Scientists have successfully transplanted a bioengineered lung into a pig | Hacker News Reader

Scientists have successfully transplanted a bioengineered lung into a pig

bbc.co.uk

274 pointsTeever71 comments

This technology could not come any sooner. I lost my 37 year old wife to metastatic cancer. We were able to arrest the spread and even shrink the primary areas with established treatments but due to the vascularization of the lungs, could not get them disease free and that's what killed her. The thought of having had the chance to replace her lungs and let the biotechnology wipe out the malignant cells everywhere else is a prayer for patients and caregivers alike. Keep up the good fight dear scientists.

My condolences for your loss.. I can’t even imagine what that must have been like.. hats off to the researchers for the accomplishment.

Does anyone know the process that would take this from pig to human?

> Does anyone know the process that would take this from pig to human?

Pre-clinical studies on animals, then the usual clinical trial series from Phase I to III on humans. And depending on the sample size required by authorities for approval, and how fast they can produce and transplant lungs, it could take 10 years or likely longer.

Scientist in the article says we could see one in patients as soon as 5 years

Trial patients?

Yes, I think that's what they meant.

thinking about all the nonsense some so called scientists are spreading: lets stop this research until all the ethical questions are answered.

What ethical issues? The pigs? We kill 300k every single day in the US...that's 3.5/second.

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> Investigators used a cocktail of sugar and detergent to get rid of all the cells and blood vessels from a lung taken from a donor pig. This left behind a support scaffold made from proteins - the lung's "skeleton" if you like.

If I'm reading this correctly, a donor is still needed, and the main advance is that the lung is less likely to be rejected because the cells match the recipient.

I’m not sure how well this works with lungs, but for less vital tissues (ligaments, cartilage for instance) it allows animal tissues to be used in humans. Instead of needing a human organ, you could potentially remove the cells from a pig organ and then be repopulated by human cells.

I imagine that this just happens an easy way to get a "scaffold" to build the lung on for the moment being.

I think, the scaffold is an extremely important part of the process, it has chemical and physical signals which allow stem cells to develop properly. I haven’t heard of a plastic scaffold being used except in Macchiarini scandal, where the patients either died or had to have their artificial windpipe replaced. And that was for a windpipe which is a layered 2D structure, not something like a lung with an enormously complicated 3D vasculature. I suspect artificial scaffolds will be far more difficult than the process covered here.

Your comment prompted me to find out about the Macchiarini scandal, which I had not previously been aware of. That's some seriously scary shit that went down there! When your experimental technique fails - again and again - and multiple people die - one after another - and you still go on doing it... that's just sick. Or dedication, I presume.

The section about the bronchoscopy is this article is terrifying:

https://www.bbc.com/news/magazine-37311038

Stem cell science must above all avoid another Jesse Gelsinger case. Superstar researchers will always want to take chances, but the risks have to be strictly managed by the community or else there will be a backlash and progress will be set back by decades.

Macchiarini seems to have told lies about everything, not just his research. Strikingly, he told one journalist that he would marry her and the Pope himself would officiate (https://www.vanityfair.com/news/2016/01/celebrity-surgeon-nb...), while he in fact did not know the pope and also was already married.

This is still ultimately a limitation not an impossibility. I can easily imagine some form of tissue deposition like 3D printing where you use laser activated gene regulation to control cell fate of the stem cells digitally at high spatial resolution.

From what I understand, artificial ECMs can be more difficult to build in some ways, but if you can figure out how to incorporate the right signaling factors into an artificial collagen matrix, you can avoid a lot of challenging biocompatibility/immune reaponse problems. Also, I believe most cells are differentiated before being seeded onto the scaffold.

Thanks for the information. I didn’t realize there were still biocompatibility issues even after the detergent process.

It might (completely guessing here) also mean that lungs that wouldn't be suitable for normal transplant due to health or condition, might be suitable to be used in this way.

I wonder how much this process reverses the age of the lungs, if you take the lungs of an 80 year old, wash them, reseed them and put them in a 20 year old, what’s the result?

I don't work in this area, but ECM scaffolds undergo significant change with age. Crosslinks and age-related remodelling degrade the mechanical properties of the scaffold and interfere with normal cell migration and differentiation.

You would want to start with a healthy organ before decellularising and reseeding.

But perhaps not quite as critical as for current transplants? At least that's my uneducated guess... anyone know?

If that would work I guess people would like to "refresh" their organs anyway from time to time to avoid failure.

Yes, though I would expect the risk of complications from this procedure will outweigh the benefit for healthy patients for many years after it becomes a "routine" operation for those with lung disease.

Weird thought what if a 20'something put cells in a bank and had organs generated from them later in life.

The difference here is before the donor had to be a near perfect fit. With this method they can build the scaffolding from any dead body then use recipients cells for the tissue.

So we go from a couple thousand lung transplants a year with 50% mortality to potentially unlimited and much lower mortality (don't really know the mortality rate here but so far looks promising and better than).

Along with that, the fact that the scaffolding isn't living cells means that they can likely preserve the lungs for longer periods of time for future recipients too. That should be a massive boon for transplants since they'll no longer need to be a "Get here in 30 minutes or the organ won't be viable long enough" kind of situation.

Additionally the donor doesn't necessarily have to be human.

If pig lungs are a good enough a fit.

Pig lungs are extemely close to human lungs --- that's why a lot of such research is done on them.

Looks like the age of chimeras is upon us.

It's already here to an extent. Pig heart valves have already been transplanted into humans.

Would pig lungs offer an advantage somehow in terms of performance?

I was thinking in terms of availability.

There are more pigs in Australia than people, comprised of about 24 million feral pigs and about 4.5 million pigs produced each year for consumption.

Australia's population is currently about 25 million.

The number of normal pigs available isn't really significant... Even if you assume that the donor pigs wouldn't be heavily genetically engineered (and they probably would be), the risk of xenogeneic infection (ie pig viruses being carried over to the patient) means that they'd have to be raised under sterile conditions, so normal pigs are useless. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88959/ https://www.ncbi.nlm.nih.gov/pubmed/11041495

Thanks for the reply.

Fair points.

We’re not talking about xenotransplantation of living tissues though.

Still, there would probably be a non-zero chance of xenoinfection from non-human non-cellular scaffold use in bioengineered organs.

You’re probably right that if this were to become a use case for non-human parts the source probably wouldn’t be regular far animals.

We’re not talking about xenotransplantation of living tissues though. I appreciate that. I did have the idea that the stringency of the washes in decellularization wouldn't be enough to get rid of viruses. Looked into it and it turns out that might not be true. Washing might be enough: https://www.ncbi.nlm.nih.gov/pubmed/12115437

Not sure how compatible this is w/ the protocol used in the OP.

That didn't even occur to me. If they were compatible for this in humans, then a huge amount of the meat industry could benefit by providing the lungs that they can't always easily sell (organ meat isn't as popular for humans at least).

it's also a boon towards eventually 3d printing the scaffolding instead of using a pregrown one

This can be done autologously, if mechanical or biological redundancy is available: heart, kidney, liver, etc. lungs are hard, but the talk from old colleagues at UTMB are near-primate & primate donors. There are significant ethical issues with the latter.

lung transplantees only live for around a year post-transplant. rejection is much more common with lungs than other organs

This is anecdotal only, but I know several CF patients who have lived for years on transplanted lungs.

This journal article suggests a median survival rate of 5.8 years:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594127/

My dad has COPD and IPF he's still going with (very expensive) medication but it's taking a toll. It sounds great to live but living well is the goal.

Lung transplants are great but most lung disease occur decades later after a long career especially blue collar jobs where a person is exposed to many irritants not toxic but cause cumulative damage. Although anecdotal sailors (Navy, Coast Guard) for some reason have an unusually high rates of lung disease mainly COPD and IPF.

Lung transplants if possible cut certain nerves and the transplant recipient no longer has a cough reflex due to cutting vagal nerve fibers. But it seems it's possible it can recover, maybe only for younger patients.

I think the recent articles about mitochondria transfer from muscle tissue to damaged tissue is more promising. It would be nice to see some studies on that involving lung tissue.

The exciting thing about this is what other organs can be developed using this technique.

While this is fascinating, I wonder if we could produce the scaffolding itself de novo, and if not, then why? It's not a living thing, just a porous biocompatible structure. At worst, we could grow a lot of skin and process it into scaffolding of arbitrary shape. Or is there some crucial trick, such as remaining chemical signals that guide the development of new cells?

I could see tolerances being an issue there are a lot of fine structures - even if we could shape the protein scaffolds successfully lungs would be far more complex than say a bladder.

Curious to see if they’ll ever be able to produce a scaffold without a donor lung to strip down

Did the pigs need the transplants, like were they sick? (I can't access the article's supplementary materials)

This is why I don't support universal health care. Health care is expensive because of basic supply and demand, everybody needs health care and doctors and drugs are expensive to train/develop. Government regulation can't just magically make a few million nurses and doctors appear, can't make cancer drugs develop themselves. It will only kill investment and innovation in the medical field.

Investing trillions in universal health care would just be wasted money on a shitty system, like trying to make horses faster rather than inventing the car and plane. The solution to affordable healthcare will be a combination of AI for diagnosis and surgery plus cloning and stem cells for organ transplants.

People need to be patient and put things in perspective, 100 years ago the richest person on earth could die from an infected scratch because we didn't have antibiotics. We've come very far in a short period of time.

How are these two things contradicting? You can have universal health care and still have the rich paying for private services and research, with their own money and with their taxes.

(In my country we have a relatively-to-the-US wonderful UHC system, and we still see a lot of research, experiments, competition and innovation)

The funding for universal health care would have to come from somewhere, probably higher taxes. So instead of being invested, the money would be stuffed into an inefficient system. There's also the matter of scale, US system would be far larger than any individual Euro country and thus more expensive due to bureaucracy. Also the issue of the US having much lower population density and how to handle that, ie are rural people going to have to drive 5 hours to get the health care their taxes pay for?

Also worth noting that the US is essentially the profit center for the entire world's pharma industry. If that was eliminated investment would be reduced globally, not just the US. US citizens are currently subsidizing European countries public healthcare.

https://www.ibtimes.com/how-us-subsidizes-cheap-drugs-europe...

re: density- Canada has even lower pop density than the US, and our universal health care system compares very favourably. Your arguments seem like nothing more than fear-mongering to me.

around 80% of Canada's population lives within 100 miles of the US boarder. Canada's density is skewed by northern land with nobody living there.

https://qph.fs.quoracdn.net/main-qimg-2c86ad127d43c7e1f9a62d...

so? you think most Canadians cross the border to go to the doctor? pretty laughable

No, but having to provide health care to citizens in rural areas is expensive. Many elderly citizens wouldn't be able to travel to large cities to get the health care their taxes paid for. This is an issue that's largely non-existent in europe.

Basic health care is available in most rural areas without issue. Yes there are some issues with attracting doctors & specialist to live outside major metro areas, but my understanding is that's true in the U.S. as well.

I live a rural area a 3hr drive (including ferry time) from a major city centre, but have a nice public health clinic 15 minutes from my house. Ambulances can reach my home in 8 minutes. We have a quite capable hospital 45 minutes drive away which has air evac capability. Advanced healthcare (eg cancer, cardiac care) is available at regional hospitals, with no-cost transport for care.

I had a heart attack a couple of months ago, and received world-class care including open-heart surgery. During that time of extreme stress for me and my family, not for one minute did I think about the financial consequences other than missing some income while I was unable to work.

I don't think of our medical system as being 'free' - I paid for that care through my taxes and a modest premium (today around $75/month per person - BC is I think the last province to still have user-paid premiums and they're scheduled to be phased out over the next couple of years).

I'm really happy with the value for $ spent. Our health care system costs taxpayers just over $4,000 CAD per person per year. Other figures put the total health care spending (including other services such as dental, chiropractic care, etc) at about $6,000 CAD /person/year. OECD sourced figures put the U.S at about $12,000 CAD /person/year. The statement that universal health care must be more expensive than a privately administered system ("money would be stuffed into an inefficient system") is simply a myth.

Again, it seems like your comments are nothing but fear-mongering. Perhaps you honestly believe them. Please consider that you might be simply repeating the arguments you've been given by those with a vested interest in keeping the U.S. system as it is now in place.

To be fair: our Canadian system isn't perfect. Some people fall through the cracks. Some people fight with their insurer (the government) about coverage for rare chronic conditions. Not everyone is completely happy with the system or the treatment they receive. I'm pretty certain that those same statements can be made of any health care system in the world. But for the vast majority of our citizens, including those like me that live in fairly rural areas, it functions pretty well.

https://www.cihi.ca/en/how-does-canadas-health-spending-comp...

Just have separate healthcare systems for each state. There, problem solved.

I mean I don't blame you. A system which worked for you in the past because of your privileges will continue to work for you and will be able to offer you even greater services because you are able to pay for it. Just a damn shame for people who can't afford it. Too bad.

Wait. I do blame you. I also want to remind you that people die in civilised countries of illnesses which can be cured but they can't afford it. And it's because of people which are full of ignorance.

Idealists like you are why 100 million+ died due to communism in the 20th century.

We've gone from borderline stone-age medical treatment where basic surgery was impossible and simple infections untreatable to where we are today in less than a century. Is everything perfect right now? No, but it's improving steadily and I think with the current advances affordable health care will be possible within the next 10-20 years without government mandating it.

this is historically illiterate, and frankly insulting. if there is any starry eyed idealist here it's.. you.

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How do you reconcile these ideas with the fact that most developed countries do have free universal healthcare and are doing fine?

As I stated in another post, their health care is subsidized massively by the US acting as a profit center to fund drug and medical technology development.

The US produces a disproportionate amount of new drugs, other countries mostly create cheaper and easier to make follow on drugs. Get rid of the profit motive and new drug creation grinds to a halt.

https://qph.fs.quoracdn.net/main-qimg-7fa1b6167f99405f82524d...

Uh, looks like if you combine all European countries on this sketchy chart, as one should considering it's only fair to compare markets of similar amounts of population, their output looks similar to USA's.

This says Western Europe alone is responsible for 22% of pharma revenue, as opposed to 33% from all of the United States: https://www.statista.com/statistics/784420/share-of-worldwid...

Surely there can be some kind of balanced situation where drug and technology development can still be profitable in the US but impoverished people can still get free healthcare instead of avoiding doctor/hospital visits and dying?

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> Health care is expensive because of basic supply and demand,

Please can you explain the principle behind certificates of need, used in the US?

Because they seem to imply that greater supply will increase, not decrease, cost.

Its all fun and games until you suddenly have chronic kidney failure diagnosed - doubt you'd be singing the same tune then

Wait, you really have no idea how taxes work in Europe? Higher taxes are an investment, not an expense.

The public pays higher taxes for free education for example so our future doctors aren't 500k in debt when they graduate.

Students entering the programs understand this, hence when they graduate they make lower salaries and then pay onto the next generations future.

Taxes are an investment in society, you get positive return on them.

Just lol at the completely broken US system of education, health care and social services. You live in a third world country, I honestly feel bad for you.

But you end up paying even more through insurance premiums than if you had paid it out straight to medical companies through your taxes. How does paying an entire middleman for-profit industry magically make things cheaper?

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