[HN Gopher] Pig heart transplant failed as its heart muscle cell...
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Pig heart transplant failed as its heart muscle cells died
Author : samizdis
Score : 197 points
Date : 2022-06-24 17:52 UTC (1 days ago)
(HTM) web link (arstechnica.com)
(TXT) w3m dump (arstechnica.com)
| walrus01 wrote:
| At this point in order to be a candidate for such a
| risky/previously untested procedure, doesn't the person need to
| be in an absolute worst case scenario, where they've been
| rejected for all forms of human heart or artificial transplant
| and highly likely to die soon?
| atian wrote:
| Huh? He was.
| beowulfey wrote:
| So then, if it does not work in those conditions, what's the
| point?
| ceejayoz wrote:
| It allows you to test the heart in a human patient without
| worsening their prognosis.
|
| Validating that it's possible allows for carefully
| expanding to the patients _not_ undergoing massive multi-
| system organ failure at the time.
| mlyle wrote:
| It may have extended life even in this first time. And now
| we have a bunch of data to try and identify what exactly
| went wrong.
|
| We can try a couple a year, steadily improving until we
| ultimately get lucky and someone's life is significantly
| extended.
| barry-cotter wrote:
| He was going to die without this. It would have been
| immoral to give him a human donor heart that could have
| gone to someone who could have lived ten or more years with
| it. Every pig heart transplant they'll get better at it
| until eventually if you need a heart transplant you'll just
| get one.
|
| That's the point.
| russfink wrote:
| What I take from your question is, were the other health
| issues the thing that actually killed the heart? Following
| from that, how can we declare something not successful when
| the odds are significantly stacked against it from the
| start?
| davidkuennen wrote:
| That's exactly the situation he was in.
| u1tron wrote:
| krapp wrote:
| We "temper and replace" body parts that "God created" all the
| time, including hearts. WTF are you even on about?
| ogogmad wrote:
| What made the patient so unwell? I can't access the original
| paper.
|
| [edit]
|
| _A 57-year-old man with chronic mild thrombocytopenia,
| hypertension, nonischemic cardiomyopathy, and previous mitral
| valve repair was hospitalized for severe heart failure with a
| left ventricular ejection fraction (LVEF) of 10%. His care was
| escalated to include multiple intravenous inotropic agents, and
| the placement of an intraaortic balloon pump was added on
| hospital day 11. Despite these measures, he had multiple
| ventricular arrythmias with arrests leading to resuscitation and
| began to receive peripheral venoarterial extracorporeal membrane
| oxygenation (ECMO) on hospital day 23._
|
| Sad.
| Aeolun wrote:
| That was before the transplant. Things were arguably a bit
| better for 7 weeks afterwards.
| typest wrote:
| The heart is fundamentally a pump. Are we not able to build a
| replacement? I understand it's not simple at all, and that people
| have tried and failed in the past, but is an artificial heart
| something that we should be able to build?
| tremon wrote:
| IIRC, the problem with conventional mechanical pumps is that
| they're continuous-flow. Various other systems in the human
| body rely in the ebb-and-flow of a pumping heart to function
| correctly, and different activities require different flow
| speeds. Yes, we can probably engineer a variflow pump as well,
| and maybe also one that increases and decreases its flow based
| on hormonal signaling, but it's not as simple as taking your
| average aquarium pump and connecting it in-place. AFAIK, we
| have no idea how the heart determines its flow rate.
| usrn wrote:
| I was under the impression there were implantable impeller
| style pumps that people used to replace the heart while
| waiting for a transplant.
| ceejayoz wrote:
| They don't replace, they assist. Longest one has lasted is
| seven years.
| https://en.wikipedia.org/wiki/Ventricular_assist_device
| davikr wrote:
| It might be a significantly hard problem: for instance,
| artificial heart valves tend to get infected by bacteria, and
| if it were the case for a whole artificial heart to get
| infected, perhaps it could spread and cause damage to the
| mediastinum (or), maybe, sepsis.
| DoreenMichele wrote:
| Significantly, the body does a poor job of fighting infection
| that occurs in artificial heart valves.
| madelyn wrote:
| Artificial hearts already exist. But they usually are only used
| while waiting for transplants, because they're not as good as
| the real deal.
|
| Hearts are critical infrastructure in the body, with 100%
| uptime requirements and not-insignificant energy consumption.
| nradov wrote:
| Artificial hearts have existed for years but require an
| external power source to operate the pump. They can generally
| only be used for a limited time while waiting for a transplant.
|
| https://syncardia.com/clinicians/our-products/freedom-portab...
| seren wrote:
| Carmat has been working on it for a few decades. I believe they
| have not been approved yet by the FDA but are in the clinical
| trials phase.
|
| https://www.carmatsa.com/en/
| koheripbal wrote:
| The point is that his heart failed, not some other organ, and
| while it was functional for a time, the surgeons had stated that
| it would be functional for longer.
|
| While you can soften the failure by highlighting the patient's
| broad systemic issues, this is still a notable failure that will
| likely put a damper on future similar pig transplants.
| picsao wrote:
| Retric wrote:
| The first human to human heart transplant failed even sooner
| and was considered wildly successful. Edit: Even though the
| immunosuppressants ended up killing him.
|
| 7 weeks doesn't sound like long, but a great many things needed
| to work for the patient to survive even 1 week.
| eterm wrote:
| I just looked to fact check this, and all the sources I can
| find says the patient died of pneumonia, not heart failure
| and that the heart didn't fail and continued to work up until
| death.
|
| So no, the first transplant didn't "fail even sooner" because
| it wasn't the heart that failed.
| steve76 wrote:
| Retric wrote:
| The heart didn't directly fail, however the procedure
| failed due to the immunosuppressants used.
|
| "After Washkansky's surgery, he was given drugs to suppress
| his immune system and keep his body from rejecting the
| heart. These drugs also left him susceptible to sickness,
| however, and 18 days later he died from double pneumonia."
| ceejayoz wrote:
| Very different contexts.
|
| Before human heart transplantation was available, you could
| pick someone with severe heart disease but otherwise in
| good condition as a test candidate. It was entirely
| ethical; they'd die without the transplant anyways.
|
| Now that we have viable human heart transplantation, you
| have to pick sicker patients as candidates - people who
| wouldn't survive _even if_ they got a human heart
| transplant. Giving someone who 'd survive with a human
| heart an experimental pig heart isn't ethical.
|
| It makes sense that the failure model would be different.
| mort96 wrote:
| Is there no shortage of human hearts to transplant? Don't
| you have people who would live with a human heart
| transplant, but where the risk of waiting a short period
| of time for a pig heart transplant is about the same as
| the risk of waiting a long period of time for a human
| heart transplant?
|
| I mean if we do have enough human hearts to transplant
| into anyone who needs it I suppose that's a good thing,
| but all I hear about transplants is how long the wait
| times usually are for human organs.
| Retric wrote:
| The shortage means the people likely to survive longest
| after transplant get preferential treatment.
|
| Which means if someone has stage 4 cancer etc they aren't
| on the list.
| arbitrage wrote:
| You're being wildly pessimistic.
|
| The first human heart transplant was successful for a little
| less than three weeks, until the patient died of systemic organ
| failure. That procedure is historically regarded as wildly
| successful.
|
| A team of medical scientists did something even more amazing.
| This procedure was a success. The next one will be better.
| ambyra wrote:
| I think so too. I wonder if they are considering editing more
| genes to make the heart more human. I bet 100 years from now,
| there will genetically modified pigs running around with
| human hearts, and other modifications to support that heart.
| mrjin wrote:
| His heart was failing for some reason(s). I don't see how
| transplant would ever make those go away, at best it would only
| buy him some time allowing those reasons to be removed. In some
| lucky cases, those do get removed automatically but I would
| expect in most of the cases, they would be left intact and will
| eventually cause heart to fail again soon. This does not even
| consider the immune system reactions, taking those into
| consideration, the chance would be very little.
| BurningFrog wrote:
| If the reason is a faulty heart, replacing the heart makes
| the reason go away.
| rkangel wrote:
| > that will likely put a damper on future similar pig
| transplants
|
| I should hope not. Not everything works first time. Hopefully
| it gives data such that the next one works for 16 weeks, and
| the one after that for 3 months, until this is a standard
| source of transplant organs.
| Aeolun wrote:
| Ah well, if you'll likely die tomorrow then even 7 weeks is
| pretty good.
|
| Not sure that's a good trade for the pig though.
| _ph_ wrote:
| Good question. Maybe not, maybe actually yes. Using animals
| for transplants gives place for all kind of discussions.
| But this pig only existed as it was raised for that
| purpose. Like basically all pigs, which are raised for meat
| production. In contrast to those, the pig in question was
| probably well raised in good conditions and fed quality
| food and no bad pharmaceuticals. And indeed, humans use
| many animals, a lot of that use involves their deaths. But
| here it at least isn't for some random food, and a lot of
| meat just goes waste, but to keep a human alive. That is at
| least a very good reason.
| Aeolun wrote:
| For the humans. I very much doubt the pig sees it that
| way (or would see it that way, if they were human).
|
| Don't misunderstand me, I love meat, and while I think
| that killing pigs (at least someone else killing pigs) is
| acceptable for that purpose, I would have a harder time
| justifying killing a whole pig to keep someone alive a
| little longer. For the same reasons we don't just raise
| humans as cattle to use as organ transplant sources. We
| tell ourselves that it is acceptable with pigs, and while
| this certainly makes it easier on the humans (and they
| grow faster), I'm not sure it's fundamentally different.
| ceejayoz wrote:
| Isn't killing a pig for meat technically "killing a whole
| pig to keep someone alive a little longer" too?
|
| I'm a little baffled by your ethical calculus here.
| Raising pigs for muscle to eat seems substantially _less_
| ethical than raising pigs for organs to transplant; you
| can eat plant-based alternatives, but good luck pumping
| blood with a soybean.
| edmcnulty101 wrote:
| I don't understand how killing pigs for meat to eat to
| survive is different than killing pigs for a heart to
| implant to survive.
| flatiron wrote:
| It's very easy to sympathize with the pig. But, if a
| doctor came into the room and said "a pig or your
| daughter" what would anyone say?
| Fargoan wrote:
| What if there were humans who only existed because they
| were bred and raised for organ transplant? It wouldn't
| surprise me if this already exists.
| maxerickson wrote:
| Why would the failure of one extremely experimental transplant
| put a damper on subsequent extremely experimental transplants?
|
| Is the idea that they should have it all worked out before they
| even try it?
| adinb wrote:
| It's because they don't know _why_ the heart muscles died.
| Aeolun wrote:
| Ideally, yes? I mean it would be strictly better. I'm not
| saying they shouldn't try even though they don't.
| bartread wrote:
| That's why it's called an experimental treatment, and is
| why you only try it out on people who will certainly die if
| only treated in more conventional ways. You can't possibly
| have everything worked out before you try an experimental
| treatment by it's very definition. It's inherently risky,
| but it's also a very important way in which medical science
| is advanced.
| amelius wrote:
| Did they try it on other primates first?
| shagie wrote:
| Yes.
|
| https://www.independent.co.uk/news/science/pig-heart-
| monkey-...
|
| https://www.bbc.com/news/science-environment-35969109
|
| https://www.scientificamerican.com/article/baboons-
| survive-f...
| [deleted]
| feet wrote:
| The human body is a system, I'm not a physiologist so I don't
| fully understand everything. That being said, if organs which
| normally supply some sort of supportive function to the heart
| no longer work, it's definitely possible for the heart to fail
| first. The heart is a mechanical pump remember, easy for it to
| fail
| rob_c wrote:
| So completely reliable virus testing there because we now from
| the last 2 years that's 100% reliable. Clearly did a full genomic
| sequencing...
| yread wrote:
| I just love that there is an H&E slide on article cover of Ars
| jwilk wrote:
| What's H&E?
| isaacimagine wrote:
| Hematoxylin and eosin stain.
|
| https://en.wikipedia.org/wiki/H%26E_stain
| imwillofficial wrote:
| rightbyte wrote:
| Wasn't that lab monkeys?
| iasay wrote:
| The chimps were artificially infected with rage. The original
| rage was isolated from someone after 30 minutes in visual
| studio classic on a corporate managed Citrix deployment.
| ccrush wrote:
| lol, well done!
| phoe-krk wrote:
| Gods, Hacker News does manage to surprise me every now and
| then. Here, have an upvote, and thank you for the laugh.
| bluedino wrote:
| Transplanting organs is an amazing feat of science.
|
| However, how does it make any financial sense? This one of those
| things that makes sense to cut when you start talking universal
| healthcare, right?
| DoreenMichele wrote:
| It makes for razzle dazzle headlines. That seems to keep it
| alive.
|
| I wish there was more emphasis on helping people keep their
| original equipment from the manufacturer, so to speak.
| sokoloff wrote:
| There are a lot of surgeries and novel treatments that don't
| make any financial sense. We don't make healthcare decisions on
| a P&L basis, but hopefully on some kind of cost vs expected
| benefit to the patient basis.
|
| Transplanting a kidney or liver into a 20 year old has more of
| my support than transplanting a heart into an 85 year old.
| maxerickson wrote:
| The financial sense comes down to how you are measuring the
| value provided, there's not a single objective way to do it.
|
| Systems that use QALYs still often end up considering organ
| transplants a viable treatment.
| cardy31 wrote:
| Transplants exist in all universal healthcare systems around
| the world. Due to the scarcity of donor organs and the cost,
| candidates for transplantation are heavily scrutinized to make
| sure the organ is used in the best way possible.
|
| In relation to this article, part of the genetic engineering of
| the pig is to try to not just have a human not reject it, but
| possibly to end up having the pig heart be less likely to
| reject than a human heart.
|
| If the chance of rejection can be reduced, that means fewer
| drugs over time, and lower cost to a universal healthcare
| system.
|
| Also, reliable transplantation would reduce long term
| traditional healthcare costs. For example, in the US dialysis
| is basically the one procedure with universal healthcare. If
| kidney transplantation was readily available with a low risk of
| rejection it could actually save the US a lot of money at this
| point.
| Qem wrote:
| People suffer accidents, and in absence of donation, perfectly
| fine organs would just rot with them in the grave. With
| transplants, we take these organs that would otherwise be
| wasted, and give other people maybe years or decades of
| additional productive life. The overall economic impact must be
| overwhelmingly positive to society as a whole.
| DoreenMichele wrote:
| _According to the web site Transplant Living, created by the
| United Network for Organ Sharing, the average total cost for
| the first year for a double lung transplant costs $657,800._
|
| And then you take immunosuppressive drugs the rest of your
| life.
|
| https://www.chron.com/neighborhood/katy/news/article/The-
| cos...
|
| Also, bear in mind the FTA is about an artificially
| engineered pig heart, not a human heart.
| DoreenMichele wrote:
| _But the reason for that death isn 't clear, and the typical
| signs of rejection by the immune system weren't present._
|
| Perhaps because it involved a pig heart, not a human heart? If
| this is new territory, I see no reason to expect failure to
| follow "typical" patterns.
| rdmirza wrote:
| That's a great thought, however, when you look at tissue under
| a microscope you should see evidence that the immune system was
| at play. This means the presence of complement activation (an
| ancient arm of the immune system), antibodies, white blood
| cells, nuclear debris, and so on. Presumably when they saw no
| evidence of immune mediated rejection, they saw none of this.
| DoreenMichele wrote:
| My lay person understanding as someone with a condition where
| people get a lot of transplants is that we don't actually
| know what causes rejection.
|
| Perhaps in some cases the organ contains unidentified
| infective agents, thus the typical pattern with white blood
| cells etc.
|
| Perhaps in this case the body decided it was straight up
| foreign matter and the process of failure was fundamentally
| different.
| balanoceous wrote:
| Your point that this is uncharted territory is well-taken,
| we can't say for sure, but the above poster has it right. I
| do not know of any circumstance in medicine in which
| evidence of immune reaction against foreign material would
| be non-obvious. I'm a pathologist and this is my area of
| expertise.
| DoreenMichele wrote:
| To be clear, I have two points:
|
| 1. This is uncharted territory.
|
| 2. My understanding is we don't actually understand
| "normal" rejection all that well to begin with.
|
| If we don't know how and why rejection occurs to begin
| with, we have no reasonable means to distinguish it from
| some other type of failure.
|
| But I shall stop annoying professionals with my amateur
| opinions here.
|
| Have a good day.
| markus92 wrote:
| We may not know what causes rejection, but are pretty
| good at seeing the signs of it. Extreme example: if a
| house collapses, you may not know immediately why it
| collapsed, but all the debris on the ground is a pretty
| good sign it's not in one piece anymore.
| DoreenMichele wrote:
| Rejection leads to death.
|
| The guy died.
|
| Anyway, trying to walk away from this particular thread.
| [deleted]
| polishdude20 wrote:
| What if it's something like the human blood cells stop
| delivering oxygen and nutrients to those tissues for one
| reason or another?
| cardy31 wrote:
| Transplantation of organs from animals into humans has been
| tried in the past. Because of that, we know what full on
| rejection of non-human organs looks like.
|
| It sounds like this was actually quite successful in that the
| immune system didn't immediately start attacking it, as would
| be the case with a normal pig heart.
| dvh wrote:
| Isn't there a risk of introducing new zoonotic diseases?
| labtheory wrote:
| [deleted]
| rwmj wrote:
| Very much - hence why the pig is "raised in conditions that
| should limit pathogen exposure" and the multiple virus tests on
| both the heart and the patient before and after the transplant.
| And even then they missed one pig virus.
| Metacelsus wrote:
| >raised in conditions that should limit pathogen exposure
|
| Except the pig still got porcine CMV from somewhere.
| ceejayoz wrote:
| Maybe.
|
| > the researchers indicate there's some question about
| whether the tests that picked it up might have been
| recognizing a closely related human virus
| mlyle wrote:
| Maybe
|
| > The presence of an apparent pig cytomegalovirus was
| worrying, but the researchers indicate there's some question
| about whether the tests that picked it up might have been
| recognizing a closely related human virus--one that's often
| associated with organ transplant problems.
| londons_explore wrote:
| Yes - the risk is substantially higher because blood flow will
| allow a virus to move from one tissue type to the other very
| efficiently repeatedly, and immune response is reduced but not
| eliminated allowing rapid adaption.
|
| As a society we need to think about the ethics implications of
| using this technique to save some lives while dramatically
| increasing the risk of zoonotic viruses which will impact many
| others.
| marsven_422 wrote:
| slowhand09 wrote:
| My friend was a member of the transplant team for this. Their
| explanation was this. His physical condition overall was pretty
| bad by the time this transplant occurred. He was on the edge of
| multiple organ failure for weeks afterwards. While his heart was
| pretty strong, his organs in general were compromised, and in
| poor condition to support each other.
|
| I'm not a medical professional. But I have been present and
| watched multiple people of systemic failures.
| idealmedtech wrote:
| I'd be very curious to see what the glucose/lactic acid curve
| looked like during and after the transplant! Usually it's a
| good leading indicator of broader issues. We've done a few
| studies in swine (they're the gold standard of blood sugar
| modelling) and if an animal was not doing well, we'd always see
| a spike in lactic acid right before death.
| pazimzadeh wrote:
| The number of people working on xenotransplantation in the
| world is very small. My mom (https://tts.org/74-ixa/889-ixa-in-
| memoriam-agnes-marie-azimz...) was part of the group who
| conducted basic research in xeno at the University of Maryland
| and established the collaboration to start testing Revivicor's
| genetically modified pigs, before her lab (https://www.massgene
| ral.org/transplant/cts/research/pierson-...) moved to Boston a
| few years ago.
|
| The international xenotransplantation community found out about
| David Bennett's heart transplant through the news, and some
| people feel as though competition between groups may have
| contributed to a lack of sharing of clinically relevant
| information that could have benefited Mr. Bennett.
| hericium wrote:
| Do you maybe know if they just wanted to check if it will work
| for some time or hoped that failing organs may benefit from new
| heart?
| petra wrote:
| Given that pig heart transplants are only a candidate for
| people that are a really bad shape, how does your friend see
| this field advance after this current result?
| DocTomoe wrote:
| The idea is that right now, this is only for people in really
| bad shape, but with advances and experience, this may become
| a more standard thing for people in less bad shape.
|
| You first try the new, experimental drug on people who may
| die soon anyways, before you hand it out like smarties at the
| local drugstore.
| throwaway48292 wrote:
| Still have to get through that stage though with some good
| results to show for it, even if we suspect healthy bodies
| would handle it much better (although I wouldn't personally
| lose faith based on one instance)
| ceejayoz wrote:
| Seven weeks with no sign of immune rejection _is_ a good
| result here, for the very first attempt. It 's largely
| what they would have been hoping for.
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