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US bid to grow human organs for transplant inside pigs

By Fergus Walsh Medical correspondent
Image caption This pregnant sow is carrying human-pig chimera embryos
Scientists in the United States are trying to grow human organs inside pigs.

They have injected human stem cells into pig embryos to produce human-pig embryos known as chimeras.

The embryos are part of research aimed at overcoming the worldwide shortage of transplant organs.

The team from University of California, Davis says they should look and behave like normal pigs except that one organ will be composed of human cells.

The human-pig chimeric embryos are being allowed to develop in the sows for 28 days before the pregnancies are terminated and the tissue removed for analysis.

The BBC's Panorama was given access to the research for Medicine's Big Breakthrough: Editing Your Genes.

Creating a chimera
Creating the chimeric embryos takes two stages. First, a technique known as CRISPR gene editing is used to remove DNA from a newly fertilised pig embryo that would enable the resulting foetus to grow a pancreas.

This creates a genetic "niche" or void. Then, human induced pluripotent (iPS) stem cells are injected into the embryo. The iPS cells were derived from adult cells and "dialled back" to become stem cells capable of developing into any tissue in the body.


The team at UC Davis hopes the human stem cells will take advantage of the genetic niche in the pig embryo and the resulting foetus will grow a human pancreas.

Gene editing technique could transform future

Pablo Ross, a reproductive biologist who is leading the research told me: "Our hope is that this pig embryo will develop normally but the pancreas will be made almost exclusively out of human cells and could be compatible with a patient for transplantation."

But the work is controversial. Last year, the main US medical research agency, the National Institutes of Health, imposed a moratorium on funding such experiments.


Image copyright Ross/UC Davis
Image caption Human stem cells being injected into a pig embryo - the cells can be seen travelling down the tube on the right of screen
The main concern is that the human cells might migrate to the developing pig's brain and make it, in some way, more human.

Pablo Ross says this is unlikely but is a key reason why the research is proceeding with such caution: "We think there is very low potential for a human brain to grow, but this is something we will be investigating."

Biological incubator
His team has previously injected human stem cells into pig embryos but without first creating the genetic niche. Prof Ross said although they later found human cells in several parts of the developing foetus, they "struggled to compete" with the pig cells. By deleting a key gene involved in the creation of the pig pancreas, they hope the human cells will have more success creating a human-like pancreas.

Other teams in the United States have created human-pig chimeric embryos but none has allowed the foetuses to be born.

Media captionScientists in the United States are trying to grow human organs inside pigs
Walter Low, professor in the department of neurosurgery, University of Minnesota, said pigs were an ideal "biological incubator" for growing human organs, and could potentially be used to create not just a pancreas but hearts, livers, kidneys, lungs and corneas.

He said if the iPS cells were taken from a patient needing a transplant then these could be injected in a pig embryo which had the key genes deleted for creating the required organ, such as the liver: "The organ would be an exact genetic copy of your liver but a much younger and healthier version and you would not need to take immunosuppressive drugs which carry side-effects."

But Prof Low stressed that the research, using another form of gene editing called TALENs, was still at the preliminary stages, trying to identify the target genes which must be removed in order to prevent the pig from developing a particular organ.

His team is also trying to create dopamine-producing human neurons from chimeric embryos to treat patients with Parkinson's disease.

These embryos have been allowed to develop for up to 62 days - the normal gestation period is around 114 days.

Like the team in California, Prof Low said they were monitoring the effects on the pig brain: "With every organ we will look at what's happening in the brain and if we find that it's too human like, then we won't let those foetuses be born".

Animal viruses
Gene editing has revitalised research into xenotransplantation, and the concept of using animal organs for humans.

In the mid-90s there were hopes that genetically modified pigs might provide an endless supply of organs for patients, and that cross-species transplants were not far off.

But clinical trials stalled because of fears that humans might be infected with animal viruses.

Last year, a team at Harvard Medical School used CRISPR gene editing to remove more than 60 copies of a pig retrovirus.

Prof George Church, who led the research, told me: "It opens up the possibility of not just transplantation from pigs to humans but the whole idea that a pig organ is perfectible.

"Gene editing could ensure the organs are very clean, available on demand and healthy, so they could be superior to human donor organs."

Animal suffering
But organisations campaigning for an end to factory farming are dismayed at the thought of organ farms.

Peter Stevenson, from Compassion in World Farming, told me: "I'm nervous about opening up a new source of animal suffering. Let's first get many more people to donate organs. If there is still a shortage after that, we can consider using pigs, but on the basis that we eat less meat so that there is no overall increase in the number of pigs being used for human purposes."

In Greek mythology, chimeras were fire-breathing monsters composed of several animals - part lion, goat and snake. The scientific teams believe human-pig chimeras should look and behave like normal pigs except that one organ will be composed of human cells.

Scott Fahrenkrug, whose Minnesota-based company Recombinetics is teaming up on the chimera research with Prof Low, told me: "Perhaps the term chimera is going to take on a new meaning and it will be one that's much more affectionate: chimeras will be seen to be what they are which is a saviour, given that they will provide, life-saving, sustaining organs for our patients."

Seven thousand people in the UK are on the transplant waiting list and hundreds die each year before a donor can be found.

Panorama - Medicine's Big Breakthrough: Editing Your Genes will be shown on BBC1 at 20.30 BST on Monday 6 June 2016 and will be available afterwards on BBC iPlayer

bbc.com/news/health-36437428
 
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Hamartia Antidote

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US bid to grow human organs for transplant inside pigs

By Fergus Walsh Medical correspondent
Image caption This pregnant sow is carrying human-pig chimera embryos
Scientists in the United States are trying to grow human organs inside pigs.

They have injected human stem cells into pig embryos to produce human-pig embryos known as chimeras.

The embryos are part of research aimed at overcoming the worldwide shortage of transplant organs.

The team from University of California, Davis says they should look and behave like normal pigs except that one organ will be composed of human cells.

The human-pig chimeric embryos are being allowed to develop in the sows for 28 days before the pregnancies are terminated and the tissue removed for analysis.

The BBC's Panorama was given access to the research for Medicine's Big Breakthrough: Editing Your Genes.

Creating a chimera
Creating the chimeric embryos takes two stages. First, a technique known as CRISPR gene editing is used to remove DNA from a newly fertilised pig embryo that would enable the resulting foetus to grow a pancreas.

This creates a genetic "niche" or void. Then, human induced pluripotent (iPS) stem cells are injected into the embryo. The iPS cells were derived from adult cells and "dialled back" to become stem cells capable of developing into any tissue in the body.


The team at UC Davis hopes the human stem cells will take advantage of the genetic niche in the pig embryo and the resulting foetus will grow a human pancreas.

Gene editing technique could transform future

Pablo Ross, a reproductive biologist who is leading the research told me: "Our hope is that this pig embryo will develop normally but the pancreas will be made almost exclusively out of human cells and could be compatible with a patient for transplantation."

But the work is controversial. Last year, the main US medical research agency, the National Institutes of Health, imposed a moratorium on funding such experiments.


Image copyright Ross/UC Davis
Image caption Human stem cells being injected into a pig embryo - the cells can be seen travelling down the tube on the right of screen
The main concern is that the human cells might migrate to the developing pig's brain and make it, in some way, more human.

Pablo Ross says this is unlikely but is a key reason why the research is proceeding with such caution: "We think there is very low potential for a human brain to grow, but this is something we will be investigating."

Biological incubator
His team has previously injected human stem cells into pig embryos but without first creating the genetic niche. Prof Ross said although they later found human cells in several parts of the developing foetus, they "struggled to compete" with the pig cells. By deleting a key gene involved in the creation of the pig pancreas, they hope the human cells will have more success creating a human-like pancreas.

Other teams in the United States have created human-pig chimeric embryos but none has allowed the foetuses to be born.

Media captionScientists in the United States are trying to grow human organs inside pigs
Walter Low, professor in the department of neurosurgery, University of Minnesota, said pigs were an ideal "biological incubator" for growing human organs, and could potentially be used to create not just a pancreas but hearts, livers, kidneys, lungs and corneas.

He said if the iPS cells were taken from a patient needing a transplant then these could be injected in a pig embryo which had the key genes deleted for creating the required organ, such as the liver: "The organ would be an exact genetic copy of your liver but a much younger and healthier version and you would not need to take immunosuppressive drugs which carry side-effects."

But Prof Low stressed that the research, using another form of gene editing called TALENs, was still at the preliminary stages, trying to identify the target genes which must be removed in order to prevent the pig from developing a particular organ.

His team is also trying to create dopamine-producing human neurons from chimeric embryos to treat patients with Parkinson's disease.

These embryos have been allowed to develop for up to 62 days - the normal gestation period is around 114 days.

Like the team in California, Prof Low said they were monitoring the effects on the pig brain: "With every organ we will look at what's happening in the brain and if we find that it's too human like, then we won't let those foetuses be born".

Animal viruses
Gene editing has revitalised research into xenotransplantation, and the concept of using animal organs for humans.

In the mid-90s there were hopes that genetically modified pigs might provide an endless supply of organs for patients, and that cross-species transplants were not far off.

But clinical trials stalled because of fears that humans might be infected with animal viruses.

Last year, a team at Harvard Medical School used CRISPR gene editing to remove more than 60 copies of a pig retrovirus.

Prof George Church, who led the research, told me: "It opens up the possibility of not just transplantation from pigs to humans but the whole idea that a pig organ is perfectible.

"Gene editing could ensure the organs are very clean, available on demand and healthy, so they could be superior to human donor organs."

Animal suffering
But organisations campaigning for an end to factory farming are dismayed at the thought of organ farms.

Peter Stevenson, from Compassion in World Farming, told me: "I'm nervous about opening up a new source of animal suffering. Let's first get many more people to donate organs. If there is still a shortage after that, we can consider using pigs, but on the basis that we eat less meat so that there is no overall increase in the number of pigs being used for human purposes."

In Greek mythology, chimeras were fire-breathing monsters composed of several animals - part lion, goat and snake. The scientific teams believe human-pig chimeras should look and behave like normal pigs except that one organ will be composed of human cells.

Scott Fahrenkrug, whose Minnesota-based company Recombinetics is teaming up on the chimera research with Prof Low, told me: "Perhaps the term chimera is going to take on a new meaning and it will be one that's much more affectionate: chimeras will be seen to be what they are which is a saviour, given that they will provide, life-saving, sustaining organs for our patients."

Seven thousand people in the UK are on the transplant waiting list and hundreds die each year before a donor can be found.

Panorama - Medicine's Big Breakthrough: Editing Your Genes will be shown on BBC1 at 20.30 BST on Monday 6 June 2016 and will be available afterwards on BBC iPlayer

bbc.com/news/health-36437428
OP article was from 2016

2017
https://www.livescience.com/57642-human-pig-chimeras.html
Human-Pig Chimeras Created, Could One Day Aid in Organ Transplants

2018
https://sea.mashable.com/science/17...was-created-in-2018-heres-what-you-didnt-know
The first sheep-human hybrid was created in 2018. Here's what you didn't know.
 
Last edited:

Shah_Deu

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Sometimes i think Dajjal might be some strange creation from such pointless experimentation in the future and the then scientific community will regard him and his super powers as normal. May Allah protect us all from Dajjal.
 

GodToons

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US bid to grow human organs for transplant inside pigs

By Fergus Walsh Medical correspondent
Image caption This pregnant sow is carrying human-pig chimera embryos
Scientists in the United States are trying to grow human organs inside pigs.

They have injected human stem cells into pig embryos to produce human-pig embryos known as chimeras.

The embryos are part of research aimed at overcoming the worldwide shortage of transplant organs.

The team from University of California, Davis says they should look and behave like normal pigs except that one organ will be composed of human cells.

The human-pig chimeric embryos are being allowed to develop in the sows for 28 days before the pregnancies are terminated and the tissue removed for analysis.

The BBC's Panorama was given access to the research for Medicine's Big Breakthrough: Editing Your Genes.

Creating a chimera
Creating the chimeric embryos takes two stages. First, a technique known as CRISPR gene editing is used to remove DNA from a newly fertilised pig embryo that would enable the resulting foetus to grow a pancreas.

This creates a genetic "niche" or void. Then, human induced pluripotent (iPS) stem cells are injected into the embryo. The iPS cells were derived from adult cells and "dialled back" to become stem cells capable of developing into any tissue in the body.


The team at UC Davis hopes the human stem cells will take advantage of the genetic niche in the pig embryo and the resulting foetus will grow a human pancreas.

Gene editing technique could transform future

Pablo Ross, a reproductive biologist who is leading the research told me: "Our hope is that this pig embryo will develop normally but the pancreas will be made almost exclusively out of human cells and could be compatible with a patient for transplantation."

But the work is controversial. Last year, the main US medical research agency, the National Institutes of Health, imposed a moratorium on funding such experiments.


Image copyright Ross/UC Davis
Image caption Human stem cells being injected into a pig embryo - the cells can be seen travelling down the tube on the right of screen
The main concern is that the human cells might migrate to the developing pig's brain and make it, in some way, more human.

Pablo Ross says this is unlikely but is a key reason why the research is proceeding with such caution: "We think there is very low potential for a human brain to grow, but this is something we will be investigating."

Biological incubator
His team has previously injected human stem cells into pig embryos but without first creating the genetic niche. Prof Ross said although they later found human cells in several parts of the developing foetus, they "struggled to compete" with the pig cells. By deleting a key gene involved in the creation of the pig pancreas, they hope the human cells will have more success creating a human-like pancreas.

Other teams in the United States have created human-pig chimeric embryos but none has allowed the foetuses to be born.

Media captionScientists in the United States are trying to grow human organs inside pigs
Walter Low, professor in the department of neurosurgery, University of Minnesota, said pigs were an ideal "biological incubator" for growing human organs, and could potentially be used to create not just a pancreas but hearts, livers, kidneys, lungs and corneas.

He said if the iPS cells were taken from a patient needing a transplant then these could be injected in a pig embryo which had the key genes deleted for creating the required organ, such as the liver: "The organ would be an exact genetic copy of your liver but a much younger and healthier version and you would not need to take immunosuppressive drugs which carry side-effects."

But Prof Low stressed that the research, using another form of gene editing called TALENs, was still at the preliminary stages, trying to identify the target genes which must be removed in order to prevent the pig from developing a particular organ.

His team is also trying to create dopamine-producing human neurons from chimeric embryos to treat patients with Parkinson's disease.

These embryos have been allowed to develop for up to 62 days - the normal gestation period is around 114 days.

Like the team in California, Prof Low said they were monitoring the effects on the pig brain: "With every organ we will look at what's happening in the brain and if we find that it's too human like, then we won't let those foetuses be born".

Animal viruses
Gene editing has revitalised research into xenotransplantation, and the concept of using animal organs for humans.

In the mid-90s there were hopes that genetically modified pigs might provide an endless supply of organs for patients, and that cross-species transplants were not far off.

But clinical trials stalled because of fears that humans might be infected with animal viruses.

Last year, a team at Harvard Medical School used CRISPR gene editing to remove more than 60 copies of a pig retrovirus.

Prof George Church, who led the research, told me: "It opens up the possibility of not just transplantation from pigs to humans but the whole idea that a pig organ is perfectible.

"Gene editing could ensure the organs are very clean, available on demand and healthy, so they could be superior to human donor organs."

Animal suffering
But organisations campaigning for an end to factory farming are dismayed at the thought of organ farms.

Peter Stevenson, from Compassion in World Farming, told me: "I'm nervous about opening up a new source of animal suffering. Let's first get many more people to donate organs. If there is still a shortage after that, we can consider using pigs, but on the basis that we eat less meat so that there is no overall increase in the number of pigs being used for human purposes."

In Greek mythology, chimeras were fire-breathing monsters composed of several animals - part lion, goat and snake. The scientific teams believe human-pig chimeras should look and behave like normal pigs except that one organ will be composed of human cells.

Scott Fahrenkrug, whose Minnesota-based company Recombinetics is teaming up on the chimera research with Prof Low, told me: "Perhaps the term chimera is going to take on a new meaning and it will be one that's much more affectionate: chimeras will be seen to be what they are which is a saviour, given that they will provide, life-saving, sustaining organs for our patients."

Seven thousand people in the UK are on the transplant waiting list and hundreds die each year before a donor can be found.

Panorama - Medicine's Big Breakthrough: Editing Your Genes will be shown on BBC1 at 20.30 BST on Monday 6 June 2016 and will be available afterwards on BBC iPlayer

bbc.com/news/health-36437428
With advancement in medical science, India should join the research and grow organs in PIGS. We have huge population in queue waiting for organ.
 

Cookie Monster

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Sometimes i think Dajjal might be some strange creation from such pointless experimentation in the future and the then scientific community will regard him and his super powers as normal. May Allah protect us all from Dajjal.
How exactly is this pointless? Can u explain in detail? Pigs have a somewhat decent compatibility with humans...for example pig's heart valves can be transplanted into humans. It works...however bcuz it is still not human(having different cell markers) the immune system can still reject it. Therefore the goal is to make it as close to that human(receiving the transplant) as possible...ideally made from that human's own stem cells. So if one could theoretically insert just the genes that are responsible for let's say the development of liver in a pig embryo...we could potentially have a human liver grown in a pig...which can then be transplanted into those who need it. If this works...it practically gives humans an organ factory. What's so wrong in that? There are so many ppl who are suffering and not enough organs are available for transplant...if there are such options...the costs can be high enough to put it out of reach of many ppl in developing countries. Don't shun something new just bcuz of some preconceived notions.

true but they r medicines but transplanting organs which will remain inside u for rest of ur life ewwww
U should thank God that everything is working properly in ur body. Many who are suffering bcuz they need organ transplants don't get to say ewww. Go ask a patient with total kidney failure who has to get dialysis regularly...and that's one of the better scenarios. Those who need liver, heart, and lung transplants...are facing much more grim outcomes.

If it comes to your life or a pig valve, then go for the pig valve or die for your religious values, choice is yours.
How is religion involved in this? Consumption of pork and pork products is haram...however if hypothetically someone has to eat pig in order to survive (as in there is no other option and they will likely die of hunger) then it is permitted. So in short...for life saving measures...there's no issue that an organ needed for a patient came from a pig.
 

Manidabest

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If it comes to your life or a pig valve, then go for the pig valve or die for your religious values, choice is yours.
i would prefer to die and please save a life by educating ur indians that beef is eaten all over the world soo dont lynch people over it ....
 

Chhatrapati

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i would prefer to die and please save a life by educating ur indians that beef is eaten all over the world soo dont lynch people over it ....
Beef is eaten in India too. Surprised?

How is religion involved in this? Consumption of pork and pork products is haram...however if hypothetically someone has to eat pig in order to survive (as in there is no other option and they will likely die of hunger) then it is permitted. So in short...for life saving measures...there's no issue that an organ needed for a patient came from a pig.
Religion certainly plays a role in it especially when it comes to organ donation, blood transfusion, animal derived proteins for organs etc... Like Manidabest said, he'd rather die. Some people don't agree with you, some does.
I agree with saving lives rather.
 

Cookie Monster

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Beef is eaten in India too. Surprised?


Religion certainly plays a role in it especially when it comes to organ donation, blood transfusion, animal derived proteins for organs etc... Like Manidabest said, he'd rather die. Some people don't agree with you, some does.
I agree with saving lives rather.
Like I said the RELIGION permits it...it's the followers u mean who may follow whatever it is they please. Islam is very lenient when it comes to some sort of hardship...Islam is not for causing suffering but rather it is a civilized, dignified, and morally righteous way to live life.

Some of the most basic examples are as follows...
- u can skip roza(fasting during Ramadan) if u r sick or travelling(back in the day travelling long distances was tough...it wouldn't count as a reason today)...u can then make it up when u r well.
- if somebody cannot stand(e.g. arthritis or some other knee problems...or if they are in an airplane) they can pray sitting down...if somebody is unable to even do that they can pray laying down. If still somehow unable...they can make it up at a later time.
- if someone financially can't afford to do Hajj they don't have to(it is forgiven). If someone financially can't afford to pay zakat(alms) they don't have to...instead they are entitled to receive zakat from those who have money.
- if someone can't afford to do qurbani(animal sacrifice) they don't have to(it is forgiven)...instead they are entitled to receive the meat (distributed by those who can afford to do qurbani).

Those above are just a few examples of some of the most core tenets of Islam that every Muslim is expected to do...and u can see how many leniencies are provided for true hardship(faking it does not count). In short the religion has provided many exceptions to make sure a person doesn't end up suffering while trying to follow the religion. This applies to the medical needs as well.
 

DESERT FIGHTER

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People here are idiots, this is wonderful.. this is revolutionary science, a hope for millions upon millions of people disabled and dying.

Who cares if its a “ewww” pig!
 

Nan Yang

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She’s hellbent on solving the organ shortage with ‘designer pigs.’ Just don’t keep her waiting
By Sharon Begley
April 6, 2017
Luhan Yang

Luhan Yang, cofounder and chief scientific officer of eGenesis, in its lab in Cambridge, Mass.KAYANA SZYMCZAK FOR STAT

CAMBRIDGE, Mass. — Where other people see bacon, biologist Luhan Yang sees lifesaving organs — hundreds and thousands of them, pig livers and pig kidneys and diabetes-curing pancreases, and possibly hearts and lungs, all growing inside droves of pampered swine.

More established scientists than Yang have dreamed of creating animal organs that are suitable for transplantation into people waiting for a human donor. But until recently, experts said it would take decades to genetically alter pig organs to make them work safely in people. Most xeno dreamers gave up.

Giving up is not in Yang’s lexicon. Urgency is. In her native China, she told STAT, 2 million people need organ transplants, “and people are dying before they get one.”

The intensely driven 31-year-old has a few things going for her that other would-be pioneers did not. As a Harvard graduate student, Yang was a lead author of a breakthrough 2013 study on the genome-editing technology CRISPR-Cas9. And in 2015, she cofounded the biotech company eGenesis with her mentor, legendary Harvard bioengineer George Church, with whom she’s also worked on trying to resurrect the Ice Age wooly mammoth through genetic legerdemain. From eGenesis’s tiny headquarters in Kendall Square, she intends to use CRISPR to accomplish what the world’s largest drug companies failed to despite investing billions of dollars: create “designer pigs” whose organs can be transplanted into people.

“Luhan is a remarkable person,” Church said, “and a force of nature.”

She better be. Daunting hurdles stand between where biology is now and where it needs to be to make transplantable pig organs. The old problems of infection and rejection of another species’ organs seem almost quaint compared to those confronting eGenesis.

There’s the challenge of CRISPR’ing an unprecedented number of genes without compromising the viability of the designer pigs and without introducing aberrant edits. And of optimizing mammalian cloning, which is how the company creates the pigs. And of persuading investors and doctors that xenotransplantation is safe, effective, ethical — and lucrative.

Yang, eGenesis’s chief scientific officer, has already made enormous strides, scientific and financial. In 2015, she and colleagues in Church’s lab used CRISPR to eliminate from pig cells 62 genes so potentially dangerous their very existence nixed previous efforts to turn pigs into organ donors. Last month, eGenesis announced that it had raised $38 million from investors. The next hurdle: get the surrogate-mother sows that are pregnant with genetically altered embryos to give birth to healthy piglets.

“Her work has the potential to change the face of transplantation and to save countless lives,” said Dr. James Markmann, chief of transplant surgery at Massachusetts General Hospital.

Yang is not only confident of success; she also sees eGenesis’s xeno work as a sort of trial run for even bolder goals. In 2016, she helped conceive Genome Project-write, whose aims include assembling a synthetic human genome from off-the-shelf parts and — because, really, as long as you’re making a human genome, why not? — doing it better than nature.

By starting from scratch, she wonders, “could we make the human genome cancer-resistant? … Or make it virus-resistant? … There is a great opportunity that xeno can tell us what would happen in humans after dramatic genome engineering.”

But if eGenesis is to succeed in making designer pigs, let alone paving the way for new and improved humans, Yang will need to fix the miscarriage problem.

Luhan Yang
A Petri dish with human embryonic kidney cells at the eGenesis lab, where scientists are taking the first steps toward creating genetically altered “designer pigs.”KAYANA SZYMCZAK FOR STAT

A ton of genetic handiwork
On a frigid March morning, Yang is holding her monthly meeting with Church and the company’s half-dozen employees, getting updates on the designer-pig pipeline and lighting a fire under her team. The big conference table in the windowless, unadorned basement room is strewn with 8.5-ounce cans of “Wild Jujube Drink” and snacks that Yang brought back from her Lunar New Year visit to China, where she spent five days with her parents and visited eGenesis’s pig colony.

The “highlight of the month,” biologist Marc Guell tells Yang, is that surrogate mother pigs didn’t reinfect fetuses with “PERVs.” That’s crucial, because the memorably named infectious agents, short for porcine endogenous retroviruses, could cause tumors, leukemia, and neuronal degeneration if transplanted into patients. To make xenotransplantation succeed, PERVs have to go.

PERV genes are interwoven into the genome of pig cells, so eGenesis scientists start their work with CRISPR-Cas9, which has made editing organisms’ genomes so simple high-schoolers can do it. It takes far more expertise, however, to remove dozens of PERV genes at once, as eGenesis does in pig fibroblasts, which are connective-tissue cells.

eGenesis ships batches of these cells to China, where each de-PERV’ed pig cell is fused with a pig ovum whose own DNA has been removed. The ova, which now contain only the PERV-free genome, start dividing and multiplying, beginning the journey to becoming pig fetuses. (This adult-cell-plus-ova technique was used to clone Dolly the sheep.) The embryos are implanted into surrogate mothers and, if all goes well, born 114 days later. (Yang won’t say how many sows are or have been pregnant.) Unfortunately, all has not gone well.

The anti-PERV work is only the start of the changes eGenesis is making to pig genomes. Its scientists are also slipping into the pig ova up to 12 human genes “to make the pig organs more human-like,” Yang said in an interview. One gene, she said, would shield its organs from attack by the human immune system; another would revamp its coagulation system to reduce the risk of clots.

That’s a ton of genetic handiwork for one little pig to handle, and early signs are it might be too much.

One batch of embryos all died, Yang said, possibly because their chromosomes had gotten scrambled by either the genetic changes or the lab manipulations. Another batch had “a lot of miscarriage,” she said.

There are other concerns, scientists noted at the March meeting. Sometimes PERVs are found in the embryos before they’re implanted into surrogate mothers. The problem, Yang says as she leaps to the front of the conference room, is that removing the DNA-containing nuclei from pig ova isn’t always complete; occasionally some of an ovum’s own PERV-infested genes remain behind, so the embryo created from it also has PERVs, genetic analyses showed.

Yang grills her team. How prevalent is this? May I see the genetic profile again? What can we do quickly to correct the protocol? A gene that was inserted to protect other genes “is the problem,” she says with finality. “Maybe we should pause this one and look for other solutions. It’s better to figure out where the problem comes from, then we don’t have the problem anymore.”

Luhan Yang
A research station at eGenesis, which is using CRISPR to rid pig genomes of viruses and make the animals’ organs safe for human transplant.KAYANA SZYMCZAK FOR STAT

‘We’re short of time’
A clue to how Yang’s mind works is that she counts. Ask her about the ethical issues around xenotransplantation and she will immediately tell you there are three, then elaborate on them. Ask her what characteristics make up the “entrepreneurial spirit” and she will say there are four, then reel them off. Colleagues say she has an uncanny knack for working backward from an ultimate goal and breaking it into a manageable sequence of steps.

She darts down corridors, speaks quickly, hates waiting, and expects others to move at her speed. Some colleagues call her impatient. Biologist Dong Niu, who worked in the Church lab and is now at eGenesis, accompanied Yang on a recent blitz of apartment hunting. Yang set such a breakneck pace, Niu said, “I couldn’t even watch.”

“Luhan is a remarkable person and a force of nature.”
GEORGE CHURCH

When eGenesis was packing up a previous office, waiting for the movers irritated Yang so much that she plopped her computer and other belongings into a child’s Radio Flyer wagon and took off.

Even on vacation, Yang operates on fast-forward, jet skiing while visiting places like Hawaii. Closer to home, she unwinds by having friends and coworkers over for dinner and karaoke, making sure to order enough so her guests can take home leftovers.

She pushes colleagues to accomplish tasks — analyzing DNA edits, checking the viability of cells — now, if not sooner, and when she asks a coworker to explain a scientific detail, she says, “We’re short of time; just get to the point.”

Yet colleagues sing her praises, saying she motivates them and brings “extraordinary passion” and a “laser focus” to her work. “Whenever you have a question, she has an answer, almost before you get it out,” said Niu.

Coworkers also mention her kindnesses, like the sweltering summer day when the tiny Yang passed a discarded air conditioner on a Cambridge street and, on foot, hauled it to the eGenesis office 30 minutes away. She left it on the desk of a colleague whose apartment had no AC.

Yang was born and grew up in a small town in a mountainous region of southwest China. Her parents were “ordinary working class people,” she told STAT, her father a government employee and her mother an accountant.

Her hometown is named for the Chinese Buddha who represents wisdom. “Because of that we have a lot of temples in the mountain,” she said. “And because of that I was very fascinated by nature when I was young. I think that had an influence on how I decided my career path.”

In 2004, as a high school senior, she was chosen for China’s four-person team in the 15th International Biology Olympiad, held in Australia. The global competition consisted of a written test on biological theory and a practical test of lab techniques. Yang was one of 16 contestants to win a gold medal, coming in 13th.

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