Human Embryo Grown in Lab
Embryonic cells grew for 12 days outside a womb.
Scientists reported Wednesday they had grown human embryos in the lab for nearly two weeks, an unprecedented feat that promises advances in assisted reproduction, stem-cell therapies and the basic understanding of how human beings form.
Besides opening a window onto the first steps in the creation of an individual, the findings in parallel studies may help explain early miscarriages and why in vitro fertilization has such a high failure rate.
The research also showed for the first time that newly-forming human embryos can mature beyond a few days outside a mother's womb, something that was previously thought to be impossible.
But the widely hailed results also set science on a collision course with national laws and ethical guidelines, experts cautioned.
Up to now, a so-called "14-day rule" -- which says that human embryos cannot be cultured in the lab for more than two weeks -- has never been seriously challenged simply because no one had succeeded in keeping them alive that long.
In this case, the scientists destroyed the embryos to avoid breaching that limit. The findings were published in Nature and Nature Cell Biology.
Next to nothing is known about how the small, hollow bundle of cells called a blastocyst -- emerging from a fertilized egg -- attach to the uterus, allowing an embryo to begin to take shape.
"This portion of human development" -- called implantation -- "was a complete black box," said Ali Brivanlou, a professor at The Rockefeller University in New York, and the main architect of the Nature study.
Building on previous work with mice, Brivanlou and colleagues concocted a chemical soup and scaffolding to duplicate this process "in vitro," or in a petri dish.
"We were able to create a system that properly recapitulates what happens during human implantation," said Rockefeller scientist and lead author Alessia Deglincerti.
As hoped, the blastocyst grew, beginning to divide into the different types of cells that eventually give rise to a fetus and its placenta.
But unlike earlier experiments, in which growth has rarely continued beyond seven days, the embryos showed an unexpected ability to self-organize.
"Amazingly, at least up to the first 12 days, development occurred normally in our system in the complete absence of maternal input," Brivanlou said in a statement.
It had long been assumed that this transformation could not persist detached from the mother's uterus.
"Up to now, it has been impossible to study implantation in human embryos," said Magdalena Zernicka-Goetz, a professor at the University of Cambridge and an author for both studies.
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"This new technique provides us with a unique opportunity to get a deeper understanding of our own development during these crucial stages and helps us understand what happens, for example, during miscarriage."
The breakthrough is also likely to provide a boost to research on the use of embryonic stem cells to treat certain diseases.
"Only with this knowledge, specifically from human cells, can we control their ability to become cell types useful for drug screening or transplantation," said Gist Croft, also from Rockefeller University.
Scientists not involved in the research hailed the results as a major milestone.
"Both studies clearly demonstrate the incredible intrinsic ability of the embryo to organize itself as it starts to create the body plan -- even in the absence of a mother," said Harry Moore, a professor of reproductive biology at the University of Sheffield in England.
Allan Pacey, also of Sheffield, said they could "revolutionize our understanding of the early events of human embryo development."
Along with most experts commenting on findings, Pacey said ethical concerns are likely overblown.
"It will not open the door to couples being able to grow babies in the laboratory -- this is not the dawn of a Brave New World scenario," he said.
But the scientific community and regulators will still be faced with a decision on whether to lift or extend the 14-day rule, which is law in a dozen countries, and accepted practice in five others, including the United States and China.
Most scientists argue for a loosening of the regulations.
"Given the potential benefits of new research in infertility, improving assisted conception methods, there may be a case in the future for reconsidering this," said Daniel Brison, head of the department of reproductive medicine at the University of Manchester.
But there remains a "slippery slope" problem, commented another expert.
"If we do not use a 14-day rule, what limit will we use?," asked Henry Greely, director of the Center for Law and the Biosciences at the Stanford School of Medicine in California.
"Twelve weeks or so as in many European abortion laws? Viability -- at around 23 weeks -- as in US abortion law?"
"Human development is a seamless process," he added. "But ultimately lines need to be drawn."
In Greek mythology, chimeras were vicious monsters feared by many. This fire-breathing animal had the head and body of a lioness, with a goat head protruding from her back and the tail of a snake. Today, “chimera” refers to an animal that has two or more different sets of genetically distinct cells working together. Remember the mouse with the ear on its back? The movie "Splice" showcases a chimera experiment gone horribly wrong: scientists create a human-animal hybrid that becomes evil and goes completely out of control. While the movie is obviously science fiction, chimera experiments with human cells are not, and real life scientists have been conducting them for decades. We take a look at a few that have been successful in the past and how they’re advancing medicine.
Rabbit Eggs with Human Cells
The first successful human-animal chimeras were reported in 2003. Chinese researchers at the Shanghai Second Medical University successfully fused human cells with rabbit eggs. They were allowed to develop the eggs for several days in a petri dish before the embryos were harvested for their stem cells. Their hope was that this process could one day be used to grow cells or tissues for transplantation.
Pigs with Human Blood
A year after the successful Chinese chimera experiment, researchers at the Mayo Clinic in Minnesota announced they had created pigs with human blood pumping through their veins. What was startling about the animal is not only did the pig blood cells flow with human cells, but some of the cells merged together, creating pig-human cell hybrids. Scientists said this experiment can give them a better understanding of how viral infections can pass from animals to humans such as HIV and various others.
Sheep with Human Livers
One of the efforts behind creating chimeras is to generate animal specimens that could grow human organs to be farmed for transplantation. In 2007, scientists at the University of Nevada-Reno announced they could grow livers made up of 20 percent human cells in sheep. Dr. Esmail Zanjani injected either human adult stem cells derived from bone marrow, or human embryonic stem cells, into growing sheep fetuses. Zanjani said he uses sheep because the circulation systems of sheep and humans are similar.
How do you develop treatments for liver infections and diseases only humans can get? Salk Institute researchers came up with one solution in February 2010. Using a mouse that was having liver problems of its own, the researchers replaced its liver with one that was made up of 95 percent human cells to study treatments for Hepatitis. Shown here is a cluster of mouse liver cells that have been replaced with human cells (shown in green). Typically, small animals can't be infected with Hepatitis, only humans and chimps can, but this "humanized" mouse not only became infected, it successfully responded to drug treatments. Scientists believe this experiment could open doors to finding cures for other human liver infections such as malaria.
Cow Eggs with Human Cells
British researchers were given approval to conduct human-animal hybrid research in 2008, a decision that researchers touted would give them the ability to possibly find a cure for Parkinson’s disease. Before, only human cells were allowed to be injected into human eggs, but the researchers argued that animal eggs are much more available. After given permission, researchers went to work using cow eggs. The nucleus of the cow egg -- the source of most DNA and shown here in blue -- was removed, and replaced with the nucleus of a human cell such as a skin cell. Once the egg was allowed to develop and multiply it would become a early-stage cloned embryo called a blastocyst. Scientists could then extract the stem cells from this blastocyst to use in disease treatments.
Cat-Human Hybrid Proteins
Allergic to cats? Then you’ll appreciate this experiment. The feline Fel d 1 protein found in cat saliva contains an allergen that affects humans. When cats lick themselves, the saliva on their fur dries and turns into dust. In April 2005, scientists at the University of California created a human-cat hybrid when they fused the Fel d 1 protein with a human protein known to suppress allergic reactions. The feline protein would bind to immune cells that would cause the reaction and the human protein would tell the immune cells to calm down. When tested in mice, the chimeric protein stifled the allergy, and researchers hope they can be used in the future to treat allergy sufferers.
Irving Weissman, Stanford University professor and cofounder of the biotech company StemCells Inc., was granted permission by Stanford to create a mouse-human hybrid in 2005. Weissman and his team transplanted human-brain stem cells into the brains of mice with the intention to study neurodegenerative diseases such as Parkinson's and Alzheimer's. In his initial experiment, the human cells only made up less than 1 percent of the mouse brain. Shown here is an isolated mouse brain cell. In 2010, Stanford researchers announced they transformed mouse skin cells into fully functional neurons in a laboratory dish for the first time. They also announced in May that they successfully used mouse stem cells to develop sensory hair cells, which could combat human hearing loss.
We share over 98 percent of our DNA with chimpanzees, so would it be possible to create a human-chimp hybrid: a "humanzee," also called a "chuman" or "chumanzee"? In the 1920s, a Soviet biologist Ilia Ivanov artificially inseminated female chimps with human sperm, but the pregnancies didn't take. A chimp named Oliver became famous in the 1970s after it was thought he could be a human-chimp hybrid, because he walked upright. However, genetic testing in the 90s proved he was a chimp. Several researchers and citizens see such experiments has highly immoral and there is no known evidence of a human-chimp hybrid.