. And while most reports of CRISPR human gene editing came from China, it seems the United States is preparing to join ranks as well.

All previous trials involving genetically modifying human embryos had been blocked by Congress due to ethical concerns. One leading issue voiced in Congress is that allowing the practice would pave the way for so-called designer babies that are intentionally bred to have superior qualities. But in early 2017, the National Academy of Sciences released a report in which it endorsed human germline modification — altering an embryo with the intended purposes of eradicating a heritable disease. The reasoning is a child born out of that embryo will pass on these modifications with his or her germ cells, the egg or sperm.

“So far as I know this will be the first study reported in the U.S.,” Jun Wu, a collaborator at the Salk Institute, in La Jolla, California, who played a role in the project told MIT Tech Review. 

The embryos modified by the Oregon team led by Shoukhrat Mitalipov were never allowed to develop for more than a couple of days. They were also never meant to be implanted in any womb. Nevertheless, it was enough for the team to learn a great deal. For instance, previous attempts commanded by Chinese scientists caused editing errors in which DNA changes were only taken up by some cells in the modified embryo, but not all of them. This type of genetic error called ‘mosaicism’ wasn’t encountered during this study since their procedure also involved injecting CRISPR segments and sperm cells into the eggs at the same time.

For now, this trial is still pending publication so we’ll have to wait maybe a year before we learn more about the official results. In any case, we’re only beginning to scratch the surface with what gene editing can do. It’s exciting at the same time to witness first hand all of this play out. Designer babies or not, CRISPR is here to stay and what scientists will come up with might change humanity forever.

An early embryo

UK scientists want to modify genes inside a human embryo

A team working at the Francis Crick Institute in London applied to the Human Fertilisation and Embryology Authority for a permit that would allow them to edit genes in a human embryo. If allowed, this would lead to the very first genetically modified embryo in the UK. The scientists claim they need approval to do basic research that may ” improve embryo development after in vitro fertilization (IVF) and might provide better clinical treatments for infertility,” and not for clinical research. Either way, the controversial practice is banned in all Western countries and virtually banned, although not explicitly, in the US.

An early embryo

The Crick group leader,  Dr Kathy Niakan, wants to make specific alterations to the genomes of human embryos using a new technique called CRIPSR/Cas9. This technique makes it a lot more easy and cheap to split and stitch DNA into the genome. A lot of biotech companies now use this technique for a wide array of innovative research. For instance, there’s Edita – startup backed by Bill Gates – which uses CRIPSR to edit somatic cells collected from live patients. These cells, like the T-cells (a type of white cells), have their genes edited or repaired to correct an abnormality and inserted back into the patient through a simple blood transfusion. Research that manipulates human embryo genomes, many consider, is unethical and is an eugenic line that shouldn’t be crossed.

The main problem with germline embryo modification is that these modifications, which can be repairs or upgrades (genes that make you smarter, faster, stronger, less prone to diseases etc.), are passed on to subsequent generations without consent. This is an extremely grey area which often loops into non-sense. One could argue that you can’t ask an embryo anything. “So, future baby, what do you think of mommy and daddy? Do you consent of them as your parents? Do you consent being born a “Christian” or “Muslim”?” Wouldn’t be funny if a newborn baby was like “heeeey, I’m out of here!”. Of course, other issues are far more serious. An artificially induced genetic defect could make its way into the gene pool and there’s no way you can pull it out, unless you manage to isolate populations, then a whole slew of complications arise. Then, there’s always a background complaint: modified human embryos is playing God. It’s like sidetracking evolution to create a human super race, one that’s immune to disease, is super smart and, possibly, can’t die of old age. This sounds scary and impressive at the same time. It’s really hard to pick sides, so it’s no wonder that most countries have decided to solve this issue in the easiest way possible: ban it!

Well, everyone except China it seems. This April, the world learnt that Chinese researchers, again using CRIPSR, edited the genome of human embryonic cells, a world first. The cells never survived but it was the first practical demonstration, one that immediately sent shivers at the prospect of “designer children”. The Chinese embryos also bore unwanted mutations as a result of the intervention. Since 1999, the Beijing Genomics Institute is carrying research to find out which genes, if any, are responsible for human genius. The project spawned wild accusations of eugenics plots, as well as more measured objections by social scientists who view such research as a distraction from pressing societal issues.

In the US, things are pretty clear: “NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes … has been viewed almost universally as a line that should not be crossed,” said Francis Collins, director of the US National Institutes of Health. As for the UK, the Crick study might receive approval, but it most likely won’t due to public pressure. If it does, it would mark a huge milestone in genetics. Let’s just hope that it’s a fortunate milestone.

embyro genetic modification

Genetically modifying human embryos: ‘a line that should not be crossed,’ NIH says

The US National Institutes of Health (NIH) has reiterated its stance against modifying human embryos, after a paper published last week by Chinese researchers reported how they modified the DNA of human embryos to eradicate certain inheritable diseases from the lineage. Modifying human embryos was banned in 1996 for US government bodies, but in some states private entities are allowed to carry out such research.

embyro genetic modification

Image: Genetics and Society

Though the agency’s policy against embryo modification is well known, NIH director Francis Collins found this is a good time to spell it once again. In his statement, Collins outlines the enormous benefits humanity might gain from genomic research like understanding genetic diseases, create resistance to HIV and so on. Using gene-editing technologies in human embryos, however, is a line that shouldn’t be crossed, Collins says. The NIH director argues that there are both technical difficulties and ethical implications of altering genes in human embryos.

As a reminder, last week Junjiu Huang and colleagues at Sun Yat-sen University in Guangzhou reported in the journal Protein & Cell how they used the CRISPR-Cas9 gene-editing system to alter the DNA of a non-viable human embryo. The embryo is called non-viable because it was fertilized by two sperm. The goal was to remove a gene mutation that caused a potentially lethal blood disease called  beta thalassemia. Most of the embryos were either non affected or badly mutated.

The paper was previously refused for publication by Nature and Science for unspecified reasons. We can guess, however, that they chose not to because of ethical implications and negative PR. In light of the controversy that spewed from the research, Protein & Cell (owned by Springer) defended the Chinese researchers and explained why the journal decided to publish the paper.

“Because germline modification is permanent and heritable, it should be given the particular concerns…In this unusual situation, the editorial decision to publish this study should not be viewed as an endorsement of this practice nor an encouragement of similar attempts, but rather the sounding of an alarm to draw immediate attention to the urgent need to rein in applications of gene-editing technologies, especially in the human germ cells or embryos.”

Other researchers in America, however, don’t agree with Collins.

“I am not in favor of the NIH policy and I believe that the Chinese paper shows a responsible way to move forward,” says David Baltimore, a biologist at the California Institute of Technology in Pasadena. “But it is the will of Congress that there be no work with human embryos and I assume that means even ones that are structurally defective.”

Scientists create see-through eggshell to reduce animal testing

If you’ve ever wondered what happens inside an egg, then science has you covered – researchers have developed transparent artificial eggshells; but they didn’t do this just out of curiosity – they want to create a controlled environment for bird embryo growth and development to aid stem cell research and drug treatment reaction.

When it comes to stem cells, you need a lot of research and testing; for this reason, numerous ‘on-a-chip’ technologies have been developed over the past few years. The point is to develop miniature replicas of human organs, to see how they react when administered certain drugs and medical substances.

“Unlike its ancestor – the conventional ‘lab-on-a-chip’, which is basically chemically based – the current ‘egg-on-a-chip’, intrinsically inherited with biological natures, opens a way to integrate biological parts or whole systems in a miniature-sized device,” the team writes in the journal Science China Technological Sciences.

The benefit here is that these transparent eggs offer a much more accurate view of how real human organs might respond to these treatments – in a way, you’re replacing animal testing with embryo testing, which is more humane, and promises to be more precise. For example, one of the practical applications would be allowing for blood and other types of organic fluids to be injected inside for early diagnosis, and rare gene variations to be cultured inside, Science Alert writes.

Personally, I really like the idea of reducing (even to a small extent) animal testing; the medical importance of animal testing cannot be overstated, but we should really look into alternatives – and this one shows some promise.

This gives researchers an unprecedented view inside the egg, without having to resort to the rather crude technique of windowing; windowing basically involved cutting a hole inside the egg, opening it and closing at will. So far, researchers have managed to culture avian embryos in their artificial, transparent egg  for just over 17 days – about three days before they would be expected to hatch. The researchers didn’t “hatch” living chickens from these artificial eggs and likely won’t do so, unless they have a specific research objective.

Meanwhile, at the very least, researchers will be able to study embryo development without having to cut holes in eggs – that’s something. Hopefully, more will come from this technique.

Journal Reference: LAI YiYu, LIU Jing. Transparent soft PDMS eggshell. DOI: 10.1007/s11431-014-5737-4

 

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First was the limb, then was the penis: study unravels Genitalia Evolution

A breakthrough study authored by Harvard University developmental biologists has finally resolved the mystery of how sexual organs appeared for the first time in vertebrates. According to their findings, shortly after our sea-dwelling ancestors migrated on land, creatures were pressured to quickly evolve genitalia – which they didn’t require up until then. These sexual organs, at least for snakes and lizards, originated from the limbs. The study also found that in mice, the sex organs had genetic origins in the tail bud.  I can smell a joke cooking up.

Where does this thing fit in?

At first, the researchers were interested in studying limb origin and evolution, but as the biological reverse engineering steadily unfolded before their eyes, they came across a more interesting objective – sexual organs. They soon found that if they ran the right tweaks, they could coax  embryonic limb cells of lizards and snakes to turn into genitals; the photos we received to illustrated this post may help you form a better idea of what’s going on.

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Genitalia bud can be seen at the tail end of this house snake embryo

At the heart of this process lies the cloaca, a cavity typically programmed to become the lower part of the gut.  This structure sends out signals to the cells around it in the embryo, telling them to turn into genitals. By moving the position of this signaling source (the cloaca), the researchers were able to grow penises where otherwise would have been a limb or tail.

[RELATED] Ancient 385-million-year old Fish pioneered Sex

“It demonstrates that there is a flexibility with what kind of cells can get recruited during development to form genitalia,” explained lead author of the research, Dr Patrick Tschopp from the Harvard Medical School in Cambridge, US.

“What we were able to show is that if you ectopically transplant this cloaca into either limb or tail bud cells, these cells respond in a way that reflect their development being redirected to a genital fate,” he added.

“In other words, by misplacing a molecular signal you can misguide these cells in their developmental trajectory,” Dr Tschopp said.

In the case of the cloaca, as in real estate, location is everything. You might be surprised to find out that snakes have two penises. Well, now that researchers have thoroughly probed the cloaca, we know for certain why. Because in snakes the cloaca is located so close to their hind legs (or where they should have been), external genital formation is signaled to form in pair – hence the two penises (they only use one penis during mating, though). For mice,  the sex organs had genetic origins in the tail bud, because of, again, the cloaca’s position. Under the same evolutionary process, human genitalia   come from the “tail bud” as well.

The same snake embryo after 11 days, showing the budding hemipenes at the tail end in the centre of the spiral

The same snake embryo after 11 days, showing the budding hemipenes at the tail end in the centre of the spiral

This information was revealed by genetic tracing of the embryonic cells which showed what genes were turned on and off by extracting and sequencing RNA molecules, the messengers from each gene.

Why the snake has two penises

The weirdest part of the study may be, ironically, related to a rooster unfortunate enough to share a nickname with the penis. Roosters don’t actually have a penis, instead it has a hole of some sort. When he mates, the rooster engages in sex by lining up this opening with the analogous one on the hen, sending sperm from his cloaca to hers. This is the case for 97% of all birds on Earth (see ducks at your own risk for some science of the 3%).  When the Harvard researchers grafted cloaca tissue next to the budding limbs of some chicken embryos, they found that the cells in the area began to grow into genitals. This adds weight to a hypothesis that says birds (most of them) used to have a genital tubercle, just like we mammals have, only to degenerate later in their evolutionary development. More importantly, the experiment yet again shows that  something as simple as a signal’s shift in location can drastically influence an animal’s evolutionary path.

“This paper dealt with the longstanding unresolved issue of the origin of genitalia. It turns out that the mouse is the odd one out, it was not similar to the snakes or the chicken.

“This paper provides a new twist to a previous hypothesis that genitals and limbs share a deep homology [shared ancestry], it provides formal evidence of how this co-evolution between the two structures can happen in an organism.”

It’s amazing how many things this study explains in one single paper published in Nature. For instance, it elegantly demonstrates why so many animals have differently shaped genitals. In some cases where animals look almost the same,  taxonomists study genitals  to distinguish otherwise nearly identical species.

“This is a great study,” said Denis Duboule, chairman of the department of genetics and evolution at the University of Geneva, who wasn’t involved in the research. “It’s a very interesting new idea. There are these master signals during development, where cells are told to make a limb, or a pancreas. But in this case the same signal is used, and depending on where it’s sent from, it will touch different cells.”

Fetal development from first cellular division to final stage [PHOTO GALLERY]

Child birth is a momentous occasion in all human cultures across the globe, and if you’ve ever witnessed one it’s easy to understand why. A new life enters the world, but the journey stars well before labor. Here‘s an incredible photo gallery showcasing a typical fetal development from ovary implantation to its final chapter.

 

Image of the ~50,000 cell nuclei of a 22-hour-old zebrafish embryo. The fluorescently labeled cell nuclei are shown in a blue-to-red color code that indicates depth in the image.

Laser-light sheets used to image life at its earliest stage [GREAT PICS]

Image of the ~50,000 cell nuclei of a 22-hour-old zebrafish embryo. The fluorescently labeled cell nuclei are shown in a blue-to-red color code that indicates depth in the image.

Image of the ~50,000 cell nuclei of a 22-hour-old zebrafish embryo. The fluorescently labeled cell nuclei are shown in a blue-to-red color code that indicates depth in the image.

A new visualization technique developed by researchers at the Howard Hughes Medical Institute used a thin sheet of laser light that beams, stepwise, into different planes of a specimen to create intricate and detailed snapshots of cells. In these pictures featured above and below you can see how zebrafish and fruit fly embryos were imaged using this novel technique.

By following the color-coded cells of a Drosophila embryo (top) over time, each cell’s lineage becomes trackable (bottom) with simultaneous multi-view light sheet microscopy.

By following the color-coded cells of a Drosophila embryo (top) over time, each cell’s lineage becomes trackable (bottom) with simultaneous multi-view light sheet microscopy.

Image of the ~6,000 cell nuclei of a 3-hour-old fruit fly embryo. The fluorescently labeled cell nuclei are shown in a blue-to-red color code that indicates depth in the image.

Image of the ~6,000 cell nuclei of a 3-hour-old fruit fly embryo. The fluorescently labeled cell nuclei are shown in a blue-to-red color code that indicates depth in the image.

Here’s how it all works:

“The laser light causes the cells in the illuminated plane to fluoresce while a set of two or four cameras gather snapshots of every cell in the plane from several different angles. By taking pictures as the embryo rotates through the beam, Keller collects a set of planar views which are assembled into a dynamic three-dimensional depiction of the embryo at any given time during its 21 or more hours of development.”

A SiMView microscope uses lasers to illuminate specimens while two cameras to the left and to the right of the central imaging chamber capture shots of the specimen’s cells from different angles.

A SiMView microscope uses lasers to illuminate specimens while two cameras to the left and to the right of the central imaging chamber capture shots of the specimen’s cells from different angles.

Shark embryos stay still to avoid predators

Sharks are the ultimate predators, comfortably sitting at the very top of the food chain; but even they have their enemies (the biggest one being us, of course), especially when they’re small – nobody fears a small shark. But even in their defenseless period, sharks have managed to find a way to adapt.

Australian researchers found that the embryos know when a predator is coming by detecting its electric field, despite being confined in the small case. Sharks use jelly-filled pores on their heads called electroreceptors to recognise other animals, and especially other predators.

“Embryonic sharks are able to recognise dangerous stimuli and react with an innate avoidance response,” explained Ryan Kempster, a shark biologist and member of the research team.

The embryos (of some sharks) are encased in a leathery egg shell, developing independently from their mothers, something which renders them vulnerable to several species. When the embryo starts to grow, the egg starts to open, marking the moment when outside predators can detect the embryos movement. Scientists were expecting to find some sort of adaptation to this problem, but they were surprised to see just how efficient the method really is.

shark embryo

“Despite being confined to a very small space within an egg case where they are vulnerable to predators, embryonic sharks are able to recognise dangerous stimuli and react with an innate avoidance response,” says Kempster. “Knowledge of such behaviours may help us to develop effective shark repellents.”

The study was conducted on bamboo sharks, a species that grows up to 1.2m in length, most often found in the western Pacific or in the Australia-New Guinea region. The thing is, this kind of study could be very useful for humans in developing shark repellants, and also for saving sharks from being killed as by-catch in fishing nets.

Via University of Western Australia

The dawn of the mamimal? MPs back creation of human-animal embryos

 

embryo

 

British scientists have received the green light to research devastating diseases such as Alzheimer’s and Parkinson’s using human-animal embryos, after the House of Commons rejected a ban yesterday. Already a wave of contradictions and the scientific world is divided into two camps.

An amendment to the Human Fertilisation and Embryology Bill was rejected in a free vote, preserving what Gordon Brown regarded as a central element of the legislation. Also, the correct term is “human admixed embryos” for medical research. It is believed that these mixed embryos would be very useful in medical research in the above mentioned areas, and not just those.

Still, conservatives led by Edward Leigh, Conservative MP for Gainsborough said that mixing human and animal DNA crossed an “ultimate boundary”. Despite this opposition, the amendment, which would have banned the creation of “true hybrids” made by fertilising an animal egg with human sperm, or vice-versa was defeated.

Still, a part of those who agreed with admixed embryos refused “true hybrids”. Evan Harris, the Liberal Democrat MP for Oxford West asked those people to explain the ethical difference between an embryo that was 99 per cent human and one that was 50 per cent human. It has to be kept in mind that this doesn’t automatically provide an answer or a cure to diseases, but it’s a good start. Still, despite the fact that it is legal to culture admixed embryos up to 14 days, it’s illegal to transfer them to a human or animal womb.

While the ethical dilemma is practically impossible to solve, and the ban was rejected, we can only hope that this research will provide answers to scientists have been searching for years, or even decades. This is another chance for people to work with scientists and doctors, for a common goal.